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Deconstructive Asymmetric Total Synthesis of Morphine‐Family Alkaloid (−)‐Thebainone A
Author(s) -
Hou SiHua,
Prichina Adriana Y.,
Dong Guangbin
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202103553
Subject(s) - enantioselective synthesis , chemistry , stereochemistry , bond cleavage , total synthesis , steric effects , rhodium , ether , cleavage (geology) , alkaloid , natural product , combinatorial chemistry , catalysis , organic chemistry , materials science , fracture (geology) , composite material
Herein, we describe the development of a deconstructive strategy for the first asymmetric synthesis of (−)‐thebainone A, capitalizing on an enantioselective C−C bond activation and a C−O bond cleavage reaction. The rhodium‐catalyzed asymmetric “cut‐and‐sew” transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimized conditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron‐mediated ether bond cleavage, we completed the synthesis of the morphine alkaloid (−)‐thebainone A by two complementary routes.