Epoxides rearrangement with hydroxide

Cycloheptanes.—One synthesis of karahanaenone (231) depends upon thermal rearrangement of a 2-methylene-5-vinyltetrahydrofuran, and the conditions for this type of reaction have been examined on a simpler model (232), which arises from the dihydrofuran (233) at 140—200 °C. The reaction to the cycloheptenone (234) occurs rapidly at active sites on a glass surface, but is arrested in tubes coated with sodium hydroxide. Higher temperatures and lower pressures give two other compounds (235) and (236). All these reactions involve the biradical (237), as does the conversion of the cyclopropane (238) into the cycloheptenone (234). Karahanaenone (231) has also been made by isomerization of terpinolene epoxide (239) with boron trifluoride etherate. Eucarvone (240 R = H) should not be... 

Reaction of the carbanion of chloromethyl phenyl sulphoxide 409 with carbonyl compounds yields the corresponding 0-hydroxy adducts 410 in 68-79% yield. Each of these compounds appears to be a single isomer (equation 242). Treatment of adducts 410 with dilute potassium hydroxide in methanol at room temperature gives the epoxy sulphoxides 411 (equation 243). The ease of this intramolecular displacement of chloride ion contrasts with a great difficulty in displacing chloride ion from chloromethyl phenyl sulphoxide by external nucleophiles . When chloromethyl methyl sulphoxide 412 is reacted with unsymmetrical ketones in the presence of potassium tcrt-butoxide in tert-butanol oxiranes are directly formed as a mixture of diastereoisomers (equation 244). a-Sulphinyl epoxides 413 rearrange to a-sulphinyl aldehydes 414 or ketones, which can be transformed by elimination of sulphenic acid into a, 8-unsaturated aldehydes or ketones (equation 245). The lithium salts (410a) of a-chloro-/ -hydroxyalkyl... 

If a polyol with a primary epoxide is treated with strong base, a rearrangement to the more stable secondary epoxide takes place, as observed by Payne [40]. If an unprotected bromodeoxyaldonolactone is treated with strong base a similar rearrangement may be expected. We found that if 6-bromo-2,6-dideoxy-D-arahzno-hexonolactone (3) (Scheme 5) was treated with 4 molar equivalents of potassium hydroxide, 2-deoxy-L-n bo-hexono-1,4-lactone (15) was isolated as the only product after work up [32]. 

Epoxidation of enones on treatment with basic hydrogen peroxide or /-butyl hydroperoxide, or with bleach, might be viewed as another form of trapping the initially produced anion.99 In this case the enol-ate, e.g. (425 Scheme 57), attacks the oxygen of the hydroperoxide to eject hydroxide and yield the epoxy ketone (426)." Finally, the initial anion can also be trapped by a sigmatropic rearrangement, as in... 

The structure of chlorosantonin (491) obtained from santonin 4,5-epoxide with hydrogen chloride gas has been solved by X-ray analysis. Undoubtedly the most remarkable sesquiterpenoid rearrangement is that observed when the dried sodio salt of (492) is heated to reflux in excess phosphorus oxychloride. The rearrangement product in question was isolated by removal of the excess POCI3, followed by neutralization with concentrated aqueous ammonia. The resultant ether extract was treated with hot 15% sodium hydroxide and the product mixture was distilled and purified by column chromatography. One of the products (about 3% yield) has been identified by X-ray analysis as (493), but as yet no mechanism has been suggested... 

Guirado et al reported a one-pot preparative process involving a benzilic acid rearrangement step followed by a spontaneous epoxidation of the intermediates. Treatment of diketone 32 with sodium hydroxide at room temperature gave 2,5,5-trichloro-l,2-epoxycyclopentane-l-carboxylic acid 35 as a single product in quantitative yield. This transformation has been explained by sequential participation of intermediates 33 and 34. 

Aldonolactones activated at the primary position very rapidly form a primary epoxide of the open aldonic acid when dissolved in aqueous base. Usually, 3 molar equivalents of potassium hydroxide are used to keep the pH above 14. This is a prerequisite for a Payne rearrangement and/or for opening of the epoxide by an intramolecular nucleophile. Using the weaker base potassium carbonate, no rearrangement will take place and hence the primary epoxide will be opened at the primary carbon by hydroxide. Pentonolactones activated at C-5 will isomerise stereospecifically at C-4 when treated with strong potassium hydroxide. This is due to the opening of the primary epoxide by the carboxylate... 

Similarly,5-0-mesyl-23-0-isopropylidene-D-lyxonolactone (3) [18] was rearranged to L-ribonolactone (4) when treated with 3 molar equivalents of potassium hydroxide followed by acidification [19] (Scheme 4). The compound was isolated as the highly crystalline 3,4-0-benzylidene-L-ribono-l,5-lactone. The method was also used to prepare L-lyxonolactone from 5-0-mesyl-23-0-iso-propylidene-D-ribonolactone (5) [19] but when during the workup the pH was adjusted to 3, the 23-0-isopropyhdene-L-lyxonolactone was isolated in 84% yield [20] (Scheme 4). Again the reactions were monitored by NMR spectroscopy to observe the intermediate epoxides. 

The advantage of using the prepared 2,3-epoxylactones for the study of the base-induced rearrangements discussed above is now clear. Direct treatment of the 2-bromolactones with aqueous base will cause rapid epimerisation at that center, and thus in aqueous base the bromodeoxylactone 17 will give both the 2,3-cis- as well as the 2,3-fra s-epoxide of the open aldonates. In the lactone form of course only cis-epoxides can be formed. The procedure for preparation of L-gluconic acid is thus performed by stirring 17 in acetone with excess of solid anhydrous potassium carbonate for about 30 min, followed by filtration, concentration, addition of water, and 3 molar equivalents of potassium hydroxide. After 3 days at room temperature the mixture is acidified and the product isolated as the ethyl ester [27]. 

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