27/01/12

Ling-Fu's paper

Stereoarrays with an All-Carbon Quaternary Center: Diastereoselective Desymmetrization of Prochiral Malonaldehyde

Dr. Bruno Linclau, Elena Cini, Catherine S. Oakes, Dr. Solen Josse, Dr. Mark Light, Dr. Victoria Ironmonge

Tamed by chelation: The MgBr₂ chelation of prochiral malonaldehydes allows diastereoselective monoaddition reactions with allyl stannane nucleophiles (see scheme; PG=protecting group, TBDMS=tert-butyldiphenylmethylsilyl, Tr=trityl). In the same pot, addition of a second nucleophile proceeds in high diastereoselectivity to generate nonsymmetric products with up to five contiguous stereogenic centers, including a chiral all-carbon quaternary center.

03/02/12

Jimmy's paper

Cu-Catalyzed Oxidative C(sp²)–H Cycloetherification of o-Arylphenols for the Preparation of Dibenzofurans

Jiaji Zhao, Yong Wang, Yimiao He, Lanying Liu, and Qiang Zhu

A new process involving copper-catalyzed aerobic C(sp²)–H activation, followed by cycloetherification, has been developed. This reaction serves as a direct method for the preparation of multisubstituted dibenzofurans starting with o-arylphenols. The presence of a strong para-electron-withdrawing group (e.g., NO₂) on the phenol is essential for the success of the reaction. DOI: 10.1021/ol203442a

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17/02/12

Jimmy's paper

Highly Enantioselective Synthesis of 3-Substituted γ-Butenolides by Palladium-Catalyzed Kinetic Resolution of Unsymmetrical Allyl Acetates

Bin Mao, Dr. Yining Ji, Dr. Martín Fañanás-Mastral, Dr. Giuseppe Caroli, Auke Meetsma, Prof. Dr. Ben L. Feringa

Resolving the issue: A near-perfect Pd-catalyzed kinetic resolution of 1,3-disubstituted unsymmetrical allylic acetates uses silyl enol ethers as nucleophiles to access the important 3-substituted-γ-butenolide scaffold (see scheme, DACH=diaminocyclohexyl; dba=dibenzylideneacetone). The reaction proceeds under mild conditions and provides the desired products with excellent chemo-, regio-, and enantioselectivity. DOI: 10.1002/anie.201109075

Ling-Fu's paper

Electron Transfer Reduction of Carboxylic Acids Using SmI₂–H₂O–Et₃N

Michal Szostak, Malcolm Spain, and David J. Procter

The first general method for efficient electron transfer reduction of carboxylic acids has been developed. The protocol using SmI₂–H₂O–Et₃N allows for reduction of a variety of carboxylic acids in excellent yields and provides an attractive alternative to processes mediated by reactive alkali metals, lithium aluminum hydride, and boron hydrides. Of broader significance, the method allows acyl radical equivalents to be generated from carboxylic acids under mild reaction conditions. DOI:10.1021/ol203361k

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24/02/12

Melanie's Paper

HighlyChemoselectiveReduction of Carbonyl Groups in the Presence of Aldehydes

Gulluzar Bastug, Steve Dierick, Frederic Lebreux, and Istvan E. Marko*

The exquisite ability of diethylaluminum benzenethiolate to efficiently discriminate between aldehydes and other carbonyl functions enables the chemoselective in situ reduction of ketones and methyl esters in the presence of aldehydes. This potent strategy avoids the usual drawbacks of traditional protecting group methodologies and could be extended to various other transformations.

to the paper

02/03/12

Melanie's Paper

Amines with Alcohols Catalyzed by a Ruthenium Pincer Complex

Santosh Agrawal, Maud Lenormand, and Belen Martı´n-Matute*

A readily available pincer ruthenium(II) complex catalyzes the selective monoalkylation of (hetero)aromatic amines with a wide range of primary alcohols (including pyridine-, furan-, and thiophene-substituted alcohols) with high efficiency when used in low catalyst loadings (1 mol %). Tertiary amine formation via polyalkylation does not occur, making this ruthenium system an excellent catalyst for the synthesis of sec-amines.

