A widely appreciated principle is that all reactions are fundamentally reversible.Observing reversible transition metal-catalyzed reactions, particularly those that include the cleavage of C-C bonds, are more challenging. The development of the palladium-and nickelcatalyzed carboiodination reactions afforded access to the syn-and anti-diastereomers of the iodo-dihydroisoquinolone products. Using these substrates, an extensive study investigating the catalytic reversibility of the C-C bond formation using a different palladium catalyst was undertaken. A combination of experimental and computational studies led to the discovery of a variety of new methodologies and concepts key to understanding the process of reversible C-C bond formations. Main Text:A fundamental tenant of chemical reactivity is that reactions are reversible. Classic organic transformations, illustrated by the Diels-Alder reaction 1-3 and the aldol condensation, [4][5][6] have been thoroughly studied in both the forward and reverse directions. Transition metalcatalyzed processes, such as β-hydride elimination, or its microscopic reverse hydrometallation process, have been widely studied. 7-10 A thorough investigation of these fundamental steps where a C-H bond is made or broken has been enabled, in part, by easily designed kinetic isotope experiments involving deuterated substrates. [7][8][9][10] Analogous transformations involving carbon have garnered less attention due to their increased rarity as the systems to interrogate this process difficult to design. Migratory insertion involving C-C bond formation is a key step in many transition metal-catalyzed transformations, including the Mizoroki-Heck reaction. Examples of the microscopic reverse process, β-carbon elimination, have been reported in the literature; [11][12][13][14][15] however, most have been observed when key structural elements are present (Scheme 1). The most prevalent β-carbon eliminations are driven by release of ring strain. [16][17][18][19][20] The most common examples of this are when cyclic alcohols are used to form metal homoenolate nucleophiles (Scheme 1a). 16 The relief of steric strain via a β-carbon elimination, as seen in the Catellani reaction, rely on the build-up of increasing steric encumbrance during the course of the reaction (Scheme 1b). 17,21,22 Other strategies to enable β-carbon eliminations rely on the formation of a strong π-bond (Scheme 1c). 17,19,[23][24][25][26][27][28][29] These biased systems make it difficult to study the effects of different parameters on the β-carbon elimination process, and thus an unbiased system would not only be conceptually novel, but allow for the examination of other parameters on reversible C-C bond cleavage. In this work, we have identified a substrate that enables insight into the β-carbon elimination, a concept that to our knowledge has not been explored. Furthermore, isotopically

A widely appreciated principle is that all reactions are fundamentally reversible. Observing reversible transition metal-catalyzed reactions, particularly those that include the cleavage of C–C bonds, are more challenging. The development of the palladium- and nickel-catalyzed carboiodination reactions afforded access to the syn- and anti-diastereomers of the iodo-dihydroisoquinolone products. Using these substrates, an extensive study investigating the catalytic reversibility of the C–C bond formation using a different palladium catalyst was undertaken. A combination of experimental and computational studies led to the discovery of a variety of new methodologies and concepts key to understanding the process of reversible C–C bond formations.