Generating Diversity in Difluoromethyl Ketone Derivatives

Two consecutive palladium-catalyzed coupling reactions from a readily available difluoroenol stannane set the stage for the synthesis of a range of difluoro- and halodifluoromethyl ketones upon a variable aryl template

[2,3]-Wittig Rearrangements of Difluoroallylic Ethers. A Facile Entry to Highly Functionalized Molecules Containing a CF₂ Group

Readily prepared primary, secondary, and tertiary difluoroallylic alcohols, derived from commercially available and inexpensive 2,2,2-trifluoroethanol, have been transformed into a range of difluoroallylic methyl ethers containing appropriate carbanion-stabilizing substituents. The [2,3]-Wittig rearrangements of these difluoroallylic ethers have been achieved cleanly, using lithium diisopropylamide in tetrahydrofuran at −30 °C, in excellent (secondary ether substrates) to good (primary and tertiary ether substrates) yields. Consequently, the approach allows convenient and rapid access to products containing a mid-chain CF2 group and with a useful level of functionality

Concise Syntheses of γ-Oxo-β,β-difluorinated Amino Acids via Chelated [3,3]-Rearrangement of Difluoroallylic Alcohols

Concise Syntheses of γ-Oxo-β,β-difluorinated Amino Acids via Chelated [3,3]-Rearrangement of Difluoroallylic Alcohol

Concise Syntheses of γ-Oxo-β,β-difluorinated Amino Acids via Chelated [3,3]-Rearrangement of Difluoroallylic Alcohols

Concise Syntheses of γ-Oxo-β,β-difluorinated Amino Acids via Chelated [3,3]-Rearrangement of Difluoroallylic Alcohol

[2,3]-Wittig Rearrangements of Difluoroallylic Ethers. A Facile Entry to Highly Functionalized Molecules Containing a CF₂ Group

Readily prepared primary, secondary, and tertiary difluoroallylic alcohols, derived from commercially available and inexpensive 2,2,2-trifluoroethanol, have been transformed into a range of difluoroallylic methyl ethers containing appropriate carbanion-stabilizing substituents. The [2,3]-Wittig rearrangements of these difluoroallylic ethers have been achieved cleanly, using lithium diisopropylamide in tetrahydrofuran at −30 °C, in excellent (secondary ether substrates) to good (primary and tertiary ether substrates) yields. Consequently, the approach allows convenient and rapid access to products containing a mid-chain CF2 group and with a useful level of functionality

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

Selected Substituent Effects on the Rate and Efficiency of Formation of an Eight-Membered Ring by RCM

Studies of a range of reactions forming cyclooctenones highlight a discrepancy between cyclization rate and cyclization efficiency. Cyclization rates change modestly as the oxygen function at the allylic position is varied, and increase upon gem-dimethylation. Cyclization efficiency has also been quantified for four substrates, revealing a range of effective molarities (EMs) of 2 orders of magnitude that are substituent dependent. The most efficient cyclization appears to result from suppression of the cross-metathesis pathway through which oligomerization begins, rather than from a particularly rapid cyclization reaction. In the presence of a Ti(IV) cocatalyst, diene monomers transform smoothly to eight-membered-ring products without the intermediacy of dimers or other oligomers, indicating that the cyclizations are kinetically and not thermodynamically controlled. The gem-dialkyl effect is also shown to be kinetic

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

Selected Substituent Effects on the Rate and Efficiency of Formation of an Eight-Membered Ring by RCM

Studies of a range of reactions forming cyclooctenones highlight a discrepancy between cyclization rate and cyclization efficiency. Cyclization rates change modestly as the oxygen function at the allylic position is varied, and increase upon gem-dimethylation. Cyclization efficiency has also been quantified for four substrates, revealing a range of effective molarities (EMs) of 2 orders of magnitude that are substituent dependent. The most efficient cyclization appears to result from suppression of the cross-metathesis pathway through which oligomerization begins, rather than from a particularly rapid cyclization reaction. In the presence of a Ti(IV) cocatalyst, diene monomers transform smoothly to eight-membered-ring products without the intermediacy of dimers or other oligomers, indicating that the cyclizations are kinetically and not thermodynamically controlled. The gem-dialkyl effect is also shown to be kinetic

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate