Decarbonylation acyl radicals

The acyl radicals obtained by hydrogen abstraction from aldehydes easily attack protonated heteroaromatic bases. With secondary and tertiary acyl radicals decarbonylation competes with the aromatic acylation [Eq. (12)]. 

Phenols. Presumably they arise exclusively via dissociative Path A, subsequent radical diffusion from the solvent cage, and abstraction of a hydrogen from the solvent (65 -> 74). The yields are (1) increased with decreasing viscosity of the reaction medium (2) higher in nonpolar and lower in polar solvents (3) practically independent of the hydrogen-donating ability of the solvent and (4) increased if a radical counterpart of a phenoxy radical, i.e., an acyl radical, decarbonylates in the solvent cage for structural reasons. 

Similar to the rates of a-cleavage reactions, the rates of acyl radical decarbonylation depend very strongly on the stability of the alkyl radicals formed. It was first suggested by Fischer and Paul that the rate... 

Although the reports by Quinkert and Turro suggested the feasibility of the decarbonylation reaction in crystals and demonstrated a very high chemo- and stereoselectivity, the factors that may facilitate or impede solid-state reactivity remained unexplained. Recognizing that the efficient a-cleavage and rapid acyl-radical decarbonylation of ketones with radical stabilizing a- and a -phenyl substituents may determine the reactivity of ketones 54 to 57 and 64 (Schemes 15 and 17), Choi et al. carried out the first systematic search for a correlation between the reactivity of solids and the stability of the radicals involved in the reaction (Scheme 18). 

The course of the reaction is controlled by the stability of the acyl radical intermediates. When less reactive acyl radicals are generated, C-C-bond formation could successfully compete with decarbonyla-tion, whereas, in the case of more reactive acyl radicals, decarbonylation preceded C-C-bond formation. 

Reaction 21 is the decarbonylation of the intermediate acyl radical and is especially important at higher temperatures it is the source of much of the carbon monoxide produced in hydrocarbon oxidations. Reaction 22 is a bimolecular radical reaction analogous to reaction 13. In this case, acyloxy radicals are generated they are unstable and decarboxylate readily, providing much of the carbon dioxide produced in hydrocarbon oxidations. An in-depth article on aldehyde oxidation has been pubHshed (43). 

The same is true for decarbonylation of acyl radicals. The rates of decarbonylation have been measured over a very wide range of structural types. There is a very strong dependence of the rate on the stability of the radical that results from decarbonylation. For example, rates for decarbonylations giving tertiary benzylic radicals are on the order of 10 s whereas the benzoyl radical decarbonylates to phenyl radical with a rate on the order of 1 s . ... 

Acyl radicals can fragment with toss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. For example, when reaction of isobutyraldehyde with carbon tetrachloride is initiated by t-butyl peroxide, both isopropyl chloride and isobutyroyl chloride are formed. Decarbonylation is competitive with the chlorine-atom abstraction. 

Acyl radicals undergo dccarbonylation. For aliphatic acyl radicals the rate constant for decarbonylation appears to be correlated with the stability of the alkyl radical formed. Values of the dccarbonylation rate constant range from 4 s for CH3C 0) to 1.5x10s s l [lor (CH.,)2C(Ph)C( )0] at 298 °C.3M The loss of carbon monoxide from phenacyl radicals is endothermic and the rate constant is extremely low (ca 10 8 s 1 at 298 nC).388 Consequently, the reaction is not observed during polymerization experiments. 

Entry 5 is an example of the use of fra-(trimethylsilyl)silane as the chain carrier. Entries 6 to 11 show additions of radicals from organomercury reagents to substituted alkenes. In general, the stereochemistry of these reactions is determined by reactant conformation and steric approach control. In Entry 9, for example, addition is from the exo face of the norbornyl ring. Entry 12 is an example of addition of an acyl radical from a selenide. These reactions are subject to competition from decarbonylation, but the relatively slow decarbonylation of aroyl radicals (see Part A, Table 11.3) favors addition in this case. 

As can be seen from Figure 3, the ratio of the isopropyl ether to isobutyrate is about 1 1. It is clear that after a-cleavage of the ketone the two radicals primarily formed are captured directly by nitroxide. This takes place without decarbonylation of the acyl radical (reaction (7)) ... 

Sometimes acylium ions lose carbon monoxide to generate an ordinary carbonium ion. It will be recalled that free acyl radicals exhibit similar behavior at high temperatures. Whether or not the loss of carbon monoxide takes place seems to depend on the stability of the resulting carbonium ion and on the speed with which the acylium ion is removed by competing reactions. Thus no decarbonylation is observed in Friedel-Crafts reactions of benzoyl chloride, the phenyl cation being rather unstable. But attempts to make pivaloyl benzene by the Friedel-Crafts reaction produce tert-butyl benzene instead. With compound XLIV cyclization competes with decarbonylation, but this competition is not successful in the case of compound XLV in which the ring is deactivated.263... 

