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Enantioselective Total Synthesis of (−)‐Deoxoapodine
Author(s) -
Kang Taek,
White Kolby L.,
Mann Tyler J.,
Hoveyda Amir H.,
Movassaghi Mohammad
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201708088
Subject(s) - enantioselective synthesis , stereocenter , desymmetrization , chemistry , total synthesis , electrophile , metathesis , stereochemistry , salt metathesis reaction , ring (chemistry) , amide , combinatorial chemistry , catalysis , organic chemistry , polymer , polymerization
The first enantioselective total synthesis of (−)‐deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum‐catalyzed enantioselective ring‐closing metathesis reaction for the desymmetrization of an advanced intermediate that introduces the C5‐quaternary stereocenter. After C21‐oxygenation, the pentacyclic core was accessed by electrophilic C19‐amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6‐etherification reaction proved highly effective to secure the F‐ring and the fourth contiguous stereocenter of (−)‐deoxoapodine with complete stereochemical control.