Methyl isocyanoacetate enantioselectivity

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)...

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... 

The neuroexcitatory amino acid a-kainic acid, a popular testing ground for new pyrrolidine syntheses, has been prepared by a number of routes that involve free-radical cyclization reactions. Bachi has reported two approaches that involve iminoyl radical cyclizations. One enantioselective route is described in Scheme 6 [35]. Isonitrile 48 was prepared in 4 steps from 4-bromo-3-methyl-2-butenal dimethyl acetal, the key reaction being an enantioselective addition of tert-butyl oc-isocyanoacetate to an aldehyde mediated by Hiyashi s catalyst. Treatment of 48 with a catalytic... 

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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