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 N1 (alkyl, aryl, acyl), N3 (aryl), and C5 (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.
Keywords: Brønsted bases; amino acids; asymmetric catalysis; chirality; hydantoins.
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