Catalytic Enantioselective Synthesis of Tertiary Thiols From 5H-Thiazol-4-ones and Nitroolefins: Bifunctional Ureidopeptide-Based Brønsted Base Catalysis

Abstract

The direct catalytic reaction between an enolizable carbonyl compound and an electrophile under proton-transfer conditions has emerged as a challenging versatile transformation in organic synthesis.1 Over the last years several chiral Brønsted bases have been developed to promote this transformation diastereo- and enantioselectively.2 However, successful examples are mostly limited to 1,3-dicarbonyl compounds and acidic carbon analogues as the pronucleophilic reaction partners. 5H-Thiazol-4-ones, in contrast, have been well known for a long time and have found several applications in pharmaceutical and medicinal chemistry.3 Although structurally related to 5H-oxazol-4-ones4 and 4H-oxazol-5-ones (azlactones),5 5H-thiazol-4-ones have, as far as we know, been never been used in asymmetric synthesis in spite of the fact that they may be easily deprotonated6 and in spite of the importance of thiols and organosulfur compounds in organic synthesis7 and chemical biology.8 In this context, whilst chiral secondary thiol derivatives have been the subject of most investigations, tertiary thiols have remained mostly unexplored owing to the insufficient catalytic enantioselective methodology for their preparation in optically pure form.9