Enantioselective synthesis of gem-disubstituted N-Boc diazaheterocycles via decarboxylative asymmetric allylic alkylation

Abstract

An enantioselective synthesis of diverse N4-Boc-protected a,a-disubstituted piperazin-2-ones using the palladiumcatalyzed decarboxylative allylic alkylation reaction has been achieved. Using a chiral Pd-catalyst derived from an electron deficient PHOX ligand, chiral piperazinones are synthesized in high yields and enantioselectivity. The chiral piperazinone products can be deprotected and reduced to valuable gem-disubstituted piperazines. This reaction is further extended to enable the enantioselective synthesis of a,a-disubstituted tetrahydropyrimidin-2-ones, which are hydrolyzed into corresponding chiral b2,2-amino acids.