:Oxanorbornadiene

While unsubstituted OND is known, the most useful OND derivatives are dialkyl OND-2,3-dicarboxylates, readily obtainable by a Diels–Alder cycloaddition between furans and acetylenedicarboxylates such as DMAD.{{cite journal|doi = 10.1002/jlac.19314900110|title = Synthesen in der hydroaromatischen Reihe. XII. Mitteilung. („Dien-Synthesen” sauerstoffhaltiger Heteroringe. 2. Dien-Synthesen des Furans.)|year = 1931|last1 = Diels|first1 = Otto|last2 = Alder|first2 = Kurt|journal = Justus Liebig's Annalen der Chemie|volume = 490|issue = 1|pages = 243–257}}

:Image:ONDwiki1DielsAlder.png synthesis of OND dicarboxylates]]{{clear-left}}

OND-2,3-dicarboxylates (thereafter referred to as OND) display unusually high reactivity towards organic azides{{cite journal|doi = 10.1002/cbic.200700278|title = Metal-Free Triazole Formation as a Tool for Bioconjugation|year = 2007|last1 = Van Berkel|first1 = Sander S.|last2 = Dirks|first2 = A. (Ton) J.|last3 = Debets|first3 = Marjoke F.|last4 = Van Delft|first4 = Floris L.|last5 = Cornelissen|first5 = Jeroen J. L. M.|last6 = Nolte|first6 = Roeland J. M.|author-link6=Roeland J. M. Nolte |last7 = Rutjes|first7 = Floris P. J. T.|journal = ChemBioChem|volume = 8|issue = 13|pages = 1504–8|pmid = 17631666|hdl = 2066/34475|hdl-access = free}} and thiols.{{cite journal|doi = 10.1021/ja809345d|title = Thiol-Selective Fluorogenic Probes for Labeling and Release|year = 2009|last2 = Kislukhin|first2 = Alexander A.| last1 = Hong|first1 = Vu P.|last3 = Finn|first3 = M.G.|journal = J. Am. Chem. Soc.|volume = 131|pages = 9986–94|pmid = 19621956|issue=29|pmc=3166955}} OND–thiol adducts are prone to retro-Diels–Alder fragmentation, which occurs with widely variable rates.{{cite journal|doi = 10.1021/ja301491h|title = Degradable Conjugates from Oxanorbornadiene Reagents|year = 2012|last1 = Kislukhin|first1 = Alexander A.|last2 = Higginson|first2 = Cody J.|last3 = Hong|first3 = Vu P.|last4 = Finn|first4 = M.G.|journal = J. Am. Chem. Soc.|volume = 134|pages = 6491–7|pmid = 22455380|issue=14|pmc = 3432588}}

ONDs react with organic azides to yield a mixture of four products, arising from initial 1,3-dipolar cycloaddition onto either of the two olefins, followed by a retro-Diels–Alder reaction (a cycloelimination reaction) to form 1,2,3-triazoles and furans. The intermediate triazolines avoid detection because of a very strong thermodynamic drive to collapse into two aromatic products. The relative preference of attack on either double bond is governed by the electronic nature of the azides. Electron-rich aliphatic azides, e.g. benzyl azide, react preferentially via their HOMO orbital. Interaction of the azide HOMO with LUMO orbital of the OND, localized on the electron-poor C-2 and C-3, leads the products consistent with path A. Electron-poor aryl azides, such as p-nitrophenyl azide, react, to a significant extent, via their LUMO orbitals, interacting with OND HOMO (C-5 and C-6), leading to higher amounts of path B products. The dipolar reactivity of OND with azides is unusually high for olefins, and even exceeds that of parent electron-poor alkyne DMAD.{{cite journal|doi = 10.1016/S0040-4020(01)92451-2|title = Site selectivity in the reactions of 1,3-dipoles with norbornadiene derivatives|year = 1981|last1 = Cristina|first1 = D.|last2 = De Amici|first2 = M.|last3 = De Micheli|first3 = S.|last4 = Gandolfi|first4 = R.|journal = Tetrahedron|volume = 37|pages = 1349–57}}

:Image:OND+Azides.png{{clear left}}

{{reflist}}

Category:Oxygen heterocycles

Category:Heterocyclic compounds with 2 rings