Synthesis of axially chiral thiazolidine derivatives and their atroposelective reactions

Abstract

In this study, various axially chiral thiazolidine-4-one and 4-thiones and their corresponding 5-benzylidene derivatives were synthesized in which the N3(sp2)-Carylbond rotation is hindered and used as scaffolds for the preparation of other axially chiral compounds. The aldol reactions were done on 2-arylimino-3-aryl-thiazolidine-4-ones with benzaldehyde at -78 oC and were found to produce sec-carbinols. Intramolecular hydrogen bonding within the aldol products forming a six membered ring enabled the assignment of stereochemistries of the major and minor diastereomers via analysis of the syn and anti3JH,H1H NMR coupling constants. The aldol reactions of axially chiral 5-methyl-2-(o-aryl)imino-3-(o-aryl)-thiazolidine-4-ones were found to proceed via an enolization mechanism and the axially chiral enolate was found to shield one face of the heterocyclic ring rendering atroposelectivity. The atroposelectivities observed at C-5 of the ring varied from 50:50 to 92:8 depending on the size of the ortho substituent. The 2-arylimino-3-aryl-thiazolidine-4-ones were converted to the corresponding 2-arylimino-3-aryl-thiazolidine-4-thiones using Lawesson’s reagent (LR) which were then converted to 5-benzylidinederivatives. The 5-benzylidine-2-arylimino-3-aryl-thiazolidine-4-thiones were used as heterodienes in the [4+2] cycloaddition reactions with norbornene as a dienophile. The reactions with norbornene were found to proceed with 100% exo selectivity with respect to the norbornane skeleton as determined through NMR experiments. Iminophenyl substituted hemiaminals were synthesized by a regio and stereoselective LiAlH4 reduction of 2-arylimino-3-aryl-thiazolidine-4-ones and have been shown to convert of a hemiaminal to an enamine with time and the kinetics of the process has been followed by a time dependent 1H NMR analysis. The compounds which have o-methoxyphenyl were also subjected to demethylation reactions to obtain axially chiral bidentate N,O and O,O compounds.