Nickel-Copper-Catalyzed C(sp2)N Cross-Coupling of Cyclic and Bridged Amides: An Access to Cyclic Enamides and Alkenyl Vince Lactams

• Published in: Advanced synthesis & catalysis Vol. 357; no. 16-17; pp. 3617 - 3626
• Main Authors: Maity, Pintu, Kundu, Debasish, Ranu, Brindaban C.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16.11.2015; WILEY‐VCH Verlag; Wiley
• Subjects: Amides; Aromatic compounds; Cesium; Chemistry; Chemistry, Applied; Chemistry, Organic; copper; Cross coupling; Halides; Iodides; Joining; Nickel; Physical Sciences; Science & Technology; Vince lactams; vinyl halides; nickel; ULLMANN SYNTHESIS; C-N; ANALOGS; SALICYLIHALAMIDE-A; ARYL HALIDES; EPIBATIDINE; cross-coupling; vinyl halides; copper; CARBON-HETEROATOM; Vince lactams; STEREOCHEMICAL ASSIGNMENT; CYCLOPEPTIDE ALKALOIDS
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201500457

An efficient C(sp2)N cross‐coupling of styrenyl and vinyl halides with cyclic and bridged amides catalyzed by nickel acetonylacetonate [Ni(acac)2] and copper(I) iodide (CuI) in the absence of any ligand has been developed. The reaction conditions are optimized to give the maximum yield of products using cesium carbonate (Cs2CO3) (2.0 equiv.) in N‐methyl‐2‐pyrrolidinone (NMP) at 110 °C under argon in the presence of Ni(acac)2/CuI (10 mol% each). A series of alkenyl derivatives of Vince lactams (bridged amides) and cyclic amides are obtained by this procedure. Halogen‐containing styrenyl bromides also underwent coupling with amides to provide the products. The coupling is highly chemoselective as during the reactions the halogens (Br, Cl, F) on the aromatic ring remained intact and these can be used for further functionalization to make these enamides more useful. Although the (E)‐styrenyl halides produced the corresponding (E)‐styrenyl enamides, reactions with (Z)‐styrenyl halides produced 1,3‐di‐ynes instead of (Z)‐styrenyl enamides. This may be explained by the possibility of E2 type elimination of (Z)‐styrenyl halides in the presence of a strong base like cesium carbonate followed by homocoupling. This catalyst system works efficiently for the N‐arylation too along with N‐styrenylation and vinylation. The bridged as well as cyclic amides successfully coupled with substituted aryl halides to provide the corresponding products. In general, the reactions are clean and high yielding. The operations are very simple and the products are obtained pure by standard column chromatography. The reaction is compatible with variety of amides and alkenyl bromides. The roles of nickel acetonylacetonate and copper(I) iodide in this reaction have been established and a possible reaction pathway has been outlined. The significant feature of this protocol is the alkenylation of Vince lactams via C(sp2)N cross‐coupling, which has not been reported so far and these products may have much potential in the pharmaceutical industry.