Atom transfer radical alkyl iodides

Electron transfer from copper or copper salts to alkyl halides has been used to initiate atom transfer radical additions. One modification of this process involves catalytic amounts of copper powder and fluorinated alkyl iodides the radicals so generated may react in either inter- or intramolecular fashion with alkenes (equation 13)19. Alternatively, a-chloroesters with remote alkene functions undergo cyclization in the presence of cat-... 

The radical intermediates from Cr(II) reduction of alkyl halides can in principle be used synthetically, but have only seen limited attention to this point. co-Haloalkynes (bromides, iodides), in the presence of excess Cr(C104)2, undergo cyclization reactions to form exo-alkylidene cycloalkanes (equation 176)347. These reactions proceed by the radical cyclization of intermediate 42 onto the alkyne unit, which undergoes subsequent reduction by Cr(II) to give a hydrolytically unstable vinylchromium(III). Rings of four, five and six members can be formed. Alternatively, a-iodo esters undergo intramolecular atom transfer radical cyclizations onto alkynes or alkenes with catalytic or stoichiometric amounts of... 

More recently, the related indium-mediated radical reactions have been widely studied (Scheme 7.13).19 Indium iodide-mediated radical cyclisation was first reported by Cook et al.20 The indium-mediated 1,4-addition of alkyl radicals to (F)-but-2-enenitrile was investigated by using 1-ethylpiperidinum hypophosphite (EPHP) as a hydrogen donor in aqueous media (Scheme 7.13).21 Atom transfer radical cyclisation and reductive radical cyclisation were studied using indium and iodine.22 Indium mediated alkyl radical addition to dehydroamino acid derivatives was also reported.23 The indium-mediated radical ring expansion of a-halomethyl cyclic (3-keto esters, shown in Scheme 7.13, was achieved in aqueous alcohols.24... 

Cyclization of alkyllithiums on to alkenes has been reported previously to be potentiaUy a one-electron process. Recent results have indicated that PhLi-initiated cycloisomerization of primary alkyl iodides involves a radical-mediated atom-transfer process similar to that previously reported for secondary and tertiary substrates. This... 

Substantial effort has been directed toward the control of vinyl acetate (VAc) radical polymerization using living radical polymerization (LRP) methods, including atom transfer radical polymerization, degenerative transfer through alkyl iodide,dialkyl tellurium, trithiocarbonate, xanthate, and cobalt acetylacetonate The focus of... 

Triethylborane in combination with oxygen provides an efficient and useful system for iodine atom abstraction from alkyl iodide, and thus is a good initiator for iodine atom transfer reactions [13,33,34]. Indeed, the ethyl radical, issued from the reaction of triethylborane with molecular oxygen, can abstract an iodine atom from the radical precursor to produce a radical R that enters into the chain process (Scheme 13). The iodine exchange is fast and efficient when R is more stable than the ethyl radical. 

Hydrogen atom transfer implies the transfer of hydrogen atoms from the chain carrier, which is the stereo-determining step in enantioselective hydrogen atom transfer reactions. These reactions are often employed as a functional group interconversion step in the synthesis of many natural products wherein an alkyl iodide or alkyl bromide is converted into an alkane, which, in simple terms, is defined as reduction [ 19,20 ]. Most of these reactions can be classified as diastereoselective in that the selectivity arises from the substrate. Enantioselective H-atom transfer reactions can be performed in two distinct ways (1) by H-atom transfer from an achiral reductant to a radical complexed to a chiral source or alternatively (2) by H-atom transfer from a chiral reductant to a radical. 

It is more difficult to conduct the addition reactions of nucleophilic radicals to electron poor alkenes because the resulting atom transfer steps are often endothermic and are too slow to propagate chains, even with iodides. An exception is illustrated in Scheme 57 resonance-stabilized vinyl radicals (especially if they are secondary or tertiary) are reactive enough to abstract iodine from alkyl iodides.178... 

Iodine atom transfer reactions between alkyl radicals and iodocarbonyls are very rapid (107 M-1 s-1 to 109 M-1 s-1).130 This means that, even when these iodides are cyclized by the tin hydride method, iodine atom transfer may supersede hydrogen transfer, and the reductively cyclized product will ultimately be derived from the reduction of a cyclic iodide. Tin hydride cyclizations of halocarbonyls also often require very low concentration to avoid reduction of the initial radical prior to cyclization. For these reasons, reductively cyclized products are best formed by atom transfer cyclization at high concentration, followed by reduction of the product in situ. In a recent full paper, we have described in detail the preparative and mechanistic features of these cyclizations,19 and Jolly and Livinghouse have reported a modification of our reaction conditions that appears to be especially useful for substrates that cyclize very slowly.131 Cyclizations of a-iodocarbonyls can also be promoted by palladium.132... 

In the presence of an alkyl iodide, selective alkyl radical addition to the C-atom of the imine generated in situ occurs, overcoming the competitive phenylation reaction (Equation 14.20) [30]. The Ph- radical, generated by decomposition of the diazonium salt, as described before, generates the alkyl radical by selective iodine atom transfer (Equation 14.21). 

A limitation of the aforementioned methods is that they are unsuitable for the use of primary alkyl iodides. Under Et3B/02 initiation conditions, the desired radical is intended to be generated by iodine atom transfer to ethyl radicals, which is not favorable in the case of primary iodides. Thus ethyl radical addition competes with the desired radical when using triethylborane initiation along with primary iodides. In addition, generating radicals by hydrogen atom transfer from ethers or acetals has limited applicability. Because of the expanded synthetic potential of primary alkyl iodides as... 

In 2007 the scope of the trialkylborane/water system was extended to the dehalogenation of alkyl iodides and the chemoselective deoxygenation of secondary alcohols in the presence of alkyl and aryl halides [86]. The rate constants for the hydrogen-atom transfer from this reagent to secondary radicals (Scheme 37) are substantially lower than those of the Ti(III) aqua-complex [78, 87]. 

In fact, the RAFT process resembles the degenerative transfer (DT) process [274]. In a polymerization in which an alkyl iodide is used as the degenerative transfer agent, the iodine atom is exchanged between a polymeric radical and a dormant chain, similar to the dithiocarbonate exchange in RAFT. However, in the case of degenerative transfer there is a direct equilibrium between the dormant and growing chains, without formation of an intermediate radical. 

In cases where hydrogen atom transfer gives primarily reduced products, BusSn—SnBus under photochemical generates the radical which can cyclize (see 15-46), but a halogen atom transfer agent, such as iodoethane, is used rather than a hydrogen-transfer agent, so the final product is an alkyl iodide. 

Cobalt(II) compounds react with an alkyl halide to give an organocobalt(III) compound, as shown in equation (32), where Y is an axial ligand. It takes place by three separate mechanisms, depending on the nature of the Co compound and the alkyl halide. The best known pathway involves the atom-transfer reactions shown in equations (33) and (34). The second mechanism involves electron transfer from the Co compound to the alkyl halide, which decomposes to give halide and organic radicals, which react with the Co compound. The third mechanism has been observed for the alkylation of vitamin B jr by alkyl iodides. 

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