Tuning the Stereoselectivity of an Intramolecular Aldol Reaction by Precisely Modifying a Metal‐Organic Framework Catalyst

We report the catalysis of an enantioselective, intramolecular aldol reaction accelerated by an organocatalyst embedded in a series of multicomponent metal‐organic frameworks. By precisely programming the pore microenvironment around the site of catalysis, we show how important features of an intramolecular aldol reaction can be tuned, such as the substrate consumption, enantioselectivity, and degree of dehydration of the products. This tunability arises from non‐covalent interactions between the reaction participants and modulator groups that occupy positions in the framework remote from the catalytic site. Further, the catalytic moiety can be switched form one framework linker to another. Deliberately building up microenvironments that can influence the outcome of reaction processes in this way is not possible in conventional homogenous catalysts but is reminiscent of enzymes.