A New Approach for Supramolecular Iminium Catalysis

Abstract

An alternative modular strategy has been developed for hydrogen-bond-mediated supramolecular iminium catalysis (SIC). To improve the efficiency of traditional iminium ion catalysis and provide a new approach to asymmetric catalysis, we recently developed a new concept which aims to activate iminium ions. To expand the scope of SIC, we reported here a rationally designed strategy involving the dual activation of both iminium ions and the nucleophilic partner that provides new opportunities for improving the reactivity and designing new reactions. We analyzed the different reaction rates of the addition reaction of malonate to alpha,beta-unsaturated aldehyde catalyzed by traditional iminium ion catalysis and supramolecular iminium catalysis by the means of H-1 NMR monitoring of the reaction conversions and comparison of the isolated yields. Moreover, different carboxylic acids were employed in iminium catalytic Michael addition reaction of malonate to alpha,beta-unsaturated aldehyde to test our hypothesis. General speaking, by using this novel supramolecular iminium catalysis, the enantioselectivities of the Michael addition products are excellent (93%similar to 95%) with moderate to good yields (61%similar to 86%), meanwhile, all these reactions were rather slow and only 33%similar to 57% conversions were obtained even after 7 days in the presence of traditional iminium ion catalysis. Further reducing the catalyst loading to 5 mol%, the reaction proceeded smoothly to give a >90% conversion with 94% ee after 12 h. The results revealed that the use of less acidic acid which generates lower concentration of iminium ion associated with stronger anion-binding stabilized conjugate base gives faster reaction rate. The experimental results indicate a new approach for SIC which involves an anion-exchange process between anion-binding stabilized carboxylate ion and malonate. The self-assembled supramolecular system has higher reactivity, better efficiency and greater turnover numbers. This general strategy has the potential to be applied in many iminium catalytic nucleophilic addition reactions and might provide new opportunities for designing new asymmetric reactions. The further study is currently underway in our laboratory.