Branched aldehydes as linchpins for the enantioselective and stereodivergent synthesis of 1,3-aminoalcohols featuring a quaternary stereocentre

Abstract

The atom-economic conversion of chemical feedstocks into biologically relevant complex molecules in a stereocontrolled fashion remains a continuous challenge to synthetic chemists. In this context, the use of simple ambiphilic starting materials as linchpins allows a bidirectional increase of molecular complexity from widely available precursors. Here, we report the use of branched aldehydes as versatile linchpins for various Zn-ProPhenol-catalysed C-C bond-forming reactions to efficiently construct enantioenriched 1,3-aminoalcohols bearing an acyclic quaternary stereogenic centre. The ability of the Zn-ProPhenol catalyst to selectively activate ambiphilic aldehydes first as nucleophiles for Mannich reactions and then as electrophiles for aldol, Henry and alkyne addition reactions allows for the one-pot synthesis of complex stereotriads from common building blocks. Moreover, this approach can be diastereodivergent by simply selecting the proper catalyst combination. Overall, this catalytic method directly transforms simple and readily available aldehydes into highly functionalized compounds and provides streamlined access to valuable 1,3-aminoalcohols relevant to the synthesis of biologically important molecules. © 2018 The Author(s).