Asymmetric (1,3)-dipolar cycloaddition reactions: synthesis of highly substituted proline derivatives

Asymmetric cycloaddition of different aldehydes and dimethyl malate to azomathine ylides is presented. The cycloaddition has high endo-selectivity with almost complete control of the generation of three stereogenic centers. Aldehydes longer than formaldehyde promote the generation of a fourth center with low stereoselectivity. The diastomers produced from the reaction can be purified using chromatography and modified through various cleavage reactions.