Straightforward assembly of the octahydroisoquinoline core of morphinan alkaloids.

The octahydroisoquinoline core of morphinan was assembled starting from readily available arylcyclohexadienes. Three different approaches were developed, including a metal- and an acid-mediated Mannich type process and an anionic-mediated cyclization. All provided the desired motif as a single diastereomer having a C9-C13-C14 trans-cis relative configuration.

Birch reductive alkylation of biaryls: scope and limitations.

Birch reductive alkylation of biaryls has been carried out by varying the nature of the substituents on the aromatic rings. Our investigations have focused on electron-rich substituents such as OMe, OH, and NR(2) groups as they are present on the skeleton of targeted alkaloids. The regioselectivity is strongly affected by the electronic nature of these substituents on both rings.

Efficient synthetic approaches to the common scaffold of indole alkaloids.

Birch reductive alkylation of 2-aminobiphenyls affords access to highly functionalized polyenes that react through a Pd(II)-catalyzed oxidative amination cascade or through a double 1,4-addition process to provide the tetracyclic skeleton of indole alkaloids with up to four stereogenic centers created in a single-pot operation.