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

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.This work was supported by the Ministerio de Economía y Competitividad (grants CTQ2013-40855-R to C.C. and CTQ2016-76155-R to P.M.) and the Gobierno de Aragón − FSE (research groups E-10 and E40). J.G.-V. thanks the Gobierno de Aragoń −FSE for the predoctoral Grant.Peer reviewe