Catalytic asymmetric dipolar cycloadditions of indolyl delocalized metal-allyl species for the enantioselective synthesis of cyclopenta [b]indoles and pyrrolo[1,2-a]indoles

The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines, pesticides, and other functional molecules. Here, we disclosed novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones, which could be regarded as two types of dipolar species through the anionic delocalization. The palladium-pi-allyl species tended to serve as an all-carbon 1,3-dipole in the asymmetric [3+2] cycloaddition with electron-deficient alkenes, which furnished polysubstituted cyclopenta[b]indoles with high regio- and stereoselectivities. Meanwhile, the iridium-pi-allyl species was recognized as an aza-1,3-dipole in asymmetric [3+2] cycloaddition with in situ generated C1 ammonium enolates, affording pyrrolo[1,2-a]indoles with high diastereo- and enantioselectivities. In addition, the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.

Automated summary

The development of efficient methods for synthesizing chiral polycyclic indoles is crucial for their wide applications in medicines, pesticides, and other functional molecules. The study revealed novel indolyl substituted metal-allyl zwitterionic intermediates that could participate in asymmetric cycloaddition reactions with high selectivities, leading to the synthesis of diverse chiral polycyclic indoles.