Redox cyclization

The initial stage of this reaction involves a nucleophilic halogen substitution followed by intermolecular redox cyclization of ort/zo-nitrohydrazobcnzcncs [642], Instead of halogen the substrate can contain another group (N02, OAlk) [643-645], It has been shown that in ethanol the aforementioned reaction proceeds with the formation of 2//-benzotriazole nitro derivatives, whereas in acetic acid their IV-oxides are formed and, when boiled in ethanol, turn into the final products (Scheme 2.123) [637, 638, 646],... 

Redox cyclization. Allylic alcohol and alkyne units that are separated by several bonds undergo cyclization that involves hydrogen transfer to the triple bond and appearance of a formyl group. The products also can participate in aldol-type condensation. 

A synthetic route to 3-pyrrolidinone and nitrone derivatives from A-sulfonyl hydroxylamines via gold-catalysed intramolecular oxygen-transfer redox cyclization and [l,3]-sulfonyl migration has been reported (Scheme 121). ... 

Synthesis of Disaccharides and their Derivatives.- In the area of non-reducing disaccharides Barrett s very elegant synthesis of sucrose, which depends on an intramolecular redox cyclization process, has been published in detail. See Vol. 24, p. 29 for a preliminary report. Enzymic transfer from UDP-Gal can be used to obtain (3-d-galactopyranosyl 3-acetamido-3-deoxy-(S-D-xylopyranoside. ... 

Yeom et al. demonstrated that the gold-catalyzed redox cyclization reaction of (Z)-isomer of o-alkynylaryl ketoximes (Z)-95 produced isoindole 96 (Scheme 27.34) [43]. The reaction proceeds through N—O bond redox reaction to form gold carbenoid intermediate 98 and subsequent cyclization and elimination of the gold catalyst, furnishing the isoindole 96. In contrast, reaction of the -isomer (E)-95 afforded isoqunoline oxide 100 [44],... 

Azirines (three-membered cyclic imines) are related to aziridines by a single redox step, and these reagents can therefore function as precursors to aziridines by way of addition reactions. The addition of carbon nucleophiles has been known for some time [52], but has recently undergone a renaissance, attracting the interest of several research groups. The cyclization of 2-(0-tosyl)oximino carbonyl compounds - the Neber reaction [53] - is the oldest known azirine synthesis, and asymmetric variants have been reported. Zwanenburg et ah, for example, prepared nonracemic chiral azirines from oximes of 3-ketoesters, using cinchona alkaloids as catalysts (Scheme 4.37) [54]. 

Hintz, S., Heidbreder, A., and Mattay, J. Radical Ion Cyclizations. 177, 77-124 (1996). Hirao, T. Selective Transformations of Small Ring Compounds in Redox Reactions. 178, 99-148 (1996). 

Indolizidines.1 The N-chloro derivative (1) of a c -2,6-dialkylsubstituted piperidine in the presence of this redox system undergoes homolytic cyclization with the alkenyl side chain at -45° to provide two isomeric indolizidines (2 and 3). 

Elimination, substitution (formation of unexpected substitution products or hydrolysis at the anomeric center), cyclization (inter- and intramolecular orthoesterification), migration and redox are only a few to mention [71]. 

The principle of electrochemical redox- Umpolung has been uniquely applied in cyclization. Thereby, one of two donors in the acyclic precursor is oxidized to an acceptor, whose reaction with the donor leads to cyclization. The same holds for the cyclization by way of reduction of one out of two acceptors [15]. 

H. Tanaka, S. Sumida, K. Sorajo et al., Ni/Pb Bimetal-redox mediated reductive addi-tion/cyclization of allenecarboxylate with allyl bromide in a electrolysis media in Novel Trends in Electroorganic Synthesis (Ed. S. Torii), Kodansha, Tokyo, 1995, pp. 193, 194. 

