The construction of lactones is one of the fundamental research topics in organic synthesis, as the molecules that contain such fragments are ubiquitously found in naturally occurring molecules and pharmaceuticals and exhibit diverse biological and pharmacological activities. Bifunctionalization reaction of carbon−carbon unsaturated bond has emerged as an important strategy for the construction of complex molecules in straightforward manner. Although continuous efforts have been devoted to the development of versatile bifunctionalization reaction of olefins, metal-free protocols for this kind of reaction are still limited. Among them, a method for constructing a lactone skeleton using bifunctionalization of olefins is devoted for pharmaceutical synthesis. We have studied aerobic photo-oxidative reactions mediated by a halogen source. During the course of this study, we have observed a metal-free catalytic photoaerobic dehydrogenative C−C bond forming reaction from two C−H bonds of indole with malonate. The active species of the reaction was a C-centered radical via C−I homolytic cleavage mediated by visible light irradiation. Based on the study, we envisioned that the generated radical from malonate as a carboesterification agent for the alkene bifunctionalization would provide an ideal route to diverse lactone rings from simple precursors. We initially investigated intramolecular lactonization reaction of malonate derivative under thermal condition using iodine. The reaction gave the corresponding lactone in high yield. And the reaction also proceeded at room temperature under visible light irradiation condition. This iodine and visible light mediated reaction could be applied to intermolecular reaction of malonate with olefins leading to lactones in moderate yield.These mechanisms proposed on the basis of control experiments and detailed results will also be discussed.

Development of metal-free bifunctionalization reaction of olefins leading to higher functionalized lactones

254th National Meeting (2017)

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