An Efficient Ruthenium-Catalyzed Formal Synthesis of (-)-Isoavenaciolide

A formal synthesis of (−)-isoavenaciolide (1) by two different routes is reported. The first approach, leading to a key precursor 2 of (−)-isoavenaciolide (1), features the stereoselective construction of the three contiguous stereogenic centers by Evans diastereoselective reduction (d.e. = 80%) of β-hydroxy ketone 8. In the more efficient second approach, the nine-step sequence leading to the key precursor 2 involves sequential ruthenium-catalyzed hydrogenation reactions of β-keto ester 4 and β-hydroxy ketone 14 to form the two hydroxyl groups with an excellent control of the anti stereochemistry (d.e. = 99%). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)