Lithium-sulfoxide-lithium exchange for the asymmetric synthesis of atropisomers under thermodynamic control

Jonathan Clayden*, David Mitjans, Latifa H. Youssef

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

91 Citations (Scopus)

Abstract

Ortholithiation and reaction with (-)-menthyl p-toluenesulfinate introduces a sulfoxide substituent ortho to the stereogenic Ar-CO axis of an aromatic amide. The sulfoxide exerts a powerful conformational bias on the axis, such that after rapid equilibration at ambient temperature essentially only one of two diastereoisomeric Ar-CO atropisomers is populated. Sulfoxide-lithium exchange by treatment with t-BuLi regenerates the ortholithiated amide in an enantiomerically pure and conformationally stable form. Rapid electrophilic trapping of the organolithium therefore generates highly enantiomerically enriched atropisomeric tertiary aromatic amides. The overall process, involving temporary substitution of lithium to sulfoxide to lithium, amounts to a dynamic resolution under thermodynamic control.

Original languageEnglish
Pages (from-to)5266-5267
Number of pages2
JournalJournal of the American Chemical Society
Volume124
Issue number19
Early online date17 Apr 2002
DOIs
Publication statusPublished - 15 May 2002

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