Enantioselective hydrogenation diketones

Influence of Achiral Tertiary Amines on the Enantioselective Hydrogenation of a,p-diketones Over Cinchonidine-Pt/Al203 Catalyst... 

Enantioselective hydrogenation of 2,3-butanedione and 3,4-hexanedione has been studied over cinchonidine - Pt/Al203 catalyst system in the presence or absence of achiral tertiary amines (quinuclidine, DABCO) using solvents such as toluene and ethanol. Kinetic results confirmed that (i) added achiral tertiary amines increase both the reaction rate and the enantioselectivity, (ii) both substrates have a strong poisoning effect, (iii) an accurate purification of the substrates is needed to get adequate kinetic data. The observed poisoning effect is attributed to the oligomers formed from diketones. 

Pt/Al2C>3-cinchona alkaloid catalyst system is widely used for enantioselective hydrogenation of different prochiral substrates, such as a-ketoesters [1-2], a,p-diketones, etc. [3-5], It has been shown that in the enantioselective hydrogenation of ethyl pyruvate (Etpy) under certain reaction conditions (low cinchonidine concentration, using toluene as a solvent) achiral tertiary amines (ATAs triethylamine, quinuclidine (Q) and DABCO) as additives increase not only the reaction rate, but the enantioselectivity [6], This observation has been explained by a virtual increase of chiral modifier concentration as a result of the shift in cinchonidine monomer - dimer equilibrium by ATAs [7],... 

In this study enantioselective hydrogenation of diketones (2,3-butanedione (BD), 3,4-hexanedione (HD)) (see Scheme 1) was investigated in the presence or absence of ATAs using solvents, such as toluene and ethanol. In addition, the importance of the purification of these substrates will be discussed. The main goal of this study is to get further information about the effect of ATAs in case of substrates, such as of a,p-diketones. 

The second, effective heterogeneous enantioselective catalytic system is nickel modified with tartaric acid and sodium bromide. This system is most effective for the hydrogenation of P keto esters giving chiral P hydroxy esters, 41, with ee s as high as 95% (Eqn. 14.29). 0,72,84,85 n also been used for the enantioselective hydrogenation of p diketones (Eqn. 14.30) and methyl ketones. ... 

As mentioned above, the best substrate in the enantioselective hydrogenation on modified Ni catalysts proved to be beta-k io esters and Z>eto-diketones, eompounds that are capable of forming an intermediate six-membered chelate with a Ni atom, or a Ni-eenter on the surfaee. Optical yields drop drastically if a monoketone substrate is used. 

In general the enantioselective hydrogenations of monoketones are less effective than the enantioselective hydrogenation of diketones, but Osawa et al. found special conditions under which methyl-ketones, such as acetone, butan-2-one and 3,3-dimethylbutan-2-one, produced optical yields of 74%, when they were hydrogenated on RNi-TA-NaBr at 100 bar hy ogen pressure and 100°C in a solution of THF, to which pivalic acid has been added. 

Ultrasonicated catalyst, RNi-U, proved to be very effective besides the hydrogenation of 3-oxoalkanoates, in the enantioselective hydrogenation of 1,3-diketones (pentan-2,4-dione, 2,3-dimethylheptan-3,5-dione) into diols, too, with ee s of 86-91%. For example, this new type of catalyst was used for the preparation of optically pure (R)- and (S)-meAyl 3-hydro alkanoates after hydrogenation in high enantioselectivity followed by crystallization of their dicyclohe g lammonium salts (see Table 4.5, Chemical yields). 

Enantioselective hydrogenation of MePy at RT and 10 bar of hydrogen over 6.3% Pt-silica modified with brucine resulted in (S)-MeLa with an ee of 20%, but no enantioselectivity was found in the hydrogenation of butane-2,3-dione. According to Wells et al. brucine adsorbs on a Pt surface to form cavities for the enantioselective adsorption of MePy but not for the diketone. On the other hand, Pt catalyst modified with the morphine alkaloid, oxycodone, works as an enantioselective catalyst in the hydrogenations of both MePy and... 

There are many classes of substrate structures involved in heterogeneous enantioselective hydrogenation on modified metal catalysts. They consist of 2-oxocarboxylic acids and their esters, ketones, diketones, keto lactones, imsaturated acids, oximes, and amides. Enantioselectivities of heterogeneous chirally modified metal catalysts are determined in an important way by the matched interactions between die functional groups of the substrate and the modifier. 

Ketone reduction The enantioselective hydrogenation of vicinal diketones such as l-phenylpropane-l,2-dione over cinchonidine-modifled Pt gave the (R)-enantiomers in excess. Faster reaction of (S)-hydroxyketone to the diols, contributed to an increase in enantioselective excess (ee) [41]. 

The scope of Michael additions with catalysts containing cyclohexane-diamine scaffolds was broadened by Li and co-workers [95]. When screening for a catalyst for the addition of phenylthiol to a,p-nnsatnrated imides, the anthors fonnd that thiourea catalyst 170 provided optimal enantioselectivities when compared to Cinchon alkaloids derivatives (Scheme 41). Electrophile scope inclnded both cyclic and acyclic substrates. Li attributed the enantioselectivity to activation of the diketone electrophiles via hydrogen-bonding to the thiourea, with simultaneous deprotonation of the thiol by the tertiary amine moiety of the diamine (170a and 170b). Based on the observed selectivity, the anthors hypothesized that the snbstrate-catalyst... 

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