Stereoselective Control of Iminium Catalysis at Elevated Temperatures

Among the most significant challenges in the field of organocatalysis are the high catalyst loading requirement, extended reaction time, and restricted substrate scope, which can largely be attributed to moderate catalytic efficiency. Stereoselective control at elevated temperatures stands out as one of the most effective strategies for mitigating these challenges. However, iminium catalysis at elevated temperatures continues to pose significant challenges in this field, largely attributable to the insufficient thermodynamic stability of iminium intermediates. We herein report the stereoselective control achieved through iminium catalysis at elevated temperatures utilizing secondary amine-strong acid catalytic systems. We have demonstrated that, under appropriate ratio of amine to strong acid, the stereoselectivity control of iminium catalysis is minimally influenced by temperature within the range of room temperature to 105 ℃. According to the construction of a hydrocarbazole polycyclic skeleton containing continuous chiral centers and all-carbon quaternary stereocenters, this strategy has demonstrated significant advantages in promoting reactions with low-reactivity substrates. Furthermore, this strategy highlights the potential to reduce catalyst loading and shorten reaction times, thus providing a robust and comprehensive foundation for broader implications for advancing the field of organocatalysis.