Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones?

Organic & Biomolecular Chemistry Pub Date: 2008-07-03 DOI: 10.1039/B804856H

Abstract

The [3 + 2] cycloaddition reaction between carbonyl ylides generated from epoxides and ketones (ethyl pyruvate, ethyl phenylglyoxylate, isatin, N-methylisatin and 5-chloroisatin) to give substituted dioxolanes and spirocyclic dioxolane indolinones was investigated. The effect of microwave irradiation on the outcome of the reaction was studied. The thermal reaction between 2,2-dicyano-3-phenyloxirane and N-methylisatin was theoretically studied using DFT methods. This reaction is a domino process that comprises two steps. The first is the thermal ring opening of the epoxide to yield a carbonyl ylide intermediate, whereas the second step is a polar [3 + 2] cycloaddition to yield the final spiro cycloadducts. The cycloaddition presents a low stereoselectivity and a large regio- and chemoselectivity. Analysis of the electrophilicity values and the Fukui functions of the reagents involved in the cycloaddition step allowed the chemical outcome to be explained.

Graphical abstract: Polar [3 + 2] cycloaddition of ketones with electrophilically activated carbonyl ylides. Synthesis of spirocyclic dioxolane indolinones
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