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

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.