Chelation-controlled diastereoselective construction of N-aryl-, N-acyl/tosylhydrazono β-substituted aspartate derivatives via Barbier-type reaction

Abstract

An entry into the stereoselective synthesis of several N-substituted-β-vinyl aspartate and β-alkyl aspartate derivatives having two contiguous stereocenters via the indium-mediated Barbier-type addition of alkyl 4-bromocrotonates or α-halo esters with N-aryl (including N-PMP) α-imino- and N-acyl/tosylhydrazono esters is reported. The formation of β-alkyl aspartate derivatives with exclusively syn stereochemistry in alcohol media revealed the involvement of a chelation-controlled TS. The synthesis of functionalized 1,4-diols, cis piperidine-2,3-dicarboxylate derivative and β-ethyl aspartic acid hydrochloride was performed using the N-substituted β-vinyl aspartates obtained in this work. The stereochemistry of representative products was unambiguously established from the single crystal X-ray structure analyses.