Metal-Hydride Hydrogen Atom Transfer (MHAT) is a process where a metal hydride (M–H) transfers a hydrogen atom (H•) to an alkene, forming a carbon-centered radical. This radical can then undergo diverse transformations.
Pioneering work by Iguchi, Halpern, and Jackman demonstrated that metal hydrides can undergo outer-sphere hydrogenation with activated olefins through a mechanism which is distinct from metal insertion, hydride addition, and protonation. MHAT has attracted increasing attention in recent years as a useful reaction that can hydrofunctionalize olefins chemoselectively following Markovnikov's rule.
Mechanism Metal hydrides involved in MHAT reactions are typically generated in situ from low-valent transition metal precursors upon treatment with silanes or borohydrides as stoichiometric reductants. The thermodynamic driving force for this process arises from the formation of strong Si–O or B–O bonds, particularly under protic conditions that promote solvolysis to reactive monoalkoxysilanes. Alcoholic solvents are thus often essential for efficient activation and turnover. In this context, Ph(i‑PrO)SiH2 has been identified as a particularly effective silane, offering operational stability and reliable hydride delivery.
The resulting metal–hydride species—typically based on first-row transition metals such as Fe, Co, Mn, or Ni—exhibit redox flexibility, moderate bond strengths, and accessible spin states. These enable hydrogen atom transfer to π-systems, generating carbon-centered radicals and transiently oxidized metal species. The radical pair initially remains in a solvent cage, where it may revert, recombine, or escape to engage in productive downstream reactivity. The use of weak-field ligands promotes high-spin configurations that enhance the radical character of the M–H bond and facilitate efficient HAT. These mechanistic features collectively distinguish MHAT from conventional hydride or proton transfer pathways, supporting its use in mild and chemoselective olefin functionalization.
C–O bond formation MHAT-mediated C–O bond formation typically proceeds via hydrogen atom transfer from a transition metal hydride to an alkene, generating a carbon-centered radical that is subsequently trapped by oxygen-based electrophiles. These radical-based processes encompass hydration, hydroalkoxylation, and hydroperoxidation, and are exemplified by the Mukaiyama hydration, in which a metal hydride and molecular oxygen effect Markovnikov-selective water addition across unactivated alkenes. Such transformations offer high chemoselectivity under mild conditions and have been increasingly applied in complex molecule synthesis. Mukaiyama hydration
Mukaiyama hydration is a formal addition of an equivalent of water across an olefin catalyzed by metal-hydride complex and atmospheric oxygen, to produce an alcohol with Markovnikov selectivity. This reaction is known as a pioneering and representative example of the Metal Hydride Atom Transfer (MHAT) mechanism via a transition metal hydride. In the recent report by Fan and co-workers in 2017, the regioselectivity of Mukaiyama hydration was found to depend on the metal catalyst. While Co(acac)2 promoted conventional Markovnikov hydration at the C12-position of anhydrolycodoline, Mn(acac)3 induced hydroxylation at a more remote γ-position, yielding 12-epi-flabelliformine. Mukaiyama hydroperoxidation
Using typical Mukaiyama conditions, peroxidation can be performed on specific substrates. Maimone and co-workers reported the oxygen-stitching strategy using hydroperoxidation to efficiently construct nortrilobolide using Co(acac)2. In this strategy, Mukaiyama-hydroperoxidation of olefins followed by reductive workup to produce triols. Iron and manganese based catalysts were almost unreactive.
C–N bond formation MHAT-mediated C–N bond formation involves hydrogen atom transfer from a transition metal hydride to an alkene, generating a carbon-centered radical that subsequently reacts with nitrogen-based electrophiles. These reactions include hydroamination, hydrazination, and azidation.
Hydrohydrazination
Carreira and co-workers expanded Mukaiyama hydrofunctionalization framework to C-N bond formation. In the report, they demonstrated that cobalt(III) complexes could catalyze the Markovnikov-selective hydrohydrazination of unactivated olefins with azodicarboxylates. These reactions proceed with high chemoselectivity, which is difficult to achieve under traditional protic conditions. This reaction could proceed via cobalt hydride-mediated hydrogen atom transfer, thus contributing to the conceptual foundation of MHAT (metal hydride atom transfer) reactivity.
Hydroazidation
Boger and co-workers developed an Fe(III)/NaBH4-mediated hydroazidation of unactivated alkenes using NaN3 as the azide source. The reaction proceeds via a radical pathway, exhibits exclusive Markovnikov selectivity, and tolerates a broad range of functional groups. This method enables direct alkene azidation, facilitating access to previously inaccessible C20′-vinblastine analogues.
C–X bond formation MHAT-mediated C–X bond formation proceeds via radical interception of alkenes with electrophilic halogen or chalcogen sources. In addition to C–F bond formation, MHAT enables hydrohalogenation and hydrochalcogenation under mild, chemoselective conditions, as demonstrated with Cl, Br, I, and S-based reagents.
Hydrofluorination
Boger and co-workers further expanded Fe(III)/NaBH4 system to free radical hydrofluorination of unactivated alkenes using Selectfluor reagent as a source of fluorine and resulting in exclusive Markovnikov addition. Baran and co-workers applied this to introduce a fluorine atom to an unactivated alkene in a steroid derivative.
C–C bond formation MHAT-mediated C–C bond formation involves the generation of carbon-centered radicals from alkenes via metal hydride hydrogen atom transfer, followed by bond formation through conjugate addition, hydroarylation, hydrocyanation, or hydroalkylation. These radical-based processes often proceed under mild, redox-neutral conditions and enable regioselective C–C coupling complementary to polar or pericyclic pathways.
Conjugate addition
In 2014, Baran and co-workers discovered a functionalized olefin cross-coupling reaction, that is initiated by MHAT followed by the conjugate addition to the electron-deficient olefin. Pronin and co-workers applied this method to radical cyclization process in the synthesis of (±)-Emindole SB.
Hydroarylation
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