Ozonolysis, selective

Cyanide Wastes. Ozone is employed as a selective oxidant in laboratory-scale synthesis (7) and in commercial-scale production of specialty organic chemicals and intermediates such as fragrances, perfumes (qv), flavors, antibiotics (qv), hormones (qv), and vitamins (qv). In Japan, several metric tons per day (t/d) of piperonal [120-57-0] (3,4-methylenedioxybenzaldehyde) is manufactured in 87% yield via ozonolysis and reduction of isosafrole [93-16-3], Piperonal (or heHotropine [120-57-0]) has a pleasant odor and is used in perfumery. Oleic acid [112-80-1/, CH3(CH2 )7CH—CH(CH2 ). C02H, from tall oil (qv) is ozonated on a t/d scale to produce pelargonic, GgH2yG02H, and azelaic, H02G(GH2)yG02H, acids. Oleic acid also is ozonated in Japan... 

By converting the A" -3-ketone into its 2-hydroxymethylene derivative, selective ozonolysis to the 2,3-seco-2,3-dicarboxylic acid can be carried out in the presence of the A -double bond. Weisenborn has thus prepared A-nortesto-sterone and A-norprogesterone. In the latter case, selective formyla-tion at C-2 was achieved by first reducing the 20-ketone to the 20-ol (4). 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

The reaction of ozone with an aromatic compound is considerably slower than the reaction with an alkene. Complete ozonolysis of one mole of benzene with workup under non-oxidative conditions will yield three moles of glyoxal. The selective ozonolysis of particular bonds in appropriate aromatic compounds is used in organic synthesis, for example in the synthesis of a substituted biphenyl 8 from phenanthrene 7 ... 

In the synthetic procedure, verbenone 118, the air oxidation product of pinene, is first treated with t-BuOK. followed by the addition of prenyl bromide to give a C-ll alkylated product. Selective ozonolysis of the more electron-rich double bond provides the aldehyde 119 with 85% yield. The A ring of taxane is then created through photorearrangement of the aldehyde 119, yielding the chrysanthenone derivative 120 (85% yield, over 94% ee). 

Hydrolysis of 20 with the aid of butanol followed by syn-selective reduction of jS-keto ester 21 and protection as the isopropylidene acetal was accomplished in 87% yield. L1A1H4 reduction and TBS protection of the primary alcohol gave 22 in very good yields. In this strategy, the furan residue serves as an aldehyde synthon and ozonolysis followed by esterification gave the corresponding methyl ester. Reduction and consecutive oxidation established aldehyde 23 in 71% yield. 

JO-C6H4CO2BUO, followed by ozonolysis, gave the a-hydroxy and a-aimno thiol acid derivatives (140). In all cases, the (l )-diastereoisomer was formed as the major component albeit with only modest levels of selectivity (33-71% de)P... 

Trioxolanes are key intermediates in the ozonolysis of alkenes (Section 4.16.8.2). This reaction is of considerable importance in synthetic chemistry where ozonide intermediates are often reduced (to aldehydes or alcohols) or oxidized (to carboxylic acids) in situ. Advantage has been taken of the stability of certain derivatives to investigate selective chemical reactions. An example of selective reduction is shown in Scheme 47 <91TL6454> with other uses of the 1,2,4-trioxolane ring as a masked aldehyde or ester referred to in Section 4.16.5.2.1. 

The final synthetic analogues we consider are the trioxolanes prepared by Vennerstrom and coworkers. These are prepared by a very efficient co-ozonolysis procedure from oxime 90 and a carbonyl compound 91 (Scheme 37A). This provides the 1,2,4-trioxolane in yields of greater than 50%. Further studies on 4-substituted cyclohexanones (e.g. 92) revealed that this reaction proceeds with very good cisitrans selectivity to produce the ester 93, which was derivatized to produce a clinical candidate OZ 277 (6) as shown. The chemistry for the synthesis of this compound has been scaled up beyond 30 kg (Scheme 37B). 

Conjugate addition to 1 proceeded across the open face of the bicyclic system to give an enolate, condensation of which with the enantiomerically-pure aldehyde 8 gave the enone 9. Conjugate reduction of the enone also removed the benzyl ether, to give the alcohol. Conversion of the alcohol to the azide gave 10. Ozonolysis followed by selective reduction then gave 2. 

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