Nickel-catalysed retro-hydroamidocarbonylation of aliphatic amides to olefins

Abstract

Amide and olefins are important synthetic intermediates with complementary reactivity which play a key role in the construction of natural products, pharmaceuticals and manmade materials. Converting the normally highly stable aliphatic amides into olefins directly is a challenging task. Here we show that a Ni/NHC-catalytic system has been established for decarbonylative elimination of aliphatic amides to generate various olefins via C–N and C–C bond cleavage. This study not only overcomes the acyl C–N bond activation in aliphatic amides, but also encompasses distinct chemical advances on a new type of elimination reaction called retro-hydroamidocarbonylation. This transformation shows good functional group compatibility and can serve as a powerful synthetic tool for late-stage olefination of amide groups in complex compounds.

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…Interestingly,i n2 017, Shi and co-workersr eported an ickelcatalyzed retro-hydroamidocarbonylation of aliphatic amides into olefinst hrough amide NÀCa ctivation (Scheme 44). [82] This methodo ffered broad functional-group tolerance andt he opportunity for late-stage olefination in complex molecules. Mechanistic studies revealed the involvement of ar adicalp rocess.…”

Amide activation: an emerging tool for chemoselective synthesis

“…181 A 2017 report by Shi and co-workers features the description of a mechanistically intriguing retro-hydroamidocarbonylation of Boc-activated amides (304), leading to the facile formation of a wide array of olefinic products (306) through b-hydride elimination of 305 (Scheme 46b). 182 Further privileged amides in selective transformations properties for (selective) transition metal-catalysed or even metalfree transformations. Azetidine amides (307) represent such a privileged class of amides, as Szostak and co-workers were able to show that their treatment with organolithium and Grignard reagents in the absence of any catalyst selectively affords the corresponding ketones (Scheme 47a).…”

N‐Boc‐Amides in Cross‐Coupling Reactions

“…Shi and co‐workers studied an amide‐to‐olefin conversion . This reaction proceeds by the oxidative addition of a nickel(0) catalyst to the amidic bond, which, after the decarbonylative process, leads to the corresponding alkyl–nickel(II).…”

“…Shi and co-workers studied an amide-to-olefin conversion. [64] This reaction proceeds by the oxidative addition of an ickel(0) catalystt ot he amidicb ond, which,a fter the decarbonylative process, leads to the corresponding alkyl-nickel(II). The latter undergoes b-H elimination to generate the corresponding olefin.L ike the other nickel catalytic systems, an NHC-type ligand is required and, in particular,a ne lectron-rich one.…”