Meetings by month

January

05/01/2018

Mahesh's paper

The Suzuki–Miyaura Coupling of Nitroarenes

M. Ramu Yadav, Masahiro Nagaoka, Myuto Kashihara, Rong-Lin Zhong, Takanori Miyazaki, Shigeyoshi Sakaki , and Yoshiaki Nakao

Synthesis of biaryls via the Suzuki–Miyaura coupling (SMC) reaction using nitroarenes as an electrophilic coupling partners is described. Mechanistic studies have revealed that the catalytic cycle of this reaction is initiated by the cleavage of the aryl–nitro (Ar–NO2) bond by palladium, which represents an unprecedented elemental reaction.

 

 

 

 

 

 

 

Enantio- and diastereoselective synthesis of trans-2,3-disubstituted indanones is achieved by intramolecular hydroacylation of 2-alkenylbenzaldehydes bearing trisubstituted alkenyl groups under cobalt-chiral diphosphine catalysis. Notably, a high level of enantioselectivity is induced regardless of the stereochemistry (E/Z ratio) of the alkenyl group of the starting material. Deuterium-labeling experiments shed light on the productive reaction pathways of the E- and Z-isomers.

Youssef's paper

Oxidative Entry into the Illicium Sesquiterpenes: Enantiospecific Synthesis of (+)-Pseudoanisatin

Kevin Hung§, Matthew L. Condakes§, Takahiro Morikawa, and Thomas J. Maimone

Graphical abstract

Abstract Image

Illicium sesquiterpenes have been the subject of numerous synthetic efforts due to their ornate and highly oxidized structures as well as significant biological activities. Herein we report the first chemical synthesis of (+)-pseudoanisatin from the abundant feedstock chemical cedrol (∼$50 USD/kg) in 12 steps using extensive site-selective C(sp3)–H bond functionalization. Significantly, this work represents a novel oxidative strategic template for future approaches to these natural products and their analogs.

February

03/02/2017

Youssef's paper

Catalytic Asymmetric Bromocyclization of Polyenes

Ramesh C. Samanta* and Hisashi Yamamoto*

Graphical abstract

Abstract Image

 

 

 

 

 

 

The first catalytic asymmetric bromonium ion-induced polyene cyclization has been achieved by using a chiral BINOL-derived thiophosphoramide catalyst and 1,3-dibromo-5,5-dimethylhydantoin as an electrophilic bromine source. Bromocyclization products are obtained in high yields, with good enantiomeric ratios and high diastereoselectivity, and are abundantly found as scaffolds in natural products.

Adrian's paper

Cobalt-catalysed C–H carbonylative cyclisation of aliphatic amides

Patrick Williamson, Alicia Galvána and Matthew J. Gaunt

Graphical abstract

Graphical abstract: Cobalt-catalysed C–H carbonylative cyclisation of aliphatic amides

A cobalt-catalysed C–H carbonylation of aliphatic carboxamide derivatives is described, employing commercially available Co(II)-salts in the presence of a silver oxidant. This operationally simple process utilises an atmospheric pressure of CO and generates a range of substituted succinimide products bearing diverse functional groups that can be successfully accessed via this methodology.

Pol's paper

Water-Enabled Catalytic Asymmetric Michael Reactions of Unreactive Nitroalkenes: One-Pot Synthesis of Chiral GABA-Analogs with All-Carbon Quaternary Stereogenic Centers

Jae Hun Sim, Prof. Choong Eui Song

Graphical abstract

Figure 1.

Water enables new catalytic reactions for otherwise unreactive substrate systems. Under the “on water” reaction conditions, extremely unreactive β,β-disubstituted nitroalkenes smoothly underwent enantioselective Michael addition reactions with dithiomalonates using a chiral squaramide catalyst, affording both enantiomers of highly enantioenriched Michael adducts with all-carbon-substituted quaternary centers. The developed “on water” protocol was successfully applied for the scalable one-pot syntheses of chiral GABA analogs with all-carbon quaternary stereogenic centers at the β-position, which might show highly interesting pharmaceutical properties.

Christian's paper

Unique physicochemical and catalytic properties dictated by the B3NO2 ring system

Hidetoshi Noda, Makoto Furutachi, Yasuko Asada, Masakatsu Shibasaki & Naoya Kumagai

Graphical abstract

Chemical space for six-membered heterocycles composed of B, C, N and O atoms and the structure of DATBs.

The expansion of molecular diversity beyond what nature can produce is a fundamental objective in chemical sciences. Despite the rich chemistry of boron-containing heterocycles, the 1,3-dioxa-5-aza-2,4,6-triborinane (DATB) ring system, which is characterized by a six-membered B3NO2 core, remains elusive. Here, we report the synthesis of m-terphenyl-templated DATB derivatives, displaying high stability and peculiar Lewis acidity arising from the three suitably arranged boron atoms. We identify a particular utility for DATB in the dehydrative amidation of carboxylic acids and amines, a reaction of high academic and industrial importance. The three boron sites are proposed to engage in substrate assembly, lowering the entropic cost of the transition state, in contrast with the operative mechanism of previously reported catalysts and amide coupling reagents. The distinct mechanistic pathway dictated by the DATB core will advance not only such amidations, but also other reactions driven by multisite activation.

10/02/2017

Wouter's paper

Chemical Stabilization of Unnatural Nucleotide Triphosphates for the in Vivo Expansion of the Genetic Alphabet

Aaron W. Feldman, Vivian T. Dien, and Floyd E. Romesberg

Graphical abstsract

Abstract Image

 

We have developed an unnatural base pair (UBP) and a semisynthetic organism (SSO) that imports the constituent unnatural nucleoside triphosphates and uses them to replicate DNA containing the UBP. However, propagation of the UBP is at least in part limited by the stability of the unnatural triphosphates, which are degraded by cellular and secreted phosphatases. To circumvent this problem, we now report the synthesis and evaluation of unnatural triphosphates with their β,γ-bridging oxygen replaced with a difluoromethylene moiety, yielding dNaMTPCF2and dTPT3TPCF2. We find that although dNaMTPCF2 cannot support in vivo replication, likely due to poor polymerase recognition, dTPT3TPCF2 can, and moreover, its increased stability can contribute to increased UBP retention. The data demonstrate the promise of this chemical approach to SSO optimization, and suggest that other modifications should be sought that confer phosphatase resistance without interfering with polymerase recognition.

Richard's paper

Pd-Catalyzed Conversion of Aryl Iodides to Sulfonyl Fluorides Using SO2 Surrogate DABSO and Selectfluor

Ariana L. Tribby†, Ismeraí Rodríguez†, Shamira Shariffudin‡, and Nicholas D. Ball

Graphical abstsract

Abstract Image

A one-pot Pd-catalyzed conversion of aryl iodide to aryl sulfonyl fluorides using DABSO and selectfluor has been developed generating aryl sulfonyl fluorides in good to excellent yields. The reaction results in the generation of electronically and sterically diverse sulfonyl fluorides. Additionally, sulfonyl fluorides can be converted to aryl sulfonamides and sulfonic esters using Cs2CO3 under mild conditions.

Christian's paper

The development and mechanistic investigation of a palladium-catalyzed 1,3-arylfluorination of chromenes

Richard T. Thornbury,a Vaneet Saini,b Talita de A. Fernandes,ac Celine B. Santiago,d Eric P. A. Talbot,ab Matthew S. Sigman,d Jeffrey M. McKennab and F. Dean Toste

Graphical abstsract

Graphical abstract: The development and mechanistic investigation of a palladium-catalyzed 1,3-arylfluorination of chromenes

 

 

 

 

 

A mild palladium-catalyzed ligand-controlled regioselective 1,3-arylfluorination of 2[H]-chromenes has been developed. The products with a syn-1,3 substitution pattern were obtained with high enantiomeric excess using a PyrOx ligand, wherein the utility of these pyranyl-fluorides was further demonstrated through their participation in a diastereoselective C–C bond forming reaction. Ligand dependent divergent formation of both the 1,3- and 1,2- alkene difunctionalization products was observed. The nature of this bifurcation was investigated through experimental studies in combination with computational and statistical analysis tools. Ultimately, the site selectivity was found to rely on ligand denticity and metal electrophilicity, the electronics of the boronic acid, and the donor ability of the directing group in the substrate.

 

17/02/2017

Richard's paper

Visible Light Copper Photoredox-Catalyzed Aerobic Oxidative Coupling of Phenols and Terminal Alkynes: Regioselective Synthesis of Functionalized Ketones via C≡C Triple Bond Cleavage

Arunachalam Sagadevan, Vaibhav Pramod Charpe, Ayyakkannu Ragupathi, and Kuo Chu Hwang

Graphical abstract

Abstract Image

Direct oxidative coupling of phenols and terminal alkynes was achieved at room temperature by a visible-light-mediated copper-catalyzed photoredox process. This method allows regioselective synthesis of hydroxyl-functionalized aryl and alkyl ketones from simple phenols and phenylacetylene via C≡C triple bond cleavage. 47 examples were presented. From a synthetic perspective, this protocol offers an efficient synthetic route for the preparation of pharmaceutical drugs, such as pitofenone and fenofibrate.

Lukas's paper

Chemoselective Acylation of Primary Amines and Amides with Potassium Acyltrifluoroborates under Acidic Conditions

Alberto Osuna Gálvez, Cédric P. Schaack, Hidetoshi Noda, and Jeffrey W. Bode*

Graphical abstract

Abstract Image

Current methods for constructing amide bonds join amines and carboxylic acids by dehydrative couplings—processes that usually require organic solvents, expensive and often dangerous coupling reagents, and masking other functional groups. Here we describe an amide formation using primary amines and potassium acyltrifluoroborates promoted by simple chlorinating agents that proceeds rapidly in water. The reaction is fast at acidic pH and tolerates alcohols, carboxylic acids, and even secondary amines in the substrates. It is applicable to the functionalization of primary amides, sulfonamides, and other N-functional groups that typically resist classical acylations and can be applied to late-stage functionalizations.

Christian's paper

Light-Driven Enantioselective Organocatalytic β-Benzylation of Enals

Dr. Luca Dell'Amico, Dr. Victor M. Fernández-Alvarez, Prof. Dr. Feliu Maseras, Prof. Dr. Paolo Melchiorre

Graphical abstract

Figure 1.

