Reductive Cleavage of C(sp²)–CF₃ Bonds in Trifluoromethylpyridines

Abstract

A reductive detrifluoromethylation protocol has been developed making use of an earth-abundant alkoxide base and silicon hydride species. A variety of pyridine and quinoline substrates bearing alkyl, aryl, and amino functional groups are reduced in moderate to high yields. The reaction is chemoselective for C(sp 2 )−CF 3 groups located at the 2-position on the pyridine ring, leaving trifluoromethyl groups located elsewhere on the molecule intact. Preliminary mechanistic studies demonstrate that the combination of silane and base generates a strongly reducing system that may transfer an electron to electron-deficient π systems.

Tandem Hydrogen‐Borrowing Dehydrogenative Coupling and Hydrodefluorination

“…While transition metal complexes are well-known to mediate dehydrogenative coupling and hydrogen borrowing, we demonstrate here that when KOtBu is employed as the base, HDF of trifluoromethyl groups present in the substrates is observed in tandem with DC reactivity leading to the formation of novel CF 2 Hcontaining products. The reactivity of KOtBu with hydrosilane reducing agents has been implicated in CF 3 -cleaving reactions [57] and alcohols have been used in transfer hydrogenation-style HDF of arylfluorides. [58] In this work, we demonstrate how KOtBu alone can perform selective HDF of CF 3 moieties to CF 2 H groups without employing an additional reducing agent.…”

“…All diffractometer manipulations were carried out using Bruker APEX3 software [61] . Structure solution and refinement was carried out using XS, XT [57] and XL software, embedded within the Bruker SHELXTL suite [58] . For each structure, the absence of additional symmetry was confirmed using ADDSYM incorporated in the PLATON program [64] .…”