Alcohols from ozonides

NOC1 and an alcohol 9-9 From ozonides 9-10 Oxidative cleavage of enol ethers 9-13 Reaction between carboxylic acids and lead tetraacetate 9-18 Oxidation of ethers 9-22 Oxidation of primary alcohols or aldehydes... 

Ozonelborane-dimethyl sulfide Alcohols from ethylene derivs. via ozonides One-pot conversion under mild conditions... 

Ozonolysis of alkenes in participating solvents such as alcohols often leads to trapping of intermediates. Most commonly, an alcohol will react with the carbonyl oxide zwitterion, generated from cycloreversion of the primary ozonide (Section 4.16.8.2), to give an alkoxy hydroperoxide. The secondary ozonide (1,2,4-trioxolane) is usually more stable to nucleophilic attack from alcohols. 

A 1989 report describes preparation of 3-alkoxy-l,2,4-trioxolanes (122) by reaction of the corresponding 3-acetoxy derivative (123) with an alcohol under basic conditions (Equation (22)) <89TLi5ii>. Apart from the unusual related reaction of diozonide (120) in Section 4.16.6.2, this sort of nucleophilic substitution at an ozonide is rare. 

These observations were applied by Dimitrov, Hesse and coworkers. On stndying ozonization of a series of allylic and homoallylic alcohols prepared from (+) camphor and (—) fenchone, they were able to isolate a certain number of ozonides and to obtain the O NMR spectrum of the diastereomeric mixture of one of them, i.e. derivative 15, whose structure and O NMR chemical shifts (5, ppm) are shown below. 

SCHEME 18. Generation of an ozonide (317) from a furan derivative in solution and paths for its disappearance, alone or in the presence of an alcohol... 

For example, Magari et al have described the preparation of alcohol (3) in 90% yield from the corresponding alkene (equation 9). It was found that each mole of ozonide required at least one mole of sodium borohydride for complete reduction to the desired alcohol. 

Scheme 7 Ozonization of alcohol (79) followed by treatment of the ozonide with Me2S afforded hydroxy ketones (80), whose acetate derivatives was converted to indenone (83). Hydroxy ketone (84), prepared from (83) was converted to compound (85), whose acetate on oxidation gave diol (87). Its transformation to butenolide (88) was easily carried out. This on oxidation and reduction produced hydroxy phytuberin lactone (89), which was converted to its sulfonyl derivative. Reductive removal of the sulfonate group yielded the cyclopropane derivative (91), which on subjection to reductive cleavage with lithium in liq. NH3 yielded phyberin lactone (92) and deacetyl phytuberin lactone (93)...

A solution of 110 mg. (0.83 mmoles) of 5ab in ether was added slowly to a solution of methyllithium (10% excess, Foote Chemical) in ether. The highly exothermic reaction was cooled in a room temperature water bath. Methane (39 ml.), ether vapor, and possibly carbon dioxide were collected [theoretical for proton abstraction reduction 19 ml. of methane]. After addition of ozonide was complete, the reaction was worked up in the same manner as the lithium aluminum hydride reduction. GPC analysis of the crude mixture revealed isopropyl alcohol (9) (>—60% by GPC standard) and 3-methyl-2-butanol (10) —60%). Methanol is normally produced in approximately the same yield (—60% ) as 9 and 10. We were unable to collect a sufiicient quantity from the labeling experiment for mass spectral analysis. Product identification was based on GPC retention times and by comparison of infrared spectra with those of authentic compounds. Mass spectral results were as follows isopropyl alcohol- assay 11.88% oxygen-18 3-methyl-2-butanol (10) assay 2.45%. 

Ozonide (5ab) prepared from acetaldehyde containing 21.05% oxygen-18 was treated with excess methyllithium in an apparatus which allowed collection of evolved gases. In every case, at least 1 mole of methane was collected (small traces of water accounted for some of the methane). Analysis of the product mixture by GPC revealed isopropyl alcohol (9) and 3-methyl-2-butanol (10) in approximately equimolar amounts and in high yield (ca. 60%, by GPC). 

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