Cyclization reactions oxidative

This approach offers unique opportunities for the generation of multi-functionalized cyclic 2-azadiene systems. A wide variation of the substitution pattern at the positions N-1 and C-6 can be determined by an appropriate choice of the aldehyde and amine. Various substituents can easily be introduced at the C-3 position via addition/elimination reactions on the sensitive imidoyl chloride moiety [24]. Upon reaction with bi-functional reagent, an adequately AT-protected 2(lH)-pyrazinone was elaborated into C-nucleoside analogues (Scheme 8). The desired skeleton and functionalities were obtained by oxidation-cyclization reaction followed by photochemical removal of the protective o-nitrobenzyl group [25]. 

Enyne metathesis is unique and interesting in synthetic organic chemistry. Since it is difficult to control intermolecular enyne metathesis, this reaction is used as intramolecular enyne metathesis. There are two types of enyne metathesis one is caused by [2+2] cycloaddition of a multiple bond and transition metal carbene complex, and the other is an oxidative cyclization reaction caused by low-valent transition metals. In these cases, the alkyli-dene part migrates from alkene to alkyne carbon. Thus, this reaction is called an alkylidene migration reaction or a skeletal reorganization reaction. Many cyclized products having a diene moiety were obtained using intramolecular enyne metathesis. Very recently, intermolecular enyne metathesis has been developed between alkyne and ethylene as novel diene synthesis. 

Amino-5-chlorobenzophenone, an impurity of chlordiazepoxide, can be determined by spectrofluorometry after oxidative cyclization (reaction 35). Chlordiazepoxide does not... 

Similar oxidative cyclization reactions involving the direct oxidation of acyclic 1,3-dicarbonyl compounds have not been reported. However, the generation of radical intermediates by the direct oxidation of cyclic 1,3-dicarbonyl compounds at an anode surface has been reported. Yoshida and coworkers have shown that the anodic oxidation of cyclic 1,3-dicarbonyl compounds in the presence of olefin trapping groups gives rise to a net cycloaddition reaction (Scheme 10) [23]. These cycloaddition reactions proceeded by initial oxidation of the 1,3-dicarbonyl compound at the anode followed by a radical addition to the second olefin. Following a second oxidation reaction, the material then... 

Although cyclizations from the direct anodic oxidation of acyclic 1,3-dicarbonyl compounds have not been reported, the analogous mediated reactions have been studied [24]. Snider and McCarthy compared oxidative cyclization reactions using a stoichiometric amount of Mn(OAc)3 with oxidations using a catalytic amount of Mn(OAc)3 that was recycled at an anode surface (Scheme 11). In the best case, the anodic oxidation procedure led to a 59% yield of the desired bridged bicyclic product with the use of only 0.2 equivalents (10% of the theoretical amount needed) of Mn(OAc)3- Evidence that the reaction was initiated by the presence of the mediator was obtained by examining the electrolysis reaction without the added Mn(OAc)3. In this case, none of the cyclized product was obtained. For comparison, the oxidation using... 

In a related set of experiments, Nishiguchi and coworkers studied oxidative cyclization reactions that were initiated by the addition of radicals derived from the oxidation of an activated methylene group to an olefin (Scheme 12) [25]. 

In addition to these studies, Swenton and coworkers have recently explored the effects of alkoxy substituents on the reactions [46]. The presence of a single methoxy group clearly enhanced the cyclization reaction (Scheme 32). For example, consider the oxidation of substrate 29a. The presence of a methoxy group para to the vinyl substituent raised the yield of cyclized product from 16% (25a above) to 47%. The methoxy group para to the vinyl substituent also proved to be compatible with the oxidative cyclization reaction having a methyl... 

In all of the cyclization reactions, Moeller has found only a small difference between the use of alkyl and silyl enol ethers. Since both styrenes and enol ethers have similar oxidation potentials, even the styrene moiety could function as the initiator for oxidative cyclization reactions. The anodic oxidation of simple styrene type precursors leads to low yields of cyclized products so that enol ether moiety seems to be the more efficient initiator for intramolecular anodic coupling reactions [93]. 

