Oxime derivatives, oxidative addition

Ketones are more stable to oxidation than aldehydes and can be purified from oxidisable impurities by refluxing with potassium permanganate until the colour persists, followed by shaking with sodium carbonate (to remove acidic impurities) and distilling. Traces of water can be removed with type 4A Linde molecular sieves. Ketones which are solids can be purified by crystallisation from alcohol, toluene, or petroleum ether, and are usually sufficiently volatile for sublimation in vacuum. Ketones can be further purified via their bisulfite, semicarbazone or oxime derivatives (vide supra). The bisulfite addition compounds are formed only by aldehydes and methyl ketones but they are readily hydrolysed in dilute acid or alkali. 

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 transformations of 136 proceed cleanly upon treatment with a catalytic amount of Pd(PPh3)4, in the presence of triethylamine and molecular sieve (MS) 4 A it apparently is initiated by oxidative addition of the N(sp )-0 bond of 136 to the Pd(0) complex, and this is succeeded by two or even three intramolecular carbopalladations followed by / -hydride elimination. This Heck-type reaction is not affected by the configuration of the oxime derivatives probably due to a facile enough if/Z-isomerization of the alkylideneaminopalladium intermediate. 

Oxidative deoximation. Aldehydes and ketones can be recovered from the oxime derivative by treatment with pyridinium chlorochromate (2 equiv.) in CH2CI2 (12-24 hours, 25°). Addition of sodium acetate inhibits epimerization in the case of a-methyl ketones. Yields range from 30 to 85%. ... 

An N-0 bond in oxime derivatives undergoes oxidative addition to form a Pd-imino bond. New Pd-catalyzed reaetions of oximes, such as the amino Heck reaction, have been discovered (see Chapter 3.2.10) [34]. 

Interestingly, this Heck-type palladium-catalyzed oxidative addition/insertion manifold can also be applied to the actual formation of the carbon-heteroatom bond. This was illustrated by Narasaka in the reaction of olefin-tethered oxime derivatives. This chemistry can be considered to arise from oxidative addition of the N—O bond to palladium (30) followed by the more classical olefin insertion and (3-hydride elimination, ultimately allowing the assembly of pyrroles (Scheme 6.58) [79]. The nature of the OR unit was found to be critical in pyrrole formation, with the pentafluorobenzoylimine leading to selective cyclization and rearrangement to the aromatic product. An analogous approach has also been applied to pyridines and imidazoles [80]. 

As we found that furan and thiophene substituted oximes can be used as substrates for the INOC reactions (Eq. 5) [29b] similarly, furan substituted nitro alkane 134 is also a good substrate for INOC reactions (Eq. 13) [40]. The furfuryl derivative 134, prepared via Michael addition of furfuryl alcohol to 4-methoxy- -nitrostyrene, was subsequently transformed without isolation of the intermediate nitrile oxide 135 to the triheterocyclic isoxazoline 136 as a 5 1 mixture of isomers in high yield. 

Regioselective Beckmann rearrangements were used as key steps in the synthesis of phosphonoalkyl azepinones (Scheme 36) [43b] and in a formal total synthesis of the protein kinase C inhibitor balanol (Scheme 37) the optically active azide 197 derived from cyclohexadiene mono-oxide was converted into ketone 198 in several steps. After preparation of the oxime tosylates 199 (2.3 1 mixture), a Lewis acid mediated regioselective Beckmann rearrangement gave the lactams 200 and 201 in 66% and 9% yield, respectively. Lactam 201 underwent a 3-e im-ination to give additional 200, which served as a key intermediate in a balanol precursor synthesis (Scheme 37) [43 cj. 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

Dipolar addition of ethyl propiolate to the nitrile oxide 285, prepared by chlorination of the corresponding oxime, gave, after removal of protecting groups, the C-glycosyl-isoxazole205 (286). These reactions further demonstrate the utility of anomerically functionalized C-/3-D-ribofuranosyl derivatives that can be prepared from the versatile aldehyde 100. 

The sesquiterpene skeleton has also been assembled by the intramolecular nitrile oxide cycloaddition sequence. Oxime 238 (obtained from epoxy silyl ether 237), on treatment with sodium hypochlorite gave isoxazoline 239, which was sequentially hydrolyzed and then subjected to the reductive hydrolysis conditions-cyclization sequence to give the furan derivative 240 (330) (Scheme 6.93). In three additional steps, compound 240 was converted to 241. This structure contains the C11-C21 segment of the furanoterpene ent-242, that could be obtained after several more steps (330). 

Many compounds have been tested as ignition quality improvers—additives which shorten the ignition delay to a desirable duration. An extensive review in 1944 (6, 43) listed 303 references, 92 dealing with alkyl nitrates and nitrites 61 with aldehydes, ketones, esters, and ethers 49 with peroxides 42 with aromatic nitro compounds 29, with metal derivatives 28 with oxidation and oxidation products 22 with polysulfides 16 with aromatic hydrocarbons nine with nitration and four with oximes and nitroso compounds. In 1950, tests at the U. S. Naval Engineering Experiment Station (48) showed that a concentration of 1.5% of certain peroxides, alkyl nitrates, nitroaikanes, and nitrocarbamates increased cetane number 20 or more units. 

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