A reductive coupling strategy towards ripostatin A.
Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim to construct the C9-C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1-C9 has been synthesized in high yield and demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10-C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted decarboxylation enables construction of the C15-C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment.
Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Ave., Cambridge, MA 02139, United States.
Kristin D
KD
Schleicher
Timothy F
TF
Jamison
catalysis; natural product; nickel; reductive coupling; ripostatin A; synthesis