Hydride-proton sequential transfer mechanism

The efficiency of oxidation of open-chain alkyl, cycloalkyl, and unsaturated alcohols in acetonitrile by 9-phenylxanthylium ion (PhXn+) was dependent on the alcohol stmc-tures. Structure-reactivity relationship was discussed with relation to formation of a carbocationic transition state (C +-OH). Kinetic isotope effects determined at a-D, p-D3, and OD positions for the reaction of 1-phenylethanol suggested a hydride-proton sequential transfer mechanism that involved a rate-limiting formation of the a-hydroxy carbocation intermediate. Unhindered secondary alkyl alcohols were selectively oxidized in the presence of primary and hindered secondary alkyl alcohols. Strained C(7)-C(ll) cycloalkyl alcohols reacted faster than cyclohexyl alcohol, whereas the strained C(5) and C(12) alcohols reacted slower. Aromatic alcohols were oxidized efficiently and selectively in the presence of aliphatic alcohols of comparable steric requirements. ... 

Protium/deuterium/tritium kinetic isotope effects are often used to support hydride transfer mechanisms over single electron transfer mechanisms. However, sequential electron/proton/electron transfer mechanisms can easily show isotope effects as well. Even though the rate limiting step in the overall two electron reduction of flavin or NADH may be the isotope independent endergonic electron tunneling to form a radical intermediate state, once formed, this radical state can return the electron to recreate the... 

In the ionic mechanism, the proton and the hydride are sequentially transferred to a substrate, whereas in the metal-ligand bifunctional mechanism, the transfer occurs simultaneously. In both cases, the source of the H is a transition metal hydride, but the source of the proton can be a metal hydride or N—H or 0—H bonds. It seems likely that some previously reported catalysts could follow nonclassical outer-sphere mechanisms... 

Ionic hydrogenation mechanisms involve the sequential transfer of hydride and proton to the substrate [67]. This was suggested by the Leitner group for the hydrogenation of C02 with the catalyst precursor RhH(dppp)2 (Scheme 17.7) [50]. Spectroscopic evidence for each of the three intermediates was obtained by studying the steps as stoichiometric reactions. However, catalyst precursors that generate the highly active RhH (diphosphine) species in solution were subsequently found to operate by a more conventional insertion mechanism [20]. 

Concerted vs. stepwise transfers. We now address the question of whether the hydride and proton transfers are concerted, or whether the hydride transfer precedes the proton in the pyruvate to lactate reaction direction. Our TPS study showed that both mechanisms are possible. In Fig. 25 we show the distribution of the time lag between the hydride and proton transfer for all reactive trajectories. We note that both concerted and sequential transfers are possible, and that 74% of the trajectories have a time lag greater than 10 fs, indicating that the majority of reactive trajectories have sequential transfer steps. 

More recently, Morris reported the hydrogenation of benzonitrile catalyzed by a ruthenium complex containing a P-NH-NH-P tetradentate ligand (Equation 15.121). The presence of an amine N-H and metal hydride make it likely that the reaction occurs by an outer-sphere mechanism involving two sequential simultaneous transfers of the hydride and the N-H proton, first to the nitrile and second to the imine (Scheme 15.27). This proposal was supported by DPT calculations. The hydrogenation of aryl and heteroaryl nitriles catalyzed by a combination of [Ru(COD)(2-methylallyl) J and DPPF has also been reported to occur in high yields. 

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