Indium-mediated addition of γ-substituted allylic halides to N-aryl α-imino esters: Diastereoselective production of β,β′- disubstituted α-amino acid derivatives with two contiguous stereocenters

Abstract

Chelation-controlled Barbier-type indium-mediated addition of γ-substituted allylic halides to N-aryl (including N-PMP) α-imino- and N-acylhydrazono esters and highly diastereoselective tailoring of functionalized γ,δ-unsaturated β,β'-disubstituted N-aryl α-amino acid derivatives, bearing two contiguous stereocenters is reported. Further N-allylation of the resulting γ,δ-unsaturated β,β'-disubstituted N-aryl amino acid derivatives followed by ring closing metathesis (RCM) led to the synthesis of 2,3-disubstituted N-aryltetrahydropyridine derivatives bearing two contiguous stereocenters. The stereochemistry of the key products was unequivocally established from X-ray structure analyses. Highly diastereoselective C-C bond formation through Barbier-type indium-mediated addition of γ-substituted allylic halides to N-aryl α-imino and α-hydrazono esters was established. Diastereoselective production of γ,δ-unsaturated β,β'-disubstituted N-aryl (including N-PMP) α-amino acid- and 2,3-disubstituted N-aryltetrahydropyridine derivatives bearing two contiguous stereocenters was accomplished.