Dynamic kinetic resolution of γ, γ-disubstituted indole 2-carboxaldehydes via NHC-Lewis acid cooperative catalysis for the synthesis of tetracyclic ε-lactones. Issue 39 (28th September 2022)

• Record Type: Journal Article
• Authors: Balanna, Kuruva; Barik, Soumen; Shee, Sayan; Gonnade, Rajesh G.; Biju, Akkattu T.
• Is Part Of: Chemical science. Volume 13:Issue 39(2022)
• Page Start: 11513
• Page End: 11518
• Publication Date: 2022-09-28
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2sc03745a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : NHC-Lewis acid cooperative catalyzed dynamic kinetic resolution (DKR) of transiently generated γ, γ-disubstituted indole 2-carboxaldehydes leading to the enantioselective synthesis of tetracyclic ε-lactones is reported. Abstract : The ubiquity of ε-lactones in various biologically active compounds inspired the development of efficient and enantioselective routes to these target compounds. Described herein is the enantioselective synthesis of indole-fused ε-lactones by the N-heterocyclic carbene (NHC)-Lewis acid cooperative catalyzed dynamic kinetic resolution (DKR) of in situ generated γ, γ-disubstituted indole 2-carboxaldehydes. The Bi(OTf)3 -catalyzed Friedel–Crafts reaction of indole-2-carboxaldehyde with 2-hydroxy phenyl p -quinone methides generates γ, γ-disubstituted indole 2-carboxaldehydes, which in the presence of NHC and Bi(OTf)3 afforded the desired tetracyclic ε-lactones in up to 93% yield and >99 : 1 er. Moreover, preliminary studies on the mechanism of this formal [4 + 3] annulation are also provided.