Aldehydes enantioselective

Keywords aldehyde, enantioselective addition, diethylzinc, secondary alcohol... 

The substrate range - scope and limitations The reaction can be performed efficiently with a broad variety of ketone donors and aldehydes. Enantioselectivity, however, depends on the enolate structure (Scheme 6.11) [60, 61]. In general, eno-lates bearing larger, branched alkyl groups or a phenyl group result in lower enantioselectivity. The best results were obtained with enolates bearing a methyl substituent (product (S)-16, 87% ee) or a siloxymethyl substituent (product (S)-17, 86% ee). 

The range of substrates tolerated by this catalytic system is broad and includes other aromatic and aliphatic aldehydes (Scheme 6.97) [218, 219]. For all aromatic or a,/ -unsaturated aldehydes enantioselectivity is high (89-94% ee) and diastereoselectivity is excellent (d.r. (trans/cis) > 98 2). Yields were in the range 55-73% [219]. For aliphatic aldehydes yields were significantly lower, 32-35% (Scheme 6.97) [218, 219]. Diastereoselectivity also was somewhat lower and enantioselectivity varied from 68 to 90% ee [218, 219]. 

Aldehydes and ketones can also be directly a-brominated using the catalytic concepts presented in Scheme 2.34 and Eq. (7) [30]. The easily synthesized and air-stable 4,4-dibromo-2,6-di-ter -butyl-cyclohexa-2,5-dienone was found to be the best reagent for the functionalization of aldehydes (enantioselectivities in the range of 68-96% ee) and for the preparation of the optically active a-... 

Asymmetric Aldol Reactions. Lithium enolates, derived from an ester, and LDA react with aldehydes enantioselectively in the presence of the chiral amide 2 (eq 3). When benzaldehyde is employed, the major diastereomer is the anrt-aldol with 94% ee, while the minor yn-aldol is only 43% ee. In this reaction, the lithium amide 2 coordinates to an additional lithium atom. There are four additional examples of aldehydes with the same ester enolate. 

P-Aminoalcohols are excellent catalysts for the enantioselective addition of dioorganozincs to aromatic aldehydes (enantioselectivities of up to 90-98% ee). This reaction was discovered by Oguni et al. in 1983 [85]. In a sense it may be considered as a case of organometallic catalysis since zinc alcoholates are involved in the catalytic cycle [86]. 

The effects of bisphosphite ligand structure on regioselectivity and enantio-selectivity in asymmetric styrene hydroformylation are shown in Table 1. Catalytic reactions were preformed at ambient temperature and 130 psi CO/H2. Hydroformylation regioselectivity was determined by GC of the product aldehydes. Enantioselectivity was determined by chiral GC after conversion to the carboxylic acid (eqn 1). The, i -enantiomer of the bisphosphites in Figure 1 all produced the... 

A catalytic tethering that employs a simple aldehyde as catalyst has been reported to facilitate hydroamination of allylic amines (116) at room temperature to produce vicinal aminohydroxyamines (118). The reaction proceeds via formation of the mixed aminal (117) from the amine, aldehyde, and hydroxylamine, resulting in a facile intramolecular hydroamination event. With chiral aldehydes, enantioselectivities up to 87% ee were attained. ... 

In the reaction of the tin(II) enolate derived from (1) with aldehydes, enantioselectivities are disappointingly low, while good diastereoselectivities are observed. Highly diastereo- and enan-tioselective aldol reactions of propionate derivatives with aldehydes have been achieved by using the ketene silyl thioacetal (7) instead of the tin(II) enolate. The complex (8) produced by mixing tin(n) triflate and the chiral diamine (6) works as an efficient chiral Lewis acid. The reaction of (7) with various aldehydes proceeds smoothly in the presence of (8) and dibutyltin diacetate in dichloromethane to afford the syn aldol adducts in high yields with almost perfect stereochemical control (eq 9). ... 

Zirconium alkoxide catalysts were used for the aldol-Tishchenko reaction shown in Equation 18 [23]. In the reaction, diacetone alcohol (55) is converted to the corresponding enol by removal of acetone, and adds to an aldehyde. Enantioselective version of the reaction was also examined [24]. 

The marked temperature dependence of the enantioselective addition of diethylz-inc to aryl aldehydes catalysed by (S)-2-(3-methyl-2-pyridyl)-3,5-di-r-butylphenol displays an inversion temperature which is affected by the para-substituent of the aldehyde. Enantioselectivities of up to 78% ee for addition of diethylzinc to ben-zaldehyde have been achieved using (15, 45)-2,5-diazabicyclo[2.2.1]heptane derivatives as catalysts however, a study of chiral compounds related to the Betti base (51a) has identified r-aminonaphthol (51b) as a much more effective catalyst (99% ee) for this reaction. The catalytic efficiency of chiral pyrrolidine derivatives and (25)-3-eJt -(dimethylamino)isobomeol have also been explored. 

Terrasson, V, van der Lee, A., de Figueiredo, R. M., Campagne, J.-M. (2010). Organocatalyzed cyclopropanation of alpha-substituted alpha.beta-unsaturated aldehydes enantioselective synthesis of cyclopropanes bearing a chiral quaternary center. Chemistry - A European Journal, 16,7875-7880. 

Although a majority of the catalytic complexes employed in the aldol reaction are bidentate, Carreira and coworkers published the synthesis of a new chiral tridentate chelating ligand for the efficient asymmetric induction of stereochemistry in aldol adducts. The Ti(IV) complex 68, an analog of the BINOL catalyst previously mentioned, was further stabilized by 3,5-di-tert-butylsalicyclic acid as a counterion to increase the yields, selectivity, and efficiency of the asymmetric reaction. This new catalyst is particularly effective in the addition of either O-trimethylsilyl, or O-ethyl, or O-methyl ketene to both aliphatic and aromatic aldehydes enantioselectively to obtain the respective aldol adduct. For example, the reaction of the silylketene acetal 90 with the aromatic aldehyde 89 in the presence of 68 obtains the aldol adduct 91 in high yield (91%) and excellent enantioselectivity (97% ee). 

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