Studies On Cascade Sulfa-Michael/Michael Addition Reaction

Chiral sulfur compounds widely present in the molecular structure of natural productsand medicines, which have special physiological activity and medicinal value. The researchon synthesis of chiral sulfur compounds have important practical value. AsymmetricMichael addition is an important method to build C S bond.In this thesis, unsaturated thioglycolic acid ethyl ester was synthesized. Thesulfa-Michael/Michael addition of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl esterand nitroalkenes was investgated. At first, we evaluated the catalysts, solvent andtemperature, and obtained the optimal reaction conditions:5mol%catalyst loading at60°Cfor48h, with toluene as the solvent. After the optimal reaction condition was established,we explored the substrate scope of the squaramide-catalyzed asymmetric cascadesulfa-Michael/Michael addition of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl esterand nitroalkenes. These reactions have obtained excellent catalytic effect: most reactionscan get high yields (up to94%yield) and excellent stereoselectivities (up to99%ee,>25:1dr). The configurations of the target products were assigned as (2R,3S,4R) according tothe experimental data and literature reports. According to analyzing the reaction processand the reaction intermediates, there may be a retro-sulfa-Michael addition process in thereaction pathway of sulfa-Michael/Michael addition. This method provides a facile andefficient way to synthesize thiochroman derivatives with three consecutive chiral centers.In order to expanding the range of the substrates, other unsaturated thio-compoundssuch as thio-chalcones and thio-nitroalkenes were tried to design and synthesize.Unfortunately, the expected products could not be obtained.The sulfa-Michael/Michael addition reaction of trans-3-(2-mercaptophenyl)-2-propenoic acid ethyl ester and a variety of other Micheal addition receptors includingα-nitroalkenes, β-nitroalkenes,3-ylide indolones, chalcones, cinnamic aldehyde and3-nitro-2H-chromene were studied. Unfortunately, these reactions could not get goodcatalytic result.