By Transfer Hydrogenation

Scheme 3.8 Generation of the active dihydride catalyst by transfer hydrogenation by reductive elimination of the product to give a ruthenium(O) intermediate ([Ru] = Ru(PPh3)3).

The reduction of imines and iminium salts present a particular difficulty in that those which are N-substituted can exist in different geometrical isomers that are reduced at different rates and with different selectivities. One way to overcome this problem is to use cyclic imines that can exist only as cis isomers. Although these are good substrates, this is not a general solution. The cyclic amines produced by transfer hydrogenation, together with best reported enantiomeric excesses, are listed in Table 35.6. Primary amines are difficult to pre-... 

The catalyst is also effective for the reduction of styrenes, ketones, and aldehydes. Cyclohexenone 16 was reduced to cyclohexanone 11 by transfer hydrogenation, and using a higher catalyst loading, styrene 17 was reduced to ethylbenzene 18. The elaboration of [Ir(cod)Cl]2 into the triazole-derived iridium carbene complex 19 provided a catalyst, which was used to reduce aUcene 20 by transfer hydrogenation [25]. 

Remarkably, complex 25 was also able to reduce CO2 by transfer hydrogenation in 2-propanol [28]. While there have been many reports using H2 to reduce CO2, the work of Peris and coworkers is the only example of a hydrogen transfer reaction to reduce CO2 with 2-propanol [29]. The reduction is run in the presence of KOH,... 

Scheme 7 Reduction of carbon dioxide by transfer hydrogenation...

Figure 1.18 The three high-field signals, C1-C3, in the C h, H NMR spectrum of the product obtained by transfer hydrogenation of PhCH=C(COOH) —CH2COOH with HCOOH/NEt3, a1 about 25% conversion. The chemical shifts for the undeuterated isotopomer 90a are d Cl 44.3, i5 C2 38.6 and d C3 35.9, respectively.

RuClj(C H )]j was used for deracemisation of alcohols, by oxidation of secondary alcohols to the ketone with [RuCl3(C H )]3/(R)-BINAP/(R,R )-DPEN/cyclo-hexanone/THF/K( BuO)/60°C. The oxidation may occur by transfer hydrogenation, followed by reduction with back to the alcohol [962],... 

Figure 1.35 Cyclic amine synthesis by transfer hydrogenation.

Blacker, A.J. and MeUor, B. J. Preparation of Chiral Arylalkanols by Transfer Hydrogenation using Chiral Metal Cyclopentadiene Complex Catalysts. PCT Int. Appl. 1998, WO 9842643 Al. 

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

Letondor, C., Humbert, N. and Ward, TR. (2005) Artificial metaUoenzymes based on biotin-avidin technology for the enantioselective reduction of ketones by transfer hydrogenation. Proc. Natl. Acad. Sci. U.S.A., 102, 4683-4687 Letondor, C., Pordea, A., Humbert, N., Ivanova, A., Mazurek, S., Novic, M. and Ward, TR. (2006) Artificial transfer hydrogenases based on the biotin-(strept)avidin technology Fine tuning the selectivity by saturation mutagenesis of the host protein. J. Am. Chem. Soc., 128, 8320-8328. 

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. 

Carbonyl groups can be transformed into amines via formation of their hydrazones followed by transfer hydrogenation. Thus the benzoyl formate shown in Scheme 4.35 was converted into the phenylhydrazone under microwave irradiation in ethylene glycol as solvent. Subsequent reduction using ammonium formate and 10% Pd/C as a catalyst provides the amine in an overall reaction time of 10 min and a total yield of 83%.14... 

The second step was also similar to the thermal method. The scientist chose to reduce the nitro group by transfer hydrogenation. While this reaction resulted in poor yields and mostly uncyclized materials in the thermal approach, in the microwave example the yields were typically high with the desired cyclized intermediate predominating in the reaction mixture (see Table 8.8). 

Chemical reduction [with aqueous titanium(III) chloride in dilute acetic acid] or catalytic reduction (in the presence of 10% palladium-on-charcoal by transfer hydrogenation from cyclohexene or with hydrogen) of 3-nitro-4//-pyrido[l,2-a]pyrimidin-4-ones 176 (R = H, 8-Me, 8-OMe, 7-C1) gave 3-amino-4//-pyrido[l,2-a]pyrimidin-4-ones [90JCR(S)308]. Chemical and catalytic reduction of 3,8-dinitro-9-hydroxy-4//-pyrido[l,2-a]pyrimidin-4-one yielded an unstable product. 

Enantioselective reduction of prochiral ketones by transfer hydrogenation is catalysed by amino acid derivatives. A mechanistic suggestion for the origin of enantioselective induction has been proposed.306 ,/M Jnsaluralcd nitriles are efficiently reduced by a Cu(I)-H species in the presence of bisphosphine ligands. The active Cu(I)-H species was generated by the reaction of copper(II) acetate and polymethylhydrosilane.307... 

A primary alcohol and amines can be used as an aldehyde precursor, because it can be oxidized by transfer hydrogenation. For example, the reaction of benzyl alcohol with excess olefin afforded the corresponding ketone in good yield in the presence of Rh complex and 2-amino-4-picoline [18]. Similarly, primary amines, which were transformed into imines by dehydrogenation, were also employed as a substrate instead of aldehydes [19]. Although various terminal olefins, alkynes [20], and even dienes [21] have been commonly used as a reaction partner in hydroiminoacylation reactions, internal olefins were ineffective. Recently, methyl sulfide-substituted aldehydes were successfully applied to the intermolecu-lar hydroacylation reaction [22], Also in the intramolecular hydroacylation, extension of substrates such as cyclopropane-substituted 4-enal [23], 4-alkynal [24], and 4,6-dienal [25] has been developed (Table 1). 

The nitropyridines can be reduced to the corresponding aminopyridine and several new methods have been developed to achieve this transformation. 3-Nitropyridine is reduced in excellent yield by the mixed borohydride prepared from 1 equiv of ZrCU and 4 equiv of NaBFLi in THF under reflux <2000SL683>. 3-Nitropyridines may be reduced to the aminopyridine using sodium hydrosulfite in THF/H20 at room temperature <2005JME5104>. 2-Nitropyridine can be reduced to the amine in near quantitative yield by transfer hydrogenation in the presence of 10% Pd/C and recyclable polymer-supported formate, prepared from aminomethylpolystyrene resin and ammonium formate <2005SC223> (Equation 64). The resin is easily recovered by filtration and may be used up to 10 times. 

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