Asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes as key components of substance P antagonists

Jeffrey T. Kuethe, Audrey Wong, Jimmy Wu, Ian W. Davies, Peter G. Dormer, Christopher J. Welch, Michael C. Hillier, David L. Hughes, Paul J. Reider

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

An efficient asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes is described. Three methods were developed for the preparation of the 2,3-disubstituted cyclopentenones and cyclohexenones, which are key achiral building blocks. These intermediates are reduced catalytically with (R)-2-methyloxazaborolidine in high yield (82-98%) and excellent ee (89-96%). Directed reduction of the chiral allylic alcohols using Red-Al gives exclusively the 1,2-anti stereochemistry (>99:1). Epimerization of the ester center followed by saponification/crystallization affords the desired hydroxyacids in good yield (65-70%) and in high enantiomeric excess (>99%).

Original languageEnglish (US)
Pages (from-to)5993-6000
Number of pages8
JournalJournal of Organic Chemistry
Volume67
Issue number17
DOIs
StatePublished - Aug 23 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Fingerprint Dive into the research topics of 'Asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes as key components of substance P antagonists'. Together they form a unique fingerprint.

  • Cite this

    Kuethe, J. T., Wong, A., Wu, J., Davies, I. W., Dormer, P. G., Welch, C. J., Hillier, M. C., Hughes, D. L., & Reider, P. J. (2002). Asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes as key components of substance P antagonists. Journal of Organic Chemistry, 67(17), 5993-6000. https://doi.org/10.1021/jo025883m