Alkyl oximes

Polyakov VA, Nelen MI, Nazarpack-Kandlousy N, Ryabov AD, Eliseev AV. Imine exchange in 0-aryl and 0-alkyl oximes as a base reaction for aqueous dynamic combinatorial libraries. A kinetic and thermodynamic study. J Phys Org Chem 1999 12 357-363. 

Oximes may be alkylated at nitrogen or oxygen both types are electrolytically reducible [1,94,95] in their protonated form. The nitrones are generally also reducible in alkaline solution, whereas the O-methyl ethers of oximes are not reducible in ordinary media containing alkali metal ions. In solutions containing quaternary ammonium /j-toluenesul-fonates, some 0-alkylated oximes give a polarographic wave,... 

The asymmetric synthesis of aziridines via these routes has been sparingly investigated. Aziridines bearing an A -alkoxy substituent can be resolved into nitrogen stereoisomers. Modest asymmetric induction was observed in the reaction of a chiral 0-alkyl oxime with dimethylsulfonium methylide (equation 41). The analogous reaction with diazomethane was not stereospecific. Earlier work in this area has been reviewed. 

As a rule, simple azavinylogues are unstable compounds, due to the easy hydrolysis of the imino bond. However, the particular case of 0-alkylated oximes (XCHNOY with Y = R or Ar) can be interesting insofar that the oximic imino... 

Toja, E., Bonetti, C., Butti, A., Hunt, R, Fortin, M., Barzaghi, F., Formento, M. L., Maggioni, A., Nencioni, A., GalUani, G. 1-Alkyl-1,2,5,6-tetrahydropyridine-3-carboxaldehyde-0-alkyl-oximes a new class of potent orally available active muscarinic agaonists related to arecoline. Eur. J. Med. Chem. 1991, 22, 853-868. 

A further example of a one-bond-forming pyridine synthesis is provided by the intramolecular cyclization of 0-alkyl-oximes such as (3) under conditions of flash vacuum pyrolysis. Cyclization occurs as a result of the generation of conjugated iminyl radicals (4) (Scheme 1). ... 

Since oximes of erythromycin are less prone to intramolecular cyclization than the parent compound, a structure-activity study was conducted on a series of 9-(0-alkyl)oxime derivatives of erythromycin [84]. From this work, roxithromycin, the 9-[D-(2-methoxyethoxy)methyl]oxime (12), was selected for further development. The isomer with E stereochemistry (oxime substituent syn to C-8 of lactone) is more active than the Z isomer [84]. The X-ray crystal structure of roxithromycin reveals a conformation of the lactone similar to that of erythromycin [85]. The similarity was also established by solution NMR studies, which suggested that the orientation of the oxime substituent helped to explain the increased hydrophobicity of roxithromycin and its greater penetration into certain tissues [86, 87]. 

In cases where the oximes or 0-alkyl oximes are sterically hindered, acidic conditions may not be necessary (Scheme 34).[85]-[S7] Excellent diastereoselectivities were observed... 

Alkynylbenzaldehyde 0-alkyl oximes were also used as precursors of isoquinolines (Scheme 16, route c). After intramolecular electrophilic cyclization, Af-alkoxy groups were eliminated to form aldehydes (for example benzaldehyde). Shin et al. synthesized 5-fluoro-3-phenylisoquinoline using a AgOTf/TfOH catalytic system (Scheme 19), [55] while Wu achieved Cu-catalyzed synthesis of several 7-fluoroisoquinoUne derivatives [56]. 

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