A photochemical organocatalytic strategy for the direct enantioselective β-benzylation of α,β-unsaturated aldehydes is reported. The chemistry capitalizes upon the light-triggered enolization of 2-alkyl-benzophenones to afford hydroxy-o-quinodinomethanes. These fleeting intermediates are stereoselectively intercepted by chiral iminium ions, transiently formed upon condensation of a secondary amine catalyst with enals. Density functional theory (DFT) studies provided an explanation for why the reaction proceeds through an unconventional Michael-type addition manifold, instead of a classical cycloaddition mechanism and subsequent ring-opening.

24/02/2017

Wouter's paper

Azido and Tetrazolo 1,2,4,5-Tetrazine N-Oxides

Dr. David E. Chavez, Dr. Damon A. Parrish, Dr. Lauren Mitchell, Dr. Greg H. Imler

Graphical abstract

Figure 1.

 

This study presents the synthesis and characterization of the oxidation products of 3,6-diazido-1,2,4,5-tetrazine (1) and 6-amino-[1,5-b]tetrazolo-1,2,4,5-tetrazine (2). 3,6-Diazido-1,2,4,5-tetrazine-1,4-dioxide was produced from oxidation with peroxytrifluoroacetic acid, and more effectively using hypofluorous acid, and 2 can be oxidized to two different products, 6-amino-[1,5-b]tetrazolo-1,2,4,5-tetrazine mono-N-oxide and di-N-oxide. These N-oxide compounds display promising performance properties as energetic materials.

Lukas's paper

Catalytic Asymmetric Intramolecular [4+2] Cycloaddition of In Situ Generated ortho-Quinone Methides

Dr. Youwei Xie, Prof. Dr. Benjamin List

Graphical abstract

Figure 1.

 

 

 

 

 

Herein, we describe the first catalytic asymmetric intramolecular [4+2] cycloaddition of in situ generated ortho-quinone methides. In the presence of a confined chiral imidodiphosphoric acid catalyst, various salicylaldehydes react with dienyl alcohols to give transient ortho-quinone methide intermediates, which undergo an intramolecular [4+2] cycloaddition to provide highly functionalized furanochromanes and pyranochromanes in excellent diastereoselectivity and enantioselectivity.

Pol's paper

Highly Regio- and Enantioselective Vicinal Dihalogenation of Allyl Amides

Bardia Soltanzadeh†, Arvind Jaganathan‡, Yi Yi†, Hajoon Yi†, Richard J. Staples†, and Babak Borhan

Graphical abstract

Abstract Image

 

We report a highly regio-, diastereo- and enantioselective vicinal dihalogenation of allyl amides. E- and Z-alkenes with both aryl and alkyl substituents were compatible with this chemistry. This is the result of exquisite catalyst controlled regioselectivity enabling use of electronically unbiased substrates. The reaction employs commercially available catalysts and halenium sources along with cheap inorganic halide salts to affect this transformation. A preliminary effort to extend this chemistry to heterodihalogenation is also presented.

March

03/03/2017

Adrian's paper

Construction of a visible light-driven hydrocarboxylation cycle of alkenes by the combined use of Rh(I) and photoredox catalysts

Kei Murata,a Nobutsugu Numasawa,a Katsuya Shimomaki,a Jun Takayaa and Nobuharu Iwasawa*a

Graphical abstract

Graphical abstract: Construction of a visible light-driven hydrocarboxylation cycle of alkenes by the combined use of Rh(i) and photoredox catalysts

A visible light driven catalytic cycle for hydrocarboxylation of alkenes with CO2 was established using a combination of a Rh(I) complex as a carboxylation catalyst and [Ru(bpy)3]2+ (bpy = 2,2′- bipyridyl) as a photoredox catalyst. Two key steps, the generation of Rh(I) hydride species and nucleophilic addition of π-benzyl Rh(I) species to CO2, were found to be mediated by light.

Christian's paper

Radical-polar crossover reactions of vinylboron ate complexes

Marvin Kischkewitz1, Kazuhiro Okamoto2, Christian Mück-Lichtenfeld1, Armido Studer

Graphical abstract

Vinyl boronic esters are valuable substrates for Suzuki-Miyaura cross-coupling reactions. However, boron-substituted alkenes have drawn little attention as radical acceptors, and the radical chemistry of vinylboron ate complexes is underexplored. We show here that carbon radicals add efficiently to vinylboron ate complexes and that their adduct radical anions undergo radical-polar crossover: A 1,2-alkyl/aryl shift from boron to the α-carbon sp2 center provides secondary or tertiary alkyl boronic esters. In contrast to the Suzuki-Miyaura coupling, a transition metal is not required, and two carbon-carbon bonds are formed. The valuable boronic ester moiety remains in the product and can be used in follow-up chemistry, enlarging the chemical space of the method. The cascade uses commercial starting materials and provides access to perfluoroalkylated alcohols, γ-lactones, γ-hydroxy alkylnitriles, and compounds bearing quaternary carbon centers.

 

10/03/2017

Lola's paper

Tf2NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles

Yingying Zhao†‡§, Yancheng Hu†§, Chunxiang Wang†, Xincheng Li*†, and Boshun Wan

Graphical abstract

Abstract Image

An unprecedented Tf2NH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

17/03/2017

Wouter's paper

Application of Methyl Bisphosphine-Ligated Palladium Complexes for Low Pressure N-11C-Acetylation of Peptides

Thomas L. Andersen, Dr. Patrik Nordeman, Heidi F. Christoffersen, Dr. Hélène Audrain, Prof. Dr. Gunnar Antoni, Prof. Dr. Troels Skrydstrup

Graphical abstract

Scheme 1.

A mild and effective method is described for 11C-labeling of peptides selectively at the N-terminal nitrogen or at internal lysine positions. The presented method relies on the use of specific biphosphine palladium–methyl complexes and their high reactivity towards amino-carbonylation of amine groups in the presence [11C]carbon monoxide. The protocol facilitates the production of native N-11C-acetylated peptides, without any structural modifications and has been applied to a selection of bioactive peptides.

Hossay's paper

Catalytic Asymmetric Diamination of Styrenes

Kilian Muñiz*†‡ , Laura Barreiro†§, R. Martín Romero†§, and Claudio Martínez

Graphical abstract

Abstract Image

 

 

 

 

 

 

An enantioselective catalytic vicinal diamination of styrenes is reported, which proceeds under entirely intermolecular reaction control. It relies on a chirally modified aryliodine(I) catalyst and proceeds within an iodine(I/III) manifold with conventional 3-chloroperbenzoic acid as a terminal oxidant. An environmentally benign solvent combination not only adds to the attractiveness of the process but also slows down the rate of the undesired background reaction. A total of 30 examples are presented, which consistently provide high enantiomeric excesses in the range 91–98%.

Pol's paper

Metal-Free Intermolecular Aminoarylation of Alkynes

Pauline T. G. Rabet, Scott Boyd, Prof. Michael F. Greaney

Graphical abstract

Scheme 1.

A metal-free aminoarylation of internal alkynes is described, yielding tetrasubstituted enaminoates. The transformation proceeds in good to excellent yields through a tandem conjugate addition/Smiles rearrangement involving aryl and heteroaryl sulfonamides. Substrate scope is very broad under simple, user-friendly conditions, and the reaction can be used to easily access biologically active phenethylamine derivatives.

 

24/03/2017

Pol's paper 

Photosensitizer-Free, Gold-Catalyzed C–C Cross-Coupling of Boronic Acids and Diazonium Salts Enabled by Visible Light

Sina Witzel, Jin Xie, Matthias Rudolph, A. Stephen K. Hashmi

Graphical abstract

Scheme 1.

The first photosensitizer-free visible light-driven, gold-catalyzed C–C cross-couplings of arylboronic acids and aryldiazonium salts are reported. The reactions can be conducted under very mild conditions, using a catalytic amount of tris(4-trifluoromethyl)phosphinegold(I) chloride [(4-CF3-C6H4)3PAuCl] with methanol as the solvent allowing an alternative access to a variety of substituted biaryls in moderate to excellent yields with broad functional group tolerance.

Wouter's paper

Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium

Zhang Feng, Qiao-Qiao Min, Xia-Ping Fu, Lun An & Xingang Zhang

Graphical abstract

A catalytic approach to difluoromethylated arenes using ClCF2H.

 

 

 

 

 

Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal–difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal–difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal–difluorocarbene complex catalysed reactions.

31/03/2017

Adrian‘s paper

Copper-catalyzed direct alkylation of heteroarenes

Cédric Theunissen,a Jianjun Wanga and Gwilherm Evano

Graphical abstract

Graphical abstract: Copper-catalyzed direct alkylation of heteroarenes

An efficient and broadly applicable process is reported for the direct alkylation of C–H bonds in heteroarenes, privileged scaffolds in many areas of science. This reaction is based on the copper-catalyzed addition of alkyl radicals generated from activated secondary and tertiary alkyl bromides to a wide range of arenes, including furans, thiophenes, pyrroles, and their benzo-fused derivatives, as well as coumarins and quinolinones.

Wouter’s paper

Ligand-Promoted meta-C−H Functionalization of Benzylamines

Dr. Peng Wang, Marcus E. Farmer, Prof. Dr. Jin-Quan Yu

Graphical abstract

Scheme 1.

 

 

 

 

 

 

Meta-C−H functionalization of benzylamines has been developed using a PdII/transient mediator strategy. Using 2-pyridone ligands and 2-carbomethoxynorbornene (NBE-CO2Me) as the mediator, arylation, amination, and chlorination of benzylamines are realized. This protocol features a broad substrate scope and is compatible with heterocylic coupling partners. Moreover, the loading of the Pd can be lowered to 2.5 mol % by using the optimal ligand.

Christian’ paper

Remote site-selective C–H activation directed by a catalytic bifunctional template

Zhipeng Zhang, Keita Tanaka & Jin-Quan Yu

Graphical abstract


Design of a cooperative bimetallic approach for remote, site-selective C–H activation.

