Efficient cyclopropanation and intermolecular C-H bond activation via carbene insertion catalysed by thiosemicarbazone Copper complexes

Cyclopropane derivatives are an important family of chemical compounds that plays a prominent role in organic chemistry.1 As a result, great efforts have been made to develop efficient stereoselective methods for the synthesis of cyclopropanes.2 A particularly versatile method is the metal-catalysed cyclopropanation of olefins with diazo compounds, for which several efficient homogeneous catalysts have been developed.3 Among transition metal catalysts for this reaction, copper complexes have attracted increasing interest in the last years, especially due to their high efficiency and to their lower cost when compared to other metal derivatives. A variety of copper(II) and copper(I) sources are known to catalyse the cyclopropanation reaction although copper(I) rather than copper(II) was established as the active catalyst, where diazo compounds were found to reduce Cu(II) salts to Cu(I).4 Nevertheless Cu(I) complexes are challenging to synthesize and isolate due to the intrinsic instability of cuprous compounds: under many conditions disproportionation of Cu(I) to Cu(0) and Cu(II) is thermodynamically favoured. We have recently reported that Schiff bases derived from the condensation of hydrazinecarbothioamide or phenyl thiosemicarbazone with 3-acetyl-2H-chromen-2-one are suitable ligands for the synthesis of copper(II) complexes very active as cyclopropanation catalysts.5 We herein report that Schiff bases derived from the condensation reaction of hydrazinecarbothioamide with substituted salicylaldehydes are suitable ligands for copper and that the derived complexes are competent catalysts for the cyclopropanation of olefins and for the intermolecular C-H bond activation by using ethyldiazoacetate (EDA) as carbene source. Rarely metal complexes can give high selectivities in cyclopropanation reactions together with high turnover number (TON). In this work, different ligands have been synthesized and characterized, by changing the steric and electronic properties of the starting aldehyde employed in the condensation reaction. Their copper complexes have been prepared by employing Cu(II) acetate hydrate, but analytical and spectroscopical data for the isolated complexes revealed that in most cases a reduction to copper (I) occurred. Cyclopropanation reactions of several olefins by ethyldiazoacetate (EDA) in the presence of catalytic amounts of the complexes were examined. The reported results showed that all complexes are competent catalysts for the cyclopropanation reaction of unactivated olefins. Cyclopropanes were obtained in high yields (up to 97 %, TON up to 18,400) with moderate to excellent diastereoselectivities (up to >99%). Moreover, we have tested the catalytic capabilities of this copper-based system toward the activation of cycloalkanes and cyclic ethers and have found moderate-to-good degrees of conversion under very mild conditions.