Chlorine atom transfer

Although head addition occurs during PVC polymerization to the extent of ca 1%, it is now thought that PVC contains few, if any, head-to-head linkages (<0.05%).61-6- Propagation from the radical formed by head addition is not competitive with a unimolecular pathway for its disappearance, namely, 1,2-chlorine atom transfer (see Scheme 4.8). 

Entries 7 and 8 illustrate conversion of diazonium salts to phenols. Entries 9 and 10 use the traditional conditions for the Sandmeyer reaction. Entry 11 is a Sandmeyer reaction under in situ diazotization conditions, whereas Entry 12 involves halogen atom transfer from solvent. Entry 13 is an example of formation of an aryl iodide. Entries 14 and 15 are Schiemann reactions. The reaction in Entry 16 was used to introduce a chlorine substituent on vancomycin. Of several procedures investigated, the CuCl-CuCl2 catalysis of chlorine atom transfer form CC14 proved to be the best. The diazonium salt was isolated as the tetrafluoroborate after in situ diazotization. Entries 17 and 18 show procedures for introducing cyano and azido groups, respectively. 

Reaction of AT-chlorosulfonyl derivatives with enol ether initiated by Et3B has been reported (Scheme 22) [57]. The reaction mechanism involves a chlorine atom transfer followed by a Et3N promoted elimination of HC1 to produce stable enol ethers. 

Arylation of activated double bonds with diazonium salts in the presence of copper catalysts is known as the Meerwin reaction. The reaction is postulated to either proceed through an organocopper intermediate or through a chlorine atom transfer from chiral CuCl complex to the a-acyl radical intermediate. Brunner and Doyle carried out the addition of mesityldiazonium tetrafluoroborate with methyl acrylate using catalytic amounts of a Cu(I)-bisoxazoline ligand complex and were able to obtain 19.5% ee for the product (data not shown) [79]. Since the mechanism of the Meerwin reaction is unclear, it is difficult to rationalize the low ee s obtained and to plan for further modifications. 

Several recent examples of metal-promoted cyclizations of perchlorocarbonyl compounds are presented in Scheme 28, and a full paper by Weinreb is recommended as an excellent source of references to prior work in this area (including mechanistic studies on the role of the metal).127 The first two examples illustrate that the choice of substrates can dictate the types of products that are formed the initially formed y-chloro esters are stable to subsequent ionic reactions, but the ris-y-chloro acids form lactones. Interestingly, Weinreb has shown that the metal can equilibrate the cis- and /rans-y-chloro esters by reversible chlorine atom transfer. The third example128 illustrates a general feature of the atom transfer method yields at high concentration are comparable to (and sometimes better than) those provided by using tin hydride at low concentrations. Indeed, in the third example, the three chlorines on the ester provided three opportunities for cyclization during the tin hydride reduction, but 40% of the product still failed to cyclize. (Unfortunately, the tin hydride concentration was not specified.)... 

A key intermediate in the synthesis of pretazettine (Eq. 8), an alkaloid that contains a ds-3a-arylhydroindole ring system and shows antiviral and anticancer properties, has been synthesized by chlorine-atom transfer cyclization of a chloroacetamide in a highly stereocontrolled manner [25]. 

When metal ion complexed amino radicals are produced by the reaction of A -chloro amines with reducing metal salts in the presence of alkenes, /6-halo amines are produced12-39 41. The reaction of 1-chloropiperidine with cyclohexene, iron(II) sulfate and iron(III) chloride in methanol afforded mainly the d.s-adduct of 2. The diastereoselectivity is attributed to coordination of the unprotonated amino group with the iron(III) salt, which is mainly responsible for the chlorine atom transfer. With A-chlorodimethylarnine and 4-chloromorpholine lower yields are obtained. 

The Kochi reaction has also been used to demonstrate polar effects of remote substituents upon free-radical stereoselectivities in chlorine atom transfer. ... 

An example of conjugate free-radical addition to methyl acrylate mediated by a copper Lewis acid has been reported (Sch. 30) [65]. In this example the Lewis acid 127 activates the substrate for conjugate addition by the aryl radical which is followed by an enantioselective chlorine atom-transfer step. Chemical and optical yield for the transformation are both low. 

