Stepwise or concerted? One-bond-nucleophilicity and -electrophilicity parameters for the mechanistic analysis of 1,3-dipolar cycloadditions

Diazoalkanes are ambiphilic molecules that may react with electrophiles at carbon to give diazonium ions, with nucleophiles at nitrogen to yield azo compounds, or with dipolarophiles to produce pyrazolines. By studying the kinetics of the reactions of methyl diazoacetate and dimethyl diazomalonate with benzhydrylium ions (Ar₂CH⁺) of known electrophilicity E, we determined their one-bond nucleophilicity parameters N and s_N using the equation lg k₂(20 °C) = s_N(N + E) (eq. (1)). Similarly, the electrophilicity parameters E of these diazoesters were obtained by measuring the rate constants of their reactions with one-bond nucleophiles of known N and s_N. These reactivity parameters enable the calculation of rate constants for 1,3-dipolar cycloadditions with dipolarophiles, which proceed stepwise with rate-determining formation of zwitterionic intermediates. Concerted cycloadditions proceed faster than calculated by eq. (1), and the difference between the observed rate constants (ΔG^‡_exptl) and those calculated by eq. (1) (ΔG^‡_{eq. 1}) gives the energy of concert (ΔG^‡_concert = ΔG^‡_{eq. 1} − ΔG^‡_exptl). Contrary to earlier reports, cycloadditions of methyl diazoacetate and dimethyl diazomalonate with enamines proceed stepwise through initial azo couplings. This involves enamine attack at the π*_(N=N) orbital of the diazoalkane, oriented perpendicularly to the commonly considered 3-center 4-electron π-system. Since this orbital was previously ignored, the common FMO analysis of the reactions of 1,3-dipoles of the propargyl anion type requires revision. A new ordering system for 1,3-dipolar cycloadditions is proposed.