Catalytic Asymmetric Synthesis Of 4-thiazolidinone Derivatives By Cinchona Alkaloids

4-Thiazolidinone derivatives have attracted continuing interest over the years because of their diverse biological activities. But there were only by chiral separation, chiral auxiliary synthesis and preparation of chiral column separation to obtain single highly active enantiomer in the past, which is low efficiency. Catalytic asymmetric synthesis, most of all the organic catalysis is not only low toxicity, efficient, and atomic economy is good. The natural cinchona alkaloid derivatives as a kind of important organic catalysts has been widely applied. This article attempts to develop the catalytic asymmetric synthesis of chiral 4-thiazolidinone and its derivatives with quinine-derived squaramides.The first successful implementation of the cinchona alkaloid to catalyze 2,5-diol-1,4-dithiane on the isatin derivative imine asymmetric [3+2] cycloaddition. Screening catalysts, solevents and temperature regulation of model reaction, we identified that the reaction could obtain the best results (enantioselectivity:97%, diastereoselectivity:2:1), when the quinine-derived squaramides as catalyst, dichloromethane as solevent and temperature for-20 ?. And applied to a range of different substrates on this basis, which could be obtained satisfactory results (enantioselectivity:86%-98%, diastereoselectivity:1:1-2:1).Using the obtained optical pure 4-thiazoline derivatives, by stepwise oxidation to get spirocyclic 4-thiazolidinone derivative(PCC, m-CPBA oxidation). Otherwise, controlling the reaction conditions, sulfone or sulfoxide of different functional groups was obtained at the same time. We provided a new methodology for constructing oxindole-based chiral spiro-4-thiazolidinone derivative.By X-ray single crystal diffraction, can determine the absolute configuration of the product.