Development of organochalcogen-catalysts as a sustainable concept for the selective amination and halogenation of unsaturated hydrocarbons in the context of the bioinspired synthesis of medicinally relevant drugs

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The goal of the postulated research program is the development of an organochalcogen-based catalysis concept (chalcogen = S, Se) for the stereo- and chemoselective, oxidative nitrogenation and halogenation of simple alkenes. As a consequence, catalytic methods arising from this campaign are expected to serve as linchpin operations in endeavors toward syntheses of medicinally relevant natural products and analogs thereof. The program is subdivided into three parts: A) On the basis of mechanistic investigations the rational development of two novel classes of chiral diaryldisulfide and -selenide catalysts as well as thio- and selenoamide catalysts for the stereoselective construction of C-N and C-halogen bonds is proposed. Regarding the postulated dichalcogenides, the conceptual focus lies on the design of an unprecedented catalyst architecture, which is expected to allow for both an efficient stereoinduction as well as substrate turnover. B) Catalysts resulting from part A will be applied in a number of asymmetric transformations, such as oxidative allylic aminations and aminocyclizations of olefins. Moreover, investigations will include oxidative allylic halogenations, dihalogenations, and halo(carbo)cyclization reactions of alkenes and polyenes. In particular, development of the latter transformation will set the basis for the total synthesis of halogenated cyclic natural products. C) In order to demonstrate the general utility of the postulated chalcogen-catalysis concept, a concise and redox-economic synthesis of the labdane alkaloids haterumaimide L and M is proposed. Key-step in this endeavor is a bioinspired, asymmetric halocarbocyclization, which is expected to provide rapid access to a common intermediate that on its part should give rise to either of the target compounds.