To the paper

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09/03/12

Melanie's paper

Iterative Asymmetric Allylic Substitutions: syn- and anti-1,2-Diols through Catalyst Control

Jin Kyoon Park, D. Tyler McQuade

A copper-catalyzed asymmetric allylic boronation (AAB) gives access to syn- and anti-1,2-diols. The method facilitates an iterative strategy for the preparation of polyols (see scheme), such as the fully differentiated L-ribo-tetrol and protected D-arabino-tetrol. P=protecting group
DOI: 10.1002/anie.201107874

20/04/12

Jimmy's paper

Asymmetric Allylic Alkylation of Pyrroles and 4,7-Dihydroindoles with Alkene–Phosphine Ligands

Yilin Liu, Ziping Cao, and Haifeng Du

A palladium-catalyzed highly enantioselective allylic alkylation of pyrroles and 4,7-dihydroindoles has been successfully developed with the use of chiral alkene-phosphine hybrid ligands to furnish the desired products in high yields with excellent ee’s. It is noteworthy that alkene–phosphine ligands are much more effective than some other types of chiral ligands in this catalytic system. DOI:10.1021/jo300539y

 

Melanie's paper

Efficient Chiral Monophosphorus Ligands for Asymmetric Suzuki–Miyaura Coupling Reactions

Wenjun Tang, Nitinchandra D. Patel, Guangqing Xu, Xiaobing Xu, Jolaine Savoie, Shengli Ma, Ming-Hong Hao, Santosh Keshipeddy, Andrew G. Capacci, Xudong Wei, Yongda Zhang, Joe J. Gao, Wenjie Li, Sonia Rodriguez, Bruce Z. Lu, Nathan K. Yee, and Chris H. Senanayake

A series of novel P-chiral monophosphorus ligands exhibit efficiency in asymmetric Suzuki–Miyaura coupling reactions, enabling the construction of an array of chiral biaryl products in high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. The carbonyl-benzooxazolidinone moiety in these chiral biaryl products allows facile derivatization for further synthetic applications. A computational study has revealed that a π–π interaction between the two coupling partners can enhance the enantioselectivity of the coupling reaction. DOI: 10.1021/ol300659d

18/05/12

Jimmy's paper

Synthesis of Eight-Membered Lactones: Intermolecular [6+2] Cyclization of Amphoteric Molecules with Siloxy Alkynes

Wanxiang Zhao, Zhaobin Wang, Prof. Dr. Jianwei Sun

That’s about the size of it: The title molecules react with siloxy alkynes in the presence of a Brønsted acid to deliver medium-sized lactones through a [6+2] cyclization (see scheme; TIPS=triisopropylsilyl). This process is the first intermolecular synthesis of such lactones and involves a sequence of several selective ring-opening/ring-closing events. DOI: 10.1002/anie.201200513

Jonas' paper

Scope and Mechanism of the (4+3) Cycloaddition Reaction of Furfuryl Cations

Dr. Johan M. Winne, Dr. Saron Catak, Prof. Dr. Michel Waroquier, Prof. Dr. Veronique Van Speybroeck

Ringe im Dutzend: Furfurylalkohole wurden als direkte Reaktionspartner in einer (4+3)-Cycloaddition für eine Vielzahl an konjugierten Dienen erkannt (siehe Schema). Dieser neuartige Lewis-Säure-vermittelte Prozess macht unterschiedliche polycyclische Gerüste mit einem siebengliedrigen Ring einfach zugänglich. Ein plausibler stufenweiser kationischer Mechanismus wird durch DFT-Rechnungen gestützt. DOI: 10.1002/ange.201104930

15/06/12

Jimmy's paper

Access to C(sp³)–C(sp²) and C(sp²)–C(sp²) Bond Formation via Sequential Intermolecular Carbopalladation of Multiple Carbon–Carbon Bonds

Yanmei Wen, Liangbin Huang, and Huanfeng Jiang

A synthetic strategy of 4-benzyl-substituted 1,3-butadiene derivatives through Pd-catalyzed three-component coupling reaction of benzyl chlorides, alkynes, and monosubstituted alkenes is described. This tandem coupling reaction forms a C(sp³)–C(sp²) bond and a C(sp²)–C(sp²) bond sequentially in a single-step operation.
DOI: 10.1021/jo300662x

