Oxidative cleavage of alkene

Cleavage of aUcenes and alkynes and the consequent degradation of large molecules and introduction of oxygen functionalities into molecules is one of the most important applications for RuO. The topic has been reviewed [4, 10-15], 

The earliest paper in this field used RuO from RuO /aq. Na(10 )/AcOH for cleavage of 4-cholesten-3-one and hexahydroindene to the corresponding carboxylic acids (Fig. 1.5) [195] minimal experimental data were given. An early example (1959) for RuOj/aq. Na(IO )/acetone involved oxidation of 3a-acetoxy-24,24-di-phenylchol-23-ene to 3a-acetoxynorcholanic acid [196], 

Oxidative cleavage of an alkene breaks both the a and n bonds of the double bond to form two carbonyl groups. Depending on the number of R groups bonded to the double bond, oxidative cleavage yields either ketones or aldehydes. 

One method of oxidative cleavage relies on a two-step procedure using ozone (O3) as the oxi-flant in the first step. Cleavage with ozone is called ozonolysis. 

The pungent odor around a heavily used photocopy machine is O3 produced from O2 during the process. O3 at ground level is an unwanted atmospheric pollutant. In the stratosphere, however, it protects us from harmful ultraviolet radiation, as discussed in Chapter 15. 

Addition of ozone to the 7t bond of the alkene forms an unstable intermediate called a molozon-ide, which then rearranges to an ozonide by a stepwise process. The unstable ozonide is then reduced without isolation to afford carbonyl compounds. Zn (in H2O) or dimethyl sulfide (CH3SCH3) are two common reagents used to convert the ozonide to carbonyl compounds. 

Sample Problem 12.3 Draw the products when each alkene Is treated with O3 followed by CH3SCH3. 

Methods for catalytic asymmetric syn dihydroxylation have been developed that significantly extend the synthetic utility of dihydroxylation. K. B. Sharpless (The Scripps Research Institute) and co-workers discovered that addition of a chiral amine to the oxidizing mixture leads to enantioselective catalytic syn dihydroxylation. Asymmetric dihydroxylation has become an important and widely used tool in the synthesis of complex organic molecules. In recognition of this and other advances in asymmetric oxidation procedures developed by his group (Section 11.13), Sharpless was awarded half of the 2001 Nobel 

Prize in Chemistry. (The other half of the 2001 prize was awarded to W. Knowles and R. Noyori for their development of catalytic asymmetric reduction reactions see Section 7.14A.) The following reaction, involved in an enantioselective synthesis of the side chain of the anticancer drug paclitaxel (Taxol), serves to illustrate Sharpless s catalytic asymmetric dihydroxylation. The example utilizes a catalytic amount of K20s02(0H)4, an OSO4 equivalent, a chiral amine ligand to induce enan-tioselectivity, and NMO as the stoichiometric co-oxidant. The product is obtained in 99% enantiomeric excess (ee)  

A chiral amine ligand used in catalytic asymmetric dihydroxylation 

Adapted with permission from Sharpless et al.. The Journal of Organic Chemistry, Vol. 59, p. 5104, 1994. Copyright 1994 American Chemical Society. 

Cleavage is believed to occur via a cyclic intermediate similar to the one formed with osminm tetroxide (Section 8.16A) and intermediate formation of a 1,2-diol. Alkenes with monosnbstitnted carbon atoms are oxidatively cleaved to salts of carboxylic acids. 

Like permanganate, ozone cleaves double bonds to give ketones and aldehydes. However, ozonolysis is milder, and both ketones and aldehydes can be recovered without further oxidation. 

Ozone is a powerful lung irritant, causing a cough, sore throat, and tiredness. It can also increase a person s sensitivity to allergens. The mechanism may involve peroxidation of the double bonds of the fatty acids that make up the surfactants and the membranes of the cells lining the bronchial airways and lungs. 

Ozone has 142 kJ/mol of excess energy over oxygen, and it is much more reactive. A Lewis structure of ozone shows that the central oxygen atom bears a positive charge, and each of the outer oxygen atoms bears half a negative charge. 

Permanganate cleavage of alkenes. Warm, concentrated KMn04 oxidizes alkenes to glycols, then cleaves the glycols. The products are initially ketones and aldehydes, but aldehydes are oxidized to carboxylic acids under these conditions. 

