Regiodivergent 1,3-Annulation of Valylene with 4-Hydroxycoumarins

Pyranocoumarins are widely distributed in natural products and exhibit intriguing biological activities, making their efficient synthesis highly desirable. Herein, we developed an efficient method for synthesizing two new types dimethylallyl-decorated pyranocoumarins in efficiency through catalytic formal [3 + 3] annulation of 4-hydroxycoumarins with valylene. Under acid catalysis, exclusive 1,3-alkenoxylation afforded natural product-like angular pyranocoumarins, while Rh catalysis switched regioselectivity to 3,1-alkenoxylation. The protocol features high atom-economy, readily available substrates, and excellent regio- and chemo-selectivity. Mechanistic studies indicated the reaction proceeds via regioselective hydroalkoxylation to form diene or allene intermediates, followed by intramolecular cyclization. This work not only represents a good paradigm in addressing selectivity challenges in reactions involving substrates with multireactive-site but also offers a robust platform for rapid construction of skeletal variants beyond naturally occurring structures.