Catalytic hydrogen atom transfer to alkenes: a roadmap for metal hydrides and radicals

Abstract

Hydrogen atom transfer from a metal hydride (MHAT) has emerged as a powerful, if puzzling, technique in chemical synthesis. In catalytic MHAT reactions, earth-abundant metal complexes generate stabilized and unstabilized carbon-centered radicals from alkenes of various substitution patterns with robust chemoselectivity. This perspective combines organic and inorganic perspectives to outline challenges and opportunities, and to propose working models to assist further developments. We attempt to demystify the putative intermediates, the basic elementary steps, and the energetic implications, especially for cage pair formation, collapse and separation. Distinctions between catalysts with strong-field (SF) and weak-field (WF) ligand environments may explain some differences in reactivity and selectivity, and provide an organizing principle for kinetics that transcends the typical thermodynamic analysis. This blueprint should aid practitioners who hope to enter and expand this exciting area of chemistry.

Scheme 1. Comparing alkene addition through polar and radical pathways: proton transfer versus hydrogen atom transfer.

Scheme 2. Intermediates to be considered during WF MHAT, highlighting one- and two-electron steps.

Scheme 3. Top: use of O or F groups (indicated as Z) provides a strong Si–Z bond that drives uphill M–H formation. Bottom: potential mechanisms of metal-hydride formation.

Scheme 4. Potential mechanisms of metal-hydride formation.

Scheme 5. Hydrides can have isomers with weakly bound H on the ligand, and deuteration experiments can test for this possibility.

Fig. 1. Contrasts between strong-field and weak-field catalyst systems for MHAT, with examples of catalysts and electronic configurations.

Fig. 2. Thermodynamic model for differences between SF (top) and WF (bottom) MHAT reactions, which explains the higher reactivity of WF systems.

Fig. 3. Trends in rates of SF MHAT reactions.

Fig. 4. Relative rates of reactivity of WF MHAT systems with alkenes.

Scheme 6. Weak-field-ligand M–H complexes display chemoselectivity for alkenes.

Scheme 7. Mechanistic basis for cage effects in MHAT reactions.

Fig. 5. Observation of CIDNP and inverse KIE in SF MHAT systems.

Scheme 8. Effects of viscosity and micellar conditions in SF MHAT.

Scheme 9. The heavy atom effect in metalloradical pairs.

Fig. 6. Microviscosity better explains cage effects than an approximation of solvent as uniform.

Fig. 7. (A) General structure of (salen)Co alkyls. (B) Proposed structure of an iron(iii) alkyl complex with an amine-bis(phenolate) supporting ligand.

Scheme 10. Diverging pathways observed in MHAT, demonstrating the importance of the solvent cage.

Scheme 11. Radical isomerization of electron-neutral alkenes by MHAT: mechanistic information from radical clock competition experiments.

Scheme 12. Reactivity and examples of π-radical traps. Possible roles of metal in these steps.

Scheme 13. Catalyst turnover in WF systems regenerating M³⁺.

Scheme 14. OLT and RPC pathways.

Scheme 15. Mechanistic possibilities including a bimetallic pathway.

Scheme 16. Pathways from the solvent cage determine how MHAT cycles intersect cross-coupling cycles.

Scheme 17. Molecular rotation occurs on the same timescale as cage collapse.

Scheme 18. Potential mechanisms for asymmetric MHAT reactions using (salen)Co catalysts.

Scheme 19. New asymmetric MHAT reactions.

(Top row) Ryan Shenvi, Patrick Holland, and Dongyoung Kim; (bottom row) Conner Wilson, Sophia Shevick, and Simona Kotesova