Haloalkyl radicals

Much attention has been increasingly directed to the chemical synthesis of halogenated peptides. As highUghted in this section, major advances in this area include diaster-eoselective metal-mediated radical haloalkyl transfer chemistry. These developments are expected to provide further entries to those related namral products. 

Beaumont, S., Ilardi, E.A., Monroe, N.R., and Zakarian, A. (2010) Valence tautomerism in titanium enolates Catalytic radical haloalkylation and application in the total synthesis of neodysidenin. J. Am. Chem. Soc., 132, 1482-1483. 

Irradiation of the A-bromo- or N- chloro-azetidin-2-ones (71) in the presence of alkenes, alkynes or radical donors induces rearrangement to the /3-haloalkyl isocyanates (72) via a... 

The traditional means of assessment of the sensitivity of radical reactions to polar factors and establishing the electrophilicity or nucleophilieity of radicals is by way of a Hammett op correlation. Thus, the reactions of radicals with substituted styrene derivatives have been examined to demonstrate that simple alkyl radicals have nucleophilic character38,39 while haloalkyl radicals40 and oxygcn-ccntcrcd radicals " have electrophilic character (Tabic 1.4). It is anticipated that electron-withdrawing substituents (e.g. Cl, F, C02R, CN) will enhance overall reactivity towards nucleophilic radicals and reduce reactivity towards electrophilic radicals. Electron-donating substituents (alkyl) will have the opposite effect. 

The halocarbons react more rapidly with nucleophilic radicals than with electrophilic radicals. Thus, values of Cir with S and VAc are substantially higher than those with acrylic monomers ( fable 6.4) where the transfer constant is close to ideal (Clr=l.0). The haloalkyl radicals formed have electrophilic character (Section 2.3,2). 

Secondly, the rates and modes of reaction of the intermediates are dependent on their detailed structure. For example, the stability of the cation radical formed by the oxidation of tertiary aromatic amines is markedly dependent on the type and degree of substitution in the p-position (Adams, 1969b Nelson and Adams, 1968 Seo et al., 1966), and the rate of loss of halogen from the anion radical formed during the reduction of haloalkyl-nitrobenzenes is dependent on the size and position of alkyl substituent and the increase in the rate of this reaction may be correlated with the degree to which the nitro group is twisted out of the plane of the benzene ring (Danen et al., 1969). 

The dehalogenation of the a-haloalkyl radical is a fast step which can take place by several possible routes . Dibromides are reduced much faster than dichlorides and rra j-l,2-dibromocylohexane is reduced 100 times faster than the m-isomer. This accords with neighbouring group assistance which bromine seems particularly capable of offering (see subsection 6.4.10). 

Alkoxy radical fragmentation is also involved in ring expansion of 3- and 4-haloalkyl cyclohexanones. The radical formed by halogen atom abstraction adds to the carbonyl group, after which fragmentation to the carboethoxy-stabilized radical... 

The cyclic sulfinates 87 and 88 have been prepared by radical cyclisation of the corresponding haloalkyl ferf-butylsulfinates as shown <06AG(E)633. 

With the exception of some fluoromethanes, absorption of light in the long wavelength region appears to result almost exclusively in dissociation at the weakest C-X bond. The primary products are thus an alkyl (or haloalkyl) radical and a halogen atom. 

The fact that cydobutanes are not readily formed is further illustrated by the reactions shown in Scheme 9.21. The radicals formed from the sketched (haloalkyl)acry-lates or related (haloalkyl)acrylonitriles [85] can, in principle, cyclize to yield cydobutane derivatives, but instead these intermediates react intermolecularly [86] or are... 

Intramolecular radical cyclization of Af-haloalkyl pyridinium salts (28) with Bu3SnH readily takes place to generate cyclic pyridinium salts (29) (eq. 5.16), although intermolecular radical alkylation with Bu3SnH does not work due to the direct reduction of the alkyl radical [39]. Since it is well known that natural quinolidine and indolidine... 

Heating or photolytic treatment of A,A-dialkyl-A-haloamine in sulfuric acid or trifluoroacetic acid, followed by neutralization with a base, generates a pyrrolidine or piperidine skeleton. This is the Hofmann-Loffler-Frey tag reaction, and the reaction comprises of the formation of an electrophilic aminium radical, 1,5-H shift (6-membered transition state) or 1,6-H shift (7-membered transition state), formation of 4-haloalkyl ammonium or 5-haloalkyl ammonium, and its polar cyclization by neutralization with a base. Eq. 6.16 shows the formation of A-alkyl pyrrolidine (31) from A-chloro-A-alkyl-A-butylamine (30) in sulfuric acid [46, 47]. 

TPDS can be also used for the preparation of biaryl through the intramolecular free radical // -substitution of A-(2-bromoaryl)arenesulfonamide (9) and radical ring expansion of a-haloalkyl cyclic (3-keto ester (11) (eqs. 12.5a and 12.5b). 

Reaction 92 with H02 results in formation of a hydroperoxide. Since the nature of the haloalkyl group is not likely to affect greatly the reactivity for this process, rate constants similar to that of 5 x lCT12cm3 molecule-1 s-1 for methylperoxy are expected. In view of the low concentrations of H02 radicals in the troposphere, this reaction is expected to be of only minor significance, except under conditions where the NO and N02 concentrations are also low. 

Thioalkyl radicals and / -haloalkyl radicals exhibit a conformation with a distortion at the / carbon, shifting S (or the halogen) towards the orbital with the unpaired electron [7]. The spin density on the a atom of (RS)3C is about 0.7 [8] the unpaired electron is in an orbital with 8-9 % s character [4]. The mean lifetime of vinyl radicals considerably increases when the centres of these radicals are sterically hindered by bulky groups such as Me3C—, Me3Si— [9, 10]. The stabilization energy of... 

Photoheterolysis of benzylic chlorides [204] yielded results signifying that simple benzyl cations, such as cumyl and 1-phenylethyl cations, can exist in the solution as free ions radicals arising from a competing photohomolysis are also observed frequently. Haloalkyl-carbocations are studied by heterolysis of the corresponding dihalides in super acid media [205]. NMR chemical shifts are interpreted as evidence for an interaction between the vacant orbital of cationic center of the haloalkyl carbocations with a lone electron pair of the halogen atom. 3-chloro-l-methylcyclopentyl cation 73, thermally eliminates hydrogen chloride and yields l-methyl-2-cyclopentyl cation 74, a similar behavior reported for y-chloroalkyl carbocations [206] (Scheme 5). 

Of the halogen compounds containing oxygen, interest has been focussed on the photochemical decomposition of the halogenated ketones as a possible source of haloalkyl radicals. 

Radical cyclizations. Radicals generated from haloalkyl propargyl ethers... 

In this reaction, one polymer chain forms per molecule of the organic halide (initiator), while the metal complex serves as a catalyst or as an activator, which catalytically activates, or homolytically cleaves, the carbon—halogen terminal. Therefore, the initiating systems for the metal-catalyzed living radical polymerization consist of an initiator and a metal catalyst. The effective metal complexes include various late transition metals such as ruthenium, copper, iron, nickel, etc., while the initiators are haloesters, (haloalkyl)benzenes, sulfonyl halides, etc. (see below). They can control the polymerizations of various monomers including methacrylates, acrylates, styrenes, etc., most of which are radically polymerizable conjugated monomers. More detailed discussion will be found in the following sections of this paper for the scope and criteria of these components (initiators, metal catalysts, monomers, etc.). 

---