Highly Stereoselective Synthesis of γ,δ‐Unsaturated Quaternary α‐Amino Esters via the Tandem N‐Alkylation/Claisen Rearrangement of α‐Imino Allylesters

A highly efficient and stereoselective method for the synthesis of a γ,δ-unsaturated quaternary α-amino esters via the tandem N-alkylation/Claisen rearrangement of α-imino allylesters has been developed. This reaction has a wide substrate scope based on the Hammett rule, and the products can be further functionalized. The mechanism of this reaction was elucidated by detailed isotopic labeling, KIE, and crossover experiments.

Abstract

γ,δ-Unsaturated amino acids are the backbone of various natural products and pharmaceuticals, while quaternary α-amino acids are also powerful enzyme inhibitors, and both are very important compounds in bioorganic chemistry. A highly efficient synthesis of γ,δ-unsaturated quaternary amino esters utilizing the tandem umpolung/Claisen rearrangement for α-iminoallyl esters was developed. This method has a wide range of substrates taking account of the Hammett rule, and highly stereoselective Claisen rearrangement were achieved by the effect of DMSO or the ortho-substituents of imino carbon. Furthermore, product functionalization also showed the usefulness of this reaction and the detailed reaction mechanism was elucidated from isotopic labeling experiments, kinetic isotope effects and crossover-experiments.

Zum Volltext