The Study Of Copper-Catalyzed Vinylation Of Amides

Enamides,a kind of drug intermediates,which are important structural skeletons of natural products,play important roles in organic synthesis,especially in the synthesis of nitrogenous compounds.Transition-metal catalyzed coupling reaction is a common way to form C-N bond,and is also an important method to synthesize enlamides.In recent years,the reports,which are related to the coupling of alkenyl or aryl halides with primary or secondary amides to form enamides and their derivatives,keep growing in the total synthesis of natural products,while the study of synthesizing enamides via cross-coupling of alkenyl ethers with amides is quiet few.Based on summarizing literature studies,we envisioned a novel catalytic systerm involving copper salts,which has been successfully applied for the cross-coupling of amides with alkenyl ethers.The detailed research includes the following two aspects.Firstly,with triethylamine as a deacid reagent,acetic anhydride or acyl chlorides as acylation reagent,we synthesized a series of secondary amides as substrates in excellent yields under relatively mild reaction conditions.Then,using N-benzylacetamide as a secondary amide,vinyl ethyl ether as an alkenyl source,we investigated and established a copper-catalyzed cross-coupling of amide with vinyl ethyl ether,and realized the vinylation of amide.The optimized results showed that,under inert atmosphere,N-benzyl-N-vinylacetamide could be synthesized in moderate to good yields using toluene as the solvent,8-hydroxyquinoline as the ligand and Cu SO₄ as the catalyst.And,under the optimal conditions,the substrate scope was also examined.The results of screening amides showed that applying the amide with electron-donating group in the aromatic ring of benzoyl was beneficial to improve the coupling products.Meanwhile,under the optimimal conditions,the coupling of N-benzylacetamide and other alkenyl ethers as the vinyl source could also occurred smoothly in moderate yield.