Ketoximes unsymmetrical

In brief communications concerning the use of dialkyl ketoximes (79IZV2840 81MI7, 81MI8) in this reaction, no comprehensive synthetic procedures are described. The experimental details for the synthesis of 2,3-dialkyl-substituted pyrroles from symmetrical and unsymmetrical dialkyl ketoximes and dichloroethane in the KOH/DMSO system (Scheme 63) were first discussed by Trofimov et al. (85KGS59). 

Reaction of hydroxylamine with tri- and tetrasubstituted pyrylium salts yields pyridine iV-oxides and/or 2-isoxazo-lines via the intermediacy of keto-ketoximes <1998T9747>. The regiochemistry of 2-isoxazoline formation from unsymmetrical pyryliums, and the Beckman rearrangement of the intermediate keto ketoximes have also been explored C1998T9747, 1999T15011>. 

Isomerism of Ketoximes.—In the case of aromatic aldehydes they all yield these stereo-isomeric oximes. With the aromatic ketones the condition is different and some yield stereo-isomers and some do not. With symmetrical aromatic ketones in which the two radicals are alike such as di-phenyl ketone, CgHb—CO—C6H,5 no different space relation of the hydroxyl group is possible as the two forms will be identical. When, however, the ketone is unsymmetrical, i.e.j the two radicals are unlike, as in mixed aromatic-aliphatic ketones such as phenyl methyl ketone, CeHs—CO—CH3, or in unsymmetrical di-aryl ketones such as phenyl tolyl ketone, CeHs—CO—C6H4—CHz then the two stereo forms are possible though both forms are not known in all cases. 

Unsymmetrical ketoximes or ketoxime methyl ethers undergo rapid deprotonation to give syn dianions or monoanions, which react regioselectively with electrophilic reagents. ° ° Axial alkylation is observed in conformationally rigid systems. Aldoximes can also be converted to their dianions and alkylated in high yields. ... 

An efficient access to substituted isoquinolines via the oxidative cyclization of aromatic and heteroaromatic ketoximes with alkynes has been developed by Jeganmohan and coworkers (Eq. (7.32)) [40]. In the presence of 2.5mol% of [RuCl2(/ -cymene)]2 and 25mol% of NaOAc, the reaction occurred with high regioselectivity. A variety of unsymmetrical alkynes even including terminal alkynes are compatible for this transformation. Under the reaction conditions, the five-membered ruthenacycle key intermediate 9 was isolated from the stoichiometric reaction. 

Unsymmetrical dialkyl ketoximes in heterocyclization reaction with acetylene can give two isomeric pyrroles or N-vinylpyrroles in the case of acetylene excess (Scheme 1.102). 

The following questions are important for an understanding of the reaction mechanism and for better preparative use of the reaction Which of the two groups of the ketoxime, the methyl (when R =H) or methylene group, primarily participates in the construction of the pyrrole ring Are there differences in the reactivity of the two a-methylene moieties (R R, R =Alk) related to different alkyl groups with normal structures Do the reaction conditions affect the ratios of the structural isomers The answers to these questions have been found during a study of the interaction between a number of unsymmetrical ketoximes with acetylene in the presence of the KOH/DMSO system under conditions that lead to N-vinylpyrroles [188]. 

SCHEME 1.102 Formation of two isomeric pyrroles from unsymmetrical dialkyl ketoximes and acetylene. 

Trofimov, B.A., A.I. Mikhaleva, A.N. Vasiliev, and M.V. Sigalov. 1978. Pyrroles from ketoximes and acetylene. I. Structural orientation of the reaction with unsymmetrical ketoximes. NMR spectra of 1-vinylpyrroles and effects of alkyl substituents. Khim Geterocicl 1 54-59. 

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