Hydrogenation of Keto-Compounds

Catalyst mol% Ph2 Solvent Diastereo- %ee meric ratio of major diastereomer TOF Refer- ence 

Major diastereomer Catalyst mol% PH2 Solvent Diastereo- %ee TOF Refer- 

Catalyst mol% Ph2 Solvent Diastereo-meric ratio TOF Reference 

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The catalyst is inactive for the hydrogenation of the (isolated) benzene nucleus and so may bo used for the hydrogenation of aromatic compounds containing aldehyde, keto, carbalkoxy or amide groups to the corresponding alcohols, amines, etc., e.g., ethyl benzoate to benzyl alcohol methyl p-toluate to p-methylbenzyl alcohol ethyl cinnamate to 3 phenyl 1-propanol. 

Fig. 32.10 Examples of biologically active compounds obtainable through BINAP-Ru-catalyzed hydrogenation of/ -keto esters.

This chemistry is applicable to the hydrogenation of acyclic compounds such as a-acylamino-, a-ammonio-, a-amidomethyl-, and a-chloro-substituted / -keto esters (Fig. 32.26) [14n, 74a, 77-79]. The (R)-BINAP-Ru-catalyzed hydrogenation of the a-acylamino and a-amidomethyl ketones in CH2C12 leads to the 2S,3R (syn) alcohols in up to 98% ee [14n, 74a]. The use of sterically hindered... 

Ruthenium complexes have been used for the hydrogenation of alkenes but they had not been used for hydrogenations of carbonyl compounds until recently, when several highly selective catalytic hydrogenations of carbonyl compounds (P-keto esters, a-diketones, a-amino ketones etc., ee > 95%) were reported using BINAP-Ru" complexes (equation 18). ° ... 

The selective hydrogenation of dicarbonyl compounds involves the saturation of one of the keto groups to produce a ketol. The a-di- and polyketonic 2-74 compounds as well as acyloins 5,76 and polyhydroxyaldehydes, such as glyceraldehyde and the sugars,2.77,78 can be hydrogenated either selectively or completely to the polyhydroxy materials under mild reaction conditions. The... 

In these reactions, catalysts of the type [Ru(BINAP)(OAc)2], [Ru2-(BINAP)2Cl4NEt3] and [(arene)Ru(BINAP) ] I were used (cf. Sections 2.9 and 3.3.1). These catalysts also proved effective in the enantioselective hydrogenation of carbonyl compounds, and specifically in the hydrogenation of )9-keto esters... 

Another example of asymmetric catalysis involving optically active polymers is provided by the work of Plate et al. [89, 90]. They first reported the asymmetric hydrogenation of keto groups of polymeric j3-ketoesters, using nickel catalysts treated with solutions of optically active compounds (such as L-glutamic acid or D-tartaric acid). Although in these examples the catalysts are low molecular weight compounds the catalytic action is ascribed to their complexation with the polymeric substrate. Reactions, usually carried out at 60—80 atm. of H2, at 60—80°C, in methanol, chloroform or dimethyl-formamide, can be shown schematically as follows ... 

The hydrogenation of 5a-cholestanone (58) in methanolic hydrobromic acid over platinum gives 3j5-methoxycholestane ° (61). This compound is also obtained from the palladium oxide reduction of (58) in methanol in the absence of acid. Hydrogenation of 5 -cholestanone also gives the 3j5-methoxy product under these conditions. Reduced palladium oxides are quite effective for the conversion of ketones to ethers. The use of aqueous ethanol as the solvent reduces the yield of ether. Ketals are formed on attempted homogeneous hydrogenation of a 3-keto group in methanol. ... 

The reaction between perfluoraarylmagnesium halides and esters of dicar-boxyltc acids gives, besides the expected keto esters, secondary alcohols as reduction products [29, 30, 31] (equation 10) Such a reduction is enhanced by higher temperature The hydrogen necessary for reduction comes from the solvent, diethyl ether, which is dehydrogenated to ethyl vinyl ether, which has been identified as a by-product in a similar reaction of perfluoroalkyllithium compound [52]... 

An alternate scheme for preparing these compounds starts with a prefabricated pyrimidone ring. Aldol condensation of that compound (95), which contains an eneamide function, with pyridine-3-aldehyde (80), gives the product 96. Catalytic hydrogenation gives the product of 1,4 reduction. The resulting pyrimidinedione, of course exists in the usual tautomeric keto (97a) and enol (97b) forms. Reaction with phosphorus oxyxchloride leads to the chloro derivative 98. Displacement with methoxide gives 99. Reaction of this last intermediate with the furylalkylamine derivative 92 leads to the H-2 blocker lupitidine (100) [22]. 

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