Cathodic addition, intramolecular

Scheme 65 Heterocycles by Nickel catalyzed intramolecular cathodic addition of halides to double bonds.

Vitamin Bi2-catalyzed intramolecular cathodic coupling leads to a regioselective 1,4-addition with formation of a spirocom-pound (Eq. 2) [95]. This chain reaction is initiated by the reduction of Co(III) to a Co(I) species, which reacts in an oxidative addition with the alkyl bromide. The resulting alkyl-Co(III)-Br species is then reduced to an alkyl anion that undergoes a Michael addition and yields Co(I) for the next cycle. 

Cathodic reduction of 1,3-diphenyl-propenone leads to l-hydroxy-2-benzoyl-3,4-diphenyl cyclopentanes with exclusive cis configuration of the two phenyl groups. With l-phenyl-l-pentene-3-one the cyclodimer 2-methyl-3,5-diphenyl-4-(l-propionyl)-cyclohexanone is formed with a 100% yield in an intramolecular Michael addition via an electrogenerated base. The substituents are all in the most stable equatorial position [277]. 

Scheme 77 Intramolecular cathodic Michael-type addition.

Cleavage of the radical-anion to give a phenyl o-radical also occurs in aprotic solvents and can be demonstrated using substrates where the phenyl radical is trapped in an intramolecular addition process. Substi ate 12 gives products analogiis to those from reduction of the 2-haiogeno-N-methylbenzanilides (p. 129) at a mercury cathode in aprotic. solvents [79], Similarly 13 undergoes a related cyclization of the o-radical intermediate [80],... 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

C-C bond formation in inter- or intramolecular additions starting with olefin [ 199, 200], ketyl [201] (generated by PET [202], chemical or cathodic [24, 203] reduction) [204, 205] or imine radical anions [206] has become a versatile method. In general, the intramolecular addition is highly suitable for the construction of five membered rings, less so for six-, and not effective for seven-membered ring formation. 

Pyridinium and related cations are well known as excellent radical traps, yielding, e.g., conveniently alkylated derivatives by addition of radicals generated by oxidants from the appropriate precursors [135]. Arylation of such derivatives can be efficiently performed at the cathode, as shown in Scheme 45 with an intermolecular example affording a precursor of cularine (63) [136] and with an intramolecular example giving aporphine (64) [137]. 

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