Direct Synthesis of Enamides via Electrophilic Activation of Amides

Abstract

A novel, one-step N-dehydrogenation of amides to enamides is reported. This reaction employs the unlikely combination of LiHMDS and triflic anhydride, which serves as both the electrophilic activator and the oxidant, and is characterized by its simple setup and broad substrate scope. The synthetic utility of the formed enamides was readily demonstrated in a range of downstream transformations.

Cobalt-catalyzed chemoselective dehydrogenation through radical translocation under visible light

“…Enamides have proven to be extremely valuable products and chemical intermediates due to their higher stability and reaction tunability compared with enamine and are widely used in further synthetic transformations. 19 However, direct dehydrogenation of carboxamide 20 to construct enamide is more difficult and more inert N-benzoyl amides usually give poor yields. 20 a , b On the basis of the above optimized conditions, we next focused on the synthesis of enamide with diverse 2-iodobenzamides.…”

para‐Selective Radical Trifluoromethylation of Benzamide Derivatives via Iminium Intermediates

“…In addition, in situ activation of amide with Tf 2 O has drawn particular attention and was widely used to convert amide into other functional groups [23] . In particular, amide activation with Tf 2 O was used to enhance acidity of nitrogen α‐H, which suggested the activation of amide could affect other bond [23d] . Therefore, whether the benzamide activation with Tf 2 O has an effect on the phenyl group is of interest to us.…”

Selective desaturation of amides: a direct approach to enamides

“… 15 Meanwhile, the desaturation of N -Boc, Cbz and Bz protected amides through manganese-catalyzed α-C(sp 3 )–H hydroxylation and electrophilic activation of amides was demonstrated by the groups of Groves and Maulide, respectively ( Scheme 1c ). 16 Magnus's group reported the first example of α-azidation of amides and their analogues using TMSN 3 and 2-iodosobenzoic acid, with enamides as by-products ( Scheme 1d ). 17 Despite the significance, a limitation is that substrates containing an acidic C(sp 3 )–H bond adjacent to the carbonyl group are not amenable for selective desaturation.…”