 

 

 

In chemical syntheses, the activation of carbon–hydrogen (C–H) bonds converts them directly into carbon–carbon or carbon–heteroatom bonds without requiring any prior functionalization. C–H activation can thus substantially reduce the number of steps involved in a synthesis. A single specific C–H bond in a substrate can be activated by using a ‘directing’ (usually a functional) group to obtain the desired product selectively1, 2, 3, 4, 5. The applicability of such a C–H activation reaction can be severely curtailed by the distance of the C–H bond in question from the directing group, and by the shape of the substrate, but several approaches have been developed to overcome these limitations6, 7, 8, 9, 10, 11, 12. In one such approach, an understanding of the distal and geometric relationships between the functional groups and C–H bonds of a substrate has been exploited to achieve meta-selective C–H activation by using a covalently attached, U-shaped template13, 14, 15, 16, 17. However, stoichiometric installation of this template has not been feasible in the absence of an appropriate functional group on which to attach it. Here we report the design of a catalytic, bifunctional nitrile template that binds a heterocyclic substrate via a reversible coordination instead of a covalent linkage. The two metal centres coordinated to this template have different roles: one reversibly anchors substrates near the catalyst, and the other cleaves remote C–H bonds. Using this strategy, we demonstrate remote, site-selective C–H olefination of heterocyclic substrates that do not have the necessary functional groups for covalently attaching templates.

April

15/04/2017

Wouter's paper

Catalytic Coupling between Unactivated Aliphatic C–H Bonds and Alkynes via a Metal–Hydride Pathway

Yan Xu†‡, Michael C. Young‡, and Guangbin Dong

Graphical abstract

Abstract Image

 

We report a Rh(I)-catalyzed site-selective coupling between ketone β-C(sp3)–H bonds and aliphatic alkynes using an in situ-installed directing group. Upon hydrogenation or hydration, various β-alkylation or β-aldol products of the ketones are obtained with broad functional group tolerance. Mechanistic investigations support the involvement of a Rh–H intermediate through oxidative addition of Rh(I) into the β-C–H bonds. Thus, to the best of our knowledge, this transformation represents the first example of catalytic couplings between unsaturated hydrocarbons and unactivated aliphatic C–H bonds via a metal–hydride pathway.

Lola's paper

Potassium bromide catalyzed N-S bond formation via oxidative dehydrogenation

Tian-Qun Yua, 1, Yong-Sheng Houa, 1, Yi Jianga, 1, Wen-Xuan Xua, 1, Tao Shia, Xia Wua, Jin-Chao Zhanga, Dian Hea, , , Zhen Wang

Graphical abstract

Image for unlabelled figure

 

 

 

 

 

N-substituted benzo[d]isothiazol-3(2H)-ones are a family of compounds with extremely important application. Recently, we have developed a new green pathway to synthesize these compounds via potassium bromide-catalyzed intramolecular oxidative dehydrogenative cyclization. This reaction has high functional group tolerance and affords excellent yield even in gram scale.

Pol's paper

Mechanism and Origins of Stereoselectivity in the Cinchona Thiourea- and Squaramide-Catalyzed Asymmetric Michael Addition of Nitroalkanes to Enones

Matthew N. Grayson

Graphical abstract

Abstract Image

We report density functional theory calculations that examine the mechanism and origins of stereoselectivity of Soós’ landmark discovery from 2005 that cinchona thioureas catalyze the asymmetric Michael addition of nitroalkanes to enones. We show that the electrophile is activated by the catalyst’s protonated amine and that the nucleophile binds to the thiourea moiety by hydrogen bonding. These results lead to the correction of published mechanistic work which did not consider this activation mode. We have also investigated the corresponding cinchona squaramide-catalyzed reaction and found that it proceeds by the same mechanism despite the differences in the geometry of the two catalysts’ hydrogen-bond-donating groups, which demonstrates the generality of this mechanistic model.

 

May

05/05/2017

Wouter's paper

Remote carboxylation of halogenated aliphatic hydrocarbons with carbon dioxide

Francisco Juliá-Hernández, Toni Moragas, Josep Cornella & Ruben Martin

Graphical abstract

Switchable site-selective catalytic carboxylation at remote sp3 C–H sites.

Catalytic carbon–carbon bond formation has enabled the streamlining of synthetic routes when assembling complex molecules1. It is particularly important when incorporating saturated hydrocarbons, which are common motifs in petrochemicals and biologically relevant molecules. However, cross-coupling methods that involve alkyl electrophiles result in catalytic bond formation only at specific and previously functionalized sites2. Here we describe a catalytic method that is capable of promoting carboxylation reactions at remote and unfunctionalized aliphatic sites with carbon dioxide at atmospheric pressure. The reaction occurs via selective migration of the catalyst along the hydrocarbon side-chain3 with excellent regio- and chemoselectivity, representing a remarkable reactivity relay when compared with classical cross-coupling reactions. Our results demonstrate that site-selectivity can be switched and controlled, enabling the functionalization of less-reactive positions in the presence of a priori more reactive ones. Furthermore, we show that raw materials obtained in bulk from petroleum processing, such as alkanes and unrefined mixtures of olefins, can be used as substrates. This offers an opportunity to integrate a catalytic platform en route to valuable fatty acids by transforming petroleum-derived feedstocks directly4.

Lola's paper

Multiple Approaches to the In Situ Generation of Anhydrous Tetraalkylammonium Fluoride Salts for SNAr Fluorination Reactions

Megan A. Cismesia†, Sarah J. Ryan†, Douglas C. Bland‡, and Melanie S. Sanford*

Graphical abstract

Abstract Image

 

 

 

 

 

This article focuses on the development of practical approaches to the in situ generation of anhydrous fluoride salts for applications in nucleophilic aromatic substitution (SNAr) reactions. We report herein that a variety of combinations of inexpensive nucleophiles (e.g., tetraalkylammonium cyanide and phenoxide salts) and fluorine-containing electrophiles (e.g., acid fluoride, fluoroformate, benzenesulfonyl fluoride, and aryl fluorosulfonate derivatives) are effective for this transformation. Ultimately, we demonstrate that the combination of tetramethylammonium 2,6-dimethylphenoxide and sulfuryl fluoride (SO2F2) serves as a particularly practical route to anhydrous tetramethylammonium fluoride. This procedure is applied to the SNAr fluorination of a range of electron-deficient aryl and heteroaryl chlorides as well as nitroarenes.

Richard's paper

Atroposelective Synthesis of Axially Chiral Biaryls by Palladium-Catalyzed Asymmetric C−H Olefination Enabled by a Transient Chiral Auxiliary

Qi-Jun Yao, Shuo Zhang, Bei-Bei Zhan, Prof. Dr. Bing-Feng Shi

Graphical abstract

Figure 1.

 

 

 

 

 

 

Atroposelective synthesis of axially chiral biaryls by palladium-catalyzed C−H olefination, using tert-leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s-factor up to 600).

12/05/2017

Youssef's paper

Synthesis of Anthropomorphic Molecules:  The NanoPutians

Stephanie H. Chanteau and James M. Tour

Graphical abstract

Abstract Image

 

 

 

 

 

 

 

Described here are the synthetic details en route to an array of 2-nm-tall anthropomorphic molecules in monomeric, dimeric, and polymeric form. These anthropomorphic figures are called, as a class, NanoPutians. Using tools of chemical synthesis, the ultimate in designed miniaturization can be attained while preparing the most widely recognized structures:  those that resemble humans.

Adrian's paper

Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides

Graphical abstract

Graphical abstract: Pyridine sulfinates as general nucleophilic coupling partners in palladium-catalyzed cross-coupling reactions with aryl halides

 

 

 

Pyridine rings are ubiquitous in drug molecules; however, the pre-eminent reaction used to form carbon–carbon bonds in the pharmaceutical industry, the Suzuki–Miyaura cross-coupling reaction, often fails when applied to these structures. This phenomenon is most pronounced in 2-substituted pyridines, and results from the difficulty in preparing, the poor stability of, and low efficiency in reactions of pyridine-2-boronates. We demonstrate that by replacing these boronates with pyridine-2-sulfinates, a cross-coupling process of unrivalled scope and utility is realized. The corresponding 3- and 4-substituted pyridine variants are also efficient coupling partners. In addition, we apply these sulfinates in a library format to the preparation of medicinally relevant derivatives of the drugs varenicline (Chantix) and mepyramine (Anthisan).

Pol's paper

A Highly Stereoselective Synthesis of Tetrahydrofurans

Johannes Appun, Dr. Michael Boomhoff, Patrick Hoffmeyer, Isa Kallweit, Maik Pahl, Prof. Dr. Detlev Belder, Prof. Dr. Christoph Schneider

Graphical abstract

Scheme 1.

 

 

 

 

The development of a direct and highly stereoselective synthesis of 2,3,5-substituted tetrahydrofurans has been accomplished through a combination of batch- and microchip-MS-experiments. This sequential transformation comprises a Lewis acid-mediated reaction of bis(silyl) dienediolate 1 and a broad range of aldehydes, furnishing products with three new σ-bonds and three stereogenic centers in a one-pot process with typically good yields and excellent stereoselectivity. Key steps which have been elucidated primarily with microchip-MS-experiments include a vinylogous aldol reaction and a Prins-type cyclization. Furthermore, a titanium BINOL complex is a powerful chiral catalyst for this process. The products were further converted into bi- and tricylic products by carbonyl–ene reactions, proceeding with excellent yields and diastereoselectivity.

19/05/2017

Pol's paper

Meta-C‒H Arylation and Alkylation of Benzylsulfonamide Enabled by a Pd(II)/Isoquinoline Catalyst

Jin-Quan Yu, Guolin Cheng, Peng Wang

No graphical abstract available yet

Palladium(II)-catalyzed meta-C‒H arylation and alkylation of benzylsulfonamide using 2-carbomethoxynorbornene (NBE-CO2Me) as a transient mediator are realized using a newly developed electron-deficient directing group and isoquinoline as a ligand. This protocol features broad substrate scope and good functional group tolerance. The meta-substituted benyzlsulfonamide can be readily transformed to sodium sulfonate, sulfonate ester, sulfonamide, as well as styrenes via Julia-type olefination. The unique impact of the isoquinoline ligand underscores the importance of subtle matching between ligands and the directing groups.

Richard's paper

One-Step Annulative π-Extension of Alkynes with Dibenzosiloles or Dibenzogermoles by Palladium/o-chloranil Catalysis

Dr. Kyohei Ozaki, Keiichiro Murai, Wataru Matsuoka, Dr. Katsuaki Kawasumi, Dr. Hideto Ito, Prof. Dr. Kenichiro Itami

Graphical abstract

Figure 1.

 

 

 

 

Reliable and short synthetic routes to polycyclic aromatic hydrocarbons and nanographenes are important in materials science. Herein, we report an efficient one-step annulative π-extension reaction of alkynes that provides access to diarylphenanthrenes and related nanographene precursors. In the presence of a cationic palladium/o-chloranil catalyst system and dibenzosiloles or dibenzogermoles as π-extending agents, a variety of diarylacetylenes are transformed successfully into 9,10-diarylphenanthrenes in a single step with good functional-group tolerance. Furthermore, double π-extension reactions of 1,4-bis(phenylethynyl)benzene and diphenyl-1,3-butadiyne are demonstrated, affording oligoarylene products, which show potential for application in the synthesis of larger polycyclic aromatic hydrocarbons and nanographenes.

