Selective Terminal Functionalization of Linear Alkanes

Abstract Selective undirected functionalization of strong primary C-H bonds of linear alkanes, that do not possess directing groups, historically stands as one of the most challenging transformation in chemistry. In this Article, we report a two-step sequential strategy involving a biocatalytic dehydrogenation / remote hydrofunctionalization, as a unified and versatile approach to selectively convert linear alkanes into a large array of valuable functionalized aliphatic derivatives. The dehydrogenation is carried out by a mutant strain of Rhodococcus and the produced alkenes are subsequently engaged in a remote functionalization through a metal-catalyzed hydrometalation/migration sequence that subsequently react with a large variety of electrophiles. The judicious implementation of this combined biocatalytic and organometallic approach enabled us to develop a high-yielding protocol to site-selectively functionalize unreactive primary C–H bonds.