Kinetic Resolution of Aziridines via Catalytic Asymmetric Ring-Opening Reaction with Mercaptobenzothiazoles

Abstract

A highly efficient kinetic resolution of racemic 2-acyl-3-aryl-N-tosylaziridines is achieved through a chiral Lewis acid promoted ring-opening reaction with 2-mercaptobenzothiazoles as the nucleophiles. The chiral N,N′-dioxide–lanthanum complex as catalyst and the 2-mercaptobenzothiazoles as active sulfur nucleophiles are the keys to the success of the reaction. A variety of enantioenriched β-amino thioethers and aziridines are obtained in good yields with good ee values.

Catalytic Asymmetric Transformations of Racemic Aziridines

“…4d,e In 2019, Lin, Feng, and co-workers realized the first kinetic resolution of trans-2,3-disubstituted aziridines via nucleophilic ring opening with mercaptobenzothiazoles by using La(OTf) 3 and Feng's chiral N,N′-dioxide ligands (Scheme 10). 21 The reaction worked well with a range of racemic chalcone-derived 2-aroyl-3-arylaziridines and exclusive regioselectivity and moderate-to-high selectivity factors were obtained. While a series of mercaptobenzothiazoles, including 4,5-dihydrothiazole-2-thiol without a phenyl ring, participated in the reaction well, 4-methylthiophenol (48) and 2-thionaphthol (47) provided poor yields and cyclohexanethiol (49) did not undergo the reaction under these conditions.…”

A Remarkable Influence of La(III)/N,N′-Dioxide Structure on Asymmetric Formal Substitution of 3-Bromo-3-substituted Oxindoles with TMSCN

“…Over the past two decades, chiral rare-earth metal complexes have emerged as potent catalysts in the realm of asymmetric synthesis . Among these, chiral lanthanum­(III) complexes have gathered considerable attention. − Due to the substantial ionic radius and high coordination number of lanthanum­(III), , the hapto number and steric hindrance of the ligands displayed a dramatic effect on coordination modes and coordination numbers of lanthanum­(III) complexes. Till now, the selection of chiral ligands compatible with it has remained limited.…”

“…The catalytically active species in this context have been identified as lanthanum­(III)/three alkali metals (M 3 )/tris­(BINOLate) complexes ( LaMB ) (Scheme a). Feng and colleagues utilized N , N ′-dioxide , as a tetradentate oxygen ligand to synthesize La­(III)/ N , N ′-dioxide complexes, which found application in several asymmetric reactions (Scheme a) . Although crystals of La­(III)/( L 3 -RaMe 2 ) 2 was obtained, the experiment studies suggested that La­(III)/ L 3 -RaMe 2 may be the catalytically active species for asymmetric ring-opening reaction of aziridines with mercaptobenzothiazoles .…”

Kinetic Resolution of trans-2,3-Aziridinyl Alcohols via Hydroxyl Directed Regio- and Enantioselective Ring Opening Reactions

“…The aziridine functionality is one of the most valuable three membered ring systems in modern synthetic chemistry, and catalytic asymmetric nucleophilic ring opening reactions of ethylenimine units have emerged as a powerful chemical tool for the synthesis of various nitrogen-containing biologically active compounds . In this context, remarkable progress has been achieved in desymmetric ring opening reactions of meso -aziridines and kinetic resolution of racemic unfunctionalized terminal or internal aziridines with various nucleophiles. For instance, the Chai group realized the kinetic resolution of 2-aryl- N -tosylaziridines and the asymmetric desymmetrization of meso - N -tosylaziridines via Ag catalyzed ring openings with amine nucleophiles in 2017.…”