Catalytic Asymmetric Synthesis of Tetrahydrofuran Spirooxindoles via a Dinuclear Zinc Catalyst

Abstract

An asymmetric Michael/hemiketalization and FridelCrafts reaction has been reported through a one-pot reaction. A number of structurally novel tetrahydrofuran spirooxindoles are synthesized in the presence of a 10 mol % dinuclear zinc catalyst with diastereomer ratios (dr) of 3:1–13:1 and an enantiomeric excess (ee) of 75–99%. The reaction can be performed on a gram scale without impacting its efficiency. The absolute configuration of products is confirmed by X-ray single crystal structure analysis, and a possible mechanism is proposed.

Transition metal-catalyzed synthesis of spirooxindoles

“…In 2020, Wang and team produced chiral tetrahydrofuran spirooxindoles 47 by using a dinuclear zinc catalyst. 47 Here, it is a two-step reaction in which Michael/Hemiketalization is followed by Friedel–Crafts reaction. In the first step, α-hydroxyaryl ketone (derivative of 38) is reacted with β,γ-unsaturated-α-ketoamide 45 in CH 2 Cl 2 solvent at 20 °C catalyzed by dinuclear zinc which was formed in situ by the reaction between 20 mol% of diethyl zinc and 10 mol% of ligand L3.…”

Recent developments in enantioselective zinc-catalyzed transformations

“…Scheme 99. Domino Michael/hemiketalization reaction of a-hydroxy aryl ketones with b,c-unsaturated a-ketoamides followed by Friedel-Crafts reaction in the presence of a ProPhenol derivative ligand [137]. Scheme 100.…”

“…The synthesis of chiral tetrahydrofuran spirooxindoles is challenging related to the potent biological activities of these products [136]. In this context, the same authors developed in 2020 an enantioselective zinc-catalyzed domino Michael/hemiketalization reaction of a-hydroxy aryl ketones 148 with b,c-unsaturated a-ketoamides 294 [137]. The reaction, performed at 20 °C in dichloromethane as solvent, was promoted by a chiral dinuclear zinc catalyst in situ generated from 20 mol% of ZnEt 2 and 10 mol % of chiral ProPhenol derivative ligand 295.…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…The second approach comprises a utilization of chiral N,N-dioxide 47-scandium(III) complexes in dichloromethane at 35 • C [46], and finally, the third work relies on the application of cationic aqua complex of 2,2 -bypiridine 48 with palladium(II) in water at room temperature [47]. Similar dinuclear zinc catalytic systems were also used in the synthesis of 2,5-pyrrolidinyl dispirooxindoles [51] and tetrahydrofuran spirooxindoles [52] via cascade reactions, where one of the steps is a Friedel-Crafts process. Moreover, this type of chiral catalyst was successfully utilized for Friedel-Crafts reaction of pyrrole with chalcones [53].…”