Highly Efficient and Stereoselective Mukaiyama Aldol Reaction with Chiral Aziridine‐2‐carboxaldehyde and Its Synthetic Applications

Abstract

A straightforward and highly diastereoselective synthesis of β-(aziridin-2-yl)-β-hydroxy ketones was achieved by the Mukaiyama aldol reaction of optically pure 1-(αmethylbenzyl)-aziridine-2-carboxaldehyde and various enolsilanes in ZnCl 2 via a chelation-controlled transition state (98 : 2 dr and > 82% yields). These β-(aziridin-2-yl)-β-hydroxy ketones were applied for the synthesis of various alkaloids including epiallo-isomuscarine, epi-enigmol, and epi-galantinic acid.

Regioselective ring opening of aziridine for synthesizing azaheterocycle

“…Changing the 2-phenylethyl to N-Cbz as protecting group from sequential reactions consisting of debenzylation followed by CbzCl in LiHMDS base at 0 °C afforded compound 14 in 80% yield. With the known established protocol of oxidation ( Srivastava and Ha, 2022 ) followed by deprotection of Cbz and cyclization under hydrogen in catalytic Pd(OH) 2 gave 2,5- cis pyrrolidine ( 6′ ), the essential core skeleton of many pyrrolidines and indolizidine alkaloids including monomorine ( Wang et al, 2009 ; Michael, 2016 ).…”

Mukaiyama aldol reaction: an effective asymmetric approach to access chiral natural products and their derivatives/analogues

“…Sirivastava and Ha 111 in 2021 developed a novel approach for the Mukaiyama aldol reaction by employing chiral substituents. A highly stereoselective synthesis of aziridine-2-carboxaldehyde was carried out by employing the Mukaiyama aldol reaction between chiral 1-(α-methylbenzyl)-aziridine-2-carboxylaldehyde and a diverse range of enol silanes by employing zinc chloride as a catalyst.…”