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.