title: Distal two-bond versus three-bond electronegative oxo-substituent effect controls the kinetics and thermodynamics of the conversion of a C-nitroso function to the corresponding oxime in the conformationally locked pentofuranose (bicyclo[2.2.1]heptane) system.
abstract: We report the high-yielding and scalable diastereospecific synthesis of isomeric bicyclo[2.2.1]heptane-7- and -8-oximes and their corresponding C-nitroso derivatives, which are the key intermediates for the synthesis of carbanucleosides. Neither the (C7-R)-nitroso- nor (C8-S)-nitrosobicycloheptane system requires any external base in DMSO-d6 to afford the corresponding oxime, and no reverse isomerization from the oxime to the C-nitroso compound was observed. The conversion of the (C8-S)-nitroso compound to the E/Z-oximes was ∼8 times faster (at 40 °C) than that of the (C7-R)-nitroso derivative. The mechanism involves first-order reaction kinetics for the conversion of either the (C7-R)- or (C8-S)-nitroso derivative to the corresponding E/Z-oximes. The lower rate of conversion of the (C7-R)-nitroso compound to the corresponding oximes compared with that of the (C8-S)-nitroso derivative is attributed to the fact that the acidic H8 ionizing center is two bonds away from the OPMB group on C1 in the latter whereas H7 is three bonds away from the C1 OMe group in the former, making the effect of the electron-withdrawing group on C1 stronger in the latter.
authors: Program of Chemical Biology, Department of Cell and Molecular Biology, Biomedical Centre, Uppsala University , SE-75123 Uppsala, Sweden.
authors: Mansoureh
authors: M
authors: Karimiahmadabadi
authors: Sayeh
authors: S
authors: Erfan
authors: Andras
authors: A
authors: Földesi
authors: Jyoti
authors: J
authors: Chattopadhyaya
mesh_terms: D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D007700:Kinetics; D008968:Molecular Conformation; D009603:Nitroso Compounds / Q000737:chemistry; D010087:Oxides / Q000737:chemistry*; D010091:Oximes / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D009603:Nitroso Compounds; D010087:Oxides; D010091:Oximes