Ketones enantioselective asymmetric

Efficient enantioselective asymmetric hydrogenation of prochiral ketones and olefins has been accompHshed under mild reaction conditions at low (0.01— 0.001 mol %) catalyst concentrations using rhodium catalysts containing chiral ligands (140,141). Practical synthesis of several optically active natural... 

CATALYTIC ASYMMETRIC ADDITIONS OF DIALKYLZINC TO KETONES ENANTIOSELECTIVE FORMATION OF TERTIARY ALCOHOLS... 

Mechanistic studies103 revealed that chiral ketone-mediated asymmetric epoxidation of hydroxyl alkenes is highly pH dependent. Lower enantioselectivity is obtained at lower pH values at high pH, epoxidation mediated by chiral ketone out-competes the racemic epoxidation, leading to higher enantioselectivity. (For another mechanistic study on ketone-mediated epoxidation of C=C bonds, see Miaskiewicz and Smith.104)... 

By the use of chiral oxazolidines derived from a chiral norephedrine and methyl ketones, an asymmetric aldol reaction proceeds in a highly enantioselective manner. In the case of ethyl or a-methoxy ketones, the corresponding anti aldol products were obtained with high diastereo- and enantioselectivities. A chiral titanium reagent, generated from... 

Recently, Shi and coworkers reported high enantioselective asymmetric epoxidation of a,/ -unsaturated esters by using the chiral ketone 35 as a catalyst and Oxone as an oxidant (equation 47) . ... 

The boron atom dominates the reactivity of the boracyclic compounds because of its inherent Lewis acidity. Consequently, there have been very few reports on the reactivity of substituents attached to the ring carbon atoms in the five-membered boronated cyclic systems. Singaram and co-workers developed a novel catalyst 31 based on dicarboxylic acid derivative of 1,3,2-dioxaborolane for the asymmetric reduction of prochiral ketones 32. This catalyst reduces a wide variety of ketones enantioselectively in the presence of a co-reductant such as LiBH4. The mechanism involves the coordination of ketone 32 with the chiral boronate 31 and the conjugation of borohydride with carboxylic acid to furnish the chiral borohydride complex 34. Subsequent transfer of hydride from the least hindered face of the ketone yields the corresponding alcohol 35 in high ee (Scheme 3) <20060PD949>. 

Enantioselective Ketone Reduction. The major application of chiral oxazaborolidines has been the stoichiometric (as the oxazaborolidine-borane complex) (eq 1) and catalytic (in the presence of a stoichiometric borane source) (eq 2) enantioselective reduction of prochiral ketones. These asymmetric catalysts work best for the reduction of aryl alkyl ketones, often providing very high (>95% ee) levels of enantioselectivity. 

Apart from the asymmetric metal catalysis, enantioselective Baeyer-Villiger oxidations mediated by enzymes have been known for some time [32,33,34]. Both whole-cell cultures and isolated enzymes, usually flavin-dependent monooxygenases, can be used to oxidize ketones enantioselectively. For future improvements in the asymmetric Baeyer-VilHger oxidation the use of chiral Lewis acids in combination with an appropriate oxidant seems worthy of intensive investigation. 

The reaction of either (R)- or (5)-a-methylbenzylamine (364) with sulphuryl chloride gives the (R,R) and (5,5) N,N bis(a-methylbenzyl) sulphamide 365. When 365 is added to LiAlH4 in the presence of A-benzylmethylamine in tetrahydrofuran, it leads to the asymmetric reduction of prochiral ketones 366 (equation 115)363. Optimization of the reaction was carried out with respect to enantioselectivity and reactivity of the reagents. The use of iV-benzylmethylamine as an additive was found to be superior to ethanol. Reaction at — 20 °C gave 87% selectivity with a one-hour reaction time. Both arylalkyl ketones and dialkyl ketones are asymmetrically reduced in the reaction. 

Tur, F. and Saa, J.M. (2007) Direct, catalytic enantioselective nitroaldol (Hemy) reaction of trifluoromethyl ketones an asymmetric run to a-trifluoromethyl-substituted quaternary carbons. Organic Letters, 9, 5079-5082. 

In 2002, a range of l-aryl-2-tetranols were generated in both high yields and enantioselectivities from the corresponding ketones via asymmetric transfer... 

Nishiyama and co-workers reported that iPr-PYBOX-Rh(III) catalyst promotes the highly enantioselective hydrosilylation of ketones (234). Asymmetric desymmetrization reactions of glutaric anhydride derivative were carried out by using Rh(I)-PHOX complexes (235). 

Magnetically recoverable heterogenized nanoparticle supported chiral Ru complexes were obtained and used in highly enantioselective asymmetric hydrogenation of aromatic ketones (Hu et al., 2005). The catalysts can be recycled by magnetic decantation and used for asymmetric hydrogenation for up to 14 times without loss of activity and enantioselectivity. 

G. Zhong, M. Lu, Y. Lu, P. Tan, Q. Lau, Synlett 2011,477-480. Highly enantioselective synthesis of fluorinated P-amino ketones via asymmetric organocatalytic Mannich reactions a case study of unusual reversal of regioselectivity. 

The complex does not involve any direct metal coordination but operates through weak interactions with functional groups and relies only on the formation of three hydrogen bonds. The Ir complex (26), (Ar = (3,5)-(Bu02C6H3, X = 6-Me), is the precatalyst for 0 the enantioselective asymmetric hydrogenation of aromatic ketones by H2 in EtOH to... 

Oxidation of the hydro>yl group followed by the highly enantioselective asymmetric reduction of the resulting ketone (in the presence of the Noyori s catalyst 52) yielded alcohol (i )-54 (ee>96%). Subsequent... 

Employment of chiral bis(oxazolinylphenyl)amines such as SJS)-BopsL-dpm (Scheme 4-328) as ligands for iron catalysts leads to almost quantitative yields and high enantioselectivities for the asymmetric hydrosilylation of ketones and asymmetric conjugate hydrosilylation of enones with (diethoxy)methylsilane as reductant (Scheme 4-329). Both enantiomers of the hydrosilylation product can be obtained from the same chiral ligand by a slight variation of the reaction conditions. The mixed catalyst system of (S -Bopa-dpm and iron(II) acetate provides the (/ )-enantiomer of the alcohol... 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

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