Imperial College London
Portrait Picture

Dr James A Bull

Faculty of Natural Sciences, Department of Chemistry

Reader in Synthetic Chemistry
 
 
 
//

Contact

 

+44 (0)20 7594 5811j.bull Website

 
 
//

Location

 

501bMolecular Sciences Research HubWhite City Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Chawner:2017:10.1002/ejoc.201701030,
author = {Chawner, SJ and Cases-Thomas, MJ and Bull, JA},
doi = {10.1002/ejoc.201701030},
journal = {European Journal of Organic Chemistry},
pages = {5015--5024},
title = {Divergent Synthesis of Cyclopropane-Containing Lead-like Compounds, Fragments and Building Blocks via a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide},
url = {http://dx.doi.org/10.1002/ejoc.201701030},
volume = {2017},
year = {2017}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cyclopropanes provide important design elements in medicinal chemistry and are widely present in drug compounds. Here we describe a strategy and extensive synthetic studies for the preparation of a diverse collection of cyclopropane-containing fragments, lead-like compounds and building blocks exploiting a single precursor. The bifunctional cyclopropane (E/Z)-ethyl 2-(phenylsulfanyl)-cyclopropane-1-carboxylate was designed to allow derivatization through the ester and sulfide functionalities to topologically varied compounds designed to fit in desirable chemical space for drug discovery. A cobalt-catalyzed cyclopropanation of phenyl vinyl sulfide affords these scaffolds on multigram scale. Divergent, orthogonal derivatization is achieved through hydrolysis, reduction, amidation and oxidation reactions as well as sulfoxide–magnesium exchange/functionalization. The cyclopropyl Grignard reagent formed from sulfoxide exchange is stable at 0 C for >2 h, enabling trapping with various electrophiles and Pd-catalyzed Negishi cross-coupling reactions. The library prepared, as well as a further virtual elaboration, is analyzed against parameters of lipophilicity (ALogP), MW, and molecular shape using the LLAMA (Lead-Likeness and Molecular Analysis) software, to illustrate the success in generating lead-like compounds and fragments.
AU  - Chawner,SJ
AU  - Cases-Thomas,MJ
AU  - Bull,JA
DO  - 10.1002/ejoc.201701030
EP  - 5024
PY  - 2017///
SN  - 1434-193X
SP  - 5015
TI  - Divergent Synthesis of Cyclopropane-Containing Lead-like Compounds, Fragments and Building Blocks via a Cobalt Catalyzed Cyclopropanation of Phenyl Vinyl Sulfide
T2  - European Journal of Organic Chemistry
UR  - http://dx.doi.org/10.1002/ejoc.201701030
UR  - http://hdl.handle.net/10044/1/50238
VL  - 2017
ER  -
Download