Development and Optimization of Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling Reaction of Tertiary Sulfones.

Suzuki-Miyaura cross-coupling reactions are a popular and useful synthetic method to create new carbon-carbon bonds, due to their relative safety and stability.1 In particular, this method has shown promise in the construction of densely functionalized quaternary carbon stereocenters that can be bulky and otherwise difficult to synthesize, making it optimal for synthesizing pharmaceuticals and natural products.1,2 Tertiary sulfones are a class of compounds that are highly versatile and have demonstrated abilities to serve as unique pseudohalides and electrophilic coupling partners, which allows for added flexibility in this powerful reaction.3 In previous work done by the Crudden group, a variety of benzylic and allylic tertiary sulfones were used to produce quaternary carbon centers, however it required naphthyl or similar p-extended groups in order to facilitate coordination of nickel-catalyzed Suzuki couplings.4 We are currently investigating the possibility of using tertiary sulfones containing conjugated olefins to overcome this limitation. This would further enhance the utility of this reaction, allowing access to synthetically challenging products with a conjugated olefin backbone that can be further functionalized, serving as a versatile lynchpin handle. This work will enable direct and efficient synthesises of natural products and further develop the scope of pharmaceutical compounds. [1] - Roughley, S. D.; Jordan, A. M. J. Med. Chem. 2011, 54, 3451-3479. [2] - Ling, T.; Garfias, J. M.; Lawson, S. L.; Rivas, F. Tetrahedron. 2025, 183, 134711. [3] - Trost, B. M.; Chem-Eur J. 2019, 25, 11193 – 1121. [4] - Ariki, Z. T.; Maekawa, Y.; Nambo, M.; Crudden, C. M. J. Am. Chem. Soc. 2017, 140 (1), 78–81.