As data for the rates of spin-trapping reactions are accumulated, so it becomes possible to use the competition experiment in reverse , i.e. to determine rates of rearrangement, fragmentation, atom transfer, etc. which can compete with spin trapping. An attempt to estimate rates of decarbonylation of acyl radicals depended on this approach (Perkins and Roberts, 1973). Although the results obtained were intuitively reasonable, they depended on the assumption that the rate of scavenging of acyl radicals by MNP would be no different from that measured for the butoxycarbonyl radical. This still awaits experimental verification. Another application, reported recently, was to the rates of rearrangement (23) of a series of (o-(alkoxycarbonyl)-alkyl radicals... 

The high reactivity of protonated heteroaromatic bases towards acyl radicals is shown by the success of the reaction with the pivaloyl radical, which usually undergoes rapid decarbonylation [Eq. (33)]. 

Protonated heteroaromatic bases are therefore more reactive than simple olefins toward acyl radicals. The radical addition of pivalaldehyde to olefins is, in fact, characterized by a radical chain, whose propagation is determined by decarbonylation of the pivaloyl radical and addition of <-butyl radical to the olefin. The synthetic interest is great in the case of substrates with only one reactive position, such as benzothiazole, ... 

Pyridine-2-thione-A-oxycarbonyl (PTOC) derivatives of carboxylic esters 53 were developed by Barton et al. and serve as a convenient source of acyloxyl radicals, which upon decarboxylation provide specific routes to free radicals (equation 82). This process can also proceed by a radical addition (equation 83). Acyl selenides (54) are a convenient source of acyl radicals, which can undergo decarbonylation also giving specific free radicals (equation 84). ° ... 

The fate of the free acyl radical 68 and radical 74 is not known. Most probably it is a constituent of polymer deposits on the wall of the irradiation vessel which hitherto have not been identified more definitely.29 Moreover, the identification of methane and carbon monoxide among the gaseous products of the photolysis of 4-methylphenyl acetate (55) provides evidence for the existence of the acetyl fragment. This intermediate is expected to decarbonylate to give carbon monoxide and a methyl radical, which in turn abstracts hydrogen from the solvent.34... 

It has been mentioned that phenol is formed via Path A, by diffusion of radicals from the solvent cage and hydrogen abstraction from the solvent. This process is undoubtedly favored (and the yield of phenol is increased) when the phenoxy radical 65 already loses its counterpart in the solvent cage, i.e., when it loses the acyl radical 68 as a consequence of its decarbonylation. From the hitherto reported results it can be assumed that decarbonylation is significant and proceeds very readily under two conditions. It occurs (1) if the acyl radical formed possesses excess energy ( hot radical) due to excitation of high energy, e.g., by y-radiolysis,41,46 and (2) if the alkyl or aryl radicals formed by the decarbonylation of the acyl radical are exceptionally stable.61... 

An unambiguous proof that decarbonylation of the acyl radical takes place at least in part in the solvent cage has been obtained by the photolysis of the 3,5-di-f-butylphenyl ester of (5,)-( + )-2-methylbutanoic acid (125) in diox-ane.62 3,5-Di-/-butylphenyl-sec-butyl ether (127), isolated in 3% yield, was shown to be completely racemic. This means that the sec-butyl radical had to exist as an independent, free-rotating radical intermediate in the solvent cage. The relatively high yield of ether, the assumed lifetime of radicals 65-68, and radical concentration at the usual solution concentrations (10-3 to 10 1... 

In 02-saturated solutions, a major portion of acyl radicals (60-80%) react with O2 as in Eq. (22), the rest undergoing decarbonylation and finally formation of tert-butylperoxyl radicals, Eqs. (20) and (23). The source of Craq02 +, which is clearly an intermediate on the basis of the effects of methanol and Mn2+, is reaction 24. As discussed in greater detail below, Craq02 + is produced by disproportionation of the initially generated Craq(V). 

Assuming that the two carbonyl species have similar molar extinction coefficients, a simple calculation suggests that about half of the acyl radicals formed abstract hydrogen before decarbonylation. This process would thus be expected to reduce the efficiency of main-chain scission via the /3-scission mechanism. 

Norrish type reactions. Type I reaction involves a-cleavage giving rise to an acyl and an alkyl radical. It is generally observed in aliphatic ketones in the vapour state and at high temperatures. The acyl radical is essentially decarbonylated at high temperatures. 

Phenyl selenoesters have been reported to undergo reduction to the corresponding aldehydes and/or alkanes in the presence of (TMS)3SiH under free-radical conditions16. The decrease of aldehyde formation through the primary, secondary and tertiary substituted series, under the same conditions, indicated that a decarbonylation of acyl radicals takes place. Equation 11 shows an example of a tertiary substituted substrate. 

Free-radical cyclization of phenyl selenide 15 to indolizidinone 16 represented a key step in the total synthesis of (—)-slaframine (equation 52). The two pairs of diastereomers were first separated and then hydrolyzed to the corresponding alcohols in 76% overall yield77. (TMS)3SiH-mediated acyl radical reactions from phenylseleno esters 17 have recently been utilized for the stereoselective synthesis of cyclic ethers78. In fact, the experimental conditions reported in equation 53 are particularly good for both improving cis diastereoselectivity and suppressing decarbonylation. 

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