Dimensional Reduction of Lewis Acidic Metal-Organic Frameworks for Multicomponent Reactions.

Owing to hindered diffusions, the application of porous catalytic materials has been limited to relatively simple organic transformations with small substrates. Herein we report a dimensional reduction strategy to construct a two-dimensional metal-organic framework (MOF), ZrOTf-BTB, with 96% accessible Lewis acidic sites as probed by the bulky Lewis base pivalonitrile. With nearly free substrate accessibility, ZrOTf-BTB outperformed two three-dimensional MOF counterparts of similar Lewis acidity (ZrOTf-BPDC and ZrOTf-BTC) in catalyzing sterically hindered multicomponent reactions (MCRs) for the construction of tetrahydroquinoline and aziridine carboxylate derivatives with high turnover numbers (TONs). ZrOTf-BTB was also superior to the homogeneous benchmark Sc(OTf) with nearly 14 times higher TON and 9 times longer catalyst lifetime. Furthermore, the topology-activity relationships in these Zr-based Lewis acidic MOFs were rationalized by comparing their Lewis acidity, numbers of Lewis acidic sites, and sterically accessible Lewis acidic sites. ZrOTf-BTB was successfully used to construct several bioactive molecules via MCRs with excellent efficiency. This dimensional reduction strategy should allow the development of other MOF catalysts for synthetically useful and complicated organic transformations.