Open AccessDivergent Total Syntheses of (−)-Pseudocopsinine and (−)-Minovincinine
Author(s) -
Xianhuang Zeng,
Vyom Shukla,
Dale L. Boger
Publication year - 2020
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.0c02493
Subject(s) - chemistry , total synthesis , aspidosperma , alkene , stereochemistry , cycloaddition , radical cyclization , diastereomer , ring (chemistry) , olefin fiber , organic chemistry , catalysis , indole test
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.