Hydroxy ketones from epoxy alcohols

A 6-endo cyclization by a y-epoxy alcohol can be accomplished through the presence of an appropriately disposed electron-withdrawing group, as found in the total synthesis of (+)-phonomactin. Treatment of the hydroxy-epoxy ketone 30 (R = H) with HC1 afforded the bicyclic compound 31, containing a pyran-4-one ring, in which nucleophilic attack of the y-OH group occurred at the oxirane carbon distal from the unfavorable electronic effect of the carbonyl group (Scheme 8.7) [20a]. 

The expected enone is obtained in 40% yield. A 15% yield of the product, resulting from hydroxy-directed epoxidation followed by oxidation to ketone, is obtained. A third product, obtained in 30% yield, can be explained by the equilibration of the initially formed allylic chromate ester with an isomeric chromate ester that directs the epoxidation of an alkene, giving an epoxy alcohol that is further oxidized to an... 

Recently an improvement in this separation technique was reported, which seemed to indicate that enantioselective inclusion in the lattices of chiral hosts could be employed on a large scale. [11] When crystalline hosts such as R,R)-(-)-S (m.p. 196 °C), [12] (/ ,/ )-(-)-9 (m.p. 165 °C), [12] and (5,5)-(-)-10 (m.p. 128 °C) are suspended in hexane or water, chiral guest molecules form the same inclusion compounds as from solution. This is by no means self-evident, since inclusion compounds have different crystal lattices than the pure host crystals. Thus crystal/liquid reactions occur, and phase rebuildings analogous to those observed in gas/solid reactions [13] must take place. Yet this suspension technique is more selective and more effective than the initially developed solution technique. Numerous racemic alcohols like 11, -hydroxy esters like 12, epoxy esters like 13, and epoxy ketones like 14 were stirred a few hours with appropriate hosts (suspensions of 8, 9, and 10) and formed 1 1 complexes that could be filtered off in yields of > 85 % and with ee values of > 97 % (the complex of 12 and 9 formed in hexane only 80% ee in one step). Recrystallization of the inclusion... 

The alkoxyl radicals produced by cleavage reaction (10) can undergo further reactions, including (11) j8-cleavage to produce aldehydes and other decomposition product (short-chain hydrocarbons, and shorter chain fatty acids) that contribute to flavor deterioration of unsaturated lipids (Chapter 4, Figure 4.7) (12) cyclization to produce epoxy derivatives, and formation of ketone and hydroxy derivatives that may or may not contribute to flavor deterioration of unsaturated lipids (Chapter 4) and (13) hydrogen abstraction from the lipid substrate to form innocuous alcohols and a chain-carrying lipid radical. 

Cineole, 13, is a natural herbicide [73]. Its hydroxy derivative 14 (2-hydroxy-1,4-cineole 1,4-epoxy-p-menthane-2-ol) is a constituent of oil from rhizomes of Ferula jaeschkeana [74]. Its 2-methylbenzyl ether 15 (cinmethylin) is a preemergence grass herbicide [75, 76]. Alcohol 14 can be prepared by microbial hydroxy-lation of 13 [77]. This also produces ketone 16 and its enantiomer [78]. The fragrance of ketone 16 and isomeric l-isopropyl-4-methyl- 7-oxabicyclo[2.2.1] heptan-2-one is very similar to that of 14 and menthone [79]. Mullilam diol 17, a dihydroxy derivative of 13, has been isolated from Zanthoxylum rhetsa, a plant that exhibits antibiotic activity which is prescribed in dyspepsia and diarrhea. The eight-carbon system rengyoxide has been found in Forsythia suspensa fruits [80] (Fig. 4). 

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