Palladium‐Catalyzed Enantioselective Three‐Component Dearomative Coupling of Bromoarenes: Modular Construction of Terpenoid Scaffolds

We report a palladium‐catalyzed asymmetric three‐component coupling of bromoarenes, diazoalkanes, and malonates. It represents a significant advancement in catalytic enantioselective dearomative 1,4‐difunctionalization of unactivated arenes. A palladium catalyst of a novel phosphoramidite enables a domino reaction consisting of enantiofacial aryl insertion of a bound diazoalkane and regioselective and stereospecific allylic substitution. The new reaction was readily applied in short total syntheses of three terpenoids, including (+)‐erogorgiaene, (−)‐7‐hydroxy‐3,4‐dihydrocadalin, and (−)‐odongrossin C. Mechanistic studies establish that stereocontrol arises from a concerted aryl migration/N 2 extrusion, which forms the key cyclic π‐allyl palladium intermediate. The C4‐regioselectivity of the malonate attack is governed by a combination of ligand effects, silyl group sterics, and stabilizing noncovalent interactions between the naphthyl ring and sodium malonate.