 
Jonas' paper

High-Yielding, Versatile, and Practical [Rh(III)Cp*]-Catalyzed Ortho Bromination and Iodination of Arenes

Nils Schröder, Joanna Wencel-Delord, and Frank Glorius

We report a uniquely high-yielding, general, and practical ortho bromination and iodination reaction of different classes of aromatic compounds. This reaction occurs by Rh(III)-catalyzed C–H bond activation methodology and is therefore the first example of the application of this cationic catalyst for C–Br and C–I bond formation.
DOI: 10.1021/ja302631j

 

Lucy's Paper

Rapid and high-yielding cysteine labelling of peptides with N-succinimidyl 4-[¹⁸F]fluorobenzoate

Sergio Abad ,  Pau Nolis ,  Juan D. Gispert ,  Jan Spengler ,  Fernando Albericio ,  Santiago Rojas and José R. Herance

Fast cysteine labelling of peptides promoted by an adjacent arginine has been observed with a standard labelling agent specific for amines, N-succinimidyl 4-[¹⁸F]fluorobenzoate. [DOI]

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01/06/12

Alan's 1st paper

Continuous-Flow Synthesis of the Anti-Malaria Drug Artemisinin

François Lévesque, Peter H. Seeberger

Malaria is a serious global health issue. Artemisinin combination treatments are the first-line drugs, but supplies are limited because artemisinin is obtained solely by extraction from Artemisia annua. A continuous-flow process that converts dihydroartemisinic acid into artemisinin (see scheme) was shown to be an inexpensive and scalable process that can ensure a steady, affordable supply of artemisinin.  DOI: 10.1002/anie.201107446

Alan's 2nd paper

Integrated 3D-printed reactionware for chemical synthesis and analysis

Mark D. Symes, Philip J. Kitson, Jun Yan, Craig J. Richmond, Geoffrey J. T. Cooper, Richard W. Bowman, Turlif Vilbrandt & Leroy Cronin

Three-dimensional (3D) printing has the potential to transform science and technology by creating bespoke, low-cost appliances that previously required dedicated facilities to make. An attractive, but unexplored, application is to use a 3D printer to initiate chemical reactions by printing the reagents directly into a 3D reactionware matrix, and so put reactionware design, construction and operation under digital control. Here, using a low-cost 3D printer and open-source design software we produced reactionware for organic and inorganic synthesis, which included printed-in catalysts and other architectures with printed-in components for electrochemical and spectroscopic analysis. This enabled reactions to be monitored in situ so that different reactionware architectures could be screened for their efficacy for a given process, with a digital feedback mechanism for device optimization. Furthermore, solely by modifying reactionware architecture, reaction outcomes can be altered. Taken together, this approach constitutes a relatively cheap, automated and reconfigurable chemical discovery platform that makes techniques from chemical engineering accessible to typical synthetic laboratories. DOI:10.1038/nchem.1313

Jimmy's paper

Ruthenium-Catalyzed Redox Isomerization of Trifluoromethylated Allylic Alcohols: Mechanistic Evidence for an Enantiospecific Pathway

Vincent Bizet, Xavier Pannecoucke, Jean-Luc Renaud, Dominique Cahard

Transfer news: A synthetic approach to chiral β-CF₃-substituted saturated carbonyl compounds has been developed in which ruthenium complexes efficiently catalyze the redox isomerization of CF₃-bearing allylic alcohols by an intramolecular suprafacial enantiospecific 1,3-hydrogen transfer (see scheme). This method was used for the enantioselective. DOI: 10.1002/anie.201200827

 
Jonas' paper

General and Selective Head-to-Head Dimerization of Terminal Alkynes Proceeding via Hydropalladation Pathway

Claire Jahier, Olga V. Zatolochnaya, Nickolay V. Zvyagintsev, Valentine P. Ananikov, and Vladimir Gevorgyan

A general highly regio- and stereoselective palladium-catalyzed head-to-head dimerization reaction of terminal acetylenes is presented. This methodology allows for the efficient synthesis of a variety of 1,4-enynes as single E stereoisomers. Computational studies reveal that this dimerization reaction proceeds via the hydropalladation pathway. DOI: 10.1021/ol3010936

