Oxime group, oxidative cyclization

A method conceptually related to Scheme 131 requires that one or both of the carbonyl groups shown in (266) be present as the oxime derivative, with cyclization leading to the 2-iV-oxide (269 Scheme 132). In actual practice (66JOC941) it was found that two of the proposed intermediates (Table 16, examples 7 and 9) cyclized spontaneously under quater-nization conditions to afford the aromatic 2-azaquinolizinium AT-oxide derivative directly. In another example (Table 16, example 4) (71JCS(C)86l) intramolecular addition occurred during quaternization, but the product, a 3-hydroxy-3,4-dihydro-2-azaquinolizinium derivative, did not lose water spontaneously to form the aromatic system until heated with acid. 

The use of aldehyde derivatives serves in lieu of the carboalkoxy group in cyclization reactions. The oxime 473, when allowed to react with triethyl orthoformate, gives the -oxide 474 (Equation 177) <1996H(43)389>. 

Rather than the expected [3 + 2] cycloaddition, a novel ene-like cycloisomerization occurs on deprotonation of allyltrimethylsilyl-oxime compounds, when the j3-sp2 carbon atom of the allyltrimethylsilyl moiety is tethered to the oxime unit. The resulting nitrile oxide group serves as an enophile, and the final cyclized product still has two functional groups suitable for further manipulations. Thus, ene-like cycloisomerization of allyltrimethylsilyl-oxime 375 with NaOCl in CH2CI2 gives 82% of cyclized product 376 (423). See also Reference 424. 

This chapter, therefore, ends the monograph with a potpourri of reactions all of which occur without a change in oxidation state. In many cases, the reaction is one of nucleophilic attack at an electrophilic C-atom. The result is often hydrolytic bond cleavage (e.g., in carbohydrate conjugates, disubstitut-ed methylene and methine groups, imines, oximes, isocyanates, and nitriles, and various ring systems) or a nucleophilic substitution (e.g., hydrolytic de-halogenation of halocarbons and chloroplatin derivatives, and cyclization reactions). The formation of multiple bonds by dehydration is a special case to be discussed separately. 

Methoxypyrazine-2-one Af-oxides 341 were prepared from oxime derivatives 340 by one-pot cyclization in the presence of DCC/DME with subsequent interaction with Me2S04/K2C03 and NaOH (equation 148) . Similar intramolecular cyclizatiou of ester and oxime O-ethers groups iu the presence of lithium arylthiolate also leads to pyrazin-2-one ring formation . ... 

A new reaction of iV-acyl thiazolidinethione enolates with enolizable aldoxime ethers has been reported to give 2-(thiazolidine-2-thione)-l-azetines 608 with excellent diastereoselectivity (Equation 235) <2003JA3690>. The absence of either a methoxy or a carbonyl group in the 1-azetines indicated a complex mechanism rather than a simple addition reaction. The formation of azetines has been rationalized by combination of the oxime and TiCh to give a highly electrophilic trichlorotitanium iminium intermediate 609, which adds onto enolate 610 to form intermediate 611, which cyclizes to azetidines 612 (Scheme 81). An irreversible elimination of bis-trichlorotitanium oxide provides the ultimate driving force to produce azetines. 

Reduction, nitrogen protection, and oxidation then gave the keto-derivative (449), which was cyclized to (450). Finally, the 3/ -amino-group in (451) was introduced by catalytic reduction of the oxime. ... 

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