Efficient synthesis of spirooxindole γ-lactones catalysed by new bis-benzimidazolinium NHC precursors

Abstract

Our internally developed bis-benzimidazolinium N-heterocyclic carbene (NHC) precursors (3a–f) have enabled the efficient synthesis of spirooxindole γ-lactones (4a–t) from isatin derivatives (1a–k) and cinnamaldehydes (2a–c). Among these precursors, the bulky NHC precursor 1,1′-(butane-1,3-diyl)bis(3-(anthracen-9-ylmethyl)-1H-benzo[d]imidazol-3-ium) chloride (3f) exhibited exceptional catalytic activity in forming spirooxindoles with the desired quaternary stereocenter. This [3+2] annulation reaction between N-substituted isatins and cinnamaldehydes demonstrates a broad substrate scope, encompassing a wide range of N-substituted isatins with both alkyl and aryl substituents. Impressively, our process offers an exceptional yield of 98% at room temperature, with the added benefits of low catalyst loading (0.1 equiv.), a broad substrate scope, and gentle reaction conditions. The structure of a sample spirooxindole γ-lactone was confirmed by single-crystal X-ray diffraction. In addition, a DFT study of the two possible diastereomers of this compound showed that both diastereomers had similar free formation energies which can explain the presence of two diastereomers in the product.