Unexpectedly Selective Formation and Reactions of Epoxycyclooctenones under Microwave-Mediated Conditions

Topologically mobile difluorinated cyclooctenones undergo rapid, high-yielding, and completely stereoselective epoxidations with methyl(trifluoromethyl)dioxirane. The epoxides resist conventional hydrolysis but react smoothly in basic media under microwave irradiation to afford unique hemiacetals and hemiaminals in good yield

Unexpectedly Selective Formation and Reactions of Epoxycyclooctenones under Microwave-Mediated Conditions

Topologically mobile difluorinated cyclooctenones undergo rapid, high-yielding, and completely stereoselective epoxidations with methyl(trifluoromethyl)dioxirane. The epoxides resist conventional hydrolysis but react smoothly in basic media under microwave irradiation to afford unique hemiacetals and hemiaminals in good yield

Cu-Catalyzed N<i>-</i>Alkynylation of Imidazoles, Benzimidazoles, Indazoles, and Pyrazoles Using PEG as Solvent Medium

A facile and efficient Cu(I)-catalyzed cross-coupling method is reported for the preparation of N-alkynyl or N-bromoalkenyl heteroarenes from bromoalkynes. Generally superior yields and functional group tolerance were obtained with microwave (MW) irradiation using imidazole, benzimidazole, pyrazole, and indazole substrates and poly(ethylene glycol) 400 (PEG400) as an additive. We speculate that PEG400 acts as both a Cu(I)-stabilizing ligand as well as a phase transfer solvent

Quantifying the Reactivity of a Remarkably Long-Lived Difluorinated Enol in Acidic Methanol via Solution Kinetics and Electronic Structure Calculations

A simple enol acetal underwent rapid cleavage in acidic solution to generate a difluorinated enol, which was sufficiently long-lived to be characterized by 2D NMR in a protic solvent at ambient temperature. Density functional theory calculations on a model reaction suggest that there are significant differences in protonation transition state timing between the fluorinated and nonfluorinated enols

Cu-Catalyzed N<i>-</i>Alkynylation of Imidazoles, Benzimidazoles, Indazoles, and Pyrazoles Using PEG as Solvent Medium

A facile and efficient Cu(I)-catalyzed cross-coupling method is reported for the preparation of N-alkynyl or N-bromoalkenyl heteroarenes from bromoalkynes. Generally superior yields and functional group tolerance were obtained with microwave (MW) irradiation using imidazole, benzimidazole, pyrazole, and indazole substrates and poly(ethylene glycol) 400 (PEG400) as an additive. We speculate that PEG400 acts as both a Cu(I)-stabilizing ligand as well as a phase transfer solvent

Cu-Catalyzed N<i>-</i>Alkynylation of Imidazoles, Benzimidazoles, Indazoles, and Pyrazoles Using PEG as Solvent Medium

A facile and efficient Cu(I)-catalyzed cross-coupling method is reported for the preparation of N-alkynyl or N-bromoalkenyl heteroarenes from bromoalkynes. Generally superior yields and functional group tolerance were obtained with microwave (MW) irradiation using imidazole, benzimidazole, pyrazole, and indazole substrates and poly(ethylene glycol) 400 (PEG400) as an additive. We speculate that PEG400 acts as both a Cu(I)-stabilizing ligand as well as a phase transfer solvent

Cu-Catalyzed N<i>-</i>Alkynylation of Imidazoles, Benzimidazoles, Indazoles, and Pyrazoles Using PEG as Solvent Medium

A facile and efficient Cu(I)-catalyzed cross-coupling method is reported for the preparation of N-alkynyl or N-bromoalkenyl heteroarenes from bromoalkynes. Generally superior yields and functional group tolerance were obtained with microwave (MW) irradiation using imidazole, benzimidazole, pyrazole, and indazole substrates and poly(ethylene glycol) 400 (PEG400) as an additive. We speculate that PEG400 acts as both a Cu(I)-stabilizing ligand as well as a phase transfer solvent

Quantifying the Reactivity of a Remarkably Long-Lived Difluorinated Enol in Acidic Methanol via Solution Kinetics and Electronic Structure Calculations

A simple enol acetal underwent rapid cleavage in acidic solution to generate a difluorinated enol, which was sufficiently long-lived to be characterized by 2D NMR in a protic solvent at ambient temperature. Density functional theory calculations on a model reaction suggest that there are significant differences in protonation transition state timing between the fluorinated and nonfluorinated enols

A Potentially Divergent and Rapid Route to Analogues of Deoxycyclitols, Pentopyranoses, 6-Deoxyhexoses, and Hexoses

Direct precursors to analogues of pentopyranoses, 6-deoxyhexoses, and hexoses, in which a CF2 center replaces the pyranose oxygen, have been synthesized rapidly from trifluoroethanol. A simple scaleable allylation reaction delivers ethers which undergo dehydrofluorination/metalation, followed by addition to either acrolein or cinnamaldehyde, to afford allylic alcohols. Fluorine-assisted [3,3]-rearrangement followed by reduction with sodium borohydride delivers diols, which undergo RCM smoothly to afford cyclohexene diols

Interplay of Structure and Reactivity in a Most Unusual Furan Diels-Alder Reaction

Difluorinated alkenoate ethyl 3,3-difluoro-2-(N,N-diethylcarbamoyloxy)-2-propenoate reacts rapidly and in high yield with furan and a range of substituted furans in the presence of a tin(IV) catalyst. Non-fluorinated congener 2-(N,N-diethylcarbamoyloxy)-2-propenoate fails to react at all under the same conditions. These reactions have been explored using density functional theory (DFT) calculations. They reveal a highly polar transition state, which is stabilized by the Lewis acid catalyst SnCl4 and by polar solvents. In the presence of both catalyst and solvent, a two-step reaction is predicted, corresponding to the stepwise formation of the two new carbon−carbon bonds via transition states which have similar energies in all cases. Our experimental observations of the lack of reaction of the non-fluorinated dienophile, the stereochemical outcomes, and the rate acceleration accompanying furan methylation are all well predicted by our calculations. The calculated free energy barriers generally correlate well with measured reaction rates, supporting a reaction mechanism in which zwitterionic character is developed strongly. An in situ ring opening reaction of exo-cycloadduct ethyl exo-2-(N,N-diethylcarbamoyloxy)-3,3-difluoro-7-oxabicyclo[2.2.1]hept-5-enyl-2-endo-carboxylate, which results in the formation of cyclic carbonate ethyl 4,4-difluoro-5-hydroxy-2-oxo-5,7a-dihydro-4H-benzo[1,3]dioxole-3a-carboxylate by a Curtin−Hammett mechanism, has also been examined. Substantial steric opposition to Lewis acid binding prevents carbonate formation from 2-substituted furans