Treatment of 2-chloropyridine 1 with LDA and the Weinreb amide 2 of benzoic acid afforded three unusual products, namely N-methylbenzamide 4, 2-chloropyridine-3-methanol 5, and the ring opened addition product 6. Here, mechanistic insight for the formation of these products is provided. The first two products are formed by the reaction of the Weinreb amide 2 with LDA leading to elimination of formaldehyde and formation of the anion of the N-methylbenzamide 4. The formaldehyde generated can then trap the 2-chloropyridin-3-yl lithium species to produce the 2-chloropyridine-3-methanol 5. The formation of the ring opened cyano aminodienone 6, presumably involves the addition of diisopropylamide to the 6-position of the 2-chloro-3-benzoylpyridine 3 to generate the stabilized anionic intermediate which can then undergo an anionic-assisted cleavage of the C-N bond of the dihydropyridine with loss of chloride to form the cyano dienone 6. We carried out a brief reaction scope with other Weinreb amides and basic amides, which showed also give the analogous ring-opened products. This same final product 6 could be also obtained from 2-chloro-3-benzoylpyridine 3 on treatment with LDA.

Formation of aryl(1-cyano-4-(dialkylamino)butadienyl)ketones from pyridines

2019 Fall National Meeting

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