Herein,
the first total syntheses of (−)-pseudocopsinine
(1) and (−)-minovincine (3) from
a common intermediate 8 are detailed, enlisting late-stage,
hydrogen atom transfer (HAT)-mediated free radical bond formations
(C20–C2 and C20–OH, respectively) that are unique to
their core or structure. The approach to 1 features an
Fe-mediated HAT reaction of the intermediate olefin 2, effecting a transannular C20–C2 free radical cyclization
of a challenging substrate with formation of a strained [2.2.1] ring
system and reaction of a poor acceptor tetrasubstituted alkene with
a hindered secondary free radical to form a bond and quaternary center
adjacent to another quaternary center. Central to the assemblage of
their underlying Aspidosperma skeleton is a powerful
[4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazole 9, which affords the stereochemically rich and highly functionalized
pentacyclic intermediate 8 as a single diastereomer in
one step. The work extends the divergent total synthesis of four to
now six different natural product alkaloid classes by distinguishing
late stage key strategic bond formations within the underlying Aspidosperma core from the common intermediate 8. Together, the work represents use of strategic bond analysis combined
with the strategy of divergent synthesis to access six different natural
product classes from a single intermediate.