Transfer hydrogenation with

Water-soluble complexes constitute an important class of rhodium catalysts as they permit hydrogenation using either molecular hydrogen or transfer hydrogenation with formic acid or propan-2-ol. The advantages of these catalysts are that they combine high reactivity and selectivity with an ability to perform the reactions in a biphasic system. This allows the product to be kept separate from the catalyst and allows for an ease of work-up and cost-effective catalyst recycling. The water-soluble Rh-TPPTS catalysts can easily be prepared in situ from the reaction of [RhCl(COD)]2 with the sulfonated phosphine (Fig. 15.4) in water [17]. 

In transfer hydrogenation with 2-propanol, the chloride ion in a Wilkinson-type catalyst (18) is rapidly replaced by an alkoxide (Scheme 20.9). / -Elimination then yields the reactive 16-electron metal monohydride species (20). The ketone substrate (10) substitutes one of the ligands and coordinates to the catalytic center to give complex 21 upon which an insertion into the metal hydride bond takes place. The formed metal alkoxide (22) can undergo a ligand exchange with the hydride donor present in the reaction mixture, liberating the product (15). 

Scheme 20.19 Transfer hydrogenation with the Henbest system.

One very fast and reliable method for the reduction of double bonds is that of transfer hydrogenation with diimine (Scheme 20.30). Under the influence of traces of copper ion and oxygen from air, hydrazine is rapidly transformed into diimine. This compound is able to hydrogenate double bonds with great success under the formation of nitrogen [120],... 

Cyclic imines 8 and 9 are intermediates or models of biologically active compounds and can be reduced with ee-values of 88 to 96% using Ti-ebthi, Ir-bcpm or Ir-binap in the presence of additives (entries 5.7, 5.9), as well as with the transfer hydrogenation catalyst Ru-dpenTs (entries 5.8, 5.10-5.12). As pointed out earlier, Ru-diphosphine-diamine complexes are also effective for imines, and the best results for 7 and 8a were 88% and 79% ee, respectively [36]. Azirines 10 are unusual substrates which could be transfer-hydrogenated with a catalyst prepared in situ from [RuCl2(p-cymene)]2 and amino alcohol L12, with ee-values of 44 to 78% and respectable TOFs of up to 3000 (entry 5.13). 

In broad terms there are three types of catalyst for transfer hydrogenation dehydrogenases heterogeneous and homogenous metal catalysts. Here, the first two are mentioned for completeness, and the main focus of this chapter will be asymmetric transfer hydrogenation with homogenous metal catalysts. 

Scheme 12 Further examples of asymmetric transfer hydrogenation with [Ir(cod)Cl]2...

List was the first to explore this possibility, examining the Hantzsch ester mediated reduction of a,P-unsaturated aldehydes [209], Using 20 mol% of the binaphthyl derived phosphonate salt of morpholine (153) in dioxane at 50 °C, a series of P-aryl a,P-unsaturated aldehydes underwent transfer hydrogenation with Hantzsch ester 154 with excellent levels of absolute stereocontrol (96-98% ee) (Scheme 63). The method was also applied to the aliphatic substrates ( )-citral and famesal to give the mono-reduced products in 90% and 92% ee, respectively. Significantly, in line with many of the chiral secondary amine catalysed transformations described above the reactions follow a simple and practical procedure without the need for exclusion of moisture and air. 

Detailed mechanistic investigations of transfer hydrogenations with Hantzsch ester by means of DFT computational studies were carried out by the groups of Goodman and Himo [42, 43]. 

SELECTIVE REDUCTION OF CARBONYL GROUP IN p,y-UNSATURATED a-KETOESTERS BY TRANSFER HYDROGENATION WITH Ru(P-CYMENE)(TsDPEN)... 

Cleavage of benzyl ethers Benzyl ethers are cleaved in high yield by catalytic transfer hydrogenation with 20% palladium on carbon (1, 782)4 as catalyst and cyclohexcne as hydrogen donor. 

Transfer hydrogenation of dienes to monoenes 1,5-Cyclooctadiene is selectively reduced to cyclooctene by transfer hydrogenation with isopropanol catalyzed by this metal carbonyl cluster. The first step is isomerization to conjugated diene isomers. 1,5-Hexadiene is reduced under these conditions to frms-3-hexene (19%), os-2-hexene (21%), trans-2-, and cw-3-hexene (56%). Ru3(CO)i2, Os3(CO)12, and Ir4(CO)i2 catalyze isomerization of 1,5-cyclooctadiene, but are less active than Rh6(CO)i6 for transfer hydrogenation. 

The rapid microwave-assisted deprotection of N-benzyl carbamate (Cbz) and AT-benzyl (Bn) derivatives in solution as well as on solid support was reported by Daga et al.26 Within this report, amino groups protected as benzyl carbamates or with simple benzyl groups could be deprotected in a few minutes by microwave-assisted catalytic transfer hydrogenation with palladium charcoal in isopropanol, employing ammonium formate as the hydrogen donor (Scheme 7.6). Both MeO-PEG and PS Wang-resin were used as soluble and solid supports, respectively, in these reactions. 

Scheme 4.6 Hydridic route established for transfer hydrogenation with Rh-, Ru- and Ir-catalysts.

In 2005, both Rueping et al. and List et al. reported the first transfer hydrogenation with Hantzsch ester 1 of several N-protected ketimines catalyzed by chiral Bronsted acids derived from l,l -binaphthol [17, 18]. The reaction typically requires 1 to 20 mol% of catalyst, is performed in benzene at 60 °C, and enantio-selectivities of up to 90% are obtained. The chiral Bronsted acid protonates the lcetimine at nitrogen, giving an ion-pair which is reduced by Hantzsch ester 1. (For experimental details see Chapter 14.21.2). A preferred transition state has... 

Catalytic transfer hydrogenation with alcohols for the CLA formation 384... 

CATALYTIC TRANSFER HYDROGENATION WITH ALCOHOLS FOR THE CLA FORMATION... 

The number of publications describing new ligands that allow the transfer hydrogenation of aromatic ketones with over 90 % ee has grown in leaps and bounds since 1996 [15]. In these reactions the use of ruthenium [15a-f] and iridium [15g] as the catalytically active metals has recently been augmented by the use of phosphorus-free ligands such as chiral diamines, amino alcohols, and bisthioureas such as 7 [15a,e-g]. A ruthenium-catalyzed transfer hydrogenation with 92 % ee has even been reported for the aliphatic ketone pinacolone (tert-butyl methyl ketone) [16]. 

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. 

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