13/07/12

Jimmy's paper

Enantioselective Rhodium-Catalyzed Nucleophilic Allylation of Cyclic Imines with Allylboron Reagents

Yunfei Luo, Hamish B. Hepburn, Nawasit Chotsaeng, Hon Wai La

Chiral allylrhodium nucleophiles: The highly diastereo- and enantioselective title reaction of a range of cyclic imines with various potassium allyltrifluoroborates most likely proceeds via allylrhodium(I) intermediates, and represents the first rhodium-catalyzed enantioselective nucleophilic allylation of π electrophiles with allylboron compounds
DOI: 10.1002/anie.201204004

 
Ling-Fu's paper

Enantioselective Organo-SOMO Cycloadditions: A Catalytic Approach to Complex Pyrrolidines from Olefins and Aldehydes 

Nathan T. Jui, Jeffrey A. O. Garber, Fernanda GadiniFinelli, and David W. C. MacMillan*

A new method to rapidly generate pyrrolidines via a SOMO-activated enantioselective (3 + 2) coupling of aldehydes and conjugated olefins has been accomplished. A radical-polar crossover mechanism is proposed wherein olefin addition to a transient enamine radical cation and oxidation of the resulting radical furnish a cationic intermediate which is vulnerable to nucleophilic addition of a tethered amine group. A range of olefins, including styrenes and dienes, are shown to provide stereochemically complex pyrrolidine products with high chemical efficiency and enantiocontrol.
DOI: 10.1021/ja305076b

Edu's paper

Small Molecule c-jun-N-Terminal Kinase Inhibitors Protect Dopaminergic Neurons in a Model of Parkinson’s Disease

Jeremy W. Chambers, Alok Pachori, ShannonHoward, Michelle Ganno, Donald Hansen, Jr., TedKamenecka, Xinyi Song, Derek Duckett, WeiminChen,Yuan Yuan Ling, Lisa Cherry, Michael D.Cameron, Li Lin, Claudia H. Ruiz, and PhilipLoGrasso

There are currently no drugs to treat neurodegeneration in Parkinson’s disease (PD), and all existing medications only treat symptoms, lose efficacy over time, and produce untoward side effects. In the current work, we report the first highly selective, orally bioavailable c-jun-N-terminal kinase (JNK) inhibitor for protection of dopaminergic neurons in vitro and in vivo. At 300 nM, this compound showed statistically significant protection of primary dopaminergic neurons exposed to 1-methyl-4-phenylpyridinium (MPP⁺), had pharmacokinetic properties in rodents consistent with twice daily (b.i.d.) dosing, and was orally efficacious at 30 mg/kg in a mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson’s disease. Moreover, a dose-dependent target modulation of c-jun phosphorylation served as a biomarker for demonstrating on-target inhibition of JNK as the mechanism of action for this compound. Collectively, these results suggest that this JNK inhibitor could be a promising therapeutic neuroprotective agent in the treatment of Parkinson’s disease.
DOI: 10.1021/cn100109k

 
Jonas' paper

Iridium-Catalyzed Reduction of Secondary Amides to Secondary Amines and Imines by Diethylsilane

Chen Cheng and Maurice Brookhart

Catalytic reduction of secondary amides to imines and secondary amines has been achieved using readily available iridium catalysts such as [Ir(COE)₂Cl]₂ with diethylsilane as reductant. The stepwise reduction to secondary amine proceeds through an imine intermediate that can be isolated when only 2 equiv of silane is used. This system requires low catalyst loading and shows high efficiency (up to 1000 turnovers at room temperature with 99% conversion have been attained) and an appreciable level of functional group tolerance. DOI: 10.1021/ja304547s

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27/7/12

Jonas's paper

Highly Efficient One-Pot Access to Functionalized Arylboronic Acids via Noncryogenic Bromine/Magnesium Exchanges

