title: 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.
abstract: 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.
authors: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
authors: Stephan M
authors: SM
authors: Rummelt
authors: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
authors: Johannes
authors: J
authors: Preindl
authors: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany).
authors: Heiko
authors: H
authors: Sommer
authors: Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr (Germany). fuerstner@kofo.mpg.de.
authors: Alois
authors: A
authors: Fürstner
mesh_terms: D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry*; D008958:Models, Molecular; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D000475:Alkenes; D001688:Biological Products; D007783:Lactones; C000602311:cineromycin B
keywords: alkyne metathesis; cross-coupling; hydrostannation; natural products; ruthenium