Tandem reactions radical addition trapping

Sibi and Chen [42] reported a related tandem intermolecular nucleophilic free-radical addition-trapping reaction of enoate 168 establishing chirality at both a and /(-centers with control over both absolute and relative stereochemistry (Scheme 9.30) using a Lewis acid catalyst and the bisoxazoline ligand 169. They observed... 

Scheme 9.30. Enantioselective tandem intermolecular free-radical addition-trapping reaction of enoates.

Scheme 7.10 Indium-mediated tandem radical addition-cyclisation-trapping reactions in aqueous media.

The same group reported indium-mediated tandem radical addition-cyclization-trap reactions in aqueous media [52c], The use of water-soluble radical initiator 2,2 -azobis[2-(2-imidazolin-2-yl)propane], water-soluble chain carrier 1-ethyl-piperidinium hypophosphite (EPHP) and surfactant cetylammonium bromide (CTAB) allowed the C-C bond-forming radical reactions of highly hydrophobic substrates in water [53], Similarly, the use of CTAB and EPHP in presence of 4,4 -azobis(4-cyanovaleric acid) promoted the indium-mediated radical addition to P-substituted conjugated alkenes in water [54]. 

A novel tandem carbonyiation/cyclization radical process has been developed for the intramolecular acylation of l-(2-iodoethyl)indoles and pyrroles <99TL7153>. In this process, an acyl radical is formed when CO is trapped by an alkyl radical formed from the AIBN-induced radical reaction of l-(2-iodoethyl)indoles 104 with BusSnH. Intramolecular addition of the acyl radical to the C-2 position of the heteroaromatic system presumably affords a benzylic radical which undergoes in situ oxidative rearomatization to the bicycloketones 105. 

By pairing an addition to an enone in the final step with an initial intramolecular radical cyclization, it is possible to accomplish tandem radical reactions of cobalamine(III) alkyls356. Tandem cyclizations are also most often done, with the final termination step being elimination to the alkene or trapping with styrene (equation 182)357. It is also possible to enter into ring-expansion reactions by retrograde radical cyclization-recyclization processes in modest yields358. 

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... 

The radical carbonylation of an alkyl iodide in the presence of Kim s sulfonyl oxime ethers [58, 59, 60] provides a new type of multicomponent coupling reaction where plural radical Cl synthons are consecutively combined [61]. In the transformation, allyltin was used to serve as a trap of benzenesulfonyl radical which converts sulfonyl radical to a tin radical, thus creating a chain. Scheme 14 illustrates such an example, where the product was easily dehydroxylated to give the corresponding tricarbonyl compound on treatment with zinc/AcOH. The radical acylation reaction by Kim s sulfonyl oxime ethers can be conducted under irradiation with the addition of hexamethylditin. This is an alternative path for achieving a similar transformation without the use of photolysis equipment. Scheme 15 illustrates several examples where carbon monoxide and Kim s sulfonyl oxime ethers are successfully combined to create new tandem radical reaction sequences [61],... 

Finally, a novel three-component radical cascade reaction involving isonitriles has just been published [6]. In this paper, aromatic disulfides, alkynes, and isonitriles have been reported to react under photolytic conditions to afford -arylthio-substituted acrylamides 49 or acrylonitriles 50 in fair yields as mixtures of the E and Z geometric isomers (Scheme 21). The procedure entails addition of a sulfanyl radical to the alkyne followed by attack of the resulting vinyl radical on the isonitrile. A fast reaction, for example, scavenging by a nitro-derivative (route a) or f-fragmentation (route b), is necessary in order to trap the final imidoyl radical, since addition of vinyl radicals to isonitriles seems to be a reversible process. The reaction provides very easy access to potentially useful poly-functionalized alkenes through a very selective tandem addition sequence. 

Sibi et al reported the first example in acyclic systems where both highly diastereo-and enantioselective tandem radical reactions occurred with carbon-carbon bond formation to achieve the vicinal functionalization of cinnamates with chiral Mg(II) catalysts (Scheme 4.5) [3]. The reactions began with the addition of nucleophilic alkylradical to cinnamate (7) and trapping of the intermediate radical with allyl-stannane using a chiral bis(oxazoline)s-Mgl2 as a Lewis acid. The reaction with cinnamate (7) (1 equiv), t-Bul (10 equiv), allyltributyltin (5 equiv), and triethylborane... 

Irradiation of cyclohexenone 32 with the tertiary a-silylamine EtjNCHjSiMej in methanol solution in the presence of the electron acceptor 9,10-dicyanoanthracene (DCA) yields predominantly the desi-lylated adduct 32b. The product ratios depend on amine concentration. " The mechanism proposed for adduct formation is outlined in Scheme 24. Oxidation of the tertiary amine by singlet DCA yields the amine cation radical, which undergoes desilylation upon nucleophilic reaction with the solvent. Addition of the a-aminoalkyl radical to the neutral enone affords the radical adduct, which is reduced by DCA and protonated by solvent. " Intramolecular trapping of the radical adduct can compete with reduction by DCA"-, as seen in the reaction of 32 with an a-silylanihne, which yields the tandem addition product 32c (Scheme 24). ... 

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