Electrochemical cyclization

The electrochemical cyclization of bis(aminomethylenemalonates) (1394) in acetonitrile containing 5% water and tetraethylammonium perchlorate afforded tetrahydroquinoxalines (1395) in 90-96% yields (81ZC286). 

Bicyclic [33] and 7,5-bicyclic [34, 35] dipeptides (Scheme 24) have been syn-thetized by a one-step electrochemical cyclization from various dipeptides. The selective anodic amide oxidation... 

A relatively recent application to natural product synthesis stems from efforts to synthesize a sesquiterpene called 1-sterpurene 7 [17]. This substance is thought to be the causative agent of the so-called silver leaf disease that affects certain species of shrubs and trees. The strategy focuses on three key steps (a) electrochemical cyclization of the bis unsaturated ester 11 to produce the five-membered ring of 10, (b) a Ruhlman-modified acyloin condensation to... 

Slomczynska, U., Chalmers, D.K., CORNILLE, F., Smythe, M.L., Beusen, D.D., Moeller, K.D., Marshall, G.R. Electrochemical cyclization of dipeptides to form novel bicyclic, reverse-turn peptidomimetics. 2. Synthesis and conformational analysis of 6,5-bicyclic systems./. Org. Chem. 1996, 63(4), 1198-1204. 

The electrochemical cyclization of enol ethers in methanol uses an undivided cell and 2,6-lutidine is added as a proton scavenger. Acid catalysed hydrolysis of the enol function is thus avoided. An advantage is gained by diluting the methanol witli a non-nucleophilic co-solvent. This lowers the extent of dimethoxylation of... 

The electrochemical cyclization reaction is less successful with the N-(3-phenylallyl)acetanilide 60 which has two potential bond cleavage sites from the radical-anion [173]. Carbon-nitrogen bond cleavage with loss of a 3-phenylallyl radical, leaving an amide nitrogen anion, is favoured over carbon-chlorine bond cleavage. 

An electrochemical cyclization leading to both benzoxazines and dihydrobenzoxazines is shown later in this section (Scheme 34). Finally, oxazine 304 was formed in a reductive, dehydrative dimerization of 303 (Scheme 33) <1961CIL254>. 

The secocorrin nickel complex (101) can also be induced to undergo an electrochemical cyclization to corrin (100) but only in low yield. The experimental conditions involve a one-electron oxidation, followed by a one-electron reduction.269 The same secocorrin complex (101) is the starting material for two cyclization sequences leading to a didehydrocorrin complex (107) with a chromophore of seven double bonds (Scheme 67).269,270 The most interesting feature of these sequences is the remarkably easy acid-catalyzed ring closure of the secocorrinoid complex (106) to corrin (107). 

Cyclizations of carbonyl-containing a. -unsaturated esters like those illustrated in Scheme 38164>16S are conceptually very similar to ketyl cyclizations, but they may be very different mechanistically. At least for electrochemical cyclizations, Litde has proposed, based on reduction potentials, that the unsaturated ester is reduced first.164 Even though questions remain about the timing of election transfer and proton transfer steps, such cyclizations often provide good yields of products. 

A series of 2,3 dihydrobenzothiophenes 451 have been synthesized by Ni-catalyzed electrochemical cyclization of allyl 2-haloaryl sulfides 450 (Equation 15) <2004SC3343>. 

A similar reaction has been used for the synthesis in 50% yield of l-aza-6-oxa-2-oxobicyclo[5.3.0]decane ring skeleton (IX) in a one-step electrochemical cyclization from the dipeptide Boc-L-homoserine-L-proline-OMe (X). The reaction is highly diastereoselec-tive, generating a new chirale center having an S configuration [37]. 

Moeller and coworkers [484] found that electrochemical cyclization (anodic intramolecular alkoxylation) of optically active dipeptides proceeded highly diasteroselectively. 

S-Deazaflavins are of biological interest and may be synthesized by a simple reaction from a chlorouracil (90.5) and o-(hydroxymethyl)aniIine [3S91J. The chlorophenylpyrroles (90.6) undergo electrochemical cyclization to the phenanthridine in moderate yield [3758]. 

It is not clear why the Mn(in)-mediated electrochemical cyclization of 20 and 22 was completely unsuccessful. It should be noted that the rate determining step in the cyclization of a-unsubstituted P-keto esters is the addition of the alkene to the Mn(ni) enolate with loss of Mn(II) while the rate determining step in the oxidation of a-alkyl substituted P-keto esters is the formation of the Mn(III) enolate, which rapidly loses Mn(II) to form the free a-keto radical (57, 40). Mn(III)-mediated electrochemical oxidation was somewhat successful for a-alkyl substituted P-keto esters, but failed for a-unsubstituted P-keto esters. 

Mn(in)-mediated electrochemical oxidative cyclization was successful in some cases, such as that of 4, which gives up to 59% of 8 with only 10% of the theoretical amount of Mn(III). However, the electrochemical cyclizations generally give lower yields than the stoichiometric Mn(III) oxidative cyclizations, and more complex product mixtures are typically obtained. One problem is that Mn(III) oxidations are relatively slow at room temperature. Therefore elevated temperatures must be used in the electrochemical cyclizations. This can lead to further oxidation as in the formation of 18 and 19 from 9 by oxidation of the initial product 14. It is hard to determine why the yields are lower in other cases since we were unable to isolate byproducts. We can only speculate that either the starting materials or the products are oxidized at the electrode to give polymeric material. NaI04 in DMSO can be used to chemically reoxidize Mn(II) to Mn(III). Under these conditions 4 affords 60% of 8 with only 5% of the theoretical amount of Mn(III). 

Miscellaneous Methods.—The electrochemical reduction of 1,3-diketones, PhCOCR 2 = H or alkyl, = alkyl or aryl), leads to cyclopropane-1,2-diols by a bielectronic process. In some cases stereoselective cyclization favours cis-diol formation and product yields are generally satisfactory. Electrochemical cyclization of 1,1-bisbromomethylcyclopropane affords spiropentane. ... 

Tokuda M, Hayashi A, Suginome H (1991) Synthesis of dimethyl 1,2-cycloalkanedicarboxylates by electrochemical cyclization of dimethyl a,a -dibromoalk-anedioates using a copper anode. Bull Chem Soc Jpn 64(8) 2590-2592. doi 10.1246/bcsj.64. 2590... 

Scheme 3 Traceless silyl template for electrochemical cyclization reaction...

Attempted cyclopropanation (CHjNj, MCjSOCHj) of the tetraquinone (147) fails to give (148). However, the desired homoquinone can be obtained by electrochemical cyclization of (149). °... 

Dialkyl w-bromoalkylidenemalonates undergo ring-closure at the a-position when they react with L-Selectride and at the P-position when electrochemically cyclized (Scheme 51) yields of between 45 and 80% are obtained. 

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