Dicarbonyl compounds oxidative cleavage

Alkenes with at least one vinjdic hydrogen undergo oxidative cleavage when treated with ozone, yielding aldehydes (Section 7.9). If the ozonolysis reaction is carried out on a cyclic alkene, a dicarbonyl compound results. 

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,... 

Despite all of the activity in pyrimidine-based synthesis, only one study has emerged of solid-phase versions of these reactions <2003TL1267, 20030BC1909>. This chemistry was based upon condensation of dicarbonyl compounds with resin-bound pyrimidine-5,6-diamines through a 2-alkylthio link and oxidative cleavage as described in Section 10.18.7.2. The value of alkylthio substituents in the synthesis of complex substituted pterins has also been demonstrated in the synthesis of nucleic acid conjugates <2004OBC3588> (see Section 10.18.12.4). 

The two major characteristic oxidation processes of alkynes are their transformation to 1,2-dicarbonyl compounds and their cleavage reaction to carboxylic acids.710 The structure of the starting compounds has a decisive effect on the selectivity of oxidation. Since 1,2-dicarbonyl compounds proved to be intermediates in further oxidations, carefully controlled reaction conditions are often necessary to achieve selective synthesis. Certain oxidizing agents such as peroxyacids and ozone are nonselective oxidants. 

As early as 1938 Rambaud reported the first synthesis of a donor-acceptor-substituted cyclopropane — obtained by the addition/elimination path (0 (Scheme 1) — and he also recognized that these cyclopropanes are prone to ring cleavage providing 1,4-dicarbonyl compounds. After saponification 19 opens to 20 which is oxidized by air to the isolated succinic acid 219). 

One of the most popular ways of using the double bond cleavage sequence envisages its utilization for the preparation of l, -dicarbonyl compounds via oxidation of the respective cycloalkene derivatives. Thus oxidation of cyclohexene represents the easiest way to prepare the 1,6-dialdehyde 460. Intramolecular aldol condensation of460 proceeds with ease to give the respective cyclopentene derivatives 461 or 462 (Scheme 2.149). 

Step [1] Oxidative cleavage of the alkene with O3, followed by Zn, HgO (Section 12.10), gives the 1,5-dicarbonyl compound. 

The oxidative cleavage of carbon-carbon bonds in vicinal diols [756, 759] is a reaction widely used in saccharide chemistry. Besides its application in this reaction, periodic acid achieves the oxidative coupling [757] or oxidation to quinones [758] of polynuclear aromatic hydrocarbons, the oxidation of methyl groups in aromatic compounds to carbonyl groups [760], the conversion of epoxides into dicarbonyl compounds [761], and the oxidative cleavage of trimethylsilyl ethers of acyloins to carboxylic acids [755]. 

The oxidative cleavage of epoxides with hydrogen peroxide gives vicinal hydroxy hydroperoxides [178]. With dimethyl sulfoxide in the presence of trifluoromethanesulfonic acid and diisopropylethylamine, epoxides are converted into a-hydroxy ketones [1014], and with periodic acid, dicarbonyl compounds are formed [761] (equations 343 and 344). 

Oxidation of enol ethers. The procedure of Sheng and Zajacek (2, 287) when applied to 5,6,7,8-tetrahydrochromane (1) leads to cleavage of the double bond to give a dicarbonyl compound, 6-ketononanolide (2), in 50% yield.1 The reaction... 

Direct oxidative activation of sp3 C—H bonds adjacent to a heteroatom is an ideal synthetic route to heteroatom-containing derivatives. Recently, our group has developed an efficient method for the alkylation of 1,3-dicarbonyl compounds using Fe2(CO)9 as a catalyst (Equation 11.2) [8]. The scope of this transformation is fairly broad and various heteroatom-containing compounds have been shown as effective alkylation reagents. Kinetic isotopic effect (KIE) experiments have shown that the reaction has a kH/kD value of 5.4 0.1, which supports a rate-determining C—H bond cleavage step for the overall transformation. 

While we must use polarity inversion to add the a-carbonyl cation synthon (1) 10 an enolate ion, no such tricks are needed to add synthon (3> ailyl halides are easily made Chapter 24) and are reactive in 8 2 reactions. The conversion of (4) to (2) by oxidative cleavage of the C=C double bond provides another route to ,4-dicarbonyl compounds. The various methods of double bond cleavage are summarised in Table 26,1. 

A facile approach to polysubstituted chiral dihydrofiirans starts from pyranose triflates and monoanions of 1,3-dicarbonyl compounds <94CC173S>. Treatment of cyclopropylsulfides of type 9 with ammonium cerium nitrate (CAN) gives furans by a tandem oxidative ring cleavage-cylization reaction <94CC1S29>. 

Ketones, Aldehydes, and Alcohols. The well-known Baeyer-Villiger oxidation of ketones by Oxone (eq 2) has been exploited in a variety of reactions. This protocol has been used with KHSO5 for cleavage of a- and /3-dicarbonyl compounds to esters or acids (eqs 30 and 31). This process is sirr5>ler, cheaper, and milder than the commonly used haloform reaction. 

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