靛红Morita-Baylis-Hillman碳酸酯与环状 N -磺酰亚胺的不对称烯丙基烷基化反应研究

Enantiomerically pure 3,3-disubstituted 2-oxindoles are important building blocks for the synthesis of diverse oxindoles which are the core structure of many natural products and biologically active compounds. A number of asymmetric reactions to access such chiral materials have been reported over the past years, most of which rely on the application of nu- cleophilic 3-subsituted oxindoles. Although these methods have been proved to be useful, some challenging issues still re- main in terms of efficiency, stereoselectivity and substrate scope. On the other hand, recently, we have developed some highly stereoselective allylic alkylation reactions with Morita-Baylis-Hillman (MBH) carbonates of isatins and diverse nucleophiles, to produce 3,3-disubstituted oxindoles under the catalysis of metal-free Lewis basic tertiary amines. In this work, the first asymmetric assembly of MBH carbonates of isatins and cyclic N-sulfonylimines is reported. An array of tertiary amine cata- lysts derived from β-isocupreidine (β-ICD) and a variety of reaction parameters have been systematically investigated, and the optimized conditions were determined to run the reaction at -20 ℃ using PhCF3 as the solvent, 4 A MS as the addi- tive, in the presence of 10 mol% of amine catalyst 1h. A number of MBH carbonates 2 derived from diversely substituted isatins and cyclic N-sulfonylimines 3 could be well tolerated under the established catalytic conditions, providing an alterna- tive electrophilic pathway to access multifunctional oxindoles bearing adjacent quaternary and tertiary stereogenic centers (up to 86% ee, dr>95∶5) in high yield (up to 96%). Moreover, the thus obtained chiral 3,3-disubstituted 2-oxindole could be used for the synthesis of complex spirocyclic 2-oxindole-3,4'-piperidine product. In this case, the chemoselective reduction of imine group of allylic alkylation product 4a has been realized by using NaBH4 as the reducing reagent at -20 ℃. A fol- lowing intramolecular aza-Michael addition reaction gave a 2-oxindole-3,4'-piperidine product 6 in a moderate yield. Keywords asymmetric organocatalysis; allylic alkylation; Morita-Baylis-Hillman carbonates; cyclic N-sulfonylimines; 2-oxindoles; quaternary chiral centre; 2-oxindole-3,4'-piperidine