26/05/2017

Pol's paper

Arylative Intramolecular Allylation of Ketones with 1,3-Enynes Enabled by Catalytic Alkenyl-to-Allyl 1,4-Rhodium(I) Migration

Dr. Benjamin M. Partridge, Michael Callingham, Dr. William Lewis, Prof. Hon Wai Lam

Graphical abstract

Scheme 1.

 

 

 

 

Alkenyl-to-allyl 1,4-rhodium(I) migration enables the generation of nucleophilic allylrhodium(I) species by remote C−H activation. This new mode of reactivity was employed in the diastereoselective reaction of arylboron reagents with substrates containing a 1,3-enyne tethered to a ketone, to give products containing three contiguous stereocenters. The products can be obtained in high enantioselectivities using a chiral sulfur-alkene ligand.

Malcom's paper

Asymmetric Synthesis of Functionalized Tricyclic Chromanes via an Organocatalytic Triple Domino Reaction

Mukesh Kumar†, Pankaj Chauhan†, Arto Valkonen‡, Kari Rissanen‡ , and Dieter Enders*†

Graphical abstract


Abstract Image

A highly stereoselective triple domino reaction for the synthesis of functionalized tricyclic chromane scaffolds has been developed. A secondary amine-catalyzed domino Michael/Michael/aldol condensation reaction between aliphatic aldehydes, nitro-chromenes, and α,β-unsaturated aldehydes leads to the formation of synthetically important tricyclic chromanes bearing four contiguous stereogenic centers including a tetrasubstituted carbon in good yields (20–66%) and excellent stereoselectivities (>20:1 dr and >99% ee).

 

June

02/06/2017

Wouter's paper

Prebiotic selection and assembly of proteinogenic amino acids and natural nucleotides from complex mixtures

Saidul Islam, Dejan-Krešimir Bučar & Matthew W. Powner

Graphical abstract

Prebiotic ribonucleotide synthesis.

 

 

 

 

 

A central problem for the prebiotic synthesis of biological amino acids and nucleotides is to avoid the concomitant synthesis of undesired or irrelevant by-products. Additionally, multistep pathways require mechanisms that enable the sequential addition of reactants and purification of intermediates that are consistent with reasonable geochemical scenarios. Here, we show that 2-aminothiazole reacts selectively with two- and three-carbon sugars (glycolaldehyde and glyceraldehyde, respectively), which results in their accumulation and purification as stable crystalline aminals. This permits ribonucleotide synthesis, even from complex sugar mixtures. Remarkably, aminal formation also overcomes the thermodynamically favoured isomerization of glyceraldehyde into dihydroxyacetone because only the aminal of glyceraldehyde separates from the equilibrating mixture. Finally, we show that aminal formation provides a novel pathway to amino acids that avoids the synthesis of the non-proteinogenic α,α-disubstituted analogues. The common physicochemical mechanism that controls the proteinogenic amino acid and ribonucleotide assembly from prebiotic mixtures suggests that these essential classes of metabolite had a unified chemical origin.

Christine's paper

Enantioselective Propargylation of Polyols and Desymmetrization of meso 1,2-Diols by Copper/Borinic Acid Dual Catalysis

Ren-Zhe Li, Hua Tang, Dr. Ke R. Yang, Li-Qiang Wan, Xia Zhang, Jie Liu, Zhengyan Fu, Prof. Dawen Niu

Graphical abstract

Scheme 1.

 

 

 

 

 

 

 

 

A copper/borinic acid dual catalytic reaction enabled the enantioselective propargylation of aliphatic polyols. Readily available reagents and catalysts were used in this transformation, which displayed good to excellent chemo- and stereoselectivity for a broad array of substrates. The method was also applicable to the desymmetrization of meso 1,2-diols to furnish products with three stereogenic centers and a terminal alkyne group in one operation.

Pol's paper

Switchable Access to Different Spirocyclopentane Oxindoles via N-Heterocyclic Carbene-Catalyzed Reactions of Isatin-Derived Enals and N-Sulfonyl Ketimines

Lei Wang, Sun Li, Marcus Blümel, Rakesh Putreddy, Anssi Peuronen, Kari Rissanen, Dieter Enders

Graphical abstract not available

A novel NHC-catalyzed annulation protocol for the asymmetric synthesis of biologically important β-lactam fused spirocyclopentane oxindoles with four contiguous stereocenters including two quaternary carbon centers was developed. Alternatively, spirocyclopentane oxindoles containing an enaminone moiety can be achieved using the same starting materials, isatin-derived enals and N-sulfonyl ketimines, in the presence of a slightly changed NHC catalytic system. This switchable annulation strategy enables the selective assembly of both heterocyclic scaffolds with good yields and excellent enantioselectivities for a broad range of substrates.

09/06/2017

Adrian's paper

Transition-Metal-Free, Visible-Light-Enabled Decarboxylative Borylation of Aryl N-Hydroxyphthalimide Esters

Lisa Candish, Michael Teders, and Frank Glorius

Graphical abstract

Abstract Image

 

 

 

 

Herein, we report a conceptually novel borylation reaction proceeding via a mild photoinduced decarboxylation of redox-activated aromatic carboxylic acids. This work constitutes the first application of cheap and easily prepared N-hydroxyphthalimide esters as aryl radical precursors and does not require the use of expensive transition metals or ligands. The reaction is operationally simple, scalable, and displays broad scope and functional group tolerance.

Yu's paper

Discovery and Biosynthesis of Gladiolin: A Burkholderia gladioli Antibiotic with Promising Activity against Mycobacterium tuberculosis

Lijiang Song†∥, Matthew Jenner†∥, Joleen Masschelein†∥, Cerith Jones‡ , Matthew J. Bull‡, Simon R. Harris§, Ruben C. Hartkoorn⊥, Anthony Vocat⊥, Isolda Romero-Canelon†, Paul Coupland‡, Gordon Webster‡, Matthew Dunn§, Rebecca Weiser‡, Christopher Paisey‡, Stewart T. Cole⊥, Julian Parkhill§, Eshwar Mahenthiralingam*‡, and Gregory L. Challis

Graphical abstract

Abstract Image

 

 

 

 

An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability. Moreover, gladiolin displayed low mammalian cytotoxicity and good activity against several M. tuberculosis clinical isolates, including four that are resistant to isoniazid and one that is resistant to both isoniazid and rifampicin. Overall, these data suggest that gladiolin may represent a useful starting point for the development of novel drugs to tackle multidrug-resistant tuberculosis. The B. gladioli BCC0238 genome was sequenced using Single Molecule Real Time (SMRT) technology. This resulted in four contiguous sequences: two large circular chromosomes and two smaller putative plasmids. Analysis of the chromosome sequences identified 49 putative specialized metabolite biosynthetic gene clusters. One such gene cluster, located on the smaller of the two chromosomes, encodes a trans-acyltransferase (trans-AT) polyketide synthase (PKS) multienzyme that was hypothesized to assemble gladiolin. Insertional inactivation of a gene in this cluster encoding one of the PKS subunits abrogated gladiolin production, confirming that the gene cluster is responsible for biosynthesis of the antibiotic. Comparison of the PKSs responsible for the assembly of gladiolin and etnangien showed that they possess a remarkably similar architecture, obfuscating the biosynthetic mechanisms responsible for most of the structural differences between the two metabolites.

16/06/2017

Lola's paper

Photo-controlled cell-specific metabolic labeling of RNA†

C. Feng‡ORCID logoa, Y. Li‡a and R. C. Spitale

Graphical abstract

image file: c7ob01009e-f1.tif

 

 

 

 

 

 

Elucidating gene expression programs within a cell-specific manner is a grand challenge for biologists. Harder still is the ability to have kinetic control over such experiments. Metabolic labeling with bioorthogonally-functionalized metabolic intermediates provides a means to profile RNA expression in a cell-specific manner, but there is still a lack of kinetic resolution. Herein we present the synthesis and evaluation of photocaged metabolic uracil intermediates. We compare the photo-decaging properties and demonstrate their utility in metabolic labeling experiments in a cell-specific manner. We anticipate that our approach will have far-reaching impact as it provides control over tagging of nascent RNA.

Adrian's paper

Palladium and visible-light mediated carbonylative Suzuki–Miyaura coupling of unactivated alkyl halides and aryl boronic acids

Sara Roslina and Luke R. Odell

Graphical abstract

Graphical abstract: Palladium and visible-light mediated carbonylative Suzuki–Miyaura coupling of unactivated alkyl halides and aryl boronic acids

 

 

 

 

Herein, a simple and efficient method for the palladium-catalyzed carbonylation of aryl boronic acids with unactivated alkyl iodides and bromides under visible-light irradiation, ambient temperature and low CO-pressure is presented. Notably, the procedure uses readily available equipment and an inexpensive palladium catalyst to generate the key alkyl radical intermediate. These mild conditions enabled the synthesis of a range of functionalized aryl alkyl ketones including the antipsychotic drug, melperone.

Richard's paper

Allyl-Palladium-Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone α,β-Vicinal Difunctionalization

Dr. Yifeng Chen, David Huang, Yizhou Zhao, Prof. Dr. Timothy R. Newhouse

Graphical abstract

Figure 1.

 

 

 

 

 

 

The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.

 

23/06/2017

Wouter's paper

Distribution of Catalytic Species as an Indicator To Overcome Reproducibility Problems

Xavier Companyó†‡ and Jordi Burés

Graphical abstract

Abstract Image

 

 

 

 

 

 

 

 

Irreproducibility is a common issue in catalysis. The ordinary way to minimize it is by ensuring enhanced control over the factors that affect the reaction. When control is insufficient, some parameters can be used as indicators of the reaction performance. Herein we describe the use of the distribution of catalytic species as an indicator to map, track, and fine-tune the performance of catalytic reactions. This indicator is very sensitive and presents a quick response to variations in the reaction conditions. We have applied this new strategy to the conjugate addition of C-nucleophiles to enals via iminium intermediates, consistently achieving maximum turnover frequencies (TOF) regardless of the quality of the starting materials used. In addition, the present method has allowed us to efficiently reduce the catalyst loading to as little as 0.1 mol %, the lowest one described for this kind of reaction.

