Asymmetric Deoxygenative Functionalization of Secondary Amides with Vinylpyridines Enabled by a Triple Iridium-Photoredox-Chiral Phosphoric Acid System

Abstract

An enantioselective deoxygenative functionalization of secondary amides with vinylpridines is developed by merging relay iridium catalysis and cooperative photoredox-chiral Brønsted acid catalysis, affording a series of valuable chiral amines in moderate to good yields with good enantioselectivities. The intriguing multiple catalytic system invoking triple-catalysis was found to be the key to the success of the current reactions, which may stimulate further development of catalytic methodologies for asymmetric deoxygenative transformations of amides.

Making Full Use of TMSCF3: Deoxygenative Trifluoromethylation/Silylation of Amides

“…Therefore, the development of effective deoxygenative methodologies of amides to various densely functionalized amines should find widespread use across academia and industry . Over the past decades, several attractive strategies have been developed for deoxygenative activation of an amide, i.e., through electrophilic activation by using Tf 2 O, transition-metal-catalyzed hydride transfer, , and single-electron-transfer (SET) activation by SmI 2 . − The amido group is first selectively transformed into active intermediates, such as iminium ion (Scheme b-i) − or α-aminocarbene/carbenoid equivalent, , followed by the reaction with a coupling partner to generally afford a deoxygenative monofunctionalization product . Considering the increased nucleophilicity and electrophilicity of α-aminocarbenes compared with N,N -dimesityl imidazolylidene (NHC), with a much less explored reactivity distinct from the well-developed carbene chemistry in organic synthesis, we envisioned that combining Sm–SmI 2 -mediated amide activation with the synthetically versatile TMSCF 3 reagent may lead to the efficient synthesis of fluorine-containing densely functionalized amines that are otherwise difficult to attain.…”