Indole-diterpene synthetic studies: Total synthesis of (-)-21-isopentenylpaxilline

An efficient, stereocontrolled total synthesis of the complex indole-diterpene alkaloid (-)-21-isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (-)-68, involving a highly efficient union of the eastern and western fragments (-)-68 and 5 exploiting our 2-substituted indole synthesis, application of the Negishi pi cycloalkylation tactic as a new, potentially general protocol for the construction of ring C, and the fragmentation of a beta,gamma-epoxy ketone to introduce the tertiary OH group at C(13) in the indole diterpene skeleton.