Hydride Transfer Mechanisms in Organic Reactions

Hydride transfer lies at the heart of numerous organic transformations, encompassing reductions of carbonyls, imines and unsaturated systems. In essence, a hydride (H–) migrates from a donor molecule to an acceptor, a process governed by both thermodynamic driving forces and kinetic barriers. Organic hydride donors range from model NADH analogues and Hantzsch esters to custom‐designed dihydropyridines and benzoheterocycles. The balance between bond strengths, solvent effects and electronic substituent patterns dictates whether hydride transfer proceeds in a concerted single‐step fashion or via discrete radical or ionic intermediates. Advances in computational chemistry and electrochemical methods now enable precise quantification of hydride affinities, proton and hydrogen atom affinities, and activation parameters. Understanding these parameters has allowed chemists to tailor hydride donors for selective reductions, fine‐tune reaction conditions to favour specific pathways and exploit photoexcited states to unlock thermodynamically challenging transfers. The implications extend from asymmetric synthesis and green chemistry to enzymatic models, offering routes to efficient and sustainable catalytic processes.

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Hydride Transfer Mechanisms in Organic Reactions publication trend

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Technical terms

Hydride transfer: The movement of a hydride ion (H–) from one molecule (donor) to another (acceptor) in a single elementary step or via intermediates.

Hydride affinity: The free‐energy change associated with addition of a hydride ion to a given species, reflecting thermodynamic favourability.

Thermodynamic driving force: The Gibbs free‐energy difference between reactants and products that determines overall spontaneity.

Kinetic barrier (activation barrier): The energy required to reach the transition state from the ground state, controlling reaction rate.

Intrinsic barrier: The inherent activation energy for bond reorganisation in the absence of thermodynamic bias.

References

1. Thermodynamics Evaluation of Selective Hydride Reduction for α,β-Unsaturated Carbonyl Compounds. Molecules (2023).
2. Essential Rule Derived from Thermodynamics and Kinetics Studies of Benzopyran Compounds. Molecules (2023).
3. Comparison between 1,2-Dihydropyridine and 1,4-Dihydropyridine on Hydride-Donating Ability and Activity. Molecules (2022).