Ozone reacts with an alkene to form a cyclic compound called aprimaiy ozonide or molozonide (because 1 mole of ozone has been added). The molozonide has two peroxy (— O — O—) linkages, so it is quite unstable. It rearranges rapidly, even at low temperatures, to form an ozonide. 

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We ve already discussed two methods of aldehyde synthesis oxidation of primary alcohols and oxidative cleavage of alkenes. 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Oxidative cleavage of alkenes, terminal alkynes, or aromatic rings... 

The oxidative cleavage of alkenes is a common reaction usually achieved by ozonolysis or the use of potassium permanganate. An example of NHC-coordina(ed Ru complex (31) capable of catalysing the oxidative cleavage of alkenes was reported by Peris and co-workers (Table 10.9) [44]. Despite a relatively limited substrate scope, this reaction reveals an intriguing reactivity of ruthenium and will surely see further elaboration. 

The oxidative cleavage of C=C bond is a common type of reaction encountered in organic synthesis and has played a historical role in the structural elucidation of organic compounds. There are two main conventional methods to oxidatively cleave a C=C bond (1) via ozonol-ysis and (2) via oxidation with high-valent transition-metal oxidizing reagents. A more recent method developed is via the osmium oxide catalyzed periodate oxidative cleavage of alkenes. All these methods can occur under aqueous conditions. 

Oxidative cleavage of alkenes using sodium periodate proceeds effectively in a monophasic solution of acetic acid, water, and THF with very low osmium content or osmium-free. The orders of reactivity of alkenes are as follows monosubstituted trisubstituted >1,2 disub-stituted > 1,1-disubstituted > tetrasubstituted alkynes.100 Cleavage with polymer-supported OSO4 catalyst combined with NaI04 allows the reuse of the catalyst.101... 

The oxidative cleavage of alkenes has been used to establish the location of the... 

A method for the catalytic oxidative cleavage of alkenes using [OSO4] and oxone in DMF has been reported. " This method provides a safer alternative to ozonolysis (Equation (1)). 

Table 3.3 Oxidative cleavage of alkenes to aldehydes or ketones...

Table 3.6 Oxidative cleavage of alkenes to acids and alkynes to ketones or acids...

Scheme 11 Indirect electrochemical oxidation cleavage of alkenes using a double-mediator system consisting of 104 and ruthenium tungstosilicate (taken from Ref 8).

Oxidative cleavage of alkenes to aldehydes, ketones or carboxylic acids is an important transformation usually carried out by ozonolysis or oxidation with stoichiometric oxidants, i.e. OSO4, MnO 1 etc.199. The serious drawbacks of most of these reagents,... 

Potassium nitrosodisulfonate, 258 Trimethylsilyl chlorochromate, 327 By hydrolysis of acetals or thioacetals Amberlyst ion-exchange resin, 152 Methylthiomethyl p-tolyl sulfone, 192 By isomerization of allylic alcohols N-Lithioethylenediamine, 157 By oxidation of aromatic side chains Trimethylsilyl chlorochromate, 327 From oxidative cleavage of alkenes [Bis(salicylidene-7-iminopropyl)-methylamine]cobalt(II)... 

This is a useful route for the preparation of aldehydes and ketones from alkenes, and is covered in this section. Photosensitized oxidative cleavage of alkenes occurs in reasonable yield using p-dimethoxybenzene in the presence of oxygen (equation 31)157. The products are aldehydes or ketones depending upon substrate structure. 

Oxidative cleavage of alkenes to carboxylic acids.1 Alkenes are oxidized to carboxylic acids by H202 (35%) catalyzed by H2W04 in a weakly acidic medium (pH 4-5) maintained by addition of KOH. The oxidation probably involves initial oxidation to a 1,2-diol followed by dehydrogenation to an a-ketol, which is then cleaved to a mono- or dicarboxylic acid. 

Fig. 17.26. Oxidative cleavages of alkenes with symmetrically (top) and asymmetrically (bottom) substituted C=C double bonds.

The reagents that effect the oxidative cleavage of alkene C=C double bonds (Figures 17.26-17.28) in principle also are suitable for the cleavage of aromatic C=C double bonds (Figures 17.29-17.31). The mechanism is unchanged. 

The oxidative cleavage of alkenes to aldehydes and ketones is commonly achieved via ozonolysis. Transition-metal catalysts, including RUCI3, Ru04, and OSO4, together with stoichiometric oxidants also may be used for this... 

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