Enantioselective assembly of tertiary stereocenters via multicomponent chemoselective cross-coupling of geminal chloro(iodo)alkanes?

Chemical Science Pub Date: 2016-01-06 DOI: 10.1039/C5SC04378F

Abstract

Tertiary stereocenters represent a ubiquitous and highly important motif in many pharmaceutically active compounds and natural products. Development of efficient and straightforward approaches to their enantioselective construction from readily available simple substrates is an important yet challenging goal for synthetic chemistry. Herein we describe an efficient, versatile and facile method for the highly enantioselective construction of tertiary stereocenters via unprecedented consecutive one-pot Suzuki reactions of non-activated racemic 1-chloro-1-iodoalkanes with alkylboranes. It represents the first cross-coupling approach which employs simple and readily available primary alkyl substrates for the direct multicomponent assembly of enantioenriched tertiary stereocenters. A simple and effective preparation of 1-chloro-1-iodoalkanes from ubiquitous α-chloroalkanoic acids is also described. Collectively, the developed methods open a door to efficient catalytic enantioselective synthesis of alkanes bearing tertiary stereocenters from carboxylic acids just in few steps.

Graphical abstract: Enantioselective assembly of tertiary stereocenters via multicomponent chemoselective cross-coupling of geminal chloro(iodo)alkanes
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