Reversible C–C bond formation using palladium catalysis

A widely appreciated principle is that all reactions are fundamentally reversible. Observing reversible transition metal-catalysed reactions, particularly those that include the cleavage of C–C bonds, is more challenging. The development of palladium- and nickel-catalysed carboiodination reactions afforded access to the cis and trans diastereomers of the iodo-dihydroisoquinolone products. Using these substrates, an extensive study investigating the reversibility of C–C bond formation using a simple palladium catalyst was undertaken. Herein we report a comprehensive investigation of reversible C–C bond formation using palladium catalysis employing diastereomeric neopentyl iodides as the starting point. It was shown that both diastereomers could be converted to a common product under identical catalytic conditions. A combination of experimental and computational studies were used to probe the operative mechanism. A variety of concepts key to understanding the process of reversible C–C bond formations were investigated, including the effect of electronic and steric parameters on the C–C bond-cleavage step. Although carbometallation reactions have been thoroughly investigated, understanding the factors responsible for the reverse reaction (β-carbon elimination) is an emerging area of research. Now, a series of substrates has been investigated to study the key factors that promote β-carbon elimination under palladium catalysis.