Highly Regio- and Diastereoselective [3+2]-Cycloadditions Involving Indolediones and α,β-Disubstituted Nitroethylenes
A highly diastereoselective [3+2]-cycloaddition strategy between multiple oxindoles and several α,β-disubstituted nitroethylenes is developed to access tetra substituted α-spiropyrrolidine frameworks. Variety of α-aminoacids were employed for the first time in order to generate azomethine ylides under thermal conditions affording regioisomers 13 and 14 by mere change of α-substituent (R=H and substituted carbon) in α-aminoacids. 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 metal and inert-free atmosphere, utility of non-halogenated solvent and easy isolation - the principles of green chemistry, is attractive for scale up opportunities. The reaction delivers good yields (80-94%), diastereoselectivities (up to 98:2) in the favor of (cis,cis)-spirooxindoles with opposite regioselectivity compared to β-nitrostyrenes, under identical conditions. Two spiropyrrolidine cycloadducts with unprotected amide exhibited significant activity against Gram-positive MRSA.
- This article is part of the themed collection: Synthetic methodology in OBC