Site-Selective C–H Benzylation of Alkanes with N-Triftosylhydrazones Leading to Alkyl Aromatics

Abstract

Summary Alkanes are an abundant and valuable resource for transformation into value-added fine chemicals. However, selective functionalization of specific C(sp3)–H bonds in alkanes for alkyl-alkyl bond formation is a significant challenge because of their intrinsic inertness and the small differences in reactivity among various C(sp3)–H bonds. Here, we report a silver-catalyzed site-selective C(sp3)–H benzylation of simple alkanes using N-triftosylhydrazones as a convenient carbene precursor, which enables the synthesis of high value-added alkylated aromatics. A one-pot two-step protocol starting from aldehydes was also realized, thereby constituting a formal reductive alkylation of aryl aldehydes by alkanes. Experimental investigations and DFT calculations reveal that the role of the [TpBr3Ag]2 catalyst is 3-fold: it modulates the carbene reactivity, inhibits carbene dimerization, and avoids over insertion of the product. All three aspects are crucial for the success of this first site-selective intermolecular insertion of donor carbenes into C(sp3)–H bonds of simple alkanes.