Access to Cyclic β‐Amino Acids by Amine‐Catalyzed Enantioselective Addition of the γ‐Carbon Atoms of α,β‐Unsaturated Imines to Enals

Abstract

Disclosed herein is a new catalytic approach for an efficient access to cyclic β‐amino acids widely found in bioactive small molecules and peptidic foldamers. Our method involves addition of the remote γ‐carbon atoms of α,β‐unsaturated imines to enals by iminium organic catalysis. This highly chemo‐ and stereo‐selective reaction affords cyclic β‐amino aldehydes that can be converted to amino acids bearing quaternary stereocenters with exceptional optical purities. Our study demonstrates the unique power of organic catalytic remote carbon reactions in rapid synthesis of functional molecules.

Enantioselective Catalyzed Synthesis of Amino Derivatives Using Electrophilic Open‐Chain N‐Activated Ketimines

“…The reaction of enals with β‐disubstituted α,β‐unsaturated ketimines catalyzed by chiral pyrrolidine 128 follows an umpoled pathway leading to the highly stereoselective synthesis of 2‐amino carbaldehyde derivatives 129 (Scheme 52). [89] Under basic conditions, the ketimine undergoes a γ‐deprotonation leading to aza‐dienolate XXVII which reacts with the chiral vinylogous iminium ion XXVIII . The enamino moiety of the resulting Michael adduct XXIX reacts with the ketimine leading to the target carbaldehyde 129 after hydrolytic regeneration of the catalyst.…”