Reductive workup

This cleavage reaction is more often seen in structural analysis than in synthesis The substitution pattern around a dou ble bond is revealed by identifying the carbonyl containing compounds that make up the product Hydrolysis of the ozonide intermediate in the presence of zinc (reductive workup) permits aide hyde products to be isolated without further oxidation... 

An interesting feature of the synthesis is the use of allyl as a two-carbon extension unit. This has been used in the stereospecific synthesis of dicyclohexano-18-crown-6 (see Eq. 3.13) and by Cram for formation of an aldehyde unit (see Eq. 3.55). In the present case, mannitol bis-acetonide was converted into its allyl ether which was ozonized (reductive workup) to afford the bis-ethyleneoxy derivative. The latter two groups were tosylated and the derivative was allowed to react with its precursor to afford the chiral crown. The entire process is shown below in Eq. (3.59). 

Besides simple alkyl-substituted sulfoxides, (a-chloroalkyl)sulfoxides have been used as reagents for diastereoselective addition reactions. Thus, a synthesis of enantiomerically pure 2-hydroxy carboxylates is based on the addition of (-)-l-[(l-chlorobutyl)sulfinyl]-4-methyl-benzene (10) to aldehydes433. The sulfoxide, optically pure with respect to the sulfoxide chirality but a mixture of diastereomers with respect to the a-sulfinyl carbon, can be readily deprotonated at — 55 °C. Subsequent addition to aldehydes afforded a mixture of the diastereomers 11A and 11B. Although the diastereoselectivity of the addition reaction is very low, the diastereomers are easily separated by flash chromatography. Thermal elimination of the sulfinyl group in refluxing xylene cleanly afforded the vinyl chlorides 12 A/12B in high chemical yield as a mixture of E- and Z-isomers. After ozonolysis in ethanol, followed by reductive workup, enantiomerically pure ethyl a-hydroxycarboxylates were obtained. 

Scheme 12.19 illustrates some cases in which ozonolysis reactions have been used in the course of syntheses. Entries 1 to 4 are examples of use of ozonolysis to introduce carbonyl groups under reductive workup. Entries 5 and 6 involve oxidative workup and give dicarboxylic acid products. The reaction in Entry 7 is an example of direct generation of a methyl ester by methoxide trapping. 

Hoye and Richardson have published an ingeneous synthesis of the tricyclic iridoid sarracenin (170) which relied on the Paterno-Buchi cycloaddition between acetaldehyde and cyclopentadiene as the intial step (Scheme 38)79. This reaction provided a 5 1 mixture of adducts 166a and 166b. The major adduct was opened with camphor-10-sulfonic acid (CSA) in methanol and the alcohol was tosylated to give 167. Displacement with malonate 168 and decarboalkoxylation/demethylation steps gave 169. Ozonolysis, reductive workup and acid-catalyzed acetalization then furnished 170. 

The ozonolysis reaction, followed by reductive workup with sulfur dioxide, as described in Part A of the present procedure, illustrates a general method which has been developed for the preparation of acetals. Application of the procedure is illustrated by conversion of the following olefins in alcoholic solution to the corresponding acetals (1) l-chloro-4-(o-nitrophenyl)-2-butene to o-nitrophenylacetaldehyde dimethyl acetal in 84% yield (2) l,4-dibromo-2-butene tobromoacetaldehyde dimethyl acetal in 67% yield (3) 3-butenoic acid to malonaldehydic acid diethyl acetal ethyl ester in 61% yield (4) cyclopentadiene to malonaldehyde bis(diethyl acetal) in 48% yield and (5)... 

Methanolysis of A -Cbz bicylic sulfonamides 43 or 115 was used to furnish tosyl-protected amino alcohol 116 after ozonolysis and reductive workup of the intermediate sulfoxides 117a and 117b (Scheme 13) <2004JOC7198>. 

Notes For organic chemists the major use of this oxidizing agent is in the cleavage of alkene bonds. This can be followed by either oxidative or reductive workups. The reaction can be run in a number of common solvents. 

Among the reducing agents for the reductive workup, peroxide is a common oxidative workup. 

Similar oxidative rearrangements to produce carbonyl compounds have been carried out with thallium(III) nitrate557 or peroxytrifluoroacetic acid-BF3.558 The Jones reagent (Cr03—H2S04) in the presence of a catalytic amount of Hg(II) is also effective.559 Chromyl chloride oxidation, when combined with reductive workup, is a simple, convenient one-step method to convert 2,2-disubstituted 1-alkenes to aldehydes.560,561... 

The double bond in 7 is cleaved to an aldehyde by ozonolysis (see Chapter 5) and subsequent reductive workup with tnbutylphos-phine Crotylation with reagent 25.15 developed by Brown, produces only a single diastereomer, which is then transformed into benzoate 8 with benzoyl chloride in pyridine. 

