Catalytic Enantioselective Aldol Reactions

To keep the concentration of trimethylsilyl triflate as low as possible during the reaction a dichloromethane solution of silyl enolate and aldehyde vras added slovrly to the solution of the catalyst 80 (20 mol%), and the aldol product 92 vas obtained in good yields vith high enantioselectivity (Eq. (44)) [70]. Selectivity is improved by using propionitrile as solvent instead of dichloromethane. The rate of metal exchange betv een Sn-Si is faster in propionitrile than in dichloromethane [71]. 

After the first reports of the above-mentioned highly eflident catalytic enantioselective aldol reaction, some groups independently reported catalytic symmetric aldol reactions of silicon enolates vith aldehydes using chiral boron [72], titanium [73], zirconium [74], and copper Le vis acids [75], or by transmetalation to chiral Pd(II) enolates [44]. Chiral phosphoramide-promoted aldol reactions of trichlorosilyl enol ethers have been reported as Le vis base-catalyzed asymmetric aldol reactions [76]. 

Typical Procedure for Catalytic Enantioselective Aldol Reaction Using a Chiral Tin(ll) Catalyst System (Eq. (45)) [71] 

Mukaiyama, T. Inomata, K. Bull. Chem. Soc. Jpn. 1971, 44, 3215. The mechanism shown in this paper was corrected as mentioned in reference 2. 

Williams, S. F. Masamune, S. in Comprehensive Organic Synthesis, (B. M. Teost, Ed.), Pergamon Press, 

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Trost s group reported direct catalytic enantioselective aldol reaction of unmodified ketones using dinuclear Zn complex 21 [Eq. (13.10)]. This reaction is noteworthy because products from linear aliphatic aldehydes were also obtained in reasonable chemical yields and enantioselectivity, in addition to secondary and tertiary alkyl-substituted aldehydes. Primary alkyl-substituted aldehydes are normally problematic substrates for direct aldol reaction because self-aldol condensation of the aldehydes complicates the reaction. Bifunctional Zn catalysis 22 was proposed, in which one Zn atom acts as a Lewis acid to activate an aldehyde and the other Zn-alkoxide acts as a Bronsted base to generate a Zn-enolate. The... 

This chemistry was extended to a catalytic enantioselective alkenylation and phenylation of aldehydes and a-ketoesters. Using CuF-DTBM-SEGPHOS complex, products were obtained with excellent enantioselectivity from a wide range of aldehydes including aromatic and aliphatic aldehdyes, [Eq. (13.26)]. Previously catalytic enantioselective vinylation and phenylation are restricted using the corresponding zinc reagents. The active nucleophile is proposed to be an alkenyl or phenyl copper, based on NMR studies. The chiral CuF catalyst can also be applied to a catalytic enantioselective aldol reaction to ketones... 

Despite the versatility of acetylenes, there has been no previous use of an acetylenic ketone as a donor in direct catalytic enantioselective aldol reactions. The aldol reaction using 26 as a donor proved to be difficult,... 

Reymond, J.L. and Chen, Y.W. (1995) Catalytic, enantioselective aldol reaction using antibodies against a quaternary ammonium ion with a primary amine cofactor. Tetrahedron Letters, 36, 2575-2578. 

Direct Catalytic Enantioselective Aldol Reactions. Yamada and Shibasaki have found that a direct catalytic enantioselective aldol reaction of an aldehyde and unmodified ketone is promoted... 

Catalytic enantioselective aldol reactions provide access to a variety of p-hydroxy carbonyl compounds, which are useful intermediates for the synthesis of natural products as well as commodity chemicals. A drawback, however, involves the use of latent enolates that must be prepared by stoiehiometric methods. Enolate... 

Demnark SE, Fujimori S (2004) Catalytic, enantioselective aldol reactions with chiral lewis bases. In Mahrwald R (ed) Modem aldol reactions. Wiley-VCH, Weinheim... 

Fig. 5.7 Chiral catalysts for catalytic enantioselective aldol reactions...

In 2000, Trost and Ito reported on a direct catalytic enantioselective aldol reaction via zinc enolate (Scheme 8.41)." The catalyst was prepared in situ by mixing chiral ligand 265 and Et2Zn. The reaction promoted in the presence of triphenylphosphine sulfide (Ph3P=S) and molecular sieves 4 A. Molecular sieves 4 A increased the turnover frequency, and the addition of triphenylphosphine sulfide further improved the turnover frequency. Triphenylphosphine... 

Trost B, Ito H. A direct catalytic enantioselective aldol reaction via a novel catalyst design. J. Am. Chem. Soc. 2000 122(48) 12003-12004. 

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