Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl -diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.
The first example of a direct catalytic asymmetric intermolecular aldol reaction of 3-isothiocyanato oxindoles to simple ketones with bifunctional thiourea-tertiary amine as catalyst is reported. This strategy provides a promising approach for the asymmetric synthesis of a range of enantioenriched spirocyclic oxindoles bearing two highly congested contiguous tetrasubstituted carbon stereocenters. Versatile transformations of the spirocyclic oxindole products into other structurally diverse spirocyclic oxindoles have also been demonstrated.The catalytic asymmetric aldol reaction is one of the most important methods for the asymmetric formation of CÀC bonds and has found widespread application in organic synthesis.1 In this respect, in contrast to the remarkable advances that have been made with aldehydes as electrophiles, 1,2 the development of aldol additions to ketones was quite slow.3 This state is attributable, at least in part, to the lower reactivity of ketones and the decreased steric discrimination compared to aldehydes. 4 Therefore, the direct asymmetric ketoneÀaldol reactions to date mainly focus on the activated ketone electrophiles 5 or intramolecular aldol additions based on enamine catalysis.
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