Optimized iminium-catalysed 1,4-reductions inside the resorcinarene capsule: achieving >90% ee with proline as catalyst

In previous work, we demonstrated that iminium-catalysed 1,4-reductions inside the supramolecular resorcinarene capsule display increased enantioselectivities as compared to their regular solution counterparts. Utilizing proline as the chiral catalyst, enantioselectivities remained below 80% ee. In this study, the reaction conditions were optimized by determining the optimal capsule loading and HCl content. Additionally, it was found that alcohol additives increase the enantioselectivity of the capsule-catalysed reaction. As a result, we report enantioselectivities of up to 92% ee for iminium-catalysed 1,4-reductions relying on proline as the sole chiral source. This is of high interest, as proline is unable to deliver high enantioselectivities for 1,4-reductions in a regular solution setting. Investigations into the role of the alcohol additive revealed a dual role: it not only slowed down the background reaction but also increased the capsule-catalysed reaction rate.

Automated summary

This study optimized the reaction conditions for iminium-catalysed 1,4-reductions within a supramolecular resorcinarene capsule, achieving enantioselectivities of up to 92% ee. Additionally, it was discovered that alcohol additives play a dual role in slowing down background reactions and increasing the rate of capsule-catalysed reactions.