Highly regio- and diastereoselective [3 + 2]-cycloadditions involving indolediones and α,β-disubstituted nitroethylenes†
A highly diastereoselective [3 + 2]-cycloaddition strategy involving multiple oxindoles and several α,β-disubstituted nitroethylenes is developed to access tetra-substituted α-spiropyrrolidine frameworks. A variety of α-amino acids were employed for the first time in order to generate azomethine ylides under thermal conditions, affording regioisomers 13 and 14 merely by changing the α-substituents (R = H and substituted carbons) of the α-amino acids. The reaction tolerates various sterically demanding, electron-rich and electron-deficient aryl and nitrogen substituents on glycines, oxindoles and nitroethylenes. The operational simplicity, such as the use of a metal-free and non-inert environment, the utilization of non-halogenated solvents and the ease of isolation, adhering to the principles of green chemistry, makes this process attractive for scale-up opportunities. The reaction delivers good yields (80–94%) and diastereoselectivities (up to 98 : 2) in favor of (cis,cis)-spirooxindoles, with opposite regioselectivity compared to β-nitrostyrenes under identical conditions. Two spiropyrrolidine cycloadducts with unprotected amides exhibited significant activity against Gram-positive MRSA.
- This article is part of the themed collection: Synthetic methodology in OBC