Synthesis of cycloheptanoids through catalytic enantioselective (4 + 3)-cycloadditions of 2-aminoallyl cations with dienol silyl ethers

Development of enantioselective cycloaddition reactions involving three-carbon units (n + 3) is challenging because of the instability of the required zwitterionic three-carbon units. The reactivity of these zwitterionic species is particularly intriguing due to the prevalence of odd-numbered carbocyclic ring motifs in natural products. Although cycloadditions with 2-oxyallyl cations are generally well developed, cycloadditions are rare with 2-aminoallyl cations, with catalytic examples limited to intramolecular reactions involving furan derivatives. Here we report a method for copper-catalysed formation of 2-aminoallyl cations from ethynyl methylene cyclic carbamates and subsequent enantioselective (4 + 3)-cycloaddition reactions between 2-aminoallyl cations and dienol silyl ethers. The seven-membered ring carbocyclic products are formed in good yields and with high enantiocontrol. The synthetic utility of the reaction products has been demonstrated through a series of reductive, cross-coupling and cyclization transformations. Mechanistic studies reveal that the reaction involves a dinuclear copper catalyst and occurs stepwise, with formation of the second C–C bond as the turnover-limiting step.