Reusable silicon-based cross-coupling agents for the production of natural products, pharmaceuticals, and other organic materials
Cross-coupling reactions without the generation of waste products
Catalytic carbon-carbon bond formation based on cross-coupling reactions (CCRs) plays a central role in the production of natural products, pharmaceuticals, agrochemicals, and organic materials. Coupling reactions with organometallic reagents and organic halides facilitate a plethora of bond-forming reactions in modern synthetic chemistry.
The problem, however, with all current cross-coupling reactions is that they lead to the formation of the stoichiometric production of waste products, such as in:
- the Suzuki CCR boronic acid;
- the Negishi CCR organozinc waste;
- the Stille CCR organotin waste; and
- Kumada organomagnesium.
The Smith Lab has developed silicon-based transfer agents for palladium-mediated cross-coupling processes to yield aryl-aryl, alkenyl-aryl, and alkenyl-alkenyl coupled products. This reaction can occur in one pot with high yield and purity of the product, while eliminating the problems of lithium-halogen exchange, homocoupling from other palladium-mediated methods, including the Suzuki organoboron, Negishi organozinc, Stille organotin, and Kumada organomagnesium, and the stoichiometric production of waste products.
Synthetic overview of silicon-based cross-coupling reaction. From Smith et al, 2012.
- High product yield
- No unwanted byproducts or homocoupling
- Excellent specificity
- Support catalyst on polymer that can be readily recovered without significant loss of cross-coupling activity
- Facile product purification
- Mild reaction conditions
- Cross-coupling synthetic reactions
- Natural products, pharmaceuticals, agrochemicals, small molecules, fine chemicals
Stage of Development:
Lab-scale synthesis of wide range of cross-coupled aryl compounds
- Martinez-Solorio D. et al. JACS, 2016, 138, p. 1836-1839.
- Nguyen M.H. et al. Org. Lett., 2014, 16(7), p. 2070-2073.
- Nguyen M.H. et al. Org. Lett., 2013, 15(16), p. 4258-4261.
- Martinez-Solorio D. et al. Org. Lett., 2013, 15, p. 2454-2457.
- Smith A.B. et al. JACS, 2012, 134, p. 4533-4536.
- Smith A.B. et al. Angew. Chem. Int. Ed., 2011, 50, p. 8904-8907.
- Penn News highlight.
Docket # Y6226, 15-7198