Modular Syntheses of Phenanthroindolizidine Natural Products

A highly concise strategy for the total synthesis of phenanthroindolizidines was developed. The one-pot iterative Suzuki-Miyaura reaction of aryl boronic acids with ortho-bromoaryl N-methyliminodiacetate (MIDA) boronate followed by a second Suzuki-Miyaura reaction with a suitable pyridyl bromide provided ortho-aza-terphenyls. Subsequent saturation of the triple bond, treatment with mesyl chloride, and reduction of the resulting dihydroindolizidinium ring afforded the hexahydroindolizines. A final vanadium-catalyzed oxidative electrocyclization provided the desired alkaloids in only three column-separation operations.