Copper-Catalyzed Asymmetric Carboboronation of Allenes to Access α-Quaternary Amino Esters with Adjacent Stereocenters

Abstract

Optically active α- quaternary amino acids have received much attention because of the important biomedical applications implicated for compounds containing this structure. Additionally, asymmetric synthesis of highly functionalized chiral α- quaternary amino esters with vicinal stereocenters by a single catalyst is still a great challenge due to the difficulty in stereocontrol of the configurations. Here, we develop a copper-catalyzed highly diastereo- and enantioselective three-component coupling of allenes, diboron, and ketiminoesters to access chiral quaternary amino esters with adjacent stereocenters. The stereochemical control is enabled by using bulky C 2 -symmetric N-heterocyclic carbene (NHC) as a chiral ligand. This protocol also features mild reaction conditions, wide substrate scope, and may subsequently have diverse applications in organic synthesis. Access α -quaternary amino esters with adjacent stereocenters Contain boron group for easy derivatization DFT calculations to elucidate the control of the diastereo- and enantioselectivity Twenty-eight examples with yields up to 96%, er up to 98:2 and dr up to >20:1 Chiral α- quaternary amino acids play an important role in the synthesis of unnatural peptides and proteins with specific biological activities. Here, Zhao et al. develop a copper-catalyzed diastereo- and enantioselective three-component coupling of allenes, boronate, and ketiminoesters to access chiral quaternary amino esters with adjacent stereocenters.