The cyclopropane ring is a very special motif found in many natural products, medicines and crop-protection agents. Synthetic methods for the preparation of cyclopropanes commonly require the use of sensitive iodomethyl zinc species or toxic and explosive diazo compounds. Recently, our group discovered a novel reactivity concept for the cyclopropanation of alkenes based on the photocatalytic generation of radical carbenoids. These species are carbon-centred radicals substituted with an excellent leaving group and its reactivity is complementary of that of singlet and triplet carbene species. Single-electron reduction of commercial diiodomethane in the presence of a photocatalyst and a tertiary amine conducts to a transient iodomethyl radical carbenoid able to cyclopropanate β-substituted styrenes and Michael acceptors. Notable features of this method are the mild reaction conditions, broad functional group tolerance and the excellent stereocontrol. Only trans-cyclopropanes are generated in a stereoconvergent manner, regardless of whether E- or Z-alkenes are utilized. With the aim of expanding this radical cyclopropanation, we wondered whether radical carbenoids substituted with electron-withdrawing groups could provide access to more complex cyclopropane cores. Herein, we present our efforts towards the development of a general cyclopropanation reaction using gem-diiodo compounds substituted with electron-withdrawing groups. During the course of the optimization studies, we were surprised to find that the reaction could efficiently worked in the absence of photocatalyst. The combination of a tertiary amine and the gem-diiodo compound under visible-light irradiation, generates novel electrophilic radical carbenoids able to cyclopropanate a broad range of simple and complex styrenes and stilbenes with high functional group tolerance. This process might be explained by the initial formation of a photoactive EDA complex via a halogen-bond between the amine lone pair and the s-hole of the carbon-iodine bond. Subsequent photoexcitation of this intermediate would deliver our electrophilic radical carbenoid through a single-electron transfer process.

Visible-light-driven alkene cyclopropanations with electrophilic radical carbenoids

256th National Meeting (2018)

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