Nickel-catalyzed preparation of acrylamides from alpha olefins and isocyanates ; Synthetic studies toward ripostatin A
Name
709596374-MIT.pdf
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65fcf18231ac50d144a8cda25ffd3e64
Author(s)
Schleicher, Kristin D. (Kristin Diann)
Advisor(s)
Timothy F. Jamison.
Alternative Title
Synthetic studies toward ripostatin A
Date Issued
2010
Publisher
Massachusetts Institute of Technology
Abstract
Chapter I. In the presence of the N-heterocyclic carbene ligand IPr, the nickel(0)-catalyzed coupling reaction of a-olefins and branched aliphatic isocyanates provides c,-unsaturated amides arising from preferential C-C bond formation at the 2-position of the olefin. This sense of regioselectivity contrasts with the observed carboxamidation at the 1-position of the olefin when phosphine ligands are used. In this reaction, a simple alkene acts as the functional equivalent of a 2-alkenylmetal reagent. ... Chapter II. Synthetic studies on the antibiotic natural product ripostatin A have been carried out with the aim of constructing the C9-C1O bond via a nickel(0)-catalyzed coupling reaction of enynes and epoxides developed in our laboratory, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. ... A cyclopropyl enyne fragment corresponding to C1-C9 of ripostatin A can be synthesized in high yield over 10 steps and was demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling reaction with a model epoxide. The origin of regioselectivity in this particular transformation is also discussed. ... Several synthetic approaches towards the desired C1O-C26 epoxide fragment have been pursued. The presence of the C19-C20 trisubstituted olefin renders introduction of the epoxide via oxidation of or iodocyclization onto a terminal alkene unsuitable. Access of the epoxide by way of nucleophlic displacement should circumvent these problems. The C13 stereocenter can be set via the allylation and reductive decyanation of a cyanohydrin acetonide. ... A mild, fluoride-promoted decarboxylation enables the construction of the C15-C16 bond via an aldol reaction. This product of this transformation is of the correct oxidation state and three steps removed from the targeted epoxide fragment.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 2010.
Vita. Cataloged from PDF version of thesis.
Includes bibliographical references.
Subjects
Chemistry.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
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