The use of N-trifluoroacetyl in place of the piotonated N-methyl function in these oxidative cyclization reactions has been explored. Generally these substrates lead to products of the O-methylflavinanthine type. In one instance, the delocalised carbonium ion intermediate 34 was found to undergo a competitive rearrangement when lack of a nucleophile in solution led to a slow demethylation step [137],... 

Intramolecular addition of hydroxylamines and hydroxamic acids to the non-activated double bonds is possible through oxidative cyclization. Reaction of O-Acyl fi,y-unsaturated hydroxamates (e.g. 56, equation 38) with bromine provides 3,4-substituted iV-hydroxy -lactams such as 57 with high diastereoselectivity. Analogous reaction of O-benzyl hydroxylamine 58 (equation 39) with iodine results in five-membered cyclization with 2 1 ratio of diastereomers. ... 

DAIB and BTIB oxidations of phenols proceed through aryloxyiodane 129 and/or aryloxenium ion 130 intermediates and are quite useful for the preparation of quinones, quinol ethers, and quinone acetals (e.g., Scheme 39) (88TL677, 92MI2, 93JCS(P1)1891, 01OR327). When phenols bearing nucleophilic side chains are used as substrates, such oxidations provide fertile ground for the assembly of heterocyclic structures. This can be accomplished by oxidative-cyclization reactions of different types. 

Fig. 1. Unreactive maleimide derivatives in the PIFA-mediated oxidative cyclization reaction.

When 7V-benzyl- or / -phenethylenaminones are anodically oxidized, cyclization reactions take place and compounds containing isoquinoline or benzazepine skeleton are formed (equation 5)6. 

On the other hand, oxidation of secondary 1,1-enediamines 176 with bromine results in the formation of isothioazole derivatives 179. The yields of the oxidation-cyclization reaction depend strongly on the substituent R2 (equation 71)21,143. It is noteworthy that oxidation of 177 under the same conditions does not furnish isothioazoles but, instead, benzothiazoles 180 are formed (equation 72)21. A similar product, 180, has been obtained in the case of the nitro-substituted enediamines of pyrrolidine143. The different outcomes of these reactions reveal that the reactivity of the secondary amino group of 1,1-... 

Since no evidence was provided in support of the above mechanistic proposals there is a priori no reason to exclude mechanism C as an alternative route to the observed products (see also Scheme 5). Interestingly, route C would also readily explain the observed regioselectivity in the oxidative cyclization reaction of enol acetates [221]. Some years later, however, Laurent and coworkers [226,227] demonstrated that in the presence of fluoride (CHjCN/EtsN, 3HF) enol acetate radical cations partially afforded rearrangement products (e.g. 141) not compatible with mechanism C. Rather, the products found suggest that fluoride adds directly to enol acetate radical cations providing the most stable radical intermediate (e.g. 140). 

A ruthenium complex catalyzed an oxidative cyclization reaction as depicted below to give 2,3-dihydrofurans with PPhj as ligand, and in the presence of allyl acetate and CO <03CL24>. 

Chapter 3 by Jie Jack Li presents a collection of very interesting total syntheses of naturally occurring indole alkaloids where palladium chemistry plays a central role in the syntheses. Five different types of palladium-mediated reactions are treated (I) oxidative cyclization reactions promoted by palladium (II) species (2) transmetallation reactions with organoboranes, organoslannanes, and organozinc reagents (3) inter- and intramolecular Heck reactions (4) reactions with it-allylpalladium as the intermediate and (5) reactions using C-N bond formation as the key step for the synthesis. 

Sasai s group [13] developed a series of bisnitrogen ligands with fused hetero spiro cyclic backbones, including spiro bis(isoxazoline) 11 and 12, spiro isoxazole-isoxazoline 13, spiro bis(oxazoline) 14, spiro bis(pyrazole) 15, and spiro bis(isoxazole) 16 (Figure 3). Ligands 11 [14] and 13 [15] exhibited excellent reactivity and enantioselectivity in the Pd-catalyzed oxidative cyclization reactions. 

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