A. Patwardhan, V. R. Pulgam, Yuzhang
Sep 26, 2005
Citations
0
Influential Citations
58
Citations
Journal
Angewandte Chemie
Abstract
Aziridines are important synthons in organic chemistry as they provide convenient entry to optically pure amines, aamino acids, amino alcohols, diamines, and a variety of other amino compounds that are useful both in industrial and academic endeavors. In the past, most optically pure aziridines were derived from acyclic members of the chiral pool, however, methods are emerging for the direct synthesis of optically pure aziridines through catalytic asymmetric reactions. We have developed a process for the catalytic asymmetric synthesis of aziridines from the reaction of benzhydryl imines with diazo compounds mediated by a chiral boron Lewis acid prepared from the VAPOL and VANOL ligands. This asymmetric aziridination (AZ) proved general for a range imines including those prepared from a variety of aryl aldehydes and also from primary, secondary, and tertiary aliphatic aldehydes (90–99% ee). Much lower enantioselectivities were observed with Nbenzyl imines. a-Amino acids which are tetrasubstituted at the a-carbon are very popular tools that are used to control conformation in peptides, and hence their biological and pharmaceutical properties. A large number of methods have been developed for the synthesis of tetrasubstituted a-amino acids, and this subject has been reviewed. Interestingly, aziridines have rarely been used for the synthesis of tetrasubstituted a-amino acids and this may be partly due to the fact that the alkylation of aziridine-2-carboxylates is virtually an unknown reaction. Typically, attempts to alkylate aziridine-2-carboxylate esters leads to either ring opening or to self-condensation. The only known examples involve the use of either thioesters of aziridine-2-carboxylates or the use of a nitrogen substituent on the aziridine that can chelate a metal enolate. A direct application of the AZ reaction to the synthesis of tetrasubstituted a-amino acids could be envisioned through the asymmetric aziridination of imine 1 with diazo compound