Cleavage alkenes

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). 

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. 

Alkene Cleavage to Aldehydes, Ketones or Acids (3.2 Tables 3.3, 3.6)... 

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]. ... 

Fig. 1.7 Possible mechanism for alkene cleavage by RuO for methyl cinnamates [347, 348]...

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. 

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]. 

Few epoxidations have been accomplished with RuO since the reagent is a prime alkene cleavage agent (but see Fig. 3.1 below). Because of the intrinsic interest in, and need for, epoxidations many Ru complexes have been studied for the purpose, but generally only those which are effective (i.e. give good yields and selectivities), are catalytic and do not require forcing conditions are included. Some of those omitted here are mentioned in Ch. 1 and listed in 3.1.1.4 below. 

Specific Examples of Alkene Cleavage to Aldehydes and Ketones... 

Natural ProductfPharmaceutical Syntheses Involving Alkene Cleavage to Acids... 

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],... 

Support-bound sulfonylhydrazones can also be used as linkers for alkenes. Cleavage is effected by heating in the presence of an alcoholate, whereby diazoalkanes are initially formed these then undergo thermal fragmentation into the alkene and nitrogen (Entry 12, Table 3.43 Bamford-Stevens reaction). Polystyrene-bound alkynyl... 

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. 

An aldol reaction in acid solution ensures that the more substituted enol is formed and the aldehyde is by far the most electrophilic of all the carbonyl groups. The Diels-Alder reaction gives the free acid 30 which was resolved with a chiral amine and each enantiomer used for a different part of the B12 molecule. The slightly unusual reagent Cr(VI) was used for the alkene cleavage and acetal formation occurred spontaneously under the acidic conditions. 

C., Schoemaker, H.E., Guebitz, G.M. and Kroutil, W. (2006) Biocatalytic single-step alkene cleavage from aryl alkenes an enzymatic equivalent to reductive ozonization. Angewandte... 

Treatment of pivalate 338 with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and ultrasound gives the 2-epimer 340. Its reduction with NaBH4 gives 341. Subsequent alkene cleavage generates 342. Inversion of the alcohol moiety C-3 of 342, followed by alkene cleavage furnishes the 2,8-anhydroheptitol 343 (O Scheme 91) [466,467]. 

Diols are oxidatively cleaved by reaction with periodic acid (HIO4) to yield carbonyl compounds, a reaction similar to the KMnO cleavage of aJkenes just discussed. The sequence of (1) alkene hydroxylation with OsO< j followed by (2) diol cleavage with HIO4 is often an excellent alternative to direct alkene cleavage with ozone or potassium permanganate. 

---