Cross-coupling reactions without the generation of waste products

Problem:

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.

Solution:

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.

Advantages: 

• 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

Applications: 

• 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

Intellectual Property: 

• UP application (US20150152216 A1)
• PCT pending (WO2016011231 A1)

Reference Media: 

• 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.

Desired Partnerships: 

• License
• Co-development

Docket # Y6226, 15-7198

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