Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

A simple and efficient synthetic route to the novel 3a,4-dihydro-3H,7H- and 4H,7H-pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazole ring systems from 3-(prop-2-en-1-yloxy)- or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes has been developed by employing the intramolecular nitrile oxide cycloaddition (INOC) reaction as the key step. The configuration of intermediate aldoximes was unambiguously determined using NOESY experimental data and comparison of the magnitudes of 1JCH coupling constants of the iminyl moiety, which were greater by approximately 13 Hz for the predominant syn isomer. The structures of the obtained heterocyclic products were confirmed by detailed 1H, 13C and 15N NMR spectroscopic experiments and HRMS measurements.

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

This work presents an examination of the selective functionalization of norbornadiene through nitrile oxide 1,3-dipolar cycloaddition/ring-opening metathesis (ROM)/cross-metathesis (CM) protocols. Functionalization of commercially available norbornadiene provided novel bicyclic scaffolds with multiple stereogenic centers. The synthesis involved selective cycloadditions, with subsequent ROM of the formed cycloalkene-fused isoxazoline scaffolds and selective CM by chemodifferentiation of the olefin bonds of the resulting alkenylated derivatives. Various experimental conditions were applied for the CM transformations with the goal of exploring substrate and steric effects, catalyst influence and chemodifferentiation of the olefin bonds furnishing the corresponding functionalized, fluorine-containing isoxazoline derivatives.

Diversity-Oriented Synthesis of Highly Functionalized Alicycles across Dipolar Cycloaddition/Metathesis Reaction

This Account gives an insight into the selective functionalization of some readily available commercial cyclodienes across simple chemical transformations into functionalized small-molecular scaffolds. The syntheses involved selective cycloadditions, followed by ring-opening metathesis (ROM) of the resulting azetidin-2-one derivatives or isoxazoline frameworks and selective cross metathesis (CM) by discrimination of the C=C bonds on the alkenylated heterocycles. The CM protocols have been described when investigated under various conditions with the purpose on exploring chemodifferentiation of the olefin bonds and a study on the access of the corresponding functionalized β-lactam or isoxazoline derivatives is presented. Due to the expanding importance of organofluorine chemistry in drug research as well as of the high biological potential of β-lactam derivatives several illustrative examples to the access of some fluorine-containing molecular entities is also presented in this synopsis.1 Introduction2 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Chlorosulfonyl Isocyanate Cycloaddition3 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Nitrile Oxide Cycloaddition4 Ring C=C Bond Functionalization of Some Cycloalkene β-Amino Acid Derivatives across Metathesis5 Functionalization of sSome Cyclodienes across Nitrile Oxide Cycloaddition6 Selective Synthesis of Functionalized Alicycles across Ring-Opening Metathesis7 Selective Synthesis of Functionalized Alicycles through Cross Metathesis8 Summary and Outlook9 List of Abbreviations

Hypervalent-Iodine Mediated One-Pot Synthesis of Isoxazolines and Isoxazoles bearing Difluoromethyl Phosphonate Moiety

A one-pot, regioselective 1,3-dipolar cycloaddition of in situ generated (diethoxyphosphoryl)difluoromethyl nitrile oxide toward selected alkenes and alkynes is reported. This protocol enables facile access to 3,5-disubstituted isoxazolines and isoxazoles bearing...

Synthesis of New Class of Functionalized Flavones/Isoxazole Derivatives-Nitrile oxide 1,3-Dipolar Cycloaddition

A new series of functionalized flavone-isoxazole derivatives have been synthesized from alkyne tethered 3-hydroxy flavone by adopting facile synthetic method, intermolecular nitrile oxide 1,3-dipolar cycloaddition in the presence of eco-friendly sodium hypochloride oxidant under mild reaction conditions. Structures of all the synthesized compounds were established on the basis of 1H NMR, 13C NMR and ESI-mass.

Synthetic Study on Acremoxanthone A, Part 2: Model Study on the EFG Xanthone Moiety through a Nitrile Oxide Cycloaddition–SNAr Sequence

Toward a total synthesis of acremoxanthone A, we report a model study on the construction of the EFG ring system. The key steps include (1) an intermolecular 1,3-dipolar cycloaddition of an aryl nitrile oxide with a dienone, and (2) an SNAr reaction for construction of the F ring.