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.

Figure 1. Development of a retro-hydroamidocarbonylation protocol.

(a) Biodegradation of nylon 66 and hydrolysis of protein. (b) Ni-catalysed activation of aryl amide C–N bonds. (c) Rh and Ir-catalysed decarbonylative elimination of aldehydes to olefins. (d) Ni-catalysed transformation of nitriles to olefins. (e) Ni-catalysed decarbonylative elimination of aliphatic amides to olefins.

Figure 2. Catalytic amide C–N bond activation.

(left cycle) Proposed mechanism on Ni-catalysed decarbonylative borylation of aryl amides. (right cycle) Reaction design for Ni-catalysed decarbonylative elimination of aliphatic amides to olefins.

Figure 3. Scope of the aliphatic amide retro-hydroamidocarbonylation.

Reaction conditions: amides (0.20 mmol), 10 mol% of Ni(COD)₂, 20 mol% of ICy, 0.5 equiv of Mg(OAc)₂, 3.0 equiv of KOAc in 3.0 ml toluene/^chexane (v/v=1:2) at 130 °C, 36 h, under Ar. ^aIsolate yield. ^bDetermined by crude ¹H NMR.

Figure 4. Synthetic applications of retro-hydroamidocarbonylation reactions.

(a) Synthesis of androstadienone (59) from etienic acid (57). (b) Synthesis of the core structure of aspewentin A.

Figure 5. Investigation for mechanistic insights.

(a) Reaction of a radical clock substrate. (b) Exclusion of the conversion from compounds 65 to 66. (c) Reaction in the presence of radical inhibitors.