Carbonyl compounds asymmetric hydrogenation

Carbonyl-selective asymmetric hydrogenation of simple 2-cyclohexenone is still difficult. The optical yield obtained with [Ir(OCH3)(cod)]2-DIOP is only 25%, while the carbonyl-selectivity is 95% at 65% conversion (Scheme 23) [80]. Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with a Ru(II)-TolBINAP-4-KOH catalyst system under 8 atm of hydrogen at 0 °C gives 2,4,4-trimethyl-2-cy-clohexenol quantitatively in 96% ee [81, 82]. Notably, the combination of (R)-TolBINAP and (S,S)-4 matched well to give the S alcohol with a high ee. The chiral allylic alcohol is the key intermediate in the synthesis of carotenoid-derived odorants and other bioactive compounds [83]. 

Scheme 9 Asymmetric hydrogen-mediated coupling of conjugated alkynes to carbonyl compounds and imines...

Although there are now several catalysts useful for hydrogenation of saturated carbonyl compounds to alcohols (see Section XII), an alternative approach has involved initial hydrosilylation (Chapter 9 in this volume) followed by acid hydrolysis [Eq. (41)]. The area first developed using principally the RhCl(PPh3)3 catalyst (207-210), and has since proved particularly useful in asymmetric syntheses (see Section III,A,4). Besides simple aliphatic and aromatic aldehydes and ketones, the ter-pene-ketones camphor and menthone were stereoselectively reduced to mainly the less stable alcohols e.g., camphor gave 9 (209). 

Asymmetric reduction of carbonyl compounds can usually be achieved either through direct catalytic hydrogenation or by metal hydride reduction. It should be mentioned here that reduction of carbonyl compounds by catalytic hydrogenation may not be chemoselective. Other co-existing functional groups such as the C=C bond may also undergo hydrogenation. 

Activation of carbonyl compounds by double hydrogen bonding an emerging tool in asymmetric catalysis (P. M. Pihko, 2004) [lb]. 

Until 1968, not a single nonenzymic catalytic asymmetric synthesis had been achieved with a yield above 50%. Now, barely 15 years later, no fewer than six types of reactions can be carried out with yields of 75-100% using amino acid catalysts, i.e., catalytic hydrogenation, intramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosilylation, and epoxidations. 

Nickel and other transition metal catalysts, when modified with a chiral compound such as (R,R)-tartaric acid 5S), become enantioselective. All attempts to modify solid surfaces with optically active substances have so far resulted in catalysts of only low stereoselectivity. This is due to the fact that too many active centers of different structures are present on the surface of the catalysts. Consequently, in asymmetric hydrogenations the technique of homogeneous catalysis is superior to heterogeneous catalysis56). However, some carbonyl compounds have been hydrogenated in the presence of tartaric-acid-supported nickel catalysts in up to 92% optical purity55 . 

Noyori, R., Yamakawa, M. and Hashiquchi, S. Metal-Ligand Bifunctional Catalysis A Nonclassical Mechanism for Asymmetric Hydrogen Transfer between Alcohols and Carbonyl Compounds. J. Org. Chem. 2001, 66, 7931-7944. 

Kumada and co-workers have introduced the ferrocene-based ligand BPPFOH (62) for the rhodium-catalyzed asymmetric hydrogenation of carbonyl compounds. 

Several reactions of carbonyl compounds that have one or more a hydrogens proceed through the enol form. Reaction of ketones with chlorine, bromine, and iodine result in substitution of halogen for a hydrogen rates are typically first-order in ketone and independent of halogen concentration and even of which halogen is used. Racemization of ketones with asymmetric centers adjacent to the... 

Acyloxy-substituted a,(3-unsaturated carbonyl compounds are also the substrate of choice for asymmetric hydrogenation. Ethyl 3-(acetyloxy)-2-butenoate can be hydrogenated by DI-PAMP- [89] and PROPHOS-Rh complexes [91] in 89 and 81% optical yields, respectively. 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

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