Stepwise or concerted? One-bond-nucleophilicity and -electrophilicity parameters for the mechanistic analysis of 1,3-dipolar cycloadditions
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Herbert Mayr
,
Le Li
Abstract
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 k 2(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.
Funding source: Deutsche Forschungsgemeinschaft
Award Identifier / Grant number: SFB749, project B1
Acknowledgments
We gratefully acknowledge the generous support of the Deutsche Forschungsgemeinschaft (SFB 749, project B1) and the Department of Chemistry, LMU München. Special thanks to Professor H.-U. Reissig, FU Berlin for valuable discussions and to Dr. David S. Stephenson for assistance with the NMR measurements.
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Research ethics: Not applicable.
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Informed consent: Not applicable.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Use of Large Language Models, AI and Machine Learning Tools: None declared.
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Conflict of interest: The authors state no conflict of interest.
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Research funding: Deutsche Forschungsgemeinschaft (SFB 749, project B1).
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Data availability: Not applicable.
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