Stereoselective synthesis towards unnatural proline based amino acids

Abstract

A catalytic diastereoselective Mannich reaction promoted by chiral bifunctional urea-type organocatalysts has been developed. Treatment of N-Boc-3-ketoproline with N-Boc-aldimines under mild conditions afforded the corresponding unnatural proline based amino acid derivatives with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 97% ee). The relative configuration of the chiral reaction products was deduced by the comparsion of the experimentally observed ECD spectra to that obtained theorectically.

Highly regio- and diastereoselective synthesis of oxo-1,2,3,4-tetrahydropyrazino[1,2-a]indoles, based on a post-Ugi condensation: joint experimental and computational study

“…Although the simulation of an ECD spectrum is not clearly documented [59], this technique to determine the relative configuration of asymmetric adducts is gaining popularity [60]. To determine the relative configuration of the reaction products, the ECD was calculated for the four possible diastereomers of 4a, 4g, 4i, and 4j using time-dependent density functional theory (TDDFT) to simulate the experimentally observed ECD spectrum [61,62]. For this discussion, the details of the resolution of structure 4a are presented.…”