Catalytic enantioselective addition of organometallics to unprotected carboxylic acids

Xingchen Yan, Syuzanna R. Harutyunyan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)
137 Downloads (Pure)

Abstract

Conjugate addition of organometallics to carbonyl based Michael acceptors is a widely used method that allows the building of new carbon-carbon (C-C) bonds and the introduction of chirality in a single step. However, conjugate additions to the simplest Michael acceptors, namely unprotected, unsaturated carboxylic acids, are considered to be prohibited by the fact that acid-base reactions overpower any other type of reactivity, including nucleophilic addition. Here we describe a transient protecting group strategy that allows efficient catalytic asymmetric additions of organomagnesium reagents to unprotected alpha,beta-unsaturated carboxylic acids. This unorthodox pathway is achieved by preventing the formation of unreactive carboxylate salts by means of a reactive intermediate, allowing modifications of the carbon chain to proceed unhindered, while the stereochemistry is controlled with a chiral copper catalyst. A wide variety of beta-chiral carboxylic acids, obtained with excellent enantioselectivities and yields, can be further transformed into valuable molecules through for instance catalytic decarboxylative cross-coupling reactions.

Original languageEnglish
Article number3402
Number of pages10
JournalNature Communications
Volume10
DOIs
Publication statusPublished - 30-Jul-2019

Keywords

  • ASYMMETRIC CONJUGATE ADDITION
  • GRIGNARD-REAGENTS
  • ARYLBORONIC ACIDS
  • ALKYLATION
  • ESTERS
  • LIGHT

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