Enantioselective Synthesis of ß-Aminoboronic Acids via Borylalkylation of Enamides.

ABSTRACT

Aminoboronic acids represent a class of significant compounds that have attracted significant attention in the fields of drug discovery and organic synthesis. Despite notable progress in their synthesis, the efficient construction of chiral ß-aminoboronic acids with alkyl side chains remains a challenging endeavor. Here, we introduce an unprecedented nickel-catalyzed asymmetric borylalkylation of enamides, employing a simple chiral diamine ligand, readily available B2pin2, and alkyl halides as coupling partners. This reaction serves as an efficient platform for assembling a diverse range of ß-aminoboronic acid derivatives with flexible alkyl side chains, displaying exceptional regio-, stereo-, and enantioselectivities. Moreover, this transformation exhibits a broad substrate scope and remarkable tolerance toward various functional groups. Theoretical calculations demonstrate that the benzyl group on the ligand is the key to the high enantiocontrol in this transformation. Additionally, we exemplify the practical application of this strategy through the concise synthesis of complex bioactive molecules.