Lewis Acid Catalyzed (3+2)-Cycloadditions of Chiral Pyrimidinyl-Substituted Cyclopropanes with Nitrosoarenes or Silyl Enol Ethers

Chiral isoxazole and carbocyclic pyrimidine nucleoside analogues were synthesized via (3+2)-cycloadditions of chiral pyrimidinyl-substituted dimethyl cyclopropanedicarboxylates. In the presence of MgI2, (3+2)-cycloadditions of chiral pyrimidinyl-substituted cyclopropanes with nitrosoarenes afforded diverse chiral isoxazole pyrimidine nucleoside analogues in up to 78 % yield and 88-96 % ee. Using Nd(OTf)(3) as the catalyst, the annulation reaction with silyl enol ethers generated a series of chiral carbocyclic pyrimidine nucleoside analogues in up to 64 % yield, >20 : 1 dr, and 87-96 % ee. The proposed methods either reduced or avoided partial racemization.

Automated summary

Chiral isoxazole and carbocyclic pyrimidine nucleoside analogues were synthesized via cycloadditions, with high yields and enantiomeric excess, while avoiding racemization.