Halogenation of pyrazoles by the <i>in situ</i> generation of electrophilic halogens from a sodium halide salt and Oxone® has proven to be an effective means of forming pyrazolyl halides. Our group has demonstrated that this reaction works in water on a wide variety of substrates and at room temperature. This development is being applied to a total synthesis of the natural product withasomnine, a pyrazole-based natural product isolated from <i>withania somnifera. </i>The synthetic strategy is to build withasomnine from pyrazole using a series of concise steps that will couple a phenyl ring to the 4-position, and form a fused heterocyclic ring system connected to the 1- and 5-positions of the ring. After halogenation of pyrazole using the reaction described above, a Suzuki cross-coupling with phenylboronic acid will install the requisite phenyl group. The fused ring system will be formed using an alkylation reaction to attach to N1 of the pyrazole, followed by an intramolecular radical cyclization onto the 5-position of the ring, thereby completing the synthesis.

Halogenation of pyrazoles with NaX and Oxone® and progress toward the total synthesis of withasomnine

251st National Meeting (2016)

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