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Stereocontrolled Total Synthesis of (−)‐Stemaphylline
Author(s) -
Varela Ana,
Garve Lennart K. B.,
Leonori Daniele,
Aggarwal Varinder K.
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201611273
Subject(s) - carbenoid , chemistry , yield (engineering) , total synthesis , borylation , amine gas treating , halide , solvent , stereochemistry , sequence (biology) , leaving group , medicinal chemistry , combinatorial chemistry , organic chemistry , rhodium , catalysis , biochemistry , materials science , alkyl , aryl , metallurgy
Homologation of readily available α‐boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl − ) are employed. By performing a solvent switch from Et 2 O to CHCl 3 , efficient 1,2‐metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (−)‐stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (>20:1 d.r.) and 11 % overall yield. The synthesis also features a late‐stage lithiation–borylation reaction with a tertiary amine containing carbenoid.
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