Highly diastereo-/enantioselective assembly of 2,3-fused indolizine derivatives could be easily available through a cascade allylation/Friedel-Crafts type reaction enabled by a synergistic Cu/Ir catalysis. This designed protocol provides an unprecedented and facile route to enantioenriched indolizines bearing three stereogenic centers in moderate to high yields with excellent stereoselective control, which also featured broad substrate generality. Remarkably, four stereoisomers of the 2,3-fused indolizine products could be efficiently constructed in a predictable manner through the pairwise combination of copper and iridium catalysts. The synthetic utility of this method was readily elaborated by a gram-scale reaction, and synthetic transformations to other important chiral indolizine derivatives. Quantum mechanical explorations constructed a plausible synergetic catalytic cycle, revealed the origins of stereodivergence, and rationalized the protonation-stimulated stereoselective Friedel-Crafts type cyclization to form the indolizine products.
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