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
2014 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 16, 7266-7276 p.Article in journal (Refereed) Published
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-d(6) 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 similar to 8 times faster (at 40 degrees 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 crimes 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.
Place, publisher, year, edition, pages
2014. Vol. 79, no 16, 7266-7276 p.
IdentifiersURN: urn:nbn:se:uu:diva-231998DOI: 10.1021/jo500266kISI: 000340517600002OAI: oai:DiVA.org:uu-231998DiVA: diva2:747005