A tandem reduction-lactamization of 2-nitrobenzyl-substituted active methylene derivatives initiated by dissolving metal reduction of the aryl nitro group has been developed and studied to prepare 2-oxoindolines, 2-oxotetrahydroquinolines and 2-oxotetrahydro-1H-benzo[b]azepines. Reductive closure of six-membered rings proceeded cleanly upon treatment with Fe/AcOH with no degradation of existing functionality at the carbon α to the ester. Additionally, electron-releasing and donating groups on the aromatic ring bearing the nitro group were well tolerated in the reaction. The scope was extended to five- and seven-membered ring closures, where the extent of substitution α to the esters proved important. While the level of substitution had no effect on closures of six-membered rings, reactions to form 2-oxoindolines required a quaternary α-carbon for successful cyclization and 2-oxotetrahydro-1H-benzo[b]azepines only formed when the α-carbon was tertiary.

Ring size and substitution effects in the tandem reduction-lactamization of ortho-substituted nitroarenes

249th National Meeting (2015)

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