Carbonylation of Chloropinacolone: A Greener Path to Commercially Useful Methyl Pivaloylacetate

摘要

Palladium catalyzed carbonylation of a-chloropinacolone (1) in the presence of methanol and tributyl amine provides a more efficient and environmentally sound process for the generation of methyl pivaloylacetate (2). After optimization, the preferred catalyst, [(cyclohexyl)_3P]_2PdCl_2, can be used to generate methyl pivaloylacetate under mild conditions (5-10 atm, 120-130deg C) with extremely high turnover frequencies (>3400 mol MPA/mol Pd/h) and very high total turnover numbers (> 10,000 mol MPA/mol Pd). The process requires very little excess amine or methanol and uses no extraneous reaction solvents. Further, extraction solvents are minimized or eliminated since the product spontaneously separates from the liquid tributylamine hydrochloride. The tributylamine can be readily recycled upon neutralization and azeotropic drying. A part of this study includes the first demonstrated use of a Pd-carbene complex as a carbonylation catalyst.