Organocatalytic Asymmetric Vinylogous Michael Addition of Dicyanoolefins to Imine Intermediates Generated in situ from Arenesulfonylalkylindoles

Abstract

An organocatalytic asymmetric vinylogous Michael addition of dicyanoolefins to vinylogous imine intermediates generated in situ from arenesulfonylalkylindoles has been developed. This protocol provides an easy and convenient approach to C-3 alkyl-substituted indole derivatives with high yields (up to 93%), diastereomeric ratios (up to 99:1 dr) and enantioselectivities (up to 99% ee). The resulting adducts can be also readily converted to pyrazolo derivatives or a-alkylation products of ketones without any decrease of the diastereoselectivities and enantioselectivities.

Catalytic, enantioselective vinylogous Michael reactions

“…Highly functionalized C3-alkyl-substituted indoles 72 were obtained with good to very good diastereo-and enantioselectivities (Scheme 28). 36 The sulfonylalkylindole served as a precursor to in situ formed α,β-unsaturated imine which was further activated and positioned by the thiourea catalyst.…”

Arenesulfonyl indole: new precursor for diversification of C-3 functionalized indoles

“…In this regard, a doubly vinylogous Michael reaction of dicyanoolens (19) with vinylogous imine intermediate 2 generated in situ from 3-arenesulfonyl indoles 11 have been reported by Zhu and co-workers. 29 The reaction catalysed by Takemoto's catalyst II provided access to 3-substituted indole derivatives 20 in 61-93% yields with enantiomeric excess >99% and up to 99 : 1 dr (Scheme 6). The product 20a was transformed to corresponding pyrazolo derivative 21a in 84% yield through its reaction with hydrazine hydrate in ethanol.…”

Sulfonyl Azoles in the Synthesis of 3-Functionalized Azole Derivatives

“…Other enolate systems obtained from compounds 52 and 53 have been made to react with sulfonyl indoles using organocatalytic methods (Scheme ) 54,55. These processes are catalyzed by bifunctional thiourea catalysts 54 and 55 , in which activation of the enolate anion is provided by hydrogen‐bonding interactions brought by the NH of the thiourea system.…”