Asymmetric addition benzaldehyde

Chiral aluminum SALEN complexes have been used by Kee for asymmetric addition of dimethyl phosphite to benzaldehyde derivatives (Scheme 5-43). 

Asymmetric addition of Grignard reagents to CJfflHO.1 Grignard reagents pretreated with (-)-l at -78° add to benzaldehyde with only slight enantiose-lectivity ( 20% ee). But if the addition is effected in the presence of 2,4,6-tri-methylphenoxyaluminum dichloride (2), the carbinol is obtained in 40-70% ee. 

Meijer et al. 84) investigated the asymmetric addition of Et2Zn to benzaldehyde catalyzed by PPI dendrimers functionalized with chiral amino alcohol ligands (94-95). 

Synopsis of Goldfuss and Houk (1998) Origin of Enantioselectivities in Chiral /i-Arnino Alcohol Catalyzed Asymmetric Additions of Organozinc Reagents to Benzaldehyde PM3 Transition State Modeling . 

On the basis of their observation that achiral 2,2 -bipyridyl promotes the reaction between crotyltrichlorosilane and benzaldehyde, the Barrett group screened chiral pyridine molecules as Lewis-base catalysts for this reaction [175]. The pyridinylox-azoline 164a was identified as the most efficient organocatalyst. In the presence of this catalyst, which was, however, used in stoichiometric amounts, asymmetric addition of (E)-crotyltrichlorosilane 158b to aldehydes gave the anti products (S,S)-159 in yields of 61-91% and with enantioselectivity from 36 to 74% ee (Scheme 6.76) [175], Diastereoselectivity is high, because only the anti diastereomers were obtained. Aromatic aldehydes and cinnamylaldehyde were used as substrates. 

The use of bis(sulfonamide) ligands derived from stilbenediamine in the asymmetric addition of diethylzinc to benzaldehyde has resulted in large changes in product ee over the course of the reaction.106 This effect has been attributed to autoinduction. During the reaction the catalyst evolves by incorporation of the product of the asymmetric addition reaction. 

Tridentate salen ligands derived from enantiopure d,v-aminoindanol were prepared in an effort to explain the relationship between the ligand structure and the enantioselectivity in the Ti(IV)-Schiff base catalyzed asymmetric addition of trimethylsilylcyanide to benzaldehyde.44 The nature and... 

Denmark utilized the asymmetric allylation methodology in the synthesis of the serotonin antagonist LY426965 (17), preclinical studies of which suggest its pharmacotherapy use for smoking cessation and depression-related disorders16 (Scheme 3.2m). The key intermediate alcohol (19) was prepared in 94% ee via the asymmetric addition of the silane 18 to benzaldehyde in the presence of the chiral ligand (.S, .S )-16. 

These mixed structures have been employed in asymmetric nucleophilic addition reactions. The asymmetric addition of acetonitrile anion to benzaldehyde gives access to synthetically important chiral hydroxy nitriles. 

The impact of achiral ligands on the TOP of the catalyst in this system was then examined by following reaction conversions with various catalysts. In the absence of both Ph2-BINOL and diamine ligands, the reaction of diethylzinc with benzaldehyde is very slow, exhibiting about 1% conversion after 8h at 0°C. When Ph2-BINOL was employed in the asymmetric addition to this substrate, the catalyst TOP increased exhibiting 25% conversion after 2 h. To evaluate the TOP of zinc centers bearing diimine derived from ethylene diamine and 2,4,6-trimethylbenzaldehyde (Table 4, entry 5) or the meso diamine (Table 5, entry 7), these ligands were... 

Table 3. Asymmetric addition of diethylzinc to benzaldehydes in tbe presence of diselenide...

Tridentate salen ligands (10) derived from 1 have given excellent results in the enantiocontrol of the hetero Diels-Alder addition reaction of dienes with aldehydes (eq 7) and in the asymmetric additions of TMS-azide to mc5o-epoxide and trimethylsilyl cyanide to benzaldehyde (up to 85% ee). Phosphino-oxazolines derived from 1 have been employed for the asymmetric control of palladium-catalyzed allylic substitution reactions products of 70-90% ee were obtained. Photolysis of crystalline adducts of enantiomerically pure 1 with prochiral alcohols results in asymmetric inductions of up to 79% in a rare example of a solid-state enantioselective reaction. ... 

The influence of molar ratio of reactants, reaction temperature, and solvent on the optical yield in the asymmetric addition of butyllithium to benzaldehyde was examined in detail using 2a as chiral ligand. The molar ratio of the aldehyde butyl-lithium 2a was found to be an optimum at 1.0 6.7 4.0. The effect of solvent is remarkable, and dimethoxymethane was found to be the solvent of choice when the addition reaction was carried out at —78 °C (entry 11). As it became apparent that lowering the temperature increased the degree of asymmetric induction (entries 2, 3, 11, and 12), in order to carry out the reaction at —123 °C a mixed solvent system of dimethoxymethane-methyl ether or dimethoxymethane-pentane (entries 13 and 14) was employed, and (S)-l-phenyl-1-pentanol was obtained in up to 95% e.e. (Table 3)... 

Results of the asymmetric addition of various alkyllithiums to benzaldehyde and an aliphatic aldehyde under the optimized reaction conditions are summarized in Table 4 shown in Table 4, the chiral ligand 2a is very effective and,... 

Table 3. Asymmetric Addition of Butyllithium to Benzaldehyde Using the Ligand (2a) ...

The early examples of peripherally functionalized dendrimers, PPl-supported amino alcohol and dendrimer-bound Ti-TADOLates, in the asymmetric addition of diethylzinc to benzaldehyde were reported by the groups of Meijer [96, 97] and Seebach [98], respectively. 

Finally, ACTCs 66 and 67 were employed in the asymmetric addition of dimethyl or diethylzinc to benzaldehyde and ferrocenecarbaldehyde [47]. In order to obtain acceptable conversion and enantioselectivities the catalyst loading had to be 10 mol%. In such circumstances, enantiomeric excess of up to 86% could be obtained. Complex 67 with its diphenylhydroxymethyl substituent performed much better than 66, which is in accord with the observation made for the series of ACTCs 59-64. 

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