Stereodivergent Synthesis of Carbocyclic Quaternary α-Amino Acid Derivatives Containing Two Contiguous Stereocenters

Comprehensive Summary A novel approach to stereodivergent synthesis of carbocyclic alpha-quaternary amino acid derivatives, bearing two contiguous stereocenters, is proposed through sequential dual Cu/Ir-catalyzed asymmetric allylation and ring-closing metathesis. A variety of five and six-membered carbocyclic alpha-quaternary amino acid derivatives could be readily achieved in good to high yields with exclusive regioselectivities, excellent diastereoselectivities (13: 1- > 20(:) 1 dr) and enantioselectivities (generally >99% ee). Of particular note is that the current protocol is also a versatile synthetic tool for the stereodivergent construction of the challenging seven and eight-membered carbocyclic alpha-amino acid derivatives. All four stereoisomers of these important molecules could be precisely synthesized through the permutation of chiral Cu/Ir catalytic system. The power of this strategy has been demonstrated for the facile access to some biologically active chiral molecules, such as spiro-hydantoins.

Automated summary

This article proposes a novel approach to the stereodivergent synthesis of carbocyclic alpha-quaternary amino acid derivatives through sequential dual Cu/Ir-catalyzed asymmetric allylation and ring-closing metathesis. The method exhibits high yields, exclusive regioselectivities, and excellent diastereoselectivities and enantioselectivities. Furthermore, it is capable of synthesizing challenging seven and eight-membered carbocyclic alpha-amino acid derivatives.