Nickel Mediated Radical Reactions

The tributyltin hydride-mediated carbon-carbon bond formation via radical addition and cyclization of alkyl halides with alkenes has often been a choice for construction of various organic molecules [1], However, the requirement for high-temperature initiators or photo initiation and the difficulties associated with purification of the products from tributyltin halides tend to limit the widespread use of these methods, despite the efforts to make the methods easier [Ic, 2], Recently, nickel-mediated radical additions and cyclizations have been introduced as promising alternatives to the tributyltin hydride methods. These are the nickel powder-acetic acid method for cyclization of haloamides to y-lactams, y -lactams and in-dolones, the borohydride exchange resin-nickel boride method for radical addition, nickel-catalyzed electroreductive cyclization and nickel-catalyzed Kharasch addition of polyhalo compounds. 

This system was also found to be capable of reducing certain halogenated derivatives to form carbon-centered radicals, which can also be captured in various 

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Cassayre J, Zard S (2001) A Short Synthesis of (—)-Dendrobine. Some Observations on the Nickel Mediated Radical Cyclisation and on the Pauson-Khand reaction. J Organomet Chem 624 316... 

Fig. 9 Nickel-catalyzed radical addition reactions mediated by borohydride exchange resins (BER)...

A mixture of a Grignard reagent and C0CI2 has also been used to initiate aryl radical cyclizations. Titanium(III)-mediated radical cyclizations are known, and Sml2-mediate reactions are possible in the presence of a nickel catalyst. Organoborane-mediated radical cyclizations are known.Electrochemically generated radicals also cyclize. The influence of the halogen atom on radical cyclization has been studied.Both phenylthio and phenylseleno... 

Radical cyclization of polyfunctional 5-hexenyl halides mediated by Et2Zn and catalyzed by nickel or palladium salts has been demonstrated to produce stereoselectively polyfunctional 5-membered carbo- and heterocycles [56, 57]. Based on this strategy a formal synthesis of methylenolactocin (11) was achieved (Scheme 20). The acetal 130, readily being built up by asymmetric alkylation of aldehyde 127 followed by reaction with butyl vinyl ether and NBS, served as the key intermediate for the construction of the lactone ring. Nickel(II)-catalyzed carbometallation was initiated with diethylzinc to yield exclusively the frans-disubstituted lactol 132, which could be oxidized directly by air to 134. Final oxidation under more forcing conditions then yielded the lactone (-)-75 as a known intermediate in the synthesis of (-)-methylenolactocin (11) [47aj. 

Ni(0) catalyst. A radical 5-exo cyclization to the potentially zinc or nickel-complexed ketone provides an alkoxyl radical that combines with the co-produced Ni(I) species. A transmetalation to a zinc alkoxide regenerates the catalyst and forms the zinc cyclopentoxide, from which products 79 are liberated on hydrolysis. A bimetallic Cu(I)-Mn(II) system provided similar results (see Sect. 8.4). Analogous samarium diiodide-mediated reactions require in contrast stoichiometric amounts of the reducing agent and are less diastereoselective [26, 27],... 

Fig. 23 Nickel-catalyzed electrochemically mediated reductive radical addition reactions...

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