0000000000627878
AUTHOR
Claribel Báez
ChemInform Abstract: A New Tandem Cross Metathesis-Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams.
Difluorinated amides are treated with methyl vinyl ketone or analogous esters to produce the desired γ- and δ-lactam units including optically active versions.
Design, Synthesis, and Biological Evaluation of Novel Fluorinated Ethanolamines
The preparation of novel fluorinated allylamines and their use as key fragments for the stereoselective synthesis of hydroxyethyl secondary amine (HEA)-type peptidomimetics is described. Our strategy employs chiral sulfinyl imines as synthesis intermediates, by treatment of hemiaminal precursors with two equivalents of vinylmagnesium bromide. The subsequent oxidation of the allylic amines to the corresponding epoxides was achieved by treatment with methyl(trifluoromethyl)dioxirane. Finally, epoxide ring opening with a range of nitrogen nucleophiles provided a library of HEA-derived peptidomimetics with a phenyldifluoromethylene moiety. The biological evaluation of these derivatives revealed…
A New Tandem Cross Metathesis-Intramolecular Aza-Michael Reaction for the Synthesis of α,α-Difluorinated Lactams
A new tandem cross metathesis–intramolecular aza-Michael reaction in which an α,α-difluorinated amide serves as a source of nucleophilic nitrogen is described. This process gives rise to a new family of fluorinated γ- and δ-lactams. The tandem protocol is catalyzed by the Hoveyda–Grubbs second-generation ruthenium catalyst with titanium(IV) tetraisopropoxide as a co-catalyst and it is highly efficient when conjugated ketones are used as the Michael acceptors. With conjugated esters, however, it is necessary to perform a step-by-step procedure in which the cyclization event is activated by the addition of a base. An asymmetric version of the process is also evaluated.