Rhodium-catalyzed cyclohydrocarbonylation: Application to the synthesis of (+)-prosopinine and (-)-deoxoprosophylline

Efficient convergent total syntheses of (+)-prosopinine (1) and (-)-deoxoprosophylline (4) were accomplished using Rh-BIPHEPHOS complex-catalyzed cyclohydrocarbonylation as the key step. The Rh-BIPHEPHOS complex-catalyzed cyclohydrocarbonylation of I, derived from (R)-serine, at 65 degrees C and 4 atm of CO and H-2 (1:1) in ethanol afforded 6-ethoxypiperidine II, which was transformed to enantiopure (+)-prosopinine (1) in 3 steps. In a similar manner, (-)-deoxoprosophylline was synthesized through cyclohydrocarbonylation of IV derived from (S)-serine, giving 6-ethoxypiperidine V. The key intermediate V was transformed to enantiopure (-)-deoxoprosophylline (4) in 4 steps. These two short total syntheses clearly demonstrate the usefulness of the extremely regioselective cyclohydrocarbonylation process developed in these laboratories for the concise syntheses of piperidine alkaloids and related compounds.