Palladium-Catalyzed Enantioselective [4 + 2] Annulation with Allenes: Direct Access to Chiral Silatetralins

Chiral tetralins represent privileged scaffolds in medicinal chemistry, and the incorporation of silicon as a bioisostere offers a valuable strategy for molecular design. Nevertheless, efficient synthetic approaches to enantiopure silicon-bridged tetralin analogues remain highly desirable and underdeveloped. Herein, we present the strategy for constructing chiral silatetralins via a highly enantioselective palladium-catalyzed [4 + 2] annulation between benzosilacyclobutenes and a wide range of allenes by employing a chiral phosphoramidite ligand. The reaction is distinguished by exclusive proximal CC bond insertion of the allene and selective Si-C-(sp(2)) bond activation of benzosilacyclobutene. This method exhibits a robust substrate scope, accommodating allenes with alkyl, alkenyl, aryl, silyl, alkoxy, and complex bioactive substituents to deliver enantioenriched functionalized silatetralins. Moreover, the protocol provides direct access to valuable exocyclic methylene-containing silatetralins, serving as versatile intermediates for further synthetic diversification.