Tetradehydro-Diels-Alder Reactions of Flexible Arylalkynes via Folding Inside a Molecular Cage

The tetradehydro-Diels-Alder (TDDA) reaction isa usefultransformation for the rapid assembly of polycyclic scaffolds fromsimple linear precursors in a single synthetic step. However, thereaction requires careful substrate design and harsh reaction conditionsto overcome the inherent entropic cost for this transformation. Hereinwe report an efficient site-selective TDDA transformation within aself-assembled Pd6L4 cage. Despite the largesize, the flexibility of the employed substrates allows for efficientencapsulation within the host cavity. The rate of thermal cyclizationof the encapsulated guest was found to be greatly enhanced, and highproduct selectivity for an unsymmetrical substrate was observed. Theefficiency of this system relies on the precise conformational controlof the substrate within the confined space of the host cage.

Automated summary

The TDDA reaction is a useful method to assemble complex molecular structures from simple precursors in a single step, but it requires careful design of substrates and harsh reaction conditions. In this study, we demonstrate an efficient and site-selective TDDA transformation within a self-assembled Pd6L4 cage. The encapsulation of substrates within the large cavity of the cage allows for enhanced cyclization rates and high selectivity for unsymmetrical substrates.