...Transfer hydrogenation is here discussed as it relates to scaling up a hydrogenation step. Chemists who are more accustomed to working in the laboratory are overwhelmingly more familiar with reactions with hydrogen in the presence of a catalyst and much less with the transfer of hydrogen atoms from a donor reagent to a substrate under catalysis. Yet this latter, transfer hydrogenation, is cheaper and safer both because no free hydrogen is used and because it does not require a special reactor, special stirring, or special gas handling auxiliaries. Indeed, the benefits of transfer hydrogenation seem to be well understood by seasoned process chemists from the evidence of descriptions in process chemistry monographs but still far too unfamiliar to new graduates, university scientists, and discovery chemists.
Since transfer hydrogenation most often use relatively expensive supported palladium catalyst, an important consideration is whether the hydrogenation using molecular hydrogen or the transfer hydrogenation using a donor results in the higher catalyst expense. I can find no generalized finding comparing the methods on economic issue. A related question is whether there is any increased or decreased tendency for traces of noble metal catalyst to be trapped in the isolated products using or the other of the two methodologies. Again this would be important because a disadvantage of catalytic hydrogenation in all its forms is the risk of residues of toxic heavy metals that can tenaciously adhere to the isolated product. From what I have seen of the literature this difficulty is neither reduced or enhanced using transfer hydrogenation....
[snip] Although other useful reviews have been devoted to transfer hydrogenation these have not been from the perspective of scale-up advantages. I have seen little that answers the general question of what makes a hydrogenation convertible to transfer hydrogenation and how one might predict situations where it is unlikely to work? A tentative rule might be that if the hydrogenation cannot be done using either palladium or a soluble catalyst it is has a reduced likelihood to work with transfer hydrogenation.I don't know why more people don't use transfer hydrogenation. I suspect that there are solubility issues involved (w/r/t cyclohexene concentrations). Also, is there a difference in speed between transfer hydrogenation and regular hydrogenation? There's gotta be, right?
Readers, what do you think?