Richard's paper

Rhodium-Catalyzed Oxygenative [2 + 2] Cycloaddition of Terminal Alkynes and Imines for the Synthesis of β-Lactams

Insu Kim, Sang Weon Roh, Dong Gil Lee, and Chulbom Lee*

Graphical abstract

Abstract Image

 

 

 

A rhodium catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high trans diastereoselectivity. In the presence of a Rh(I) catalyst and 4-picoline N-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate. The new method taking advantage of catalytic generation of a ketene species directly from a terminal alkyne provides a novel and efficient entry to the Staudinger synthesis of β-lactams under mild conditions.

30/06/2017

Lola's paper

Biomimetic Total Synthesis of (±)-Homodimericin A

Dr. Donghui Ma, Dr. Yangbin Liu, Prof. Dr. Zhang Wang

Graphical abstract

Figure 1.

 

 

 

 

 

 

 

 

 

 

 

 

A biomimetic total synthesis of racemic homodimericin A was achieved in seven steps, including two cascade reactions. Aqueous buffer solutions are found to help both the oxidative dimerization cascade and the intramolecular Diels–Alder cascade. This synthetic sequence validates key steps in the biogenetic proposal of homodimericin A.

Malcom's paper

Bioinspired Total Synthesis of Homodimericin A

Dr. Jun Huang, Yueqing Gu, Kai Guo, Lei Zhu, Prof. Dr. Yu Lan, Prof. Dr. Jianxian Gong, Prof. Dr. Zhen Yang

Graphical abstract

Figure 1.

 

 

 

 

 

 

 

 

 

 

Homodimericin A is a remarkable fungal metabolite. This highly oxygenated racemic unsaturated polyketide poses a significant synthetic challenge owing to its sterically demanding central cagelike core containing eight contiguous stereogenic centers (including three quaternary stereocenters) and several carbonyl functionalities. On the basis of its proposed biogenetic synthesis, we designed a total synthesis of homodimericin A that proceeds in seven steps and features a double Michael reaction, an intramolecular Diels–Alder reaction, and an ene reaction.

 

 

July

07/07/2017

Wouter's paper

Selective sp3 C–H alkylation via polarity-match-based cross-coupling

Chip Le, Yufan Liang, Ryan W. Evans, Ximing Li & David W. C. MacMillan

Graphical abstract

Selective sp3 C–H alkylations via polarity-matched hydrogen-atom transfer (HAT).

The functionalization of carbon–hydrogen (C–H) bonds is one of the most attractive strategies for molecular construction in organic chemistry. The hydrogen atom is considered to be an ideal coupling handle, owing to its relative abundance in organic molecules and its availability for functionalization at almost any stage in a synthetic sequence1. Although many C–H functionalization reactions involve C(sp3)–C(sp2) coupling, there is a growing demand for C–H alkylation reactions, wherein sp3 C–H bonds are replaced with sp3 C–alkyl groups. Here we describe a polarity-match-based selective sp3 C–H alkylation via the combination of photoredox, nickel and hydrogen-atom transfer catalysis. This methodology simultaneously uses three catalytic cycles to achieve hydridic C–H bond abstraction (enabled by polarity matching), alkyl halide oxidative addition, and reductive elimination to enable alkyl–alkyl fragment coupling. The sp3 C–H alkylation is highly selective for the α-C–H of amines, ethers and sulphides, which are commonly found in pharmaceutically relevant architectures. This cross-coupling protocol should enable broad synthetic applications in de novo synthesis and late-stage functionalization chemistry.

Christine's paper

Direct Visible-Light-Excited Asymmetric Lewis Acid Catalysis of Intermolecular [2+2] Photocycloadditions

Xiaoqiang Huang, Taylor R. Quinn, Klaus Harms, Richard D. Webster§, Lilu Zhang, Olaf Wiest, and Eric Meggers

Graphical abstract

Abstract Image

 

 

 

 

 

A reaction design is reported in which a substrate-bound chiral Lewis acid complex absorbs visible light and generates an excited state that directly reacts with a cosubstrate in a highly stereocontrolled fashion. Specifically, a chiral rhodium complex catalyzes visible-light-activated intermolecular [2+2] cycloadditions, providing a wide range of cyclobutanes with up to >99% ee and up to >20:1 d.r. Noteworthy is the ability to create vicinal all-carbon-quaternary stereocenters including spiro centers in an intermolecular fashion.

Richard's paper

Elemental Sulfur-Promoted Oxidative Rearranging Coupling between o-Aminophenols and Ketones: A Synthesis of 2-Alkyl benzoxazoles under Mild Conditions

Thanh Binh Nguyen* and Pascal Retailleau

Graphical abstract

Abstract Image

 

 

 

 

In the presence of N-methylpiperidine, elemental sulfur was found to act as excellent oxidant in promoting oxidative rearranging coupling between o-aminophenols and ketones. A wide range of 2-alkylbenzoxazoles was obtained under mild conditions.

14/07/2017

Richard's paper

Methylenecyclopropane Annulation by Manganese(I)-Catalyzed Stereoselective C−H/C−C Activation

Dr. Yu-Feng Liang, Valentin Müller, Dr. Weiping Liu, Annika Münch, Prof. Dr. Dietmar Stalke, Prof. Dr. Lutz Ackermann

Graphical abstract

Figure 1.

 

 

 

C−H/C−C functionalizations with methylenecyclopropanes (MCPs) were accomplished with a versatile base-metal catalyst. A robust manganese(I) complex enabled the expedient annulation of MCPs by synthetically meaningful ketimines to deliver, upon one-pot hydroarylation, densely substituted polycylic anilines in a step-economical fashion. Mechanistic studies provided strong support for a facile organometallic C−H manganation, while typical cobalt, ruthenium, rhodium, and palladium catalysts were found completely ineffective.

Malcolm's paper

Catalytic allylic oxidation of internal alkenes to a multifunctional chiral building block

Liela Bayeh, Phong Q. Le & Uttam K. Tambar

Graphical abstract

Catalytic enantioselective oxidation of unactivated terminal and internal alkenes.

 

 

 

 

 

 

 

 

 

 

The stereoselective oxidation of hydrocarbons is one of the most notable advances in synthetic chemistry over the past fifty years1, 2, 3. Inspired by nature, enantioselective dihydroxylations, epoxidations and other oxidations of unsaturated hydrocarbons have been developed. More recently, the catalytic enantioselective allylic carbon–hydrogen oxidation of alkenes has streamlined the production of pharmaceuticals, natural products, fine chemicals and other functional materials4, 5, 6, 7. Allylic functionalization provides a direct path to chiral building blocks with a newly formed stereocentre from petrochemical feedstocks while preserving the olefin functionality as a handle for further chemical elaboration. Various metal-based catalysts have been discovered for the enantioselective allylic carbon–hydrogen oxidation of simple alkenes with cyclic or terminal double bonds8, 9, 10, 11, 12, 13, 14, 15, 16. However, a general and selective allylic oxidation using the more common internal alkenes remains elusive. Here we report the enantioselective, regioselective and E/Z-selective allylic oxidation of unactivated internal alkenes via a catalytic hetero-ene reaction with a chalcogen-based oxidant. Our method enables non-symmetric internal alkenes to be selectively converted into allylic functionalized products with high stereoselectivity and regioselectivity. Stereospecific transformations of the resulting multifunctional chiral building blocks highlight the potential for rapidly converting internal alkenes into a broad range of enantioenriched structures that can be used in the synthesis of complex target molecules.

Sarah's paper

CO- and HCl-free synthesis of acid chlorides from unsaturated hydrocarbons via shuttle catalysis

Xianjie Fang, Bastien Cacherat & Bill Morandi

Graphical abstract

Conceptual blueprint for the development of a CO- and HCl-free synthesis of acid chlorides via shuttle catalysis.

The synthesis of carboxylic acid derivatives from unsaturated hydrocarbons is an important process for the preparation of polymers, pharmaceuticals, cosmetics and agrochemicals. Despite its industrial relevance, the traditional Reppe-type carbonylation reaction using pressurized CO is of limited applicability to laboratory-scale synthesis because of: (1) the safety hazards associated with the use of CO, (2) the need for special equipment to handle pressurized gas, (3) the low reactivity of several relevant nucleophiles and (4) the necessity to employ different, often tailor-made, catalytic systems for each nucleophile. Herein we demonstrate that a shuttle-catalysis approach enables a CO- and HCl-free transfer process between an inexpensive reagent, butyryl chloride, and a wide range of unsaturated substrates to access the corresponding acid chlorides in good yields. This new transformation provides access to a broad range of carbonyl-containing products through the in situ transformation of the reactive acid chloride intermediate. In a broader context, this work demonstrates that isodesmic shuttle-catalysis reactions can unlock elusive catalytic reactions.

21/07/2017

Christine's paper

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

Hongyin Gao, Zhe Zhou, Doo-Hyun Kwon, James Coombs, Steven Jones, Nicole Erin Behnke, Daniel H. Ess & László Kürti

Graphical abstract

Current approaches to primary arylamine and phenol synthesis from arylmetals in the absence of transition-metal catalysts, impact of steric hindrance on kinetic acidity and the discovery of multifunctional oxaziridine reagents for heteroatom-transfer reactions.

Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C−C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (−NH2) and hydroxyl (−OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N−H and N−alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts, ligands and additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.

Sarah's paper

Practical and Asymmetric Reductive Coupling of Isoquinolines Templated by Chiral Diborons

Dongping Chen†, Guangqing Xu‡, Qinghai Zhou§∥, Lung Wa Chung§ , and Wenjun Tang

Graphical abstract

Abstract Image

 

 

 

 

We herein describe a chiral diboron-templated highly diastereoselective and enantioselective reductive coupling of isoquinolines that provided expedited access to a series of chiral substituted bisisoquinolines in good yields and excellent ee’s under mild conditions. The method enjoys a broad substrate scope and good functional group compatibility. Mechanistic investigation suggests the reaction proceeds through a concerted [3,3]-sigmatropic rearrangement.

28/07/2017

Wouter's paper

Photoinduced decarboxylative borylation of carboxylic acids

Alexander Fawcett, Johan Pradeilles, Yahui Wang, Tatsuya Mutsuga, Eddie L. Myers, Varinder K. Aggarwa

Graphical abstract

The conversion of widely available carboxylic acids into versatile boronic esters would be highly enabling for synthesis. We found that this transformation can be effected by illuminating the N-hydroxyphthalimide ester derivative of the carboxylic acid under visible light at room temperature in the presence of the diboron reagent bis(catecholato)diboron. A simple workup allows isolation of the pinacol boronic ester. Experimental evidence suggests that boryl radical intermediates are involved in the process. The methodology is illustrated by the transformation of primary, secondary, and tertiary alkyl carboxylic acids as well as a diverse range of natural-product carboxylic acids, thereby demonstrating its broad utility and functional group tolerance.

