Aldehydes free-radical addition reactions

Commercial phosphine derivatives are produced either by the acid-cataly2ed addition of phosphine to an aldehyde or by free-radical addition to olefins, particulady a-olefins. The reactions usually take place in an autoclave under moderate pressures (<4 MPa (580 psi)) and at temperatures between 60 and 100°C. 

The neuroexcitatory amino acid a-kainic acid, a popular testing ground for new pyrrolidine syntheses, has been prepared by a number of routes that involve free-radical cyclization reactions. Bachi has reported two approaches that involve iminoyl radical cyclizations. One enantioselective route is described in Scheme 6 [35]. Isonitrile 48 was prepared in 4 steps from 4-bromo-3-methyl-2-butenal dimethyl acetal, the key reaction being an enantioselective addition of tert-butyl oc-isocyanoacetate to an aldehyde mediated by Hiyashi s catalyst. Treatment of 48 with a catalytic... 

A procedure widely applied for effecting O-atom insertions (olefin epoxidation, hydrocarbon hydroxylation or ketonization) with cobalt(II) catalyts is the addition of sacrificial 2-methylpropanal. It is converted via H-atom abstraction to an acyl radical, which upon reaction with O2 produces an acylperoxyl radical. H-atom abstraction by the latter leads to a hydroperoxide, which is capable of effecting O-atom insertions via free-radical chain reactions. The sacrificial aldehyde is lost via oxidation to an acid or an ester. 

Substituted v-butyrolactones can be prepared by reaction of aldehydes or ketones with tbe dianion (28), and direct condensation of symmetrical ketones with diethyl 2-oxomalonate provides a useful synthetic route to the butenolides (29). A number of initiators have been used previously to promote the free-radical addition of ketones to alkenes now transition-metal oxides have been shown to be effective. Pent-4-enal is cyclized to cyclopentanone by chlorotris(triphenylphos-phine)rhodium(i) through a non-radical pathway. ... 

Aldehydes are important because they are temporary reservoirs of free radicals (see eqs. 11 and 12). HCHO is a known carcinogen. Nitric acid is formed by OH attack on NO2 and by a dark-phase series of reactions initiated by O3 + NO2. Nitric acid is important because it is the second most abundant acid in precipitation. In addition, in southern California it is the major cause of acid fog. 

Similar additions have been successfully carried out with carboxylic acids, anhydrides, acyl halides, carboxylic esters, nitriles, and other types of compounds. These reactions are not successful when the alkene contains electron-withdrawing groups such as halo or carbonyl groups. A free-radical initiator is required, usually peroxides or UV light. The mechanism is illustrated for aldehydes but is similar for the other compounds ... 

These reactions involve the addition of acyl free radicals RCO, which may result either from the ejection of a hydrogen atom from the photoexcited aldehyde or through hydrogen abstraction from a ground state aldehyde by a photoexcited molecule. 

The same group recently disclosed a related free radical process, namely an efficient one-pot sequence comprising a homolytic aromatic substitution followed by an ionic Homer-Wadsworth-Emmons olefination, for the production of a small library of a,/3-unsaturated oxindoles (Scheme 6.164) [311]. Suitable TEMPO-derived alkoxy-amine precursors were exposed to microwave irradiation in N,N-dimethylformam-ide for 2 min to generate an oxindole intermediate via a radical reaction pathway (intramolecular homolytic aromatic substitution). After the addition of potassium tert-butoxide base (1.2 equivalents) and a suitable aromatic aldehyde (10-20 equivalents), the mixture was further exposed to microwave irradiation at 180 °C for 6 min to provide the a,jS-unsaturated oxindoles in moderate to high overall yields. A number of related oxindoles were also prepared via the same one-pot radical/ionic pathway (Scheme 6.164). 

In real systems (hydrocarbon-02-catalyst), various oxidation products, such as alcohols, aldehydes, ketones, bifunctional compounds, are formed in the course of oxidation. Many of them readily react with ion-oxidants in oxidative reactions. Therefore, radicals are generated via several routes in the developed oxidative process, and the ratio of rates of these processes changes with the development of the process [5], The products of hydrocarbon oxidation interact with the catalyst and change the ligand sphere around the transition metal ion. This phenomenon was studied for the decomposition of sec-decyl hydroperoxide to free radicals catalyzed by cupric stearate in the presence of alcohol, ketone, and carbon acid [70-74], The addition of all these compounds was found to lower the effective rate constant of catalytic hydroperoxide decomposition. The experimental data are in agreement with the following scheme of the parallel equilibrium reactions with the formation of Cu-hydroperoxide complexes with a lower activity. 

Consideration of reasonable mechanisms for producing formic acid from an aldose led to the hypothesis that the sugar forms an addition product with the hydroperoxide anion, comparable with an aldehyde sulfite or the addition product of aldoses with chlorous acid (52). The intermediate product (12) could decompose by a free-radical or an ionic mechanism. In the absence of a free-radical catalyst, the ionic mechanism of Scheme VIII seems probable. By either mechanism the products are formic acid and the next lower sugar. The lower sugar then repeats the process, with the result that the aldose is degraded stepwise to formic acid. Addition of the hydroperoxide anion to the carbonyl carbon is in accord with its strong nucleophilic character (53) and with certain reaction mechanisms suggested in the literature (54) for related substances. 

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