An Optically Active 4‐Aryl‐3,4‐dihydroisocoumarin‐3‐carboxylate

A four step sequence for the preparation of optically active (R,R)‐ethyl 4‐phenyl‐3,4‐dihydroisocoumarin‐3‐carboxylate is reported. In the first step the first stereocenter was installed by palladium catalyzed asymmetric conjugate addition of PhB(OH)2 to indenone (88% ee). After deprotonation, the ester moiety was introduced with Mander's reagent. The α‐hydroxylation of the resulting β‐oxoester was then achieved with cerium‐catalysis under an air atmosphere. Key transformation was the cyanide‐catalyzed ring transformation of α‐hydroxy‐β‐oxoester furnishing the δ‐lactone moiety of the target compound, which was formed as a mixture of separable cis‐ and trans‐diastereoisomers, both with 88% ee. The cis‐isomer could be epimerized to the trans‐compound. The relative trans and the absolute (R,R)‐configuration of the target compound was established by X‐ray single crystal structure analysis.