Diastereo- and Enantioselective Synthesis of Chiral Pyrrolidine-Fused Spirooxindoles via Organocatalytic [3+2] 1,3-Dipolar Cycloaddition of Azomethine Ylides with Maleimides

摘要

In the presence of a Cinchona alkaloid-based squaramide organocatalyst, the [3+2] cycloaddition of isatin-derived azomethine ylides with maleimides proceeded readily, thus delivering the desired pyrrolidine-fused spirooxindoles in 61-89% yields with >20:1 dr and 12 to >99% ee. The absolute configuration of 5-chloro-1,5-dimethyl-3-phenyl-3,3a-dihydro-2H-spiro[indoline-3,1-pyrrolo[3,4-c]pyrrole]-2,4,6(5H,6aH)-trione was unambiguously determined by means of X-ray single crystal structure analysis. The reaction mechanism was hypothesized to account for the enantioselective formation of 5-chloro-1,5-dimethyl-3-phenyl-3,3a-dihydro-2H-spiro[indoline-3,1-pyrrolo[3,4-c]pyrrole]-2,4,6(5H,6aH)-trione.