Alkene cleavage oxidation

Abstract This chapter covers one of the most important areas of Ru-catalysed oxidative chemistry. First, alkene oxidations are covered in which the double bond is not cleaved (3.1) epoxidation, cis-dihydroxylation, ketohydroxylation and miscellaneous non-cleavage reactions follow. The second section (3.2) concerns reactions in which C=C bond cleavage does occur (oxidation of alkenes to aldehydes, ketones or carboxylic acids), followed by a short survey of other alkene cleavage oxidations. Section 3.3 covers arene oxidations, and finally, in section 3.4, the corresponding topics for aUcyne oxidations are considered, most being cleavage reactions. 

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. 

The obvious Vfittig disconnection gives stabilised ylid (5fi) and keto-aldehyde (57). We have used many such long-chain dicarbonyl compounds in this Chapter and they are mostly produced from available alkenes by oxidative cleavage (e.g. ozonolysis). In this case, cyclic alkene (58) is the right starting material, and this can be made from alcohol (59) by elimination,... 

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.191 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.192 In these procedures the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 to 4 in Scheme 12.18 are examples of these procedures. Entries 5 and 6 show reactions carried out in the course of multistep syntheses. The reaction in Entry 5 followed a 5-exo radical cyclization and served to excise an extraneous carbon. The reaction in Entry 6 followed introduction of the allyl group by enolate alkylation. The aldehyde group in the product was used to introduce an amino group by reductive alkylation (see Section 5.3.1.2). 

Coenzyme M was shown to function as the central cofactor of aliphatic epoxide carboxylation in Xanthobacter strain Py2, an aerobe from the Bacteria domain (AUen et al. 1999). The organism metabolizes short-chain aliphatic alkenes via oxidation to epoxyalkanes, followed by carboxylation to p-ketoacids. An enzyme in the pathway catalyzes the addition of coenzyme M to epoxypropane to form 2-(2-hydroxypropylthio)ethanesulfonate. This intermediate is oxidized to 2-(2-ketopropylthio)ethanesulfonate, followed by a NADPH-dependent cleavage and carboxylation of the P-ketothioether to form acetoacetate and coenzyme M. This is the only known function for coenzyme M outside the methanoarchaea. 

Osmium tetroxide used in combination with sodium periodate can also effect alkene cleavage.135 Successful oxidative cleavage of double bonds using ruthenium tetroxide and sodium periodate has also been reported.136 In these procedures, the osmium or ruthenium can be used in substoichiometric amounts because the periodate reoxidizes the metal to the tetroxide state. Entries 1 4 in Scheme 12.17 are examples of these procedures. 

As mentioned in 1.2.1 above, there are several reviews on the properties of RuO as an oxidant in organic chemistry, both as a stoicheiometric but also as a catalytic reagent [12, 34-36, 39, 60, 64, 201-203]. It is one of the most important and versatile of Ru oxidants. In the first few years after its properties in the field were realised it was often used for oxidation of alcohol groups in carbohydrates, but its versatility as an oxidant quickly became apparent and its use was extended to a variety of other reactions, notably to alkene cleavage and, more recently, to the c/x-dihydroxylation and ketohydroxylation of alkenes. 

There is a rich chemistry of alkene and alkyne oxidation by RuO. The main application lies in alkene cleavage, bnt there is growing interest in cw-dihydroxylation by the reagent. In the sections below we first consider oxidations which do not sever the C=C bond (epoxidation, ctT-dihydroxylation, ketohydroxylation), and then alkene cleavage reactions. 

Early work on the mechanisms of alkene cleavage by RuO has been briefly reviewed [50]. In the oxidation of 1,5-dienes to cA-tetrahydrofurandiols by RuO / aq. Na(10 )/EtOAc-acetone it is likely that there is cyclo-addition of RuO to one double bond of two 1,5-diene molecules to give a Ru(lV) diester this is oxidised by Na(lO ) to a Ru(Vl) diester, which is then hydrolysed to the organic product (Fig. 3.12) [345], and indeed Ru(Vl) diesters RuOlO R) have been isolated (Fig. 1.31) [323, 346]. ... 

Oxidations of alkenes and alkynes have been reviewed, including mechanistic information in some cases. They include treatment of epoxidations [1-9], ketohydroxylations [7-9] and alkene cleavage [4, 6,10-14]. Oxidations of alkynes have been reviewed in [4, 12, 14, 15]. 

As with alkene cleavage the main reagent for alkyne oxidations is RuO. Oxidative cleavage of alkynes by a variety of reagents has been reviewed [4, 6, 12, 14, 15], The first oxidation of alkynes was noted by Pappo and Becker in 1956 they showed that l,2-fc/x(l-acetoxycyclohexyl)ethyne (2) (Fig. 1.5) gave the diketone. Minimal experimental details were given [195],... 

Problem 6.64 Alkenes undergo oxidative cleavage with acidic KMnO and as a result each C of the 0=C ends up in a molecule in its highest oxidation state. Give the products resulting from the oxidative cleavage of (a) H,C=CHCHjCH, (b) ( )- or (Z)-CH,CH=CHCH (c) (CH,)jC==CHCHjCH3. ... 

The Griesbaum Coozonolysis allows the preparation of defined, tetrasubsituted ozonides (1,2,4-trioxolanes) by the reaction of O-methyl oximes with a carbonyl compound in the presence of ozone. In contrast to their traditional role as intermediates in oxidative alkene cleavage, 1,2,4-trioxolanes with bulky substituents are isolable and relatively stable compounds. 

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. 

The cis-vic-Dihydroxylation of Alkenes No Oxidative Cleavage, but an Important Prelude... 

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