Radical reactions acylation

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). 

In radical reactions not involving bromine or chlorine on the substrate, rearrangements are much rarer One example is the fluorination of di-tert butyl ketone which produces perfluormated / rt-buty isobutyl ketone [J5] Although isolated yields are poor only the rearranged ketone could be isolated This is perhaps only the second example of a 1,2-acyl shift Low fluorine substrate ratios show that this rearrangement occurs after monofluorination... 

Radicals with adjacent Jt-bonds [e.g. allyl radicals (7), cyclohexadienyl radicals (8), acyl radicals (9) and cyanoalkyl radicals (10)] have a delocalized structure. They may be depicted as a hybrid of several resonance forms. In a chemical reaction they may, in principle, react through any of the sites on which the spin can be located. The preferred site of reaction is dictated by spin density, steric, polar and perhaps other factors. Maximum orbital overlap requires that the atoms contained in the delocalized system are coplanar. 

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)) ... 

The observed formation of isobutyrate (Figs. 5 and 6) would appear to be one of the possible reasons for the slow decrease in the nitroxide concentration. The formation of isobutyrate can be seen as a reaction competing with the capture of the acyl radicals by oxygen. The absence of isopropyl ether in the reaction mixture is explained by its immediate cleavage - following its formation analogous to isobutyrate - to nitroxide by oxygen-centered radicals (mainly acyl peroxy radicals). 

Kinetic analysis of the results of ketone oxidation in the presence of amine II reveals that the velocity constant of the oxidation of amines by acyl per-oxy radicals must be greater (by a factor of 2 - 3) than that of the interaction of these radicals with the nitroxide-i. In this reaction, acyl peroxy radicals are captured and destroyed by amines. 

Carbonyl group of the aldehyde decreases the BDE of the adjacent C—H bond. This is due to the stabilization of the formed acyl radical, resulting from the interaction of the formed free valence with Tr-electrons of the carbonyl group. For example, DC—H = 422kJmol 1 in ethane and D( n 373.8 kJ mol 1 in acetaldehyde. The values of Dc H in aldehydes of different structures are presented in Table 8.1. In addition, the values of the enthalpies of acylperoxyl radical reactions with aldehydes were calculated (D0 H= 387.1 kJ mol-1 in RC(0)00 H). 

The acyl anion chemistry of acylzirconocene chlorides has also been applied to the stereoselective preparation of ( )-a,(3-unsaturated selenoesters and telluroesters (Scheme 5.35) [38]. Although no carbon—carbon bond was formed, this reaction reflects the synthetic interest in ( )-a,(3-unsaturated selenoesters and telluroesters, which are well-known precursors of acyl radicals and acyl anions, respectively. 

The method used by Bawn and Mellish relies on the presence of a radical trap in the reaction mixture, that is, a compound that reacts very fast with the acyl radicals produced, thus preventing their recombination. This substance was the vivid colored 2,2-diphenyl-1-picrylhydrazyl radical (figure 15.1). When these nitrogen-centered radicals, herein abbreviated by P, react with an acyl radical (reaction 15.6), the solution color change can be monitored with a spectrophotometer. 

Tris[(2-perfluorohexyl)ethyl]tin hydride has three perfluorinated segments with ethylene spacers and it partitions primarily (> 98%) into the fluorous phase in a liquid-liquid extraction. This feature not only facilitates the purification of the product from the tin residue but also recovers toxic tin residue for further reuse. Stoichiometric reductive radical reactions with the fluorous tin hydride 3 have been previously reported and a catalytic procedure is also well established. The reduction of adamantyl bromide in BTF (benzotrifluoride) " using 1.2 equiv of the fluorous tin hydride and a catalytic amount of azobisisobutyronitrile (AIBN) was complete in 3 hr (Scheme 1). After the simple liquid-liquid extraction, adamantane was obtained in 90% yield in the organic layer and the fluorous tin bromide was separated from the fluorous phase. The recovered fluorous tin bromide was reduced and reused to give the same results. Phenylselenides, tertiary nitro compounds, and xanthates were also successfully reduced by the fluorous fin hydride. Standard radical additions and cyclizations can also be conducted as shown by the examples in Scheme 1. Hydrostannation reactions are also possible, and these are useful in the techniques of fluorous phase switching. Carbonylations are also possible. Rate constants for the reaction of the fluorous tin hydride with primary radicals and acyl radicals have been measured it is marginally more reactive than tributlytin hydrides. ... 

A novel tandem carbonyiation/cyclization radical process has been developed for the intramolecular acylation of l-(2-iodoethyl)indoles and pyrroles <99TL7153>. In this process, an acyl radical is formed when CO is trapped by an alkyl radical formed from the AIBN-induced radical reaction of l-(2-iodoethyl)indoles 104 with BusSnH. Intramolecular addition of the acyl radical to the C-2 position of the heteroaromatic system presumably affords a benzylic radical which undergoes in situ oxidative rearomatization to the bicycloketones 105. 

The stereospecific preparation of E- and Z-a-fluorovinylstannanes via the radical reaction of the corresponding a-fluorovinylsulfones with tributyltin hydride has been reported by McCarthy et al. These reagents undergo a variety of destannylation reactions including protolysis, deuterolysis, acylation, iodina-tion, electrophilic fluorination and the Stille coupling reaction [186-189] (Scheme 66). The last reaction has been employed successfully in the synthesis of a fluorinated thymidylate synthetase inhibitor [189] (Scheme 67). 

The relative rates of acylation and of deoxygenation have been determined with these various reagents [44]. As expected, the pentafluoro reagent reacts the fastest with an alcohol under standard conditions, followed by the 4-fluoro reagent, and the phenyl derivative is the slowest. However, for the deoxygenation reaction the fastest group is the methyl xanthate. The slowest is the pentafluorophenyl derivative. This is not important because all of the thiocarbonyl derivatives mentioned give very fast radical reactions 144],... 

This chapter shows how radical chemistry based on thiocarbonyl derivatives of secondary alcohols can be useful in the manipulation of natural products and especially in the deoxygenation of carbohydrates. From the original conception in 1975, the variety of thiocarbonyl derivatives used has increased, but the methyl xanthate function still remains the simplest and cheapest, when other functionality in the molecule does not interfere. Otherwise, selective acylation with aryloxythiocarbonyl reagents is important. Many of the functional groups present in carbohydrates and other natural products do not interfere with radical reactions. 

D. H. R. Barton, J. Dorchak, and J. C. Jaszberenyi, The invention of radical reactions. Part XXIV. Relative rates of acylation and radical deoxygenation of secondary alcohols, Tetrahedron, 48 7435 (1992). 

The simplest vapor phase reaction of aliphatic carbonyl compounds in their triplet states is cleavage into acyl and alkyl radicals. The acyl radicals, especially at high temperatures, eventually decar-bonylate. 

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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