Transfer hydrogenation and hydrogenolysis

Transfer hydrogenation is a reaction in which hydrogen is catalytically transferred from a suitable hydrogen donor (DH2) to a reducible substrate (S) yielding the hydrogenated product (SH2) and the oxidized form of the donor molecule (D) [236-238]. 

Several of the most common hydrogen donors, such as formic acid and formates, ascorbic acid, EDTA or 2-propanol are well or at least sufficiently soluble in water. In addition, H20 itself can serve as a source of hydrogen. Frequently, hydrogenation of unsaturated substrates is achieved by using C0/H20 mixtures such reactions are discussed in 3.8. As written in eq. (3.11) the hydrogen transfer reaction is often reversible, an obvious example being the reduction of ketones using 2-propanol as donor. 

Formic acid and formates were among the most effective donors used for the reduction of olefins with [RuCl2(PPhj)j] or [RhCl(PPh3)3] catalysts in non-aqueous systems [239-241], No wonder, the water soluble analogues of these catalysts became widely used in aqueous solutions. In a series of investigations [242-245] with Ru/IPPMS and Rh/TPPMS catalysts olefins (such as 1-heptene) were hydrogenated in mixtures of HCOOH/HCOONa. Crotonaldehyde was selectively reduced to butyraldehyde by the [RhCl(TPPMS)3] catalyst [245], It was also established that (unfiltered) ultraviolet irradiation accelerated the reactions [245], 

Water-soluble Rh(I) complexes containing TPPTS catalyzed the transfer hydrogenation of itaconic, mesaconic, citraconic and tiglic acids as well as that of a-acetamidoacrylic and a-acetamidocinnamic acids from HCOOM (M = Na+, K+, NH,+) [235], The reactions were ran at 50 °C for 15-67 h, during which 48-100 % conversions were achieved. Use of the chiral tetrasulfonated cyclobutanediop, 37, led to an enantiomeric excess of up to 43 %, which is close to the value obtained in biphasic hydrogenations catalyzed by the same rhodium complex [100], 

Although there is no evidence for this process taking place in the reduction of ketones with hydrogen transfer from formate [251], in a related system the rate of hydrogenation of acetophenone, catalyzed by the same catalyst in the presence of NEt3 was substantially increased upon mixing the 

---

Transfer hydrogenation and hydrogenolysis Hydrogenation of carbon dioxide in aqueous solution Hydrogenations of biological interest... 

Pd/CaC03 is also used for the hydrogenolysis of benzyl-oxygen bonds.152 Hydrogenation and hydrogenolysis of an unsaturated benzyl ether over 5% Pt/ C and Pd(OH)2 gave the saturated and deprotected product.153 In contrast, transfer hydrogenolysis with 1,4-cylohexadiene or ammonium formate failed to provide the product cleanly, rapidly, or dependably. 

Tagawa,T.,Nishiguchi,T., and Fukuzumi, K. 1978. Transfer hydrogenation and transfer hydrogenolysis XII. Selective hydrogenation of fatty acid methyl esters by various hydrogen donors. J. Am. Oil Chem. Soc., 55, 332-336. 

Catalytic transfer hydrogenation (entries 2 and 3 below) can be used to cleave benzyl esters in some compounds that contain sulfur, a poison for hydrogenolysis catalysts. 

The synthesis of (f )-a-methylhistamine (12) starts with esterification of the amino acid L-histidine which is then hydrogenated and halogenated (Figure 1). Subsequent dehalogenation yielding (/ )-a-methylhistamine (12) can be performed either under high pressure [16] or by transfer hydrogenolysis, which is more convenient [18],... 

An excellent method for cleaving benzylic ethers, esters, carbamates, and amines uses hydrogen In the presence of a transition metal catalyst such as Pd. Alternatively a process known as catalytic transfer hydrogenation can be employed which uses 1,4-cyclohexadiene, cyclohexene, formic acid or ammonium formate as the source of hydrogen24 The method Is exceptionally mild and compatible with most functional groups devoid of unsaturation. Hydrogenolysis of benzyloxycarbonyl (Z or Cbz) groups of amines was a major advance in the... 

Transfer hydrogenation. Hydrazine is apparently superior to cyclohexene for transfer hydrogenation with palladium black as catalyst for hydrogenolysis of various protective groups of peptides. It can be used for cleavage of CBZ groups, benzyl esters, and benzyl ethers it is particularly useful for removal of nitro groups. 

It is also worthwhile to note that the relatively slow catalytic hydrogenolysis of A/ -Z-protected peptide derivatives pemnits some interesting chemical transformations to be performed in situ. For example, direct conversion of Z protection to Boc protection is possible when the hydrogenation is conducted in the presence of di-tert-butyl dicarbonate under neutral conditions.h Alternatively, the same transformation is achieved by the use of triethylsilane and di-tert-butyl dicarbonate in ethanol with catalytic amounts of palladium(II) acetate.h 1 More efficiently this one-pot transformation is achieved by catalytic transfer hydrogenation in the presence of di-terf-butyl dicarbonate (cf. Section 2.1.1.1.3.1.1.6).h l Similarly, peptide cyclization reactions have been performed in situ over Pd/C and the high yields of cyclic monomers are attributed to the high dilution effect as well as to catalysis of the charcoal surface.h l... 

Many of the difficulties experienced with heterogeneous Pd-catalyzed hydrogenolysis of benzyl groups have been overcome by deploying such alternatives to molecular hydrogen as cyclohexene and formate anion. A recent review of catalytic transfer hydrogenation describes the application to hydrogenolysis of benzyl and allyl derivatives. ... 

---