In the synthesis of the monocyclic bisabolene-type sesquiterpenoids (-f)-curcuquinone and (—)-curcuhydro-quinone, 1,3-diol 107 was obtained by ozonolysis of 4,5-dihydro-l,3-dioxepin 106 (obtained by Heck reaction, see Section 13.11.10) and reductive workup (Scheme 25) <2003ARK232>. 

Step 5a-b Ozonolysis followed by reductive workup leads to the (3-diketone. Reference Wipf, P. Lim, S. J. Am. Chem. Soc. 1995,117, 558. 

Intramolecular interception of the Criegee carbonyl/carbonyl oxide intermediate was observed in the ozonolysis of steroidal allylic alcohols at — 70 °C. In hexane, the 1,2,4-trioxolane 132 (a mixture of ( Vcpimers) was isolated in 26% yield. Reductive workup afforded the hemiacetal of the dioxolane 133 which could be oxidized to the dioxolane-lactone the hydroperoxide 134 can be isolated in other solvents. When the ozonolysis was carried out in ethyl acetate at —78°C, the yield of the dioxolane-hemiacetal 133 was 95% (Scheme 51) <1990J(P1)1220>. 

The major synthetic problem associated with the synthesis of compounds such as NK-104 is the stereoselective construction of the lactone moiety and its connection to an aromatic or ethylenic core. This has been overcome by Minami and colleagues with the enantioselective synthesis of methyl 6-oxo-3,5-isopropylidenehexanoate (52) by ozonolysis of the ester 53, followed by reductive workup using dimethyl sulfide (Scheme 11,14).54 With the required aldehyde 52 now formed, further reaction could permit the production of NK-104 51 to take place enantioselectively. 

Ozonolysis is carried out preferentially in a methanol-dichloromethane mixed solvent system, followed by a reductive workup to produce the desired (3-keto ester 91, which is then further reacted to the 1-carbacephalosporin 89, providing a versatile and viable route to an important intermediate compound for monocyclic (3-lactam antibiotics. 

One method for the synthesis of hydroxyalkyl-substituted P-lactams is by the Staudinger reaction, the most frequently used method for the synthesis of P-lactams.86 This method for the preparation of 4-acetoxy- and 4-formyl-substituted P-lactams involves the use of diazoketones prepared from amino acids. These diazoketones are precursors for ketenes, in a diastereoselective, photochemically induced reaction to produce exclusively tram-substituted P-lactams. The use of cinnamaldimines 96, considered as vinylogous benzaldimines, resulted in the formation of styryl-substituted P-lactams. Ozonolysis, followed by reductive workup with dimethyl sulfide, led to the formation of the aldehyde 97, whereas addition of trimethyl orthoformate permitted the production of the dimethyl acetal 98 (Scheme 11.26). 

Ozonoylsis followed by reductive workup with triphenyl phosphine produced aldehyde 2 which was subsequently oxidized to furnish the C-linked galactosyl pyranose derivative 3. 

Hemiacetals are formed from hydroxy aldehydes " or ketones which are usually first in a protected form and are deblocked prior to cyclization. Ozonolysis of cyclohexene derivative 5 and reductive workup, followed by hydrolysis of the acid chloride formed in situ and borane reduction of the carboxylic acid, leads to the six-membered hemiacetal 6. a precursor for fluo-rinated sugars that are potentially versatile as molecular probes in the elucidation of biochemical processes. ... 

Oxidation with ozone is a common method for the preparation of fluorinated compounds. Cyclic or linear alkenes can be treated with ozone and, depending on the workup of the reaction mixture, aldehydes, ketones or carboxylic acids are produced. This is illustrated by the ozonoly-sis of. l,.3,4.4-tetrafluorocyclohexene. Oxidative workup gives, depending on the oxidizing agent, formylpentanoic acid 3 or the diaeid 4 with reductive workup the dialdehyde 2 is obtained. If the alkene is substituted by an alkyl group, the product is a ketone. 

Dichloro-3.3,3-trifluoropropanal, an intermediate for the production of substituted pyridines, was prepared by ozonolysis of methyl 4,4-dichloro-5,5.5-trifluoro-2-methylpent-2-enoate with reductive workup. ... 

Cyclohexene is converted to tnmv-1-(4-mcthylphcnylsulfonylamino)-2-(phenylseleno)cyclohexane (59) by treatment with diphenyl diselenide and chloramine-T, followed by reductive workup with sodium borohydride66. The intermediate product A formed from diselenide and chlor-amine-T is believed to play the role of an electrophile attacking the alkene. 

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