Electrochemically promoted cyclization

The electrochemically promoted cyclization has proven far superior to the use of traditional reducing agents [62]. Table 9 illustrates the range of reducing agents and conditions that have been examined. With the exception of sodium in 2 1 HMPA/THF, they all failed to afford cyclized material. 

Scheme 16.11 Electrochemically promoted cyclization of linear substrates to P-lactams...

Electrochemically Promoted Cyclization in Room Temperature Ionic Liquids (RTILs)... 

Several bicyclic hydrazinium ions have been prepared and two synthetic strategies have emerged as generally useful, i.e., electrochemical oxidation and Lewis or Brpnsted acid-promoted cyclization.93 Oxidation of l,6-diazabicyclo[4.4.4]tetradecane, for example, (194) gives the intermediate radical cation (195) and the bicylic dication (196, eq 50).93a... 

The Staudinger reaction, i.e. the [2+2] ketene-imine cycloaddition, is the most frequently employed procedure of synthesis of the azetidin-2-one nucleus. Base-promoted cyclization of suitable linear substrates is another frequently employed procedure. We wish to report the electrochemical methodologies of synthesis of P-lactams, according to both procedures, and the possible utilization of RTILs (as solvents and/or as parent of intermediates). 

Indolizidine (115) has been prepared by the silver ion-promoted cyclization of A-chlorooctahydro-1/f-azonine (116). The A-chloroamine was prepared by the reaction of the free amine with dichlor-amine-T, and a nitrene was proposed as the reactive intermediate <65JA678>. The same authors later found, however, that purified chloramines that were completely free of amine were inert to silver ions, and a free radical mechanism involving transannular hydrogen abstraction was proposed <72CJC1167>. The same reaction has been found to proceed in 71 % yield, by electrochemical oxidation under carefully optimized conditions (Equation (3)) <85CJC1170>. The methiodide salt of (115) has been prepared by acid treatment of A-methyloctahydro-l//-azonin-5-ol <67JOC2026>. 

Discoveries of new types of electro-organic reactions based on coupling and substitution reactions, cyclization and elimination reactions, electrochemically promoted rearrangements, recent advances in selective electrochemical fluorination, electrochemical versions of the classical synthetic reactions, and successful use of these reactions in multistep targeted synthesis allow the synthetic chemist to consider electrochemical methods as one of the powerful tools of organic synthesis. 

Cobaloxime(I), electrochemically regenerated from chloro(pyridine)-cobaloxime (III) (232), has been employed as a mediator in the reductive cleavage of the C—Br bond of 2-bromoalkyl 2-alkynyl ethers (253), giving (254) through radical trapping ofthe internal olefin (Scheme 95) [390]. An interesting feature of the radical cyclization (253) (254) is the reaction in methanol, unlike the trialkyltin hydride-promoted radical reactions that need an aprotic nonpolar solvent. An improved procedure for the electroreductive radical cyclization of (253) has been attained by the combined use of cobaloxime(III) (232) and a zinc plate as a sacrificial anode in an undivided cell [391]. The procedure is advantageous in terms of the turnover of the catalyst and the convenience of the operation. 

The apparent dichotomy between good yields of pyrrolidine products from anodic oxidation of lithium alkenylamides and the generally low reactivity of neutral aminyl radicals toward cyclization might be explained by the presence of lithium cations in the electrochemical reactions. The lithium cation has been shown to act as a Lewis acid in promoting aminyl... 

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