Open AccessGold(I)-Mediated Cycloisomerization/Cycloaddition Enables Bioinspired Syntheses of Neonectrolides B–E and Analogues
Author(s) -
Thomas J. Purgett,
Matthew W. Dyer,
Bryce Bickel,
James McNeely,
John A. Porco
Publication year - 2019
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.9b06355
Subject(s) - cycloisomerization , chemistry , cycloaddition , tandem , stereochemistry , formylation , diastereomer , natural product , combinatorial chemistry , sequence (biology) , cascade reaction , substrate (aquarium) , organic chemistry , catalysis , biochemistry , materials science , oceanography , composite material , geology
Development of a synthetic route to the oxaphenalenone (OP) natural products neonectrolides B-E is described. The synthesis relies on gold-catalyzed 6- endo -dig hydroarylation of an unusual enynol substrate as well as a one-pot Rieche formylation/cyclization/deprotection sequence to efficiently construct the tricyclic oxaphenalenone framework in the form of a masked ortho -quinone methide ( o -QM). A tandem cycloisomerization/[4 + 2] cycloaddition strategy was employed to quickly construct molecules resembling the neonectrolides. The tricyclic OP natural product SF226 could be converted to corymbiferan lactone E and a related masked o- QM. Our study culminates with the application of the tandem reaction sequence to syntheses of neonectrolides B-E as well as previously unreported exo -diastereomers.