A mechanistic study directed towards understanding transmetalation in iron-based cross coupling reactions led to the development of an iron-based catalyst for the Suzuki-Miyaura cross coupling of alkyl halides with unactivated aryl boronic esters. Unlike previous methods that require activation of boronic acids with pyrophoric organometallic reagents, the method effects the Suzuki-Miyaura cross coupling using less dangerous amide bases and likely without the intermediacy of borates. A key mechanistic feature that enabled efficient catalysis was the development of conditions that avoided iron aggregation. Application of the method for a variety of cross coupling reactions is presented along with a practical demonstration of the utility of the method for the efficient synthesis of Cinacalcet, a blockbuster drug used to treat secondary hyperparathyroidism. Extension of the method to enantioselective variants as well as efforts directed towards the development of a greener protocol that uses alkoxide bases and more environmentally friendly solvents will also be discussed.

Iron-based catalysts for cross coupling reactions

256th National Meeting (2018)

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