Walking metals: catalytic difunctionalization of alkenes at nonclassical sites.

Migration of metals along a carbon chain is triggered by two of the most common organometallic elementary steps - β-hydride (β-H) elimination and alkene hydrometallation. This process heralds a new future for creating bonds at carbon sites that fall outside the tenets of the conventional wisdom for reactivity and bond formation, and provides an opportunity to leverage β-H elimination to advance the very reaction of alkene difunctionalization it is intrinsically predestined to disrupt. Almost four decades since its genesis, the early adventure for alkene difunctionalization by metal migration was sporadic, and its later development went on a hiatus primarily due to original impetus on arresting β-H elimination for vicinal alkene difunctionalization. With the recent surge on alkene difunctionalization, efforts have been gradually shifting to harnessing the process of β-H elimination to difunctionalize alkenes at sites other than the classical vicinal carbons, termed henceforth nonclassical reaction sites for pedagogical simplicity. In this review article, we extricate and examine the origin and the development of such reactions over the years. This review covers a wide range of reactions for the difunctionalization of alkenes at geminal (1,1), allylic (1,3) and remote (1,n) carbon sites with a variety of coupling partners. These reactions have enabled engineering of complex molecular frameworks with the generation of new carbon-carbon (C-C)/C-C, C-C/C-heteroatom (halogens, O, N, B) and C-B/C-B bonds. The development of these unique transformations is also presented with mechanistic hypotheses and experimental evidences put forward by researchers. Judged by the number of reports emerging recently, it is now strikingly evident that the field of alkene difunctionalization by metal migration has begun to gain momentum, which holds a great future prospect to develop into a synthetic method of enormous potential.