Gold and Silver-Catalyzed Asymmetric Aldol Reactions of a-Isocyanocarboxylates

4 Gold and Silver-Catalyzed Asymmetric Aldol Reactions of a-Isocyanocarboxylates 

Determined by NMR spectroscopy with chiral shift reagent Eu(dcm)3. 

The chiral ferrocenylphosphine.gold(I)-catalyzed aldol reaction of a-alkyl a-isocya-nocarboxylates 92 with paraformaldehyde gives optically active 4-alkyl-2-oxazoline-4-carboxylates 93 with moderate to good enantioselectivity [46], The absolute configuration (S) of the product indicates that the reaction occurs selectively at the si face of the enolate as illustrated in Fig. 2. These oxazolines 93 can be converted into a-alkyl-serine derivatives 94 (Sch. 24). 

This enantioselective aldol reaction employing isocyanoacetate 27 is quite effective for aromatic aldehydes or tertiary alkyl aldehydes, but not for sterically less hindered aliphatic aldehydes as described above. Ito and coworkers found that very high enantioselectivity is obtained even for acetaldehyde (R = Me) in the aldol reaction with Af,A -dimethyl-a-isocyanoacetamide (95) (Sch. 25) [47]. Use of a-keto esters in place of aldehydes also results in moderate to high enantioselectivity of up to 90 % ee [48]. 

The same group further developed the asymmetric aldol reaction of A -methoxy-A -methyl-a-isocyanoacetamide (a-isocyano Weinreb amide) with aldehydes (Sch. 25). The reaction of the Weinreb amide 96 with acetaldehyde in the presence of 86c Au(I) catalyst gives the optically active tram-oxazoline 98 (E = CON(Me)OMe R = Me) with high diastereo- and enantioselectivities similar to those of 95 [49], The oxazoline can be transformed into A,0-protected /3-hydroxy-a-amino aldehydes or ketones. 

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