Alkyl iodides, intermolecular radical

The occurrence of the indole subunit is well established within the class of natural products and pharmaceutically active compounds. Recently, the Reissig group developed an impressive procedure for the assembly of highly functionalized in-dolizidine derivatives, highlighting again the versatility of domino reactions [8]. The approach is based on a samarium(II) iodide-mediated radical cydization terminated by a subsequent alkylation which can be carried out in an intermolecular - as well as in an intramolecular - fashion. Reaction of ketone 3-11 with samarium(ll) iodide induced a 6-exo-trig cydization, furnishing a samarium enolate intermediate... 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

The second key to success in making sure that the alkyl radical behaves well is to use a reactive radical trap. In fact, this is a major limitation of intermolecular radical carbon-carbon bond-forming reactions for the trapping of alkyl radicals only electrophilic alkenes (attached to electron-withdrawing groups such as -CN, -CC Me, -COMe) will do. This is a limitation, but nonetheless, cyclohexyl iodide adds to all these alkenes with the yields shown and the rate of addition to most of these alkenes is 103 to 104 times that of addition to 1-hexene. 

The intermolecular radical addition of alkyl iodides to terminal alkynes has been used in cyclization cascades performed under radical chain conditions (Scheme 2.3). For example, Oshima and coworkers applied triethylborane as radical initiator to... 

Caddick [19] has reported the use of a novel polymer-supported tetra-fluorophenol-Unked acrylate as an activated acceptor for intermolecular radical reactions. Treatment of immobiUzed acrylate 132 with a variety of alkyl iodides in the presence of tributyltin hydride and AIBN gave the corresponding esters 133 (Scheme 29). NucleophiUc cleavage using amines gave amides 134 in good overall yield whilst regenerating phenol resin 131. 

As mentioned above, EIbB produces an ethyl radical that is reactive enough to abstract iodine atom from alkyl iodide without the help of a radical mediator such as "BuaSnH. A carbon-iodine bond in secondary alkyl, tertiary alkyl and car-bonylmethyl iodide is easily cleaved homolytically by an ethyl radical. The newly formed radical species adds to an olefinic moiety intermolecularly or intra-molecularly to afford the corresponding radical species. 

Intermolecular atom transfer reactions of simple alkyl iodides to acetylenes bearing electron-withdrawing substituents have been observed [15] and are exemplified in Scheme 4. Yields were relatively poor when primary iodides are employed, but improved when secondary or tertiary iodides were added. Electron-withdrawing activating groups are needed on the acetylene in order to accentuate the polar effects and hence increase the initial rate of radical attack. This is done at the cost, however, of diminishing the rate of subsequent iodine transfer to the better-stabilized radical. 

The Naito group has also prepared pyrrolidines [23] on solid phase by a combination of intermolecular radical addition to alkene 43 (Scheme 10) followed by intramolecular oxime ether cyclization to yield 44. These reactions proceeded sluggishly with triethylborane at room temperature, while the analogous solution-phase process was kinetically much faster. Radical additions to the phenylsulfonyl oxime ether 45 were reported by Jeon et al. [24]. Yields were better with primary and secondary alkyl iodides, and the tandem cyclization sequence with iodide 46 to afford bicyclic 47 was also accomplished, albeit in modest yield. 

The 5-hexenyl system has been used by Garst to demonstrate that the intermolecular portion of the Wittig rearrangement of aralkyl alkyl ethers and the ketyl-alkyl iodide reaction involve free radical intermediates. " ... 

Oxoesters are oxidized with Mn(OAc)3 to the corresponding radicals that can add intermolecularly or intramolecularly (eq Ib)" to generate alkyl radicals. In the presence of Cu(OAc)2 the latter are rapidly quenched and oxidized to give alkenes. Radical arylation with alkyl iodides can be induced with dibenzoyl peroxide the yield of the reaction can be improved using a catalytic amount of Cu(0Ac)2-H20, which minimizes hydrogen abstraction by the intermediate radical but introduces a competitive electron-transfer oxidation of the intermediate radical. The oxidative addition of disulfides to alkenes (Trost hydroxysulfenylation ) can be promoted by catalytic amounts ofCu(OAc)2. ... 

The Amax values reported for 151, X=C1, Br, and I are 390,400, and 410 nm, respectively. There is another reason for interest in these species. As already mentioned, oxidation of sulfides to the corresponding radical cation under pulse radiolysis conditions is sometimes accomplished using Cl27, Br2T, or I2 - as oxidant. The intermediates in these oxidations are 151. Alkyl bromides and iodides but not chlorides can also participate in S/.X bonding at least intramolecularly [369,381]. Oxidation of 152,X=Br or I with OH, under pulse radiolysis conditions forms 153, X=Br or I, identified by their absorption spectrum. As the concentration of 152 is increased and, in all cases for 152, X=C1, the spectrum of the intermolecularly S/.S bonded species is observed. 

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