Iridium-Catalyzed Asymmetric Allylic Alkylation of Boron Enolates to Construct Acyclic All-Carbon Quaternary Stereocenters

Abstract

Enolates are ubiquitous intermediates in organic synthesis. Among them, boron enolates exhibit distinctive reactivity patterns and selectivities due to the presence of a boron atom, making their synthesis highly attractive. Although methods for accessing ketone- or ester-derived boron enolates are well-developed, much less progress has been made in the development of aldehyde-derived boron enolates due to aldehydes′ high tendency toward self-condensation. Therefore, the practical applications of aldehyde-derived boron enolates are significantly hindered. We present herein an efficient method for the preparation of aldehyde-derived boron enolates via the 1,2-hydroboration of ketenes with boranes, avoiding the use of acidic R₂BCl/R₂BOTf and bases and leading to improved functional group tolerance. Utilizing this convenient protocol, we developed an Ir-catalyzed asymmetric allylic alkylation of boron enolates, yielding a wide array of chiral aldehydes bearing acyclic all-carbon quaternary centers with high chemo-, regio-, and enantioselectivity, which are prevalent in various natural products and bioactive molecules. The synthetic utility and practicality of this method are demonstrated through gram-scale reactions and asymmetric syntheses of the ent-5HT1 A antagonist as well as biological activity studies in inhibiting the growth of plant pathogens.