Richard's paper

High-Yielding Syntheses of Crown Ether-Based Pyridyl Cryptands

Terry L. PriceJr.§, Hanlie R. Wessels, Carla Slebodnick, and Harry W. Gibson

Graphical abstract

Abstract Image

Pyridinium bis(trifluoromethylsulfonyl)imide (PyTFSI)-templated syntheses of 2,6-pyridyl cryptands of cis(4,4′)-dibenzo-30-crown-10 (3a), the p-bromobenzyloxy derivative 3b, bis(m-phenylene)-32-crown-10 (5), cis(4,4′)-dibenzo-27S-crown-9 (7), cis(4,4′)-dibenzo-27L-crown-9 (9), and cis(4,4′)-dibenzo-24-crown-8 (11) are reported. Here we provide a fast (12 h), high-yielding (89%, 74%, 80%, and 62% for 3a, 3b, 5, and 9, respectively) templation method without the use of a syringe pump. The yields for 7 (19%) and 11 (26%) were lower than with the previous pseudo-high-dilution method, indicating ineffective templation in these cases. Coupled with our previously developed templated syntheses of dibenzo crown ethers, this protocol makes powerful cryptand hosts readily available in gram quantities in good yields from methyl 4(or 3)-hydroxy-3(or 4)-benzyloxybenzoate.

August

18/08/2017

Sarah's paper

Praseodymium(III)-Catalyzed Regioselective Synthesis of C3-N-Substituted Coumarins with Coumarins and Azides

Jiu-ling Li†, Da-chao Hu†, Xin-ping Liang†, Ying-Chun Wang‡, Heng-Shan Wang*† , and Ying-ming Pan

Graphical abstract

Abstract Image

 

 

 

 

A series of C3-N-substituted coumarins were synthesized in good yields directly from coumarins and azides in the presence of Pr(OTf)3 without any additives or ligands needed. The selected compounds 3a3ce3g3i3q3u, and 3v exhibited good anticancer activities against MGC-803, A549, and NCI-H460 cell lines with IC50 in the range 8.75–38.54 μmol L–1.

Lola's paper

Chemical proteomics reveal CD147 as a functional target of pseudolaric acid B in human cancer cells

Yiqing Zhou,a  Zhengao Di,a  Xiaoming Li,bc  Yuanhong Shan,d  Weichao Li,a  Haibing Zhangb  and  Youli Xiao

Graphical abstract

Graphical abstract: Chemical proteomics reveal CD147 as a functional target of pseudolaric acid B in human cancer cells

CD147 is a glycosylated transmembrane protein highly expressed on the surface of various tumor cells which plays vital roles in tumor invasion, progression and metastasis. We report the discovery of the natural product pseudolaric acid B (PAB) directly targeting CD147 by chemical proteomics utilizing a PAB-derived photoaffinity probe which could serve as a novel type of anticancer reagent.

Wouter's paper

Metal-catalyzed electrochemical diazidation of alkenes

Niankai Fu, Gregory S. Sauer, Ambarneil Saha, Aaron Loo, Song Lin

Graphical abstract

Vicinal diamines are a common structural motif in bioactive natural products, therapeutic agents, and molecular catalysts, motivating the continuing development of efficient, selective, and sustainable technologies for their preparation. We report an operationally simple and environmentally friendly protocol that converts alkenes and sodium azide—both readily available feedstocks—to 1,2-diazides. Powered by electricity and catalyzed by Earth-abundant manganese, this transformation proceeds under mild conditions and exhibits exceptional substrate generality and functional group compatibility. Using standard protocols, the resultant 1,2-diazides can be smoothly reduced to vicinal diamines in a single step, with high chemoselectivity. Mechanistic studies are consistent with metal-mediated azidyl radical transfer as the predominant pathway, enabling dual carbon-nitrogen bond formation.

25/08/2017

 

Sarah's paper

A Concise Enantioselective Total Synthesis of (−)-Virosaine A

Jonathan M. E. Hughes, Prof. Dr. James L. Gleason

Graphical abstract

Figure 1.

The total synthesis of (−)-virosaine A (1) was achieved in ten steps starting from furan and 2-bromoacrolein. A one-pot Diels–Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C−H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1.

Richard's paper

Palladium-Catalyzed Alkylation with Alkyl Halides by C(sp3)−H Activation
Zhuo Wu, Ding Ma, Bo Zhou, Xiaoming Ji, Xiaotian Ma, Xiaoling Wang, Prof. Dr. Yanghui Zhang

Graphical abstract

Figure 1.

Utilizing halogens as traceless directing goups represents an attractive strategy for C−H functionalization. A two C−H alkylation system, initiated by the oxidative addition of organohalides to Pd0, has been developed. The first reaction involves an intermolecular alkylation of palladacycles to form C(sp3)−C(sp2) bonds followed by C(sp2)−H activation/cyclization to deliver alkylated benzocyclobutenes as the final products. In the second reaction, two C−C bonds are formed by the reaction of palladacycles with CH2Br2, and provides a facile and efficient method for the synthesis of indanes. The alkylated benzocyclobutene products can be transformed into tricyclic hyrocarbons, and the indane derivatives are essential structural motifs in bioactive and odorant molecules.

 

 

September

01/09/2017

Richard's paper

Photoredox Catalysis: The Need to Elucidate the Photochemical Mechanism

Dr. Marianna Marchini, Prof. Giacomo Bergamini, Prof. Pier Giorgio Cozzi, Prof. Paola Ceroni, Prof. Vincenzo Balzani

Graphical abstract

original image

The photocatalytic mechanism reported in a recent Communication to produce the radical anion of pyrenes postulates a highly endergonic electron transfer process. An analysis of the thermodynamics is reported together with the proposal of an alternative thermodynamically feasible mechanism.

A reply published to Richard's paper

Reply to “Photoredox Catalysis: The Need to Elucidate the Photochemical Mechanism”

Indrajit Ghosh, Javier I. Bardagi, Prof. Dr. Burkhard König

Graphical abstract

image

 

 

 

 

Spectroscopic measurements and estimated thermodynamic values are important tools for the investigation of photocatalytic reaction mechanisms. However, data derived under idealized conditions fail to capture the complexity of reaction mixtures in preparative organic synthesis.

Christine's paper

Divergent Asymmetric Synthesis of Polycyclic Compounds via Vinyl Triazenes

David Kossler+, Florian G. Perrin+, Abdusalom A. Suleymanov, Gregor Kiefer, Rosario Scopelliti, Kay Severin,* and Nicolai Cramer

Graphical abstract

Scheme 1.

 

 

 

 

Vinyl triazenes were obtained by enantioselective [2+2] cycloaddition reactions of bicyclic alkenes with 1-alkynyl triazenes in the presence of a RuII catalyst with a chiral cyclopentadienyl ligand. These triazenes serve as unique vinyl cation surrogates. Under acidic conditions, the triazene functionality can be replaced with a variety of groups, including halides, alkoxides, sulfoxides, amides, arenes, and heteroarenes, thus providing efficient access to a pool of chiral polycyclic compounds.

08/09/2017

Lola's paper

Copper-Catalyzed TBHP-Mediated Radical Cross-Coupling Reaction of Sulfonylhydrazides with Thiols Leading to Thiosulfonates

Guo-Yu Zhang, Shuai-Shuai Lv, Adedamola Shoberu, and Jian-Ping Zou*

Graphical abstract

Abstract Image

A tert-butyl hydroperoxide (TBHP)-mediated coupling of sulfonylhydrazides with thiols catalyzed by CuBr2 to afford thiosulfonates via a radical process is described.

Richard's paper

Heavily Substituted Atropisomeric Diarylamines by Unactivated Smiles Rearrangement of N-Aryl Anthranilamides

Romain Costil, Harvey J. A. Dale, Dr. Natalie Fey, George Whitcombe, Dr. Johnathan V. Matlock, Prof. Jonathan Clayden

Graphical abstract

Scheme 1.

 

 

 

 

 

 

Diarylamines find use as metal ligands and as structural components of drug molecules, and are commonly made by metal-catalyzed C−N coupling. However, the limited tolerance to steric hindrance of these couplings restricts the synthetic availability of more substituted diarylamines. Here we report a remarkable variant of the Smiles rearrangement that employs readily accessible N-aryl anthranilamides as precursors to diarylamines. Conformational predisposition of the anthranilamide starting material brings the aryl rings into proximity and allows the rearrangement to take place despite the absence of electron-withdrawing substituents, and even with sterically encumbered doubly ortho-substituted substrates. Some of the diarylamine products are resolvable into atropisomeric enantiomers, and are the first simple diarylamines to display atropisomerism.

15/09/2017

Lukas's paper

Exploiting and Understanding the Selectivity of Ru-N-Heterocyclic Carbene Metathesis Catalysts for the Ethenolysis of Cyclic Olefins to α,ω-Dienes

Pascal S. Engl, Celine B. Santiago, Christopher P. Gordon, Wei-Chih Liao, Alexey Fedorov, Christophe Copéret, Matthew S. Sigman, and Antonio Togni

Graphical abstract

Abstract Image

A library of 29 homologous Ru-based olefin metathesis catalysts has been tested for ethenolysis of cyclic olefins toward the goal of selectively forming α,ω-diene using cis-cyclooctene as a prototypical substrate. Dissymmetry at the N-heterocyclic carbene (NHC) ligand was identified as a key parameter for controlling the selectivity. The best-performing catalyst bearing an N-CF3 group significantly outperformed the benchmark second-generation Grubbs catalyst in the ethenolysis of cis-cyclooctene. Application of this optimal catalyst to the ethenolysis of various norbornenes allows the efficient synthesis of valuable diene intermediates in good yields. The observed ligand effect trends could be rationalized through univariate and multivariate parameter analysis involving steric and electronic descriptors of the NHC ligand in the form of the buried volume and the 77Se NMR chemical shift, in particular the σyy component of the shielding tensor of [Se(NHC)] model compounds, respectively. Natural chemical shift analysis of this chemical shielding tensor shows that σyy probes the π-acceptor property of the NHC ligand, the essential electronic parameter that drives the relative rate of degenerate metathesis and selectivity in ethenolysis with catalysts bearing dissymmetric NHC ligands.

