Enantioselective Synthesis of 5, 5‐Disubstituted Hydantoins by Brønsted Base/H‐Bond Catalyst Assisted Michael Reactions of a Design Template. Issue 28 (30th April 2018)

• Record Type: Journal Article
• Authors: Izquierdo, Joseba; Etxabe, Julen; Duñabeitia, Eider; Landa, Aitor; Oiarbide, Mikel; Palomo, Claudio
• Is Part Of: Chemistry. Volume 24:Issue 28(2018)
• Page Start: 7217
• Page End: 7227
• Publication Date: 2018-04-30
• Subjects: amino acids -- asymmetric catalysis -- Brønsted bases -- chirality -- hydantoins; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201800506
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: A new method for the enantioselective synthesis of 5, 5‐disubstituted (quaternary) hydantoins was developed on the basis of an organocatalytic Michael reaction approach involving the use of 2‐benzylthio‐3, 5‐dihydroimidazol‐4‐ones as key hydantoin surrogates. The method is general with respect to the substitution pattern at the hydantoin N 1 (alkyl, aryl, acyl), N 3 (aryl), and C 5 (linear/branched alkyl, aryl) positions and affords essentially single diastereomeric products with enantioselectivities higher than 95 % ee in most cases. Among the bifunctional Brønsted base/H‐bond catalysts examined, a known squaramide–tertiary amine catalyst and a newly prepared squaramide–tertiary amine catalyst provide the highest selectivity so far with either nitroolefins or vinyl ketones as the acceptor components. Kinetic measurements support a first‐order rate dependence on both reaction partners, the donor template and the Michael acceptor, whereas competitive 1 H NMR spectroscopy experiments reveal the high ability of the template for catalyst binding. Abstract : Hydantoins made easy : A general, catalytic, and asymmetric procedure to access 5, 5‐disubstituted (quaternary) hydantoins is developed by relying on the Brønsted base (BB*)‐catalyzed enantioselective C‐functionalization of a design dihydroimidazolone template with Michael acceptors.