A general and convenient protocol for the electrophilic borylation of aryl Grignard reagents prepared from arylbromides by direct insertion of magnesium in the presence of LiCl or by Mg/Br exchange with ⁱPrMgCl·LiCl has been developed. Various aryl boronic acids were synthesized in a straightforward manner in excellent yields at 0 °C.
DOI : 10.1021/ol2016252

 
Ling-Fu's paper

Intermolecular Radical Reaction of O,Se-Acetals Generated via Seleno-Pummerer Rearrangement

A new general protocol for the synthesis of O,Se-acetals using the seleno-Pummerer reaction has been developed, and their radical-based two- and three-component coupling reactions were studied. The three-component coupling employed the O,Se-acetal, cyclopentenone, and an allylstannane derivative, and enabled stereoselective installations of α-acyloxy alkyl and functionalized allyl groups to generate the 2,3-trans-disubstituted cyclopentanone in a single operation. The obtained highly functionalized structure was used as an intermediate for facile assembly of the zedoarondiol carboskeleton.
DOI : 10.1021/ol301482f

 

No meetings.

14/09/12

Ling-Fu's paper

Highly Enantioselective Hetero-Diels–Alder Reaction of 1,3-Bis(silyloxy)-1,3-dienes with Aldehydes Catalyzed by Chiral Disulfonimide^†

Bulking up with F: The title reaction proceeds using 1 mol % of the new perfluoroisopropyl chiral disulfonimide catalyst 1 to deliver several 2,6-disubstituted and 2,5,6-trisubstituted dihydropyrones in good yields and with excellent enantiomeric ratios. The utility of this methodology is illustrated with the first enantioselective synthesis of a potent aromatase inhibitor.
DOI: 10.1002/anie.201204262

Melanie's paper

Suzuki–Miyaura Coupling of Aryl Iodides, Bromides, and Chlorides Catalyzed by Bis(thiazole) Pincer Palladium Complexes

Bis(thiazole) pincer palladium complexes showed efficient catalytic activity for the Suzuki–Miyaura coupling of aryl halides, allowing the synthesis of biaryls with very high turnover numbers and turnover frequencies. The complexes were successfully applied in the scalable and green synthesis of the key intermediates of bioactive LUF5771 and its analogues.
DOI: 10.1021/jo3011733

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21/09/12

Claire's paper

Practical Method for the Cu-Mediated Trifluoromethylation of Arylboronic Acids with CF₃ Radicals Derived from NaSO₂CF₃ and tert-Butyl Hydroperoxide (TBHP)

A mild and practical protocol for the copper-mediated trifluoromethylation of aryl and heteroaryl boronic acids using NaSO₂CF₃ (Langlois’ reagent) and TBHP is described. The reaction proceeds at room temperature under ambient conditions, and the products can be readily purified by extraction or column chromatography. DOI: 10.1021/ol3022726

 Ling-Fu's paper

A Doubly Axially Chiral Phosphoric Acid Catalyst for the Asymmetric Tandem Oxyfluorination of Enamides

Keywords:

• Brønsted acid catalysis;
• enantioselectivity;
• fluorination;
• phase-transfer catalysis;
• phosphoric acids

Double agent: Enantioselective tandem oxyfluorination of enamides using a doubly axially chiral phosphoric acid catalyst is reported. The chiral phosphoric acid catalyst controls both a fluorination step, using a chiral anion phase-transfer strategy, and addition to the resulting imine under the guise of Brønsted acid catalysis. DOI: 10.1002/anie.201205338

 
Melanie's paper

Synchronized Aromaticity as an Enthalpic Driving Force for the Aromatic Cope Rearrangement

We report herein experimental and theoretical evidence for an aromatic Cope rearrangement. Along with several successful examples, our data include the first isolation and full characterization of the putative intermediate that is formed immediately after the initial [3,3] sigmatropic rearrangement. Calculations at the B3LYP/6-31G(d) level of theory predict reaction energy barriers in the range 22–23 kcal/mol for the [3,3]-rearrangement consistent with the exceptionally mild reaction conditions for these reactions. The experimental and computational results support a significant enthalpic contribution of the concomitant pyrazole ring formation that serves as both a kinetic and thermodynamic driving force for the aromatic Cope rearrangement. DOI: 10.1021/ja307213m

 

05/10/12

Claire's paper

A copper-catalyzed arylation of tryptamines for the direct synthesis of aryl pyrroloindolines

Madeleine E. Kieffer , Kangway V. Chuang and Sarah E. Reisman

An operationally simple, copper-catalyzed arylation of N-tosyltryptamines provides direct access to C3-aryl pyrroloindolines. A range of electron-donating and electron-withdrawing substituents is tolerated on both the indole backbone and the aryl electrophile. These reactions occur under ambient temperatures and with equimolar quantities of the coupling partners.