Christian's paper

Real-time control of the enantioselectivity of a supramolecular catalyst allows selecting the configuration of consecutively formed stereogenic centres

Jeremy M. Zimbron, Xavier Caumes, Yan Li, Christophe M. Thomas, Matthieu Raynal, Laurent Bouteiller

Graphical abstract

pic

The enantiomeric state of a supramolecular copper catalyst can be switched in situ in ca. five seconds. The dynamic property of the catalyst is provided by the non-covalent nature of the helical assemblies supporting the copper centres. These assemblies are formed by mixing an achiral benzene-1,3,5-tricarboxamide (BTA) phosphine ligand (for copper coordination) and both enantiomers of a chiral phosphine-free BTA co-monomer (for chirality amplification). The enantioselectivity of the hydrosilylation reaction is fixed by the BTA enantiomer in excess, which can be altered by simple BTA addition. As a result of the complete and fast stereochemical switch, any combination of the enantiomers was obtained during the conversion of a mixture of two substrates.

Christine's paper

Selective α-Oxyamination and Hydroxylation of Aliphatic Amides

Xinwei Li, Fengguirong Lin, Kaimeng Huang, Jialiang Wei, Xinyao Li, Xiaoyang Wang, Xiaoyu Geng, Dr. Ning Jiao

Graphical abstract

Scheme 1.

Compared to the α-functionalization of aldehydes, ketones, even esters, the direct α-modification of amides is still a challenge because of the low acidity of α-CH groups. The α-functionalization of N−H (primary and secondary) amides, containing both an unactived α-C−H bond and a competitively active N−H bond, remains elusive. Shown herein is the general and efficient oxidative α-oxyamination and hydroxylation of aliphatic amides including secondary N−H amides. This transition-metal-free chemistry with high chemoselectivity provides an efficient approach to α-hydroxy amides. This oxidative protocol significantly enables the selective functionalization of inert α-C−H bonds with the complete preservation of active N−H bond.

October

06/10/2017

Christian's paper

Catalytic Asymmetric [8+2] Annulation Reactions Promoted by a Recyclable Immobilized Isothiourea

Shoulei Wang,[a] Carles Rodríguez-Escrich,[a] and Miquel A. Pericàs

Graphical abstract

Chris

Higher order cycloadditions constitute an efficient approach towards the construction of medium to large ring systems. However, enantioselective versions of these transformations remain scarce, which hampers their deployment in medicinal chemistry, or any other discipline where homochirality is deemed crucial. Herein, we report a novel methodology for the production of enantioenriched cycloheptatrienes fused to a pyrrolidone ring, based on an isothiourea-catalyzed periselective [8+2] cycloaddition between chiral ammonium enolates (generated in situ from carboxylic acids) and azaheptafulvenes. The resulting bicyclic compounds can be hydrogenated, but most remarkably, they can undergo a completely regioselective [4+2] cycloaddition with active dienophiles to give rise to architecturally complex polycyclic compounds in a straightforward manner.

Mahesh's paper

Rapid heteroatom transfer to arylmetals utilizing multifunctional reagent scaffolds

Hongyin Gao, Zhe Zhou, Doo-Hyun Kwon, James Coombs, Steven Jones, Nicole Erin Behnke, Daniel H. Ess & László Kürti

Graphical abstract

Current approaches to primary arylamine and phenol synthesis from arylmetals in the absence of transition-metal catalysts, impact of steric hindrance on kinetic acidity and the discovery of multifunctional oxaziridine reagents for heteroatom-transfer reactions.

 

 

 

 

 

Arylmetals are highly valuable carbon nucleophiles that are readily and inexpensively prepared from aryl halides or arenes and widely used on both laboratory and industrial scales to react directly with a wide range of electrophiles. Although C−C bond formation has been a staple of organic synthesis, the direct transfer of primary amino (−NH2) and hydroxyl (−OH) groups to arylmetals in a scalable and environmentally friendly fashion remains a formidable synthetic challenge because of the absence of suitable heteroatom-transfer reagents. Here, we demonstrate the use of bench-stable N−H and N−alkyl oxaziridines derived from readily available terpenoid scaffolds as efficient multifunctional reagents for the direct primary amination and hydroxylation of structurally diverse aryl- and heteroarylmetals. This practical and scalable method provides one-step synthetic access to primary anilines and phenols at low temperature and avoids the use of transition-metal catalysts, ligands and additives, nitrogen-protecting groups, excess reagents and harsh workup conditions.

13/10/2017

Mahesh's paper

Asymmetric Catalysis via Cyclic, Aliphatic Oxocarbenium Ions

Sunggi Lee, Philip S. J. Kaib, and Benjamin List

Graphical abstract

Abstract Image

 

 

 

 

 

A direct enantioselective synthesis of substituted oxygen heterocycles from lactol acetates and enolsilanes has been realized using a highly reactive and confined imidodiphosphorimidate (IDPi) catalyst. Various chiral oxygen heterocycles, including tetrahydrofurans, tetrahydropyrans, oxepanes, chromans, and dihydrobenzofurans, were obtained in excellent enantioselectivities by reacting the corresponding lactol acetates with diverse enol silanes. Mechanistic studies suggest the reaction to proceed via a nonstabilized, aliphatic, cyclic oxocarbenium ion intermediate paired with the confined chiral counteranion.

Christian's paper

Nickel-Catalyzed Cyanation of Aryl Chlorides and Triflates Using Butyronitrile: Merging Retro-Hydrocyanation with Cross-coupling

Peng Yu, Bill Morandi

Graphical abstract

ChrisWe describe here a nickel-catalyzed cyanation reaction of aryl  (pseudo)halides  that  employs  butyronitrile  as  a  cyanating reagent  instead  of  highly toxic  cyanide  salts.  A  dual  catalytic  cycle merging  retro-hydrocyanation  and  cross-coupling  enables  the conversion  of  a  broad  array  of  aryl  chlorides  and  aryl/vinyl  triflates into  their  corresponding  nitriles.  This  new  reaction  provides  a strategically  distinct  approach  to  the  safe  preparation  of  aryl cyanides,  which  are  essential  compounds  in  agrochemistry  and medicinal chemistry.

20/10/2017

Richard's paper

Fast, Efficient and Low E-Factor One-Pot Palladium-Catalyzed Cross-Coupling of (Hetero)ArenesAuthors

Erik B. Pinxterhuis, Paco Visser, Iwan Esser, Dr. Jean-Baptiste Gualtierotti, Prof. Dr. Ben L. Feringa

Figure 1.

 

 

 

 

 

 

 

The homocoupling of aryl halides and the heterocoupling of aryl halides with either aryl bromides or arenes bearing an ortho-lithiation directing group are presented. The use of a Pd catalyst, in combination with t-BuLi, allows for the rapid and efficient formation of a wide range of polyaromatic compounds in a one pot procedure bypassing the need for the separate preformation of an organometallic coupling partner. These polyaromatic structures are obtained in high yields, in 10 min at room temperature, with minimal waste generation (E-factors as low as 1.5) and without the need for strict inert conditions, making this process highly efficient and practical in comparison to classical methods. As illustration, several key intermediates of widely used BINOL-derived structures are readily prepared including the highly desired precursor to the chiral TRIP phosphoric acid.

27/10/2017

Elizabeth's paper

A Lewis Base Catalysis Approach for the Photoredox Activation of Boronic Acids and Esters

Authors Fabio Lima, Dr. Upendra K. Sharma, Lars Grunenberg, Dr. Debasmita Saha, Sandra Johannsen, Dr. Joerg Sedelmeier, Prof. Erik V. Van der Eycken, Prof. Steven V. Ley

27/10 paper 1

We report herein the use of a dual catalytic systemcomprising a Lewis base catalyst such as quinuclidin-3-ol or4-dimethylaminopyridine and a photoredox catalyst to gener-ate carbon radicals from either boronic acids or esters. Thissystem enabled a wide range of alkyl boronic esters and aryl oralkyl boronic acids to react with electron-deficient olefins viaradical addition to efficiently form CC coupled products ina redox-neutral fashion. The Lewis base catalyst was shown toform a redox-active complex with either the boronic esters orthe trimeric form of the boronic acids (boroxines) in solution.

Charlie's paper

Asymmetric Oxidative Coupling of Phenols and Hydroxycarbazoles

Houng Kang, Young Eun Lee, Peddiahgari Vasu Govardhana Reddy, Sangeeta Dey, Scott E. Allen, Kyle A. Niederer, Paul Sung, Kirsten Hewitt, Carilyn Torruellas, Madison R. Herling, and Marisa C. Kozlowski*

27/10 paper 2

The first examples of asymmetric oxidative coupling of simple phenols and 2-hydroxycarbazoles are outlined.

Generation of a more vanadium catalyst by ligand design and by addition of an exogenous Brønsted or Lewis acid was found to
be key to coupling the more oxidatively resistant phenols. The resultant vanadium complex is both more Lewis acidic and more
strongly oxidizing. Good to excellent levels of enantioselectivity could be obtained, and simple trituration readily provided the
products with ≥95% ee.

 

 

November

03/11/2017

Alan's papers

Tunneling Control of Chemical Reactions: The Third Reactivity Paradigm

Peter R. Schreiner

Tunneling

This Perspective describes the emergence of tunneling control as a new reactivity paradigm in chemistry. The term denotes a tunneling reaction that passes through a high but narrow potential energy barrier, leading to formation of a product that would be disfavored if the reaction proceeded by passage over kinetic barriers rather than through them. This reactivity paradigm should be considered along with thermodynamic and kinetic control as a factor that can determine which of two or more possible products is likely to be the one obtained. Tunneling control is a concept that can provide a deep and detailed understanding of a variety of reactions that undergo facile (and possibly unrecognized) tunneling.

