Enantioselective Synthesis of Quaternary Carbon Stereocenters by Asymmetric Allylic Alkylation: A Review

Chem Asian J. 2021 Jul 19;16(14):1864-1877. doi: 10.1002/asia.202100432. Epub 2021 Jun 7.

Abstract

Quaternary stereocenters are of great importance to the three-dimensionality and enhanced properties of new molecules, but the synthetic challenges in creating quaternary stereocenters greatly hinder their wide use in drug discovery, organic material design, and natural product synthesis. The asymmetric allylic alkylation (AAA) of allylic substrates has proven to be a powerful methodology for enantioselective formation of structure skeletons bearing single or more quaternary carbon centers in modern asymmetric organocatalysis. AAA has certain advantages in constructing the tetrasubstituted stereocenters, including but not limited to mild reactive conditions, effective reaction rates, new functional group introduction, and carbon chains length extension. This review outlines the key considerations in the application of AAA reactions and summarizes the recent progress of AAA reactions in the enantioselective synthesis of products containing quaternary stereocenters. Meanwhile, a detailed discussion of the AAA reactions such as ligands, scope of substrates, transformations and the general reaction mechanisms is also provided. We hope this review could stimulate further advances in much broader areas, including organic synthesis, asymmetric catalysis, C-H activation, and symmetrical pharmaceutical chemistry.

Keywords: asymmetric allylic alkylation; cooperative catalysis; quaternary stereocenter; transition metal catalysis.

Publication types

  • Review

MeSH terms

  • Alkylation
  • Allyl Compounds / chemical synthesis*
  • Catalysis
  • Stereoisomerism
  • Transition Elements / chemistry

Substances

  • Allyl Compounds
  • Transition Elements