Conjugate addition/cyclization of propanal with isatylidene malononitriles: an efficient one-pot organocatalytic approach for the synthesis of 3′-methyl spiro[2H-pyran-3,4′-indoline]

Abstract

The organocatalyzed one-pot Michael addition reaction of propanal to isatylidene malononitriles remains largely unexplored due to challenges in controlling the reaction and preventing side processes such as aldol condensation, self-aldolization, and 1,3-dipolar cycloaddition. In this study, we introduce a one-pot methodology for the synthesis of 3′-alkyl spiro[2H-pyran-3,4′-indoline] via an organocatalyzed Michael addition of simple propanal to isatylidene malononitrile derivatives, which are generated in situ from isatin derivatives and malononitrile. Subsequent reduction of the Michael adduct with NaBH₄ leads to the target product with high efficiency under mild conditions. This strategy offers several advantages, including environmental sustainability, high to excellent yields, shorter reaction times, cost-effectiveness, and ease of implementation.