A reevaluation of the origin of the rate acceleration for enzyme-catalyzed hydride transfer

tunneling 2

There is no consensus of opinion on the origin of the large rate accelerations observed for enzyme-catalyzed hydride transfer. The interpretation of recent results from studies on hydride transfer reactions catalyzed by alcohol dehydrogenase (ADH) focus on the proposal that the effective barrier height is reduced by quantum-mechanical tunneling through the energy barrier. This interpretation contrasts sharply with the notion that enzymatic rate accelerations are obtained through direct stabilization of the transition state for the nonenzymatic reaction in water. The binding energy of the dianion of substrate DHAP provides 11 kcal mol−1 stabilization of the transition state for the hydride transfer reaction catalyzed by glycerol-3-phosphate dehydrogenase (GPDH). We summarize evidence that the binding interactions between (GPDH) and dianion activators are utilized directly for stabilization of the transition state for enzyme-catalyzed hydride transfer. The possibility is considered, and then discounted, that these dianion binding interactions are utilized for the stabilization of a tunnel ready state (TRS) that enables efficient tunneling of the transferred hydride through the energy barrier, and underneath the energy maximum for the transition state. It is noted that the evidence to support the existence of a tunnel-ready state for the hydride transfer reactions catalyzed by ADH is ambiguous. We propose that the rate acceleration for ADH is due to the utilization of the binding energy of the cofactor NAD+/NADH in the stabilization of the transition state for enzyme-catalyzed hydride transfer.

Mahesh's paper

Harnessing Alkyl Amines as Electrophiles for Nickel-Catalyzed Cross Couplings via C–N Bond Activation

Corey H. Basch, Jennie Liao, Jianyu Xu, Jacob J. Piane, and Mary P. Watson

mahesh paper

We developed a strategy to harness alkyl amines as alkylating agents via C–N bond activation. This Suzuki–Miyaura cross coupling of alkylpyridinium salts, readily formed from primary amines, is the first example of a metal-catalyzed cross coupling via C–N bond activation of an amine with an unactivated alkyl group. This reaction enjoys broad scope and functional group tolerance. Primary and secondary alkyl groups can be installed. Preliminary studies suggest a NiI/NiIII catalytic cycle.

 10/11/2017

Mahesh's paper

A Copper-Catalyzed Aerobic [1,3]-Nitrogen Shift through Nitrogen-Radical 4-exo-trig Cyclization

Dr. Yan Li, Rui Wang, Tao Wang, Xiu-Fen Cheng, Xin Zhou, Fan Fei, Prof. Dr. Xi-Sheng Wa

mahesh paper

A novel radical [1,3]-nitrogen shift catalyzed by copper diacetate under an oxygen atmosphere (1 atm) has been developed for the construction of a diverse range of indole derivatives from α,α-disubstituted benzylamine. In this reaction, oxygen was used as a clean terminal oxidant, and water was produced as the only by-product. Five inert bonds were cleaved, and two C−N bonds and one C−C double bond were constructed in one pot during this transformation. This unique method demonstrated broad application protential for the late-stage modification of biologically active natural products and drugs. Mechanistic investigations indicate that a unique 4-exo-trig cyclization of an aminyl radical onto a phenyl ring is involved in the catalytic cycle.

Richard's Paper

 
María de Gracia Retamosa, Andrea Ruiz-Olalla,   Tamara Bello,Abel de Cózar, and Fernando P. Cossío
 
A new three-component diastereo- and enantioselective cyclization reaction is described. The reaction takes place between a ketone, a carboxylic acid and a nitroalkene to yield a bicyclic octahydro-2H-indol-2-one scaffold possessing three chiral centers. This reaction involves a rearrangement of the nitro group under simple thermal conditions. A plausible mechanism is proposed for this new reactio based on DFT calculations and isotope labeling experiments. A new concise enantioselective synthesis of alkaloid (+)-pancracine  is presented as an example of the potential of this novel organocatalytic cyclization reaction in the synthesis of natural products.

 

17/11/2017

Mahesh's paper

Cation Radical Accelerated Nucleophilic Aromatic Substitution via Organic Photoredox Catalysis

Nicholas E. S. Tay and David A. Nicewicz* 

Maheshs paper

 

 

 

 

 

 

Nucleophilic aromatic substitution (SNAr) is a direct method for arene functionalization; however, it can be hampered by low reactivity of arene substrates and their availability. Herein we describe a cation radical-accelerated nucleophilic aromatic substitution using methoxy- and benzyloxy-groups as nucleofuges. In particular, lignin-derived aromatics containing guaiacol and veratrole motifs were competent substrates for functionalization. We also demonstrate an example of site-selective substitutive oxygenation with trifluoroethanol to afford the desired trifluoromethylaryl ether.

24/11/2017

Elizabeth's paper

Unveiling Mechanism of a Quinine-Squaramide Catalyzed Enantioselective Aza-Friedel–Crafts Reaction between Cyclic Trifluoromethyl Ketimine and Naphthol: A DFT Study

Ping Wang, Yun Gao, Yang Zhao, Wei Liu*, and Yong Wang*

Liz paper

 

 

 

 

 

 

A mechanism study of quinine-squaramide catalyzed enantioselective aza-Friedel–Crafts (aza-F–C) reaction is described using density functional theory (DFT). The most favorable pathway is obtained through the discussions of four possible modes of hydrogen bond interactions, in which the nucleophile is activated by the squaramide N–H groups (N–Ha and N–Hb) and the electrophile binds to the protonated amine by hydrogen bonding. Meanwhile, we have also studied the energy barrier of the stereocontrolling transition states that might play a role of stereoselectivity. In addition, noncovalent interaction (NCI) analyses show a series of favorable cooperative noncovalent interactions, including N–H···O and C–H···F hydrogen-bonding, and π···π interactions. The strong interactions and lower barrier were found for TS3R, indicating the preference for the R-configuration adduct, which is in good agreement with the experimental observations.

Chris's paper

Photoredox-catalyzed deuteration and tritiation of pharmaceutical compounds

Yong Yao Loh1,*, Kazunori Nagao1,*, Andrew J. Hoover2, David Hesk2, Nelo R. Rivera2, Steven L. Colletti3, Ian W. Davies1,2, David W. C. MacMillan1,†

Chris paper

Deuterium- and tritium-labeled pharmaceutical compounds are pivotal diagnostic tools in drug discovery research, providing vital information about the biological fate of drugs and drug metabolites. Herein we demonstrate that a photoredox-mediated hydrogen atom transfer protocol can efficiently and selectively install deuterium (D) and tritium (T) at a-amino sp3 carbon-hydrogen bonds in a single step, using isotopically labeled water (D2O or T2O) as the source of hydrogen isotope. In this context, we also report a convenient synthesis of T2O from T2, providing access to high-specific-activity T2O. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 18 drug molecules, which meet the requirements for use in ligand-binding assays and absorption, distribution, metabolism, and excretion studies.

 

December

8/12/2017

Mahesh's paper

Irradiation-Induced Heck Reaction of Unactivated Alkyl Halides at Room Temperature

Guang-Zu Wang†, Rui Shang*†‡ , Wan-Min Cheng†, and Yao Fu*† Mahesh's paper

The palladium-catalyzed Mizoroki–Heck reaction is arguably one of the most significant carbon–carbon bond-construction reactions to be discovered in the last 50 years, with a tremendous number of applications in the production of chemicals. This Nobel-Prize-winning transformation has yet to overcome the obstacle of its general application in a range of alkyl electrophiles, especially tertiary alkyl halides that possess eliminable β-hydrogen atoms. Whereas most palladium-catalyzed cross-coupling reactions utilize the ground-state reactivity of palladium complexes under thermal conditions and generally apply a single ligand system, we report that the palladium-catalyzed Heck reaction proceeds smoothly at room temperature with a variety of tertiary, secondary, and primary alkyl bromides upon irradiation with blue light-emitting diodes in the presence of a dual phosphine ligand system. We rationalize that this unprecedented transformation is achieved by utilizing the photoexcited-state reactivity of the palladium complex to enhance oxidative addition and suppress undesired β-hydride elimination.

Chris' paper

Catalytic allylic oxidation of internal alkenes to a multifunctional chiral building block

Liela Bayeh, Phong Q. Le & Uttam K. Tambar

Chris' Paper

The stereoselective oxidation of hydrocarbons is one of the most notable advances in synthetic chemistry over the past fifty years1–3. Inspired by nature, enantioselective dihydroxylations, epoxidations and other oxidations of unsaturated hydrocarbons have been developed. More recently, the catalytic enantioselective allylic carbon–hydrogen oxidation of alkenes has streamlined the production of pharmaceuticals, natural products, fine chemicals and other functional materials4–7. Allylic functionalization provides a direct path to chiral building blocks with a newly formed stereocentre from petrochemical feedstocks while preserving the olefin functionality as a handle for further chemical elaboration. Various metal-based catalysts have been discovered for the enantioselective allylic carbon–hydrogen oxidation of simple alkenes with cyclic or terminal double bonds8–16. However, a general and selective allylic oxidation using the more common internal alkenes remains elusive. Here we report the enantioselective, regioselective and E/Z-selective allylic oxidation of unactivated internal alkenes via a catalytic hetero-ene reaction with a chalcogen-based oxidant. Our method enables non-symmetric internal alkenes to be selectively converted into allylic functionalized products with high stereoselectivity and regioselectivity. Stereospecific transformations of the resulting multifunctional chiral building blocks highlight the potential for rapidly converting internal alkenes into a broad range of enantioenriched structures that can be used in the synthesis of complex target molecules.

15/12/2017

Chris' paper

Synthesis of a-Chiral Ketones and Chiral Alkanes Using Radical Polar Crossover Reactions of Vinyl Boron Ate Complexes

Carolin Gerleve, Marvin Kischkewitz, Prof. Dr. Armido Studer

Chris paper

Vinyl boron ate complexes of enantioenriched secondary alkyl pinacolboronic esters undergo stereospecific radical-induced 1,2-migration in radical polar crossover reactions. In this three-component process various commercially available alkyl iodides act as radical precursors and light is used for chain initiation. Subsequent oxidation and protodeborylation leads to valuable α-chiral ketones and chiral alkanes, respectively, with excellent enantiopurity.

Kari's paper

Palladium-Catalyzed Intermolecular Acylation of Aryl Diazoesters with ortho-Bromobenzaldehydes

Yinghua Yu, Dr. Qianqian Lu, Prof. Dr. Gui Chen, Prof. Dr. Chunsen Li, Prof. Dr. Xueliang Huang

Karis paper

 

 

 

 

 

 

In this work, we describe a palladium-catalyzed intermolecular O acylation of α-diazoesters with ortho-bromobenzaldehydes. The C(sp2)−H bond activation of the aldehyde is enabled by migratory insertion of a palladium carbene intermediate. The diazoesters act as modular three-atom units to build up key seven-membered palladacycles, which are transformed into a variety of isocoumarin derivatives upon reductive elimination. Mechanistic experiments and DFT calculations provide insight into the reaction pathway.