Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

An important challenge in asymmetric synthesis is the development of fully stereodivergent strategies to access the full complement of stereoisomers of products bearing multiple stereocenters. In the ideal case, where four products are possible, applying distinct catalysts to the same set of starting materials under identical conditions would in a single step afford any given stereoisomer. Herein, we describe the realization of this concept in a fully stereodivergent dual-catalytic synthesis of γ,δ-unsaturated aldehydes bearing vicinal quaternary/tertiary stereogenic centers. The reaction is enabled by chiral iridium and amine catalysts, which activate the allylic alcohol and aldehyde substrates, respectively. Each catalyst exerts high local stereocontrol irrespective of the other's inherent preference.

Synergistic catalysis is a synthetic strategy wherein both the nucleophile and the electrophile are simultaneously activated by two separate and distinct catalysts to afford a single chemical transformation. This powerful catalysis strategy leads to several benefits, specifically synergistic catalysis can (i) introduce new, previously unattainable chemical transformations, (ii) improve the efficiency of existing transformations, and (iii) create or improve catalytic enantioselectivity where stereocontrol was previously absent or challenging. This perspective aims to highlight these benefits using many of the successful examples of synergistic catalysis found in the literature.

In recent years, the concept of combining transition metal catalysis and organocatalysis has emerged as a promising strategy for developing new and valuable reactions, and has attracted considerable attention as it could potentially enable unprecedented transformations not currently possible by use of the transition metal complex or the organocatalyst alone. In this critical review, this strategy is illustrated with several recent outstanding examples, with the aim of shedding light on the synthetic utilities and potentials of this concept as a novel tool in organic synthesis (118 references).