In order to illustrate the application of LSV in mechanistic analysis we can look at the redox behavior of the formazan-tetrazolium salt system which we studied some years ago [17], 1,3,5-Triphenyl formazane was oxidized at controlled potential in CH3CN-Et4NC104 solution to 2,3,5-triphenyl tetrazolium perchlorate which was then isolated in quantitative yield. Coulometry showed that the overall electrode reaction was a two-electron oxidation. It has been shown that the rate of variation of Ep with log v was 30 mV per decade of sweep rate and that there was no variation of the peak potential with the concentration of 1,3,5-triphenylformazan. According to Saveant s diagnostic criteria (Table 1), four mechanistic schemes were possible e-C-e-p-p, e-C-d-p-p, e-c-P-e-p and e-c-P-d-p. If cyclization is the rate-determining step, then the resulting e-C-e-p-p and e-C-d-p-p mechanisms would not imply variation of Ep with the concentration of base. However, we have observed the 35 mV shift of Ep cathodically in the presence of 4-cyanopyridine as a b e. These observations ruled out the first two mechanisms. The remaining possibilities were then e-c-P-e and e-c-P-d, as shown in Scheme 3. 

McCleland has reported that 3-phenylpropan-l-ol [125] and 3-(p-methyl-phenyl)propan-l-ol 99 [126] cyclize to chromans when oxidized by the radical anion SO4, generated by redox decomposition of S20 with Fe. The intermediate arene radical cation 100 is attacked by the nucleophilic hydroxy group. Whereas 1,6-cyclization yields 7-methylchroman 102, 1,5-cyclization with subsequent C-migration leads to the regioisomer 6-methylchroman 105. A dependence of the isomeric ratio and the combined yields to the pH value is determined. While 7-methylchroman 102 is the main product over a wide pH range, 6-methylchroman 105 is only formed at low pH. When the pH is lowered, the combined yields decrease due to the formation of an a-oxidized non-cyclized product. 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

A new method for the preparation of pyrrolo[2,l-c][l,4]benzothiazepine 292 starting from aldehyde 291 with an intramolecular Mitsunobu cyclization in the last step has been reported (Scheme 63 (1999T1479)). A disadvantage of this procedure is the redox nature of the Mitsunobu reaction, which is responsible for a side oxidation of the thiol group and poor isolated yields of the product. 

The above observations are consistent with a thermodynamically controlled process shown in Figure 9.17. Thus, when two strands, A and B, with complementary H bonding sequences and termini that can be reversible cross-linked, are present in the same solution under redox conditions, products A-A (or self-cyclized A ), B-B (or self-cyclized B ), and A-B, may be generated. Among these products, A-B gains the most stabilization from the newly generated, complementary intramolecular H bonds because of the formation of the two disulfide bonds. Thus,... 

Figure 4.11. Examples of redox-initiated radical reactions. Samarium diiodide reduction of the bromide gives a radical that cyclizes faster than the second reduction reaction. Manganese triacetate oxidation of the P-keto ester gives an enol radical that is not further oxidized by the manganese reagent. The IBX oxidizes anilides to the corresponding radicals. Hexamethylphosphoramide = HMPA and Tetrahydrofuran = THE.

In several examples the reductive halide-hydrogen exchange has been studied on a preparative scale. For example, the indirect electroreduction of 2-chloropyridine in DMF using anthracene as mediator gives pyridine in 83-86 % yield 2 . For the dehalogenation of 1-chlorohexane (80% yield), naphthalene is applied as redox catalyst. Similarly, 6-chloro-hexene yields 1-hexene (60%) and methylcyclopentane (25%), which is the product of the radical cyclization . The indirect electrochemical reduction of p- and y-bromocarboxylic esters forms coupling and elimination products besides the dehalogenated products... 

Caiboxylate ions are also effective nucleophiles in palladium-catalyzed reactions of alkenes and several classes of lactones including 7-pyrones (equation 11)17 and isocoumarins (equation 12)18 have been made in this manner. These early studies used stoichiometric amounts of palladium salts, since efficient redox systems had not yet been developed. However, with more modem techniques catalysis in these systems should be relatively straightforward. The more recent catalytic cyclization-caibonylation process in equation (13) is indicative of this.19... 

In contrast, the closely related palladium acetate-promoted intramolecular alkylation of alkenes by tri-methylsilyl enol ethers (Scheme 4)6,7 has been used to synthesize a large number of bridged carbocyclic systems (Table 1). In principle, this process should be capable of being made catalytic in palladium(II), since silyl enol ethers are stable to a range of oxidants used to carry the Pd° -> Pd11 redox chemistry required for catalysis. In practice, catalytically efficient conditions have not yet been developed, and the reaction is usually carried out using a full equivalent of palladium(II) acetate. This chemistry has been used in the synthesis of quadrone (equation 2).8 With the more electrophilic palladium(II) trifluoroace-tate, methyl enol ethers underwent this cyclization process (equation 3).9... 

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