Investigation of Electronic Effects of Rh(II)-Mediated r-Methyl-Substituted Carbenoid Intramolecular C-H Insertion

The electronic effects of Rh(II)-mediated carbenoid intramolecular C-H insertion have been intensively investigated. The chemo-, regio-, and stereoselectivity of the reaction have been observed to be affected by the electrophilicity of the carbene-Rh intermediate, the substituents on the carbon at which the C-H insertion occurs, and steric and conformational factors.1 It has been well documented that the electronic properties of the ligands of the Rh(II) catalyst have a marked influence over the electrophilicity of carbene-Rh intermediate.1c,e,2 In addition, the R-substituent on the carbenoid carbon is expected to exert a similar effect on the reactivity of carbene-Rh complex.2c,3 According to the reaction mechanism proposed by Doyle, an electron-donating R-substituent decreases the electrophilicity of the carbeneRh complex and causes the C-H insertion to occur with a later transition state, while an electron-withdrawing R-substituent operates in the opposite way.1c However, this prediction lacks solid support by experimental data. The R-substituent effect, although important, is generally subtle and may be readily overridden by other effects, such as steric and conformational effects.3b Most of the studies on the electronic effects have so far been concentrated on electron-withdrawing R-substituents, such as ester or acetyl groups. We have recently reported a linear free energy correlation study of the carbenoid C-H insertion.4 In the study, the electronic effects are evaluated under the condition where possible steric and conformational interference is minimized through the measurement of the relative reactivity of the carbenoid insertion into a series of para-substituted benzylic C-H bonds. We envisaged that the same approach could be employed to address the problem of R-substituent effects. We report in this paper the study on the Hammett correlation of the R-methyl-substituted carbenoid C-H insertion. Diazo compounds 1a-e, in which the R-substituent is a methyl group rather than an ester group, are employed in this study (Scheme 1). By assuming that kA is constant through the series of insertion reactions, the relative reactivity of the para-substituted benzylic C-H to nonsubstituted benzylic C-H, kX/kA, is obtained by the ratio 4/3.