Transfer hydrogenation and borrowing hydrogen

Hydrogen donors

• Propan-2-ol (usually with base): cheap and benign, but the reaction is reversible because acetone is also a hydrogen acceptor. Conversion is limited by equilibrium, so a large excess of donor is used, and product ee can erode by reverse reaction.
• Formic acid/triethylamine (often the 5:2 azeotrope) or formate salts: irreversible, since CO_2 escapes, so high conversions are possible.

Mechanistic families

Direct hydrogen transfer (Meerwein–Ponndorf–Verley). Al(OiPr)_3 binds both the ketone and the isopropoxide; hydride shifts from the isopropoxide carbon to the carbonyl carbon through a six-membered cyclic transition state. No metal hydride is formed.

Inner-sphere hydride routes. Ru, Rh or Ir alkoxides undergo β-hydride elimination to release acetone and form M–H (monohydride or dihydride pathways). The substrate then coordinates to the metal and inserts into M–H; protonolysis by the donor alcohol releases the product.

Outer-sphere metal–ligand bifunctional catalysis. In Noyori-type [\mathrm{RuCl(\eta^6\text{-}arene)(TsDPEN)}] catalysts, base generates a 16-electron Ru amido complex that dehydrogenates the donor to give an 18-electron Ru–H/N–H species. The ketone never binds the metal: it is reduced by a concerted six-membered pericyclic transition state in which Ru delivers the hydridic H to carbon and N–H delivers the protic H to oxygen. A CH–π interaction between the arene ligand and an aromatic substrate helps control enantioselectivity, and aryl alkyl ketones and imines are reduced with high ee.

Remote cooperation. In Shvo's catalyst, a dimeric Ru complex of a hydroxycyclopentadienyl ligand splits thermally into a Ru–H/O–H donor and a cyclopentadienone acceptor; the ligand OH, not an N–H on the metal, supplies the proton. It racemises secondary alcohols efficiently, and combined with a lipase enables dynamic kinetic resolution: the enzyme acylates one alcohol enantiomer while the Ru catalyst interconverts the two.

Borrowing hydrogen

1. Catalyst dehydrogenates an alcohol to an aldehyde or ketone (catalyst stores the H_2). 2. The carbonyl condenses with a nucleophile, e.g. an amine to an imine, or an enolate in an aldol. 3. The catalyst returns the hydrogen, reducing the imine or enone.

Net: \mathrm{RCH_2OH + R'NH_2 \to RCH_2NHR' + H_2O}, a direct alcohol amination with no halide or reducing agent. The Guerbet upgrading of ethanol to butan-1-ol follows the same logic via an aldol condensation of acetaldehyde.

Transfer hydrogenation and borrowing hydrogen sit at the crossroads of mechanism, sustainability and synthesis.

Is it really bifunctional? The concerted outer-sphere model for Noyori catalysts has been re-examined. Computational and kinetic studies suggest that in alcohol solvents the N–H proton may not be transferred in the turnover-limiting step; instead the N–H stabilises the developing alkoxide by hydrogen bonding, with alkali-metal cations and solvent molecules involved. Similar debates apply to pincer complexes that cooperate through aromatisation–dearomatisation of the ligand backbone. Isotope labelling, kinetic isotope effects for the C–H and N–H positions, and explicit-solvent calculations are used to settle such questions.

Base metals. Mn(I), Fe(II) and Co pincer complexes now perform transfer hydrogenation, borrowing-hydrogen alkylation of amines and ketones, and acceptorless dehydrogenative coupling (releasing H_2 gas) to form amides, esters and heterocycles. Their mechanisms frequently rely on ligand participation rather than metal redox changes.

Selectivity and cascades. Borrowing hydrogen with secondary alcohols and chiral catalysts can create stereocentres; combined with enzymes it gives chemo-enzymatic cascades, but compatibility (temperature, solvent, mutual inhibition) is a practical limit. Shvo-type racemisation catalysts that need high temperature to split the dimer clash with heat-sensitive enzymes, motivating room-temperature racemisation catalysts.

Fuels and feedstocks. Ethanol upgrading to butan-1-ol by Guerbet chemistry is limited by selectivity: acetaldehyde self-condensation competes with over-condensation, and the choice of base strongly affects outcome. Ru and Mn pincer catalysts reach high turnover numbers, but catalyst lifetime under basic, hot conditions remains a problem.

Hydrogen storage. Formic acid and methanol dehydrogenation, and the reverse hydrogenation of CO_2, are studied as liquid organic hydrogen carriers using the same cooperative catalysts.