Syntheses of New Multisubstituted 1-Acyloxyindole Compounds

Abstract

The syntheses of novel 1-acyloxyindole compounds 1 and the investigations on reaction pathways are presented. Nitro ketoester substrate 2, obtained in a two-step synthetic process, underwent reduction, intramolecular addition, nucleophilic 1,5-addition, and acylation to afford 1-acyloxyindoles 1 in one pot. Based on the systematic studies, we established the optimized reaction conditions for 1 focusing on the final acylation step of the intermediate 1-hydroxyindole 8. With the optimized conditions, we succeeded in synthesizing 21 examples of new 1-acyloxyindole derivatives 1 in modest yields (Y = 24 − 35%). Among the 1-acyloxyindole compounds, 1-acetoxyindole compounds 1x were generally unstable, and their yields were relatively lower than the other 1-acyloxyindoles. We expect that a bulkier alkyl or aromatic group on R2 could stabilize the 1-acyloxyindole compounds. Significantly, one-pot reactions of a four-step sequence successfully generated compounds 1 that are all new and might be difficult to be synthesized otherwise.

Indole Derivatives: Unveiling New Frontiers in Medicinal and Synthetic Organic Chemistry

“…The 1-acetoxy indole compounds exhibit lower stability and yields than other 1-acyloxy indoles. Remarkably, the one-pot reactions involving a four-step sequence enable the efficient synthesis of these new compounds, which might otherwise be challenging to obtain [ 9 ]. New indole-containing hybrids derived from millepachine were synthesized and subjected to evaluation.…”