Metalated Unsaturated Amides. Regio- and Stereoselective γ-Alkylation

Article abstract of DOI:10.1021/jo00323a012

The reactions of lithiated and dilithiated unsaturated amides 4, 5, 12, 15, 18, 34, and 36 with a variety of electrophiles have been shown to produce deconjugated, α-alkylated products 6, 7, 13, 16, 19, 35, and 37, respectively, in good to excellent yields (Tables I, II, IV, and VI).Whereas lithiated 4 and dilithiated 5 do not undergo γ-alkylation, the corresponding species of 12 and 15, when converted to their cuprates by using cuprous iodide, afford γ products 4 and 17 with good regio- (67-90percent) and Z stereoselectivity (67-80percent) for E = allyl, prenyl, and geranyl.Differences between the reactions of cuprated, unsaturated amides and unsaturated carboxylic acids with nonallylic alkylating agents are discussed.The reaction of dicuprated N-methylsenecioamide (15) with prenyl bromide leads to a complex mixture of products which have been separated and characterized (Scheme III).The reaction of lithiated N,N-dimethylsenecioamide (18) with aromatic and pyridine aldehydes and some ketones has been shown to provide α (19) or γ (20) products, depending on the conditions of the reaction (Table VI).In this reaction, the reversible formation of the α product 19 and its conversion into the γ product 20 have been demonstrated (Scheme IV).The utility of the α- and γ-alkylated unsaturated amide products is illustrated by the syntheses of the monoterpenoid lavandulol (42) and the amide alkaloid piperlonguminine (43), respectively.