Selective Aliphatic Aldimine Formation and Stabilization by a Hydrophobic Capsule in Water

Imines and enamines are useful intermediates in biochemical aldol-type reactions since their acid/base characteristics are accessible near neutrality. However, the generation of aldimines in water is a challenge as the equilibrium favors the components alkyl amines and aldehydes. Here, we report the generation, recognition, and protection of aldimines accomplished by a water-soluble capsule. The capsule provides a well-defined hydrophobic cavity isolating aldimines from the medium by a dry seam of Se-N chalcogen bonds instead of a wet seam of hydrogen bonds in water. A series of diverse aldimines are formed in situ and trapped rapidly (within 45 min at mM concentrations) in D₂O with more than 90% yields. The encapsulated aldimines are stable for at least one month under ambient conditions. The aliphatic aldimines are selectively formed in the capsule even though they are less stable than aromatic imines in solution. The aldimines can be released from the capsule containers by competitive guests such as adamantane.