DOI: 10.1039/C2SC20914D

James' paper

Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones

Piotr Kwiatkowski , Teresa D. Beeson , Jay C. Conrad, and David W. C. MacMillan

The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio-, and chemoselective catalyst control in fluorinations involving complex carbonyl systems.
DOI: 10.1021/ja111163u

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12/10/12

Ling-Fu's paper

A Nonmetal Approach to α-Heterofunctionalized Carbonyl Derivatives by Formal Reductive X H Insertion

Eric J. Miller,  Wei Zhao,  Jonathan D. Herr,  Prof. Dr. Alexander T. Radosevich

Keeping it organic: A direct synthesis of α-alkoxy and α-amino ester derivatives by direct reductive coupling of widely available, stable α-keto esters and protic pronucleophiles is described (see scheme; X=OR, NR₂). The method serves as a convenient nonmetal alternative to X H insertion by diazo decomposition.
DOI : 10.1002/anie.201205604

Melanie's paper

Chelation-Controlled Addition of Organozincs to α-Chloro Aldimines

Gretchen R. Stanton, Per-Ola Norrby, Patrick J. Carroll and Patrick J. Walsh

Nucleophilic additions to α-chiral α-halo carbonyl derivatives are well-known to generate Cornforth–Evans products via a nonchelation pathway. What was unprecedented before this report is C–X bonds reversing the diastereoselectivity through coordination to metals during C–C bond-forming reactions (chelation control). Herein we describe chelation control involving C–X bonds in highly diastereoselective additions of organozinc reagents to a variety of α-chloro aldimines. The unique ability of alkylzinc halide Lewis acids to coordinate to the Cl, N, and O of α-chloro sulfonyl imine substrates is supported by computational studies.
DOI: 10.1021/ja306781z

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19/10/12

Claire's paper

Nickel-Mediated Oxidative Fluorination for PET with Aqueous [18F] Fluoride

Eunsung Lee, Jacob M. Hooker, and Tobias Ritter

A one-step oxidative fluorination for carbon–fluorine bond formation from well-defined nickel complexes with oxidant and aqueous fluoride is presented, which enables a straightforward and practical ¹⁸F late-stage fluorination of complex small molecules with potential for PET imaging.
DOI : /10.1021/ja3084797

Lucy's paper

Enabling Wittig reaction on site-specific protein modification

Ming-Jie Han , De-Cai Xiong and Xin-Shan Ye

An efficient aqueous Wittig reaction was enabled on protein bioconjugation for the first time. By investigating the reaction on small molecules, peptides, and proteins, a site-specific reaction targeting “aldehyde tag” was presented. A variety of functional groups could be introduced into the protein of interest.
DOI: 10.1039/C2CC35738K

Zsofia's Paper

One-Pot Synthesis of 1-Iodoalkynes and Trisubstituted Alkenes from Benzylic and Allylic Bromides

Guillaume Pelletier , Sharon Lie , James J. Mousseau, and André B. Charette

1-Iodoalkynes are formed in moderate to high yields from readily accessible benzylic and allylic alkyl bromides by a one-pot homologation/double elimination procedure with iodoform (CHI₃). The developed conditions include facile purification and avoid the use of an excess of triphenylphosphine (PPh₃), as described in classical Corey–Fuchs iodoalkynylation conditions. Replacing CHI₃ with CHI₂Cl allows the isolation of the corresponding gem-(Z)-chloro-(E)-iodoalkene in good yield and stereoselectivity. Moreover, the use of benzhydryl bromides as nucleophiles enables the synthesis of trisubstituted alkenes under similar reaction conditions.
DOI : 10.1021/ol302544s 

