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

Abstract

The tetradehydro-Diels–Alder (TDDA) reaction is a useful transformation for the rapid assembly of polycyclic scaffolds from simple linear precursors in a single synthetic step. However, the reaction requires careful substrate design and harsh reaction conditions to overcome the inherent entropic cost for this transformation. Herein we report an efficient site-selective TDDA transformation within a self-assembled Pd 6 L 4 cage. Despite the large size, the flexibility of the employed substrates allows for efficient encapsulation within the host cavity. The rate of thermal cyclization of the encapsulated guest was found to be greatly enhanced, and high product selectivity for an unsymmetrical substrate was observed. The efficiency of this system relies on the precise conformational control of the substrate within the confined space of the host cage.