Synthesis of enantiopure constrained α,β-cycloaliphatic cystines via Diels−Alder reaction with homochiral thiazolines

Abstract

The behavior of homochiral 2,3-dihydrothiazoles, easily available from l-cysteine in Diels-Alder reaction with different dienes, "en route" to sterically constrained modified cystines, has been studied. The oxidation level of the sulfur atom of the heterocyclic ring was crucial for the course of the reaction. Whereas 2,3-dihydrothiazoles did not lead to Diels-Alder adducts, 1-oxide and 1,1-dioxide derivatives afforded the exo adduct enantiopurely in high yields and diastereoselectivities. Further elaboration of the resulting adducts provided conformationally restricted quaternary cystines. DFT calculations correctly predict both the reactivity and stereoselectivity observed experimentally.