Methyl isocyanoacetate aldol reaction

The asymmetric aldol reaction of a-ketoesters (RCOCOOMe R=Me, z-Bu, Ph) with methyl isocyanoacetate or A,A-dimethyl-isocyanoacetamide in the... 

Asymmetric aldol reaction. In the presence of a gold(I) complex (1) and a chiral ferrocenylphosphine (2), various aldehydes react with methyl isocyanoacetate... 

The neutral and cationic [Pd(II)NCN] pincer-containing dendritic assemblies 14 and 15 have been used as Lewis acid catalysts in the aldol condensation of benzaldehyde and methyl isocyanoacetate. These showed conversions, turnover frequencies and cis/trans ratios of the oxazoline products that were essentially identical to those of the monomeric model complex applied in the same reaction. 

Table 3. Diastereo- and enantioselective aldol reaction of methyl isocyanoacetate (27) with tildehydes catalyzed by chiral ferrocenylphosphine 86c gold(I) complex.

Ito and coworkers found that chiral ferrocenylphosphine-silver(I) complexes also catalyze the asymmetric aldol reaction of isocyanoacetate with aldehydes (Sch. 26) [51]. It is essential to keep the isocyanoacetate at a low concentration to obtain a product with high optical purity. They performed IR studies on the structures of gold(I) and silver(I) complexes with chiral ferrocenylphosphine 86a in the presence of methyl isocyanoacetate (27) and found significant differences between the iso-cyanoacetate-to-metal coordination numbers of these metal complexes (Sch. 27). The gold(I) complex has the tricoordinated structure 100, which results in high ee, whereas for the silver(I) complex there is an equilibrium between the tricoordinated structure 101 and the tetracoordinated structure 102, which results in low enantioselectivity. Slow addition of isocyanoacetate 27 to a solution of the silver(I) catalyst and aldehyde is effective in reducing the undesirable tetracoordinated species and results in high enantioselectivity. 

For the aldol reaction of small alkyl aldehydes such as acetaldehyde, the enantioselectivity is improved by the use of Ar,A -dialkyl-oe-isocyanoacetamides instead of isocyanoacetate esters (Scheme 2-54) [76]. For example, the reaction of acetaldehyde with AT,iV-dialkyl-a-isocyanoacetamides 64 in the presence of R)- S)-8g/gold catalyst gives the corresponding /ranj-oxazoline 65 of 99% ee, which is much higher than the enantioselectivity (85% ee) observed in the reaction with methyl isocyanoacetate under the same reaction conditions. 

Table 11 Enantioselectivity and Diastereoselectivity in the Aldol Reactions of Methyl Isocyanoacetate Under Catalysis by Chiral Ferrocenylphosphine-Gold Complexes (equation 22)...

T Hayashi, E Kishi, VA Soloshonok, Y Uozumi. Erythro-selective aldol-type reaction of N-sulfonylaldimines with methyl isocyanoacetate catalyzed by gold(I). Tet Lett 37 4969-4972, 1996. 

The use of chiral platinum complex as Lewis acid catalysts for the aldol reaction has been documented and studied by several groups. The platinum catalysts are generated upon the treatment of platinum salts and phosphines in generally. The PCP-type chiral platinum complexes 31 have been shown to function effectively in the aldol addition of methyl isocyanoacetate and aldehydes in excellent yields and promising enantioselectivities (Scheme 9) (78-80). The first... 

Asymmetric aldol reactions of a-keto esters (R-CO-COOMe R = Me, iBu, Ph) with methyl isocyanoacetate or N,N-dimethyl-a-isocyanoacetamide in the presence of 1 mol% of a chiral ferrocenylphosphine-gold(I) catalyst proceed enantiose-lectively (up to 90% cc) to give the corresponding oxazolines, which can be converted into optically active j8-alkyl-j8-hydroxyaspartic acid derivatives [1197]. Dehydration of the intermediate formamide to the corresponding isocyanide is accomplished in 97% yield with phosphoryl chloride at room temperature within 2h. 

Van Koten et al. have found that NCN-palladium complexes, for example, [(NCN)Pd-(H20)][BF4], (146) are active catalysts in various C-C bond formation reactions, such as aldol condensation and the Michael reaction. Recently, they have developed the attachment of palladium(II) complexes (146) to Cgo (Scheme 16.38) [45]. The corresponding cationic aqua complexes were evaluated as Lewis acid catalysts for the Michael addition reaction of (49a) and (64), and aldol condensation of (la) and methyl isocyanoacetate (64). In the case of Michael reactions catalyzed by methanofullerenes (18)-(20) are significantly slower than the reaction catalyzed by (146). On the other hand, no such deactivation process was observed using... 

Remarkably, an overview on aldol reactions with transition metal enolates published in 1991 refers to a single asymmetric catalysis with a late transition metal, the gold-catalyzed reaction of methyl isocyanoacetate with aldehydes cf. Paterson, I. (1991) in Comprehensive Organic Synthesis (eds B.M. Trost and... 

On the other hand, another cooperative catalysis approach was developed by Oh and Kim with a highly diastereo- and enantioselective domino aldol-cyclisation reaction occurring between aldehydes and methyl a-isocyanoacetate. The process employed a combination of a chiral cobalt complex derived from brucine amino diol and an achiral thiourea. The reaction was applicable to a range of aliphatic, aromatic and heteroaromatic aldehydes, providing the corresponding chiral oxazolines in good yields and diastereoselectivities of up to >90% de combined with good to excellent enantioselectivities of up to 98% ee, as shown in Scheme 7.12. 

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