NHC-catalyzed oxidative γ-addition of α,β-unsaturated aldehydes to isatins: a high-efficiency synthesis of spirocyclic oxindole-dihydropyranones

Abstract

This manuscript discloses an efficient construction of the spirocyclic oxindole-dihydropyranone scaffold via the N-heterocyclic carbene (NHC)-catalyzed oxidative γ-functionalization of α,β-unsaturated aldehydes bearing γ-H with isatin derivatives. The ready availability of the starting materials, easy work-up, mild reaction conditions and the potential utilization value of the products make this strategy attractive.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…70 In the absence of any additional cocatalyst and under oxidative conditions, the reactions proceeded successfully giving, again, the corresponding spiroxindole δ-lactones of type 49 in good yields and enantioselectivities. 71 As already stated, the NHC-catalyzed formal [4 + 2] annulation involving the γ/ipso carbon sites of γ-enolizable enals proved viable when the vinylogous enolate pathway prevails over the homoenolate pathway, and this was attained by placing biasing β-substituents in the starting enals (e.g., Scheme 18). As a clever alternative, Ye and collaborators were able to perform this chemistry by exploiting β-unsubstituted-γpreoxidized enals, which are able to generate the expected unsubstituted dienolates in situ, en route to the formation of the δ-lactone targets (Scheme 19).…”

Kooperative Katalyse mit N‐heterocyclischen Carbenen

“…[48] Sie lieferten ein Beispiel fürd ie kooperative NHC/ Lewis-Säure-Katalyse,i ndem sie Yb(OTf) 3 bei dieser Umwandlung einsetzten (Schema 24). [48] Sie lieferten ein Beispiel fürd ie kooperative NHC/ Lewis-Säure-Katalyse,i ndem sie Yb(OTf) 3 bei dieser Umwandlung einsetzten (Schema 24).…”

“…In einer späteren Studie beschrieben Yaound Mitarbeiter eine Va riante ihrer oxidativen g-Addition mit einem chiralen NHC. [48] Sie lieferten ein Beispiel fürd ie kooperative NHC/ Lewis-Säure-Katalyse,i ndem sie Yb(OTf) 3 [49] In einer Folgestudie verlängerten sie die Alkylkette des sekundären Nukleophils und fügten ungesättigte Einheiten hinzu, wodurch die Synthese der d-Lactone 79 mçglich wurde (Schema 25 b). [50] Ye und Mitarbeiter verçffentlichten kurz darauf ähnliche Ergebnisse,d ie den Befund stützten, dass durch die Zugabe einer Lewis-Säure die Enantioselektivitätdrastisch gesteigert wird.…”

Enantioselective Assembly of Spirolactones through NHC-Catalyzed Remote γ-Carbon Addition of Enals with Isatins

“…Recently, N -heterocyclic carbene (NHC) organocatalysis has been studied widely because of its special ability to deteriorate the natural reactivity of a functional group, which offers unconventional access to a set of umpolung reactions . However, the activation of the γ-carbon of enals still remains a significant challenge: it is very difficult to obtain good chemoselectivity and enantioselectivity because of the occurrence of competitive homoenolate, enolate or acyl anion intermediates and the fact that chiral auxiliaries are more remote from the γ-carbon than α- or β-carbons of carbonyl compounds . In our previous work, we successfully developed three highly efficient organocatalyzed methods for the asymmetric synthesis of spiro-oxindoles as part of the construction of a natural product-like library for further bioactivity screening, , and we also successfully achieved γ-carbon activation of carbonyl compounds to enantioselectively assemble δ-lactams with NHC/Brønsted acids cooperative catalysis …”