Generation of Diazomethyl Radicals by Hydrogen Atom Abstraction and Their Cycloaddition with Alkenes

• Published in: Angewandte Chemie International Edition 2021-08, Vol.60 (34), p.18484-18488
• Main Authors: Su, Yong‐Liang, Dong, Kuiyong, Zheng, Haifeng, Doyle, Michael P.
• Format: Article
• Language: English
• Subjects: Alkenes; Carbon; Chemical synthesis; Cycloaddition; diazo compounds; diazomethyl radical; pyrazolines; radical addition; Radicals; Regioselectivity; umpolung
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202105472

A general catalytic methodology for the synthesis of pyrazolines from α‐diazo compounds and conjugated alkenes is reported. The direct hydrogen atom transfer (HAT) process of α‐diazo compounds promoted by the tert‐butylperoxy radical generates electrophilic diazomethyl radicals, thereby reversing the reactivity of the carbon atom attached with the diazo group. The regiocontrolled addition of diazomethyl radicals to carbon‐carbon double bonds followed by intramolecular ring closure on the terminal diazo nitrogen and tautomerization affords a diverse set of pyrazolines in good yields with excellent regioselectivity. This strategy overcomes the limitations of electron‐deficient alkenes in traditional dipolar [3+2]‐cycloaddition of α‐diazo compounds with alkenes. Furthermore, the straightforward formation of the diazomethyl radicals provides umpolung reactivity, thus opening new opportunities for the versatile transformations of diazo compounds. A new approach for the generation of diazomethyl radicals and their addition to alkenes is described. The direct hydrogen atom transfer (HAT) from α‐diazo compounds generates electrophilic diazomethyl radicals, thereby reversing the reactivity of the diazo carbon. This umpolung strategy overcomes the limitations of electron‐deficient alkenes in traditional dipolar [3+2]‐cycloaddition of α‐diazo compounds with alkenes.