Iodine atom-transfer addition reaction

Iodoalkyl-(231) and 3-iodoalkenyl-(232) phosphonates have been synthesised from the 1-iodoalkylphosphonates (230) by an iodine atom-transfer addition reaction (Scheme 35). ... 

Electron-deficient alkynes undergo an iodine atom-transfer addition reaction with secondary or tertiary alkyl iodides in the presence of hexabutyldistannane and under sunlamp irradiation to give iodoalkenes methyl propiolate and -butyl iodide, for instance, afford a 4 1 mixture of the ( )- and (Z)-adducts 231 Analogous reactions with simple... 

In an extension of atom-transfer radical reactions to heterocyclic systems, Byers has introduced a novel methodology for the addition of electron-deficient radicals to unprotected pyrroles and indoles in a stannane-fi ee, non-oxidative process <99TL2677>. For exanqrle, photochemical reaction of pyrrole (33) with etl l iodoacetate (34) in presence of thiosulfiite as an iodine reductant, phase transfer catalyst and propylene oxide led to high yields of the 2-alkylated pyrrole 35 <99TL2677>. 

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). 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

Naito has also described analogous tandem radical addition-cyclization processes under iodine atom-transfer reaction conditions [16,32], Treatment of 186 with z-PrI (30 eq.) and triethylborane (3x3 eq.) in toluene at 100 °C gave, after cleavage from the resin, the desired lactam product 190 in 69% yield (Scheme 46). Similar reactions involving cyclohexyl iodide, cyclopentyl iodide, and butyl iodide were also reported as well as the reaction with ethyl radical from triethylborane [16,32], The relative stereochemistry of the products was not discussed. 

Following the pioneer work of Kharasch [60], methods involving radical transfer of halides have been developed. The atom transfer method has emerged in the 1980s as one of the best method for conducting intra- and intermolecular radical additions to olefins [61]. This approach is particularly appealing from an atom economy point of view since all atoms remains in the final product. The non-reductive nature of these reactions is also particularly important for the preparation of functionalized molecules. Halides transfers and more particularly iodine atom transfers have found nice applications for cyclizations, annula-tions and cascade reactions [62]. These reactions are based on exothermic radical steps, such as the addition of an alkyl radical to an olefin, followed by an... 

Scheme 6.4 Intermolecular addition reactions through iodine atom transfer.

Et3B is an effective tool for halogen atom transfer radical reactions (see also Chap. 1.5). Perfluoroalkyl iodide [29], a-halo nitrile and a-halo ester [30] added to alkenes and alkynes at low temperature. Not only terminal alkenes but also internal alkenes can be employed to furnish iodine atom transfer adducts (Scheme 23). Furthermore, addition of perfluoroalkyl iodide to silyl and germyl enolate provided a-perfluoroalkyl ketones [31]. The reaction would involve the elimination of a tri-... 

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... 

Fiirstner reported the first McMurry-type reactions working with 5-10 mol% of titanium trichloride and stoichiometric amounts of zinc powder in the presence of chlorotrimethylsilane. The amount of TiCl3 could be reduced to 2 mol% when (ClMe2SiCH2)2 was used as a reagent [125, 131]. At the same time, Burton and coworkers reported atom transfer radical additions of perfluoroalkyl iodides 39 to alkenes 40 catalyzed by 20 mol% of a low-valent titanium compound generated from TiCLt and zinc powder affording 41 in 10-85% yield (Fig. 13). A tandem radical addition/5-exo cyclization/iodine transfer reaction with diallyl ether proceeded in 66% yield [132]. 

Evidence based on product mixtures now suggests, at least in the cases of a-halocarbonyl and perhaloalkyl starting marterials, that these reactions are in fact atom transfer radical cyclizations (equation 166)324,325. In them, the palladium catalyst is proposed to have roles both as the radical initiator and as a trap for iodine, similar to the more commonly used hexabutylditin. Intramolecular allyl halide-alkyne cyclizations proceed with trans-addition to the triple bond this is evidence that a still different mechanism may be operating in these cases (equation 167)1,326. 

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... 

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