Research Projects

The project aims to revolutionize the vicinal carbothiolation of ortho-(alkynyl)benzyl thiosulfonates and sulfurothioates by utilizing a novel anti-carbometalation-cyclization cascade. It addresses the challenges related to the reactivity and regioselectivity of carbometallation transformations involving internal triple bonds. By exploiting the unique electronic properties of ortho-(alkynyl)benzyl thiosulfonates and sulfurothioates, the project seeks to form key anti-carbometalation intermediates that facilitate the creation of C-S bonds through cyclization. The research will investigate the reactivity of internal alkynes in ortho-(alkynyl)benzyl thiosulfonates and sulfurothioates during vicinal carbothiolation processes, particularly with various (hetero)aryl-metal intermediates. This proposal addresses several significant and conceptually challenging problems: (i) the initial syn-carbometallation across the triple bond must be stereospecific; (ii) conversion from the syn isomer to the anti form must occur to facilitate favorable anti-carbometalation; and (iii) the generated intermediate must quickly and efficiently form an intramolecular C-S bond. To overcome these challenges, we will carefully select appropriate catalysts, ligands, and reaction conditions. We hypothesize that the rational design of this project will demonstrate the broad applicability of ortho-(alkynyl)benzyl thiosulfonates and sulfurothioates in advanced synthesis and catalysis. In this context, thiosulfonates and sulfurothioates will function as directing groups and/or strongly coordinate or chelate with sulfur-metal bonds, enabling the formation of intramolecular C-S bonds. The primary goals of the project are to achieve high chemoselectivity and regioselectivity while introducing useful aryl or heteroaryl groups at the fourth position of isothiochromenes. Additionally, the project aims to identify competitive reaction pathways and confirm the synthetic viability of residual cyclic thioether functionality. By establishing vicinal carbothiolation as a versatile platform for the synthesis of isothiochromene-heterocycles, this project seeks to significantly advance the scope and utility of π-activation using metal complexes, thereby opening new opportunities for sustainable chemical synthesis. Ultimately, the success of this project will produce a diverse range of heteroaryl-isothiochromenes that may exhibit promising biological activities and have potential as pharmaceutically active marketed drugs. The outcomes of the project will provide valuable insights and tools for the scientific community, fostering innovation and paving the way for future breakthroughs in organic synthesis.