Enols oxidative rearrangements

We had two possible routes in which alcohol 72 could be used (Scheme 8.19). Route A would involve rearrangement of tertiary alcohol 72 to enone 76. Deprotonation at C5 and generation of the enolate followed by exposure to an oxaziridine or other oxygen electrophile equivalents might directly afford the hydrated furan C-ring of phomactin A (see 82) via hydroxy enone 81. We had also hoped to make use of a chromium-mediated oxidative rearrangement of tertiary allylic alcohols. Unfortunately, treatment of 72 to PCC produced only unidentified baseline materials, thereby quickly eliminating this route. 

The full paper on the synthesis of onikulactone and mitsugashiwalactone (Vol. 7, p. 24) has been published.Whitesell reports two further useful sequences (cf. Vol. 7, p. 26) from accessible bicyclo[3,3,0]octanes which may lead to iridoids (123 X=H2, Y = H) may be converted into (124) via (123 X = H2, Y = C02Me), the product of ester enolate Claisen rearrangement of the derived allylic alcohol and oxidative decarboxylation/ whereas (123 X = 0, Y = H) readily leads to (125), a known derivative of antirride (126) via an alkylation-dehydration-epoxi-dation-rearrangement sequence. Aucubigenin (121 X = OH, R = H), which is stable at —20°C and readily obtained by enzymic hydrolysis of aucubin (121 X = OH, R = j8-Glu), is converted by mild acid into (127) ° with no dialdehyde detected sodium borohydride reduction of aucubigenin yields the non-naturally occurring isoeucommiol (128 X=H,OH) probably via the aldehyde (128 X = O). ... 

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. 

Mechanism The reaction of the enol form of the carbonyl compound A with selenium dioxide gives selenous enol ester B. The oxidative rearrangement of selenous enol ester B gives C. Loss of selenium and water from C gives the dicarbonyl compound (Scheme 7.16). 

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. 

The unstable enol, first formed after oxidation, rearranges to a carbonyl group. 

The reaction between the acid chloride of chromone-2-carboxylic acid and ethyl ethoxymagnesioacetoacetate probably leads to the expected fi-diketone which enolizes and cyclizes spontaneously to spirofuranone(52).127 A different approach was made by Hungarian workers in their synthesis of tachrosin (53), an unusual kind of flavone isolated from Tephrosia poly-stachyoides and one of the earliest natural furanones to be isolated. They subjected an unsaturated ketone (Scheme 32) to oxidative rearrangement by thallium(III) salts, a reaction well known in chalcone chemistry, and eliminated methanol from the product to obtain the necessary starting material.128... 

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). 

Further reactions on these compounds lead to other oxidised products in which the lack of stereochemical control in the epoxidation is unimportant, so, for example isophorone oxide rearranges with various catalysts to the cyclopentanone 182 (80% yield) while both isomers of pulegone oxide 179 gives the cycloheptadione29 183 (78% yield). Exhaustive methylation of the extended enolate produced by reduction of 181 gives 184 in good yield.28... 

When an alkyne undergoes the acid-catalyzed addition of water, the product of the reaction is an enol. The enol immediately rearranges to a ketone. A ketone is a compound that has two alkyl groups bonded to a carbonyl (C=0) group. An aldehyde is a compound that has at least one hydrogen bonded to a carbonyl group. The ketone and enol are called keto-enol tautomers they differ in the location of a double bond and a hydrogen. Interconversion of the tautomers is called tautomerization. The keto tautomer predominates at equilibrium. Terminal alkynes add water if mercuric ion is added to the acidic mixture. In hydroboration-oxidation, H is not the electrophile, H is the nucleophile. Consequently, mercuric-ion-catalyzed addition of water to a terminal alkyne produces a ketone, whereas hydroboration-oxidation of a terminal alkyne produces an aldehyde. 

A second major application of selenium dioxide is the oxidation of aldehydes and ketones to the corresponding l,2-dicarbonyl.533 7 55 conversion proceeds by reaction of the enol form of the carbonyl (386) with selenium dioxide to give the selenous enol ester, 387. Oxidative rearrangement to 388 is followed by loss of... 

An electrochemical oxidative decarboxylation in combination with an ester enolate Claisen rearrangement was reported by Wuts et al. (Scheme 5.2.26) [51]. A variety of allylic esters such as 97 was subjected to an Ireland-Qaisen rearrangement, and the resulting acids (98) obtained were submitted to electrolytic decarboxylation in a divided cell to afford ketals 99. The use of the divided cell was necessary to suppress side reactions such as alkene reduction. 

Ketones are rearranged oxidatively by reaction of the corresponding enols with thallium(III), e.g. to yield pyrroleacetic acids from acetyl pyrroles (G.W. Kenner, 1973 B W. Rotermund, 1975). 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

Catalytic reduction of codeine (2) affords the analgesic dihydrocodeine (7) Oxidation of the alcohol at 6 by means of the Oppenauer reaction gives hydrocodone (9)an agent once used extensively as an antitussive. It is of note that treatment of codeine under strongly acidic conditions similarly affords hydrocodone by a very unusual rearrangement of an allyl alcohol to the corresponding enol, followed by ketonization. 

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