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26/10/12

Claire's paper

Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation

Phillip A. Lichtor and Scott J. Miller

Selectivity in the catalytic functionalization of complex molecules is a major challenge in chemical synthesis. The problem is magnified when there are several possible stereochemical outcomes and when similar functional groups occur repeatedly within the same molecule. Selective polyene oxidation provides an archetypical example of this challenge. Historically, enzymatic catalysis has provided the only precedents. Although non-enzymatic catalysts that meet some of these challenges became known, a comprehensive solution has remained elusive. Here, we describe low molecular weight peptide-based catalysts, discovered through a combinatorial synthesis and screening protocol, that exhibit site- and enantioselective oxidation of certain positions of various isoprenols. This diversity-based approach, which exhibits features reminiscent of the directed evolution of enzymes, delivers catalysts that compare favourably to the state-of-the-art for the asymmetric oxidation of these compounds. Moreover, the approach culminated in catalysts that exhibit alternative-site selectivity in comparison to oxidation catalysts previously described. DOI:10.1038/NCHEM.1469

Ling-Fu's paper

Asymmetric Approach toward Chiral Cyclohex-2-enones from Anisoles via an Enantioselective Isomerization by a New Chiral Diamine Catalyst

Jung Hwa Lee and Li Deng

A 3 step asymmetric approach toward the optically active chiral cyclohex-2-enones from anisoles has been developed. The crucial asymmetric induction step is an unprecedented catalytic enantioselective isomerization of β,γ-unsaturated cyclohex-3-en-1-ones to the corresponding α,β-unsaturated chiral enones. This new asymmetric transformation was realized by cooperative iminium-base catalysis with an electronically tunable new organic catalyst. The synthetic utility of this methodology is highlighted by the enantioselective total synthesis of (−)-isoacanthodoral.

DOI:10.1021/ja308623n

02/11/12

Jimmy's paper

Ruthenium-Catalyzed ortho-Alkylation of Phenols with Alcohols by Dehydrative Coupling

James W. Walton and Jonathan M. J. Williams

Graphical Abstract

Only water: Phenols have been shown to undergo a ruthenium-catalyzed ortho-alkylation reaction (see scheme; Cy=cyclohexyl). Unactivated alcohols are used as the alkylating agents and water is the only by-product that is generated, making this transformation more atom-economical and greener than traditional methods. 

Melanie's paper

Palladium-Catalyzed Dehydrogenation/Oxidative Cross-Coupling Sequence of b-Heteroatom-Substituted Ketones

Youngtaek Moon, Daeil Kwon and Sungwoo Hong

Concise and selective: The title one-pot sequence allows formation of the enone functionality and subsequent cross-coupling. The process provides access to highly functionalized cyclic enolones and enaminones from readily accessible β-heteroatom-substituted cyclic ketones

Zsofi's paper

Azobisisobutyronitrile Initiated Aerobic Oxidative Transformation of Amines: Coupling of Primary Amines and Cyanation of Tertiary Amines

Lianghui Liu , Zikuan Wang , Xuefeng Fu, and Chun-Hua Yan

In the presence of a catalytic amount of radical initiator AIBN, primary amines are oxidatively coupled to imines and tertiary amines are cyanated to α-aminonitriles. These “metal-free” aerobic oxidative coupling reactions may find applications in a wide range of “green” oxidation chemistry.

 

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09/11/12

Claire's paper

Functionalization of C H and C H Bonds: Synthesis of Spiroindenes by Enolate-Directed Ruthenium-Catalyzed Oxidative Annulation of Alkynes with 2-Aryl-1,3-dicarbonyl Compounds

Suresh Reddy Chidipudi, Imtiaz Khan, Hon Wai Lam

Ru(de) awakening: The synthesis of carbocycles by the ruthenium-catalyzed oxidative annulation of alkynes with 2-aryl cyclic 1,3-dicarbonyl substrates is described. Proceeding by the functionalization of C H and C H bonds, and the formation of an all-carbon quaternary center, the reaction provides a diverse range of spiroindenes in good yields with high levels of regioselectivity. 

