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Selective Formation of a Trisubstituted Alkene Motif by trans ‐Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late‐Stage Modification of 5,6‐Dihydrocineromycin B
Author(s) -
Rummelt Stephan M.,
Preindl Johannes,
Sommer Heiko,
Fürstner Alois
Publication year - 2015
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.201501608
Subject(s) - total synthesis , stille reaction , metathesis , stereochemistry , alkene , chemistry , sonogashira coupling , polyketide , combinatorial chemistry , palladium , organic chemistry , catalysis , biosynthesis , polymer , polymerization , enzyme
Countless natural products of polyketide origin have an E‐configured 2‐methyl‐but‐2‐en‐1‐ol substructure. An unconventional entry into this important motif was developed as part of a concise total synthesis of 5,6‐dihydrocineromycin B. The choice of this particular target was inspired by a recent study, which suggested that the cineromycin family of antibiotics might have overlooked lead qualities, although our biodata do not necessarily support this view. The new approach consists of a sequence of alkyne metathesis followed by a hydroxy‐directed trans‐hydrostannation and a largely unprecedented methyl‐Stille coupling. The excellent yield and remarkable selectivity with which the signature trisubstituted alkene site of the target was procured is noteworthy considering the rather poor outcome of a classical ring‐closing metathesis reaction. Moreover, the unorthodox ruthenium‐catalyzed trans‐hydrostannation is shown to be a versatile handle for diversity‐oriented synthesis.