Enol ethers oxidative rearrangement

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

Bromination of the enol ether product with two equivalents of bromine followed by dehydrobromination afforded the Z-bromoenol ether (Eq. 79) which could be converted to the zinc reagent and cross-coupled with aryl halides [242]. Dehydrobromination in the presence of thiophenol followed by bromination/dehydrobromination affords an enol thioether [243]. Oxidation to the sulfone, followed by exposure to triethylamine in ether, resulted in dehydrobromination to the unstable alkynyl sulfone which could be trapped with dienes in situ. Alternatively, dehydrobromination of the sulfide in the presence of allylic alcohols results in the formation of allyl vinyl ethers which undergo Claisen rearrangements [244]. Further oxidation followed by sulfoxide elimination results in highly unsaturated trifluoromethyl ketonic products (Eq. 80). 

Oxidation of organic substrates. This hydroperoxide converts 2,3-dimethyl-2-butcne into tetramethylethylene oxide with simultaneous formation of 3-bromo-4,5-dihydro-5-hydroxy-4,4-dimethyl-3,5-diphenyl-3H-pyrazole (2). Dialkyl olefins, however, are not epoxidized by I. Enol ethers are converted to a variety of epoxide rearrangement products.2... 

Two key intermediates in the production of vitamin A are citral and the so-called C5 aldehyde. In the modem routes to these intermediates, developed by BASF and Hoffmann-La Roche, catalytic technologies are used (see Fig. 2.29 and 2.30). Thus, in the synthesis of citral, the key intermediate is 2-methyl-l-butene-4-ol, formed by acid-catalyzed condensation of isobutene with formaldehyde. Air oxidation of this alcohol over a silver catalyst at 500°C (the same catalyst as is used for the oxidation of methanol to formaldehyde) affords the corresponding aldehyde. Isomerization of 2-methyl-l-butene-4-ol over a palladium-on-charcoal catalyst affords 2-methyl-2-butene-4-ol. The latter is then reacted with the aldehyde from the oxidation step to form an enol ether. Thermal Claisen rearrangement of the enol ether gives citral (see Fig. 2.29). 

We also observed similar phenomena in the reaction of silyl enol ethers with cation radicals derived from allylic sulfides. For example, oxidation of allyl phenyl sulfide (3) with ammonium hexanitratocerate (CAN) in the presence of silyl enol ether 4 gave a-phenylthio-Y,5-un-saturated ketone 5. In this reaction, silyl enol ether 4 reacts with cation radical of allyl phenyl sulfide CR3 to give sulfonium intermediate C3, and successive deprotonation and [2,3]-Wittig rearrangement affords a-phenylthio-Y,6-unsaturated ketone 5 (Scheme 2). Direct carbon-carbon bond formation is so difficult that nucleophiles attack the heteroatom of the cation radicals. 

Cyclobutenediones. A general route to these diones involves the regiospecific cycloaddition of dichloroketene to the phenylthio enol ether (1) of a ketone. The adduct (2) on treatment with triethylamine eliminates (J MsSCI and rearranges to 3. Peracid oxidation of 3 results directly in a cyclobutenedione (4). 

The best results are obtained with the above-named oxidants in a mixed solvent of methanol and trimethyl orthoformate in the presence of a strong acid these conditions presumably oisure rq>id acetaliza-tion of the carbonyl to prevent a-oxidation. This side reaction is more smous when is alkyl and the orthoformate is omitted, or if ethyl carbonate or acetonitrile is used as solvent. Prefenol ethers and enamines give the desired oxidative rearrangement in hig yield. 

The oxidation of the cyclobutylcarbinol in equation (52) with buffered PCC proceeds with partial rearrangement a 1 2 ratio of the expected aldehyde (58) to foe ring-expanded cyclic enol ether (59) is ob-... 

The oxidative rearrangement most widely used in synthesis is the oxidative 1,2-shift of an alkene or enol, which is shown in the formal sense in equation (33). The alkene may be electron deficient such as an unsaturated ketone, or electron rich such as an enol, enol ether or enamine. 

Cycloheptane annelation (7, 212). The mixed cuprate 1 reacts with acid chlorides to afford vinylcyclopropyl ketones. Previously these ketones were prepared from aldehydes by condensation with l-lithio-2-vinylcyclopropane followed by oxidation (7, 192-193). These compounds are rearranged to 4-cycloheptenones on conversion to trimethylsilyl enol ethers, thermolysis, and hydrolysis. ... 

The total synthesis of (+)- -onocerin via four-component coupling and tetracyclization steps was achieved in the laboratory of E.J. Corey. The farnesyl acetate-derived acyl silane was treated with vinyllithium, which brought about the stereospecific formation of a (Z)-silyl enol ether as a result of a spontaneous Brook rearrangement. In the same pot, the solution of I2 was added to obtain the desired diepoxide via oxidative dimerization. 

Block has described a further use for a-haloalkanesulfonyl bromides radical addition to silyl enol ethers followed by simple Ramberg-BScklund rearrangement yields a,p-unsaturated ketones (Scheme 31) 94,98 Ethylene oxide, an acid scavenger, is used as solvent for the radical addition to prevent hydrolysis of the silyl enol ether. 

Snider has shown that thermolysis of 2,6-dimethyl-2,7-octadienal at 350°C yielded three compounds, 365-367, having the iridoid skeleton. The lactone 368 was made by cyclization of the corresponding hydroxy acid ( 8-hydroxy-citronellic acid ), and its tert-butyldimethylsilyl enol ether rearranged in an Ireland-type Claisen rearrangement, yielding the iridoid acid 369 after removal of the silyl group with HF in acetonitrile. The latter was converted (by hydrobora-tion-oxidation) into both isomers of dihydronepetalactone (370) (erroneously considered to be unsynthesized by the authors, who clearly did not read Vol. 4, p. 497). Iridomyrmecin (371) is also accessible from 369 (Scheme 30). 

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