N‐Heterocyclic Carbene Catalyzed [3+2] Annulations of β‐Halocycloenals with Isatins and Mechanism Study

Abstract

An NHC‐catalyzed [3+2] annulations of β‐halocycloenals with isatins upon a dual‐activation mode was developed for the synthesis of tetracyclic 3‐spirooxindoles. DFT calculations were performed for the mechanism study of this transformation.

NHC-Catalyzed Reaction of Aldehydes for C(sp2)–O Bond Formation

“…For oxidant-free redox [3 + 2] annulation, the reducible aldehydes are employed [170][171][172][173][174][175][176][177][178][179][180]. The NHC-linked homoenolate derivatives act as a C3 synthon for [3 + 2] annulation [170][171][172][173][174][175][176][177][178].…”

Recent Advances in Nucleophilic Lewis Base‐Catalyzed Cycloadditions for Synthesis of Spirooxindoles

“…[83] In 2021, He, Zhong and coworkers used α, β, β-trisubstituted cycloenals as starting materials, reporting an NHC catalyzed [3 + 2] annulations of β-halocycloenals with isatins to give tetracyclic 3-spirooxindole lactones in good yields. [84] Recently, Qi, Duan and coworkers used α-bromoenals with bisoxindoles as reactive substrates, developing an NHC-catalyzed enantio-and diastereoselective [3 + 2] annulation. This transformation tolerated a broad substrates scope, affording highly enantiopure bispirooxindole derivatives in good yields with good enantioselectivites (Scheme 48).…”

“…In 2016, Hui and coworkers reported an NHC‐catalyzed [3+2] annulation reaction of isatin N‐Boc ketimines and 3‐bromoenals, constructing the desired spiro[indoline‐3,2′‐pyrrole] derivatives in good yields with excellent enantioselectivity [83] . In 2021, He, Zhong and coworkers used α , β , β ‐trisubstituted cycloenals as starting materials, reporting an NHC catalyzed [3+2] annulations of β ‐halocycloenals with isatins to give tetracyclic 3‐spirooxindole lactones in good yields [84] …”

Multi-Component Syntheses of Spiro[furan-2,3′-indoline]-3-carboxylate Derivatives Using Ionic Liquid Catalysts

“…The furan-2(5 H )-one cores, generally named butenolides, have been known for their interesting chemical, biological, and medical properties ( Scheme 1 ) [ 9 , 10 , 11 ]. In particular, spirocyclic butanolide derivatives have recently come into the focus of interest [ 12 , 13 , 14 , 15 , 16 ]. Thus, the development of synthetic methods for butenolides is of great importance.…”

“…Thus, the development of synthetic methods for butenolides is of great importance. Amongst them are formylation at the ortho position of aromatic carboxylic acids and its derivatives [ 17 , 18 ], [3+2] annulation reactions between electrophilic carbonyls and homoenolate nucleophiles [ 12 , 13 , 14 , 15 , 16 ], ring-opening [3+2] annulation reactions of cyclopropenones with amides [ 19 ], Ph 3 P catalyzed ring-opening of functionalized cyclopropenones [ 20 ], base-controlled azirine ring expansion [ 21 ], Baeyer–Villiger oxidation of 3-arylcyclobutanones [ 9 , 22 ], and Passerini-like three-component condensation reactions [ 23 ]. Further routes include Aldol reactions, asymmetric Aldol reaction of silyloxyfurans, asymmetric Mannich reaction, asymmetric Mukaiyama–Michael reaction of silyloxyfurans, and enantioselective radical oxyfunctionalizations [ 9 , 24 , 25 ].…”