Work in the group of Speckamp has shown that C-Cl bonds in a captodative position are weak enough to lead to radical chain cyclization reactions by chlorine atom transfer [28], Chlorine atom transfer from 34 to the catalyst, Cu Cl-bipyridine, leads to radical 35 which then undergoes 5-exo intramolecular addition to form the proline derivative 36 (Eq. 1). The captodative substitution is necessary for this radical process in the absence of an electron-withdrawing substituent, a cationic reaction leading to a piperidine occurs instead [29]. 

In a similar process, the a-chloro-a-thioacetamide 37 leads to the pyrrolizidines 38 and 39 upon chlorine atom-transfer cyclization initiated by catalytic ruthenium chloride (Eq. 2). The high efficiency of this method, which was applied to alkaloid synthesis, was attributed to the captodative effect [30],... 

The jV-chloro-compounds were the first to be employed as radical cyclization precursors in the synthesis of pyrrolidines and piperidines, as well as fused and bridged heterocyclic skeletons [7], Aminyl and amidyl radicals were thus generated and used in intramolecular additions. Higher yields and selectivities are obtained with the metal-complexed species. Some selected examples are reported in Table 4. Generally, a typical radical chain mechanism is involved (with chlorine atom transfer from 7V-chloro-compound). In the particular case of copper-cornplexed aminyl radical cyclization, a redox chain process operates (with fast chlorine ligand transfer from cupric chloride)... 

Acyl radicals can fragment by loss of carbon monoxide. Decarbonylation is slower than decarboxylation, but the rate also depends on the stability of the radical that is formed. 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 (see also Table 11.3, Entries 45 to 48). When reaction of isobutyraldehyde with carbon tetrachloride is initiated by f-butyl peroxide, both isopropyl chloride and isobutyroyl chloride are formed, indicating that decarbonylation is competitive with the chlorine atom transfer. 

Metathetical reactions of chlorine atoms transfer of hydrogen atoms... 

Since this study led to a number of extensions, it is desirable to explain why the process works, and what its advantages are. The rate advantage of a radical relay process is that the hydrogen abstraction is intramolecular, rather than the intermolecular abstraction that would occur without the relay by the template. However, this explains it only in part, since the relaying of a chlorine atom from the radical in solution to the iodine of the template is of course an intermolecular process. Why is the two-step sequence - intermolecular chlorine atom transfer, then intramolecular hydrogen abstraction - faster than an intermolecular hydrogen abstraction by the free radical in solution The answer is relat-... 

Chlorine atom transfers of the type depicted in Reaction 10 are well known for aliphatic radicals. From crude (O2/CI2) mixed scavenger experiments with CF4, the phenomenological rate coefficient ratio (kio Ai3 ) diibits an upper-bound value of 0.10 (49). 

N-Chlorocompounds are themselves capable of reacting with some organic compounds to produce oxidation or chlorination products. 4-N-Chlorocytosine (47), for example, reacts with phenylalanine to give a low yield of phenylacetaldehyde (Patton et ah, 1972). Presumably, the N-chloro amino acid is formed as an intermediate by direct chlorine atom transfer between 47 and phenylalanine. 

The other chain scissions are accompanied by chlorine-atom transfer to the break site to form two fragments (by disproportionation) of lower molecular mass than the original polymer. Trifluoronitrosomethane copolymers are the least thermally stable. Trifluorochloroethylene copolymers occupy an intermediate position, while polyvinylidene fluoride and polytetrafluoroethylene are the most thermally stable. 

The chain transfer to vinyl chloride monomer involves a chlorine atom transfer reaction, following a head-to-head addition of a monomer molecule to the growing macroradical (184-186). The head-to-head addition leads to a highly unstable radical that stabilizes itself via a chlorine abstraction. This reaction pathway (eq. 31) accounts for Cm being much greater than for other commercially important monomers. 

These processes were described above in connection with chlorine atom transfer from a cobalt(III) complex to Cr + and with the electron transfer from Cr to IrCl " without accompanying chlorine atom transfer. Activated states probably contain Cl bridges in each case. 

Pulse radiolysis studies of the reactions between a -substituted alkyl radicals and [IrCU] indicate two distinct processes. Diffusion-controlled rates with a-OH and a-OR derivatives involve electron transfer, while, with alkyl and alkylchloride radicals, a chlorine atom transfer from [IrCU] to give [IrCl4(OH)2] predominates with considerably slower rate constants. The comparable reactions with [Fe(CN)6] are also slow and structure dependent but there is no evidence for CN transfer. 

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