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Enantioselective Synthesis of 5,5‐Disubstituted Hydantoins by Brønsted Base/H‐Bond Catalyst Assisted Michael Reactions of a Design Template
Author(s) -
Izquierdo Joseba,
Etxabe Julen,
Duñabeitia Eider,
Landa Aitor,
Oiarbide Mikel,
Palomo Claudio
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201800506
Subject(s) - squaramide , enantioselective synthesis , chemistry , michael reaction , aryl , hydantoin , bifunctional , catalysis , organocatalysis , tertiary amine , organic chemistry , diastereomer , brønsted–lowry acid–base theory , alkyl , medicinal chemistry , combinatorial chemistry
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.