H-phosphonates Mediated Copper Catalyzed Synthesis Of(E)-vinyl Alkylsulfones From Alkynes And DMSO Or T-butylsufinamide

Vinyl sulfones are widely used as building blocks in synthetic organic chemistry. For example, the chemical versatility of the sulfone moiety enables these compounds to undergo highly stereoselective nucleophilic conjugate additions and cyclo-additions, epoxidation and reduction. Furthermore, the sulfone group can be removed at the end of a synthetic sequence by a variety of reductive, alkylative or oxidative methods. Moreover, Vinyl sulfones in medicinal chemistry represent a new class of inhibitors of such as cysteine proteases, depeptidyl peptidase I(DPPI) and transpeptidase. Due to their wide applications, various methodologies for the synthesis of vinyl sulfones have been developed. The traditionally available methodologies for vinyl sulfones mainly include the following:(1) the knoevenagel condensations of aldehydes with sulfonylacetic acids,(2) wittig reactions of carbonyl compounds and sulfonylphosphones,(3) β-elimination of selenosulfones, and(4) oxidation of the corresponding vinyl sulfides. However, most of these methods suffer from some limitations such as inaccessible starting materials, tedious procedures, relatively harsh reaction conditions, or generation of large amounts of unwanted byproducts. Therefore, looking for establishing a simple, cheap, highly effective new synthesis methods is imperative.H-phosphonate, as a kind of important intermediates, due to its easy to store, cheap, reaction sites more features, is often used in all kinds of chemical synthesis. Such as amine phosphate, alkynyl phosphate, nucleoside phosphate and amine phosphate, etc. H-phosphonate occupies very important position in the research and application of organic phosphorus chemical. However, H-phosphite as auxiliary synthesis of important intermediates of organic compounds is rarely reported.Herein, we report an efficient method for the synthesis of vinyl sulfones from alkynes and DMSO or t-butylsufinamide, using much cheap, easily available Cu SO4?5H2O-H-phosphonate catalytic system. In mechanism research, through the isotope labeling, radicals block experiment means, etc, the mechanism of the reaction was in-depth studied. Cu SO4?5H2O-H-phosphonate catalytic systems play an key role in cleavage of C-S bond of DMSO and N-S bond of t-butylsufinamide.The main contents of this paper are as follows:1.the bio active, chemcial properties and methodologies for the synthesis of vinyl sulfones were introduced and summarized. Then we summarized the chemcial properties of H-phosphonate.2. We optimized the reaction conditions of reaction of DMSO and alkynes; and then the scope of the reaction were investigated; 24 compounds was synthesized. Finally, the mechanism of the reaction was studied by designed experiments.3. Encouraged by the hydrosulfonylation between DMSO and alkynes, another easily available sulfur resource, t-butylsufinamide was also investigated subsequently. We optimized the reaction conditions of reaction of t-butylsufinamide and alkynes; and then the scope of the reaction were investigated; 21 compounds was synthesized.4. We use a variety of means to verify the mechanism of the reaction. Take alkynes and DMSO for example, the Cu SO4·5H2O- H-phosphonate catalytic system play a important role in the C-S bond repture of DMSO in the synthesis of sulfone compounds.