Enantioselective Alpha-Alkylation of Aldehydes Via Photoredox Catalysis

Abstract

In recent years, organocatalysis has emerged as a highly versatile catalytic strategy for

the construction of carbon–carbon and carbon-heteroatom bonds in an asymmetric manner. In particular, enamine catalysis has enabled the rapid, enantioselective synthesis of a number of highly valuable, functionalized carbonyl motifs. Although this mode of activation is highly versatile, many important moieties remain difficult to access. As a result, new chemical activation modes, namely SOMO–organocatalysis and photoredox–organocatalysis, have been developed to surpass many limitations in current methodologies. Despite these efforts, the generation of the alpha-alkyl carbonyl motif in a general manner remains a significant challenge in the field of catalytic asymmetric synthesis.

The design and development of a new strategy towards the enantioselective, catalytic alpha-alkylation of aldehydes is discussed. This strategy utilizes a combination of three unique catalytic species to enable the coupling of simple aldehydes with olefins as alkylating agents. This process is termed as photoredox–SOMO catalysis and utilized a key hydrogen-atom transfer event to facilitate the overall transformation. The application of this activation mode is investigated first through an intramolecular alkylation transformation with pendant olefins. This process is then investigated in the context of an intermolecular functionalization to rapidly generate the alpha-functionalized aldehyde products in an enantioselective manner.