Aldehydes by ozonolysis of alkenes

In the preparation of aldehydes by ozonolysis of alkenes, it is important to add the correct amount of ozone to the solution because an excess of O3 can lead to side reactions. Ozonolysis in alcoholic solvents traps the carbonyl oxide as a hydroperoxide. Dimethyl sulfide reduces hydroperoxides under very mild conditions and generates the corresponding aldehydes in excellent yields. This workup procedure is recommended when the aldehyde is the desired reaction product. 

In Chapter 8 we also saw how this procedure has utility in structure determination. The following examples illustrate the synthesis of aldehydes by ozonolysis of alkenes. 

We have seen three laboratory methods for the preparation of ketones in earlier chapters 1. Ketones (and aldehydes) by ozonolysis of alkenes (discussed in Section 8.17B). 

Aldehydes and ketones are obtained by ozonolysis of alkenes (see Section 5.7.6) and hydration of alkynes (see Section 5.3.1). 

An older paper <1971MI873> reported that ozonolysis of alkenes in the presence of tertiary amines resulted in the formation of aldehydes. A recent reinvestigation <20060L3199> has shown that amine oxides were responsible for this reductive ozonolysis . Indeed, pretreatment of the tertiary amines with ozone, giving rise to amine oxides, accounted for this phenomenon. A preparative method emerged, by treating the alkene (e.g., 1-decene) at 0 °C with a solution of 2% 03/02 in dichloromethane (2 equiv of ozone relative to the alkene) in the presence of an excess (about threefold molar excess) of A-methylmorpholine A-oxide, pyridine A-oxide, or l,4-diazabicyclo[2.2.2]octane A-oxide (DABCO A-oxide). Yields of aldehydes (nonanal in the above example) were 80-96%, and the excess of amine oxide ensured the absence of residual ozonide (Scheme 21). 

One of the key steps in the synthesis of the depsipeptide jasplakinolide involved the preparation of an aldehyde 273 by ozonolysis of an alkene 271 with the correct stereochemistry of the substituents (Scheme 83). The hydroxyl group was protected with R = fer7-butyl(dimethyl)silyl <2004ASC855>. 

Diols (glycols), such as those formed by dihydroxylation of alkenes, are cleaved by periodic acid (HI04). The products are the same ketones and aldehydes that would be formed by ozonolysis-reduction of the alkene. Dihydroxylation followed by periodic acid cleavage serves as a useful alternative to ozonolysis, and the periodate cleavage by itself is useful for determining the structures of sugars (Chapter 23). 

C.ii. Ozonides. Ozonolysis is a powerful method for cleaving alkenes to carbonyl products (sec. 3.7.B). Ozonolysis of alkenes initially generates an ozonide that can be reduced by a variety of reagents. Dimethyl sulfide or zinc in acetic acid are the most common reagents for the reduction of an ozonide to an aldehyde or ketone. Reduction of the ozonide with the more powerful lithium aluminum hydride, however, gives direct conversion to the alcohol. 

Aldehydes and ketones can be prepared by the ozonolysis of alkenes. Sample reaction 22-3... 

Having streamlined the synthesis of acyl chloride 54, the indirect preparation of methyl enol ester 51a was addressed. As previously discussed, attempts to synthesize 53a from formyl Meldrum s acid 58 had proven unsuccessful. However, Cossy and coworkers have reported the preparation of 53a via the ozonolysis of alkene 82 and subsequent use of the crude aldehyde in the total synthesis of octalactin. Thus, methyl vinyl acetate (82) was subjected to ozonolysis at —78 °C, followed by a reductive quench to provide formyl acetate 53a (Scheme 24). The crude methyl formyl acetate was acylated with acyl chloride 54, using the previously optimized conditions, to afford methyl enol ester 51a in 74% yield over two steps. This modification to the synthesis removes a further two reactions from the sequence with a formal synthesis of (—)-7-deoxyloganin (24) now achieved in 10 steps, a length more in keeping with the complexity of this target. 

Ozonolysis of alkenes (Section 6.20) This cleavage reaction is more often seen in structural analysis than in synthesis. The substitution pattern around a double 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 aldehyde products to be isolated without further oxidation. 

Alkenes can be cleaved by ozonolysis of their double bond (Section 8.17B). The products are aldehydes and ketones. 

Oxidation of a 2° alcohol produces a ketone, while partial oxidation of a 1° alcohol (PCC or Swem) gives aldehyde products. Ozonolysis of an alkene, followed by a reductive workup, gives ketone and/or aldehyde products, depending on the alkene starting material. Esters, acid chlorides, and nitriles can be partially reduced with diisobutylaluminum hydride (DIBAL-H) to produce aldehydes as well. 

ANSWER Carboxylic acids can be made from oxidative ozonolysis of alkenes, by oxidation of primary alcohols using dichromate under aqueous conditions, and by oxidation of aldehydes. 

Lactol 257 (or 259) is commonly accessed by the spontaneous closure of alcohol 256 (or 258) on an aldehyde (or ketone) six atoms away (Scheme 68, Eq. 1-2) [125]. Note that lactols derived from ketones can lead to a 2,6-cis arrangement for R and R using a hydride nucleophile in the presence of a Lewis acid. a-Alkoxy ether 260 is typically synthesized by ozonolysis of the 5-alken-l-ol 7 followed by treatment with dimethyl sulfide and aqueous acid (Scheme 68, Eq. 3). Lactone... 

When the aldehyde or ketone is being named as a substituent, the term "oxo" is used. Aldehydes can be prepared by oxidation of primary alcohols, hydroboration of 1-alkynes, or ozonolysis of alkenes. Aryl aldehydes can be prepared from the arene with CO/HCI in the presence of AlClj/CuCI. 

The mixture of aldehydes can be made by ozonolysis of this disubstituted alkene (/raws-2-methyl-4-decene), as described above. (Note that the E alkene is shown here, but ozonolysis of the Z alkene would also produce the same two aldehydes.)... 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

Alkenes are cleaved to carbonyl compounds by ozonolysis This reaction IS useful both for synthesis (preparation of aldehydes ketones or car boxyhc acids) and analysis When applied to analysis the carbonyl com pounds are isolated and identified allowing the substituents attached to the double bond to be deduced... 

The alkenes 149 and 150 are easily cleaved by ozonolysis either directly or after protection of the hydroxy gronp. Depending on the workup conditions of the ozonolysis, either diols 151 or 0-protected aldehydes 152 can be obtained. The C2 symmetric ketone 153 dr 75 25) is available from another addition of the dilithium reagent 148 (R = Ph)... 

The oxidation of an alkene with ozone followed by treatment with zinc in the presence of acid gives aldehydes and/or ketones. The reaction breaks the carbon-carbon double bond and changes each of carbon atoms of the C=C to a carbonyl group. Figure 10-7 shows an excimple of the ozonolysis of an alkene. 

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