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16/11/12

Claire's paper

Accelerated Carbon Carbon Bond-Forming Reactions in Preparative Electrospray

Thomas Müller, Abraham Badu-Tawiah and R. Graham Cooks

From analysis towards synthesis: Charged microdroplets act as microreaction vessels, extending the use of electrospray mass spectrometry from chemical analysis to synthesis. Application of this unique reaction conditions allows microscale carbon–carbon bond forming reactions to be performed rapidly and in high yields (see picture).

Keith's paper

Tuning the Reactivity of TEMPO by Coordination to a Lewis Acid: Isolation and Reactivity of MCl3(η1-TEMPO) (M = Fe, Al)

Jeremiah J. Scepaniak , Ashley M. Wright , Richard A. Lewis , Guang Wu , and Trevor W. Hayton

Addition of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) to MCl₃ (M = Fe, Al) results in the formation of MCl₃(η¹-TEMPO) [M = Fe (1), Al (2)]. Both 1 and 2 oxidize alcohols to generate ketones or aldehydes along with the reduced complexes MCl₃(η¹-TEMPOH) [M = Fe (3), Al (4)]. Complexes 1–4 were fully characterized, including analysis by X-ray crystallography. Additionally, control experiments indicated that neither MCl₃ (M = Al, Fe) nor TEMPO are capable of effecting the oxidation of alcohols independently.

Ling-Fu's paper

Copper-Catalyzed Amination of Ketene Silyl Acetals with Hydroxylamines: Electrophilic Amination Approach to α-Amino Acids

Naoki Matsuda, Koji Hirano, Tetsuya Satoh and Masahiro Miura

Role reversal: The title reaction has been developed to deliver α-amino acids under very mild reaction conditions (see scheme; dpppen=1,5-bis(diphenylphosphino)pentane). The catalysis provides a new C N bond-forming approach for the synthesis of α-amino acids by using an umpolung, electrophilic amination strategy.

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23/11/12

Zsofia's paper

 

Benzazoles from Aliphatic Amines and o-Amino/Mercaptan/Hydroxyanilines: Elemental Sulfur as a Highly Efficient and Traceless Oxidizing Agent

Thanh Binh Nguyen, Ludmila Ermolenko, William A. Dean and Ali Al-Mourabit

A novel remarkably simple solvent-free and catalyst-free synthesis of benzazoles from alkylamines and o-hydroxy/amino/mercaptan anilines using elemental sulfur as traceless oxidizing agent has been developed.

Melanie's paper

Dehydrogenative Amide Synthesis: Azide as a Nitrogen Source

Zhenqian Fu, Jeongbin Lee, Byungjoon Kang and Soon Hyeok Hong

A new atom-economical strategy to amide linkage from an azide and alcohol liberating hydrogen and nitrogen was developed with an in situ generated ruthenium catalytic system. The reaction has broad substrate generality including diols for the synthesis of cyclic imides.

Jimmy's paper

Copper-Promoted Trifluoromethylation of Primary and Secondary Alkylboronic Acids

Jun Xu^, Bin Xiao^, Chuan-Qi Xie^, Dong-Fen Luo^, Lei Liu and Yao Fu

New couple: The Cu-promoted trifluoromethylation of primary and secondary alkylboronic acids with TMSCF₃ extends the scope of transition-metal-catalyzed trifluoromethylation reactions to sp³-hybridized carbon centers. It also represents one of the first examples for Cu-catalyzed CC cross-coupling reactions of alkylboronic acid derivatives.

 

 

14/12/12

Ling-Fu's paper

Asymmetric Brønsted Acid Catalyzed Cycloadditions—Efficient Enantioselective Synthesis of Pyrazolidines, Pyrazolines, and 1,3-Diamines from N-Acyl Hyrazones and Alkenes

Magnus Rueping, Modhu Sudan Maji, Hatice Başpınar Küçük and Iuliana Atodiresei

A general, metal-free, highly enantioselective Brønsted acid catalyzed [3+2] cycloaddition between hydrazones and alkenes has been developed that affords pyrazolidine derivatives (see scheme). The resulting optically active pyrazolidines can undergo many chemical transformations which allow, for example, the enantioselective synthesis of valuable pyrazolines and 1,3-diamines.