Oxidative cyclization Subject

The authors used silver salts since gold salts catalyzed the reaction with R=H (giving oxazole 34, Scheme 5.16) but not with R=Me. Moreover, only traces of the desired furopyrrolidinone were formed with the use of a cationic gold species activated with silver additives. Therefore, silver traces were thought to be the active reagent. Indeed, on activation of compound 33 mediated by AgN03 in the presence of sodium acetate (Scheme 5.16), the enol moiety V can then accomplish a nucleophilic attack to produce the pyrrolidinone W and after protonolysis give compound X. Pyrrolidinone Y (the enol version of X) can, in turn, be subject to an oxidative cyclization to yield the furopyrrolidinone 35. Two equivalents of silver salts are needed for the activation step and the oxidative cyclization. 

When 3-aminopyridine A-oxide was subjected to the conditions of the Skraup reaction, 1,5-naphthyridine itself was obtained, presumably due to prior deoxygenation of the starting material followed by cyclization.424... 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

Yamamura and coworkers [158] developed an oxidative cyclization method to construct biphenyl ether bonds by thallium trinitrate (TTN) oxidation of the corresponding O,0 -dihalophenols followed by zinc reduction. The antibiotic piperazinomycin 266) was synthesized using this method as a key cyclization step [159]. As shown in Scheme 89, the diketopiperazine 263 was subjected to TTN oxidation in MeOH to afford an inseparable mixture containing plausible intermediate 264, which was directly reduced with zinc powder in AcOH-THF to give rise to the strained 14-membered biphenyl ether 265 in 19% yield together with two other isomers. 

Thus, Elhnan and coworkers adopted the TTN-mediated oxidative cyclization strategy to synthesize the macrocychc diaryl ether as a key compound , because of the simple procedures and the ready availability of the amino acid starting materials as compared with other synthetic strategies . The easily available tripeptide 839 was subjected to TTN-mediated oxidation, followed by zinc reduction under similar conditions as reported by Yamamura and coworkers to give a 45-60% overall yield of the desired diaryl ether 840, from which a number of receptors such as 841 were synthesized (Scheme 168). The oligopeptide 841 exhibited binding to tripeptide N-Ac2-L-Lys-D-Ala-D-Ala that is... 

Photolytic oxidative cyclization followed by iodination afforded the iodo derivative 20, which was subjected to (3-elimination using DBU in THE to furnish the olefin 21. 

Oxidative radical cyclization sequences have also been used to generate 1,2-fused indoles. Treatment of amides 152 and 154 with dimethyl methylmalonate in the presence of manganese(III) acetate and sodium acetate in acetic acid, gave the expected cyclized product in 63% and 40%, respectively [97]. The proposed mechanistic sequence involves the intermolecular addition of the dimethyl methylmalonate radical to the tethered exocyclic alkene followed by cyclization and finally rearomatization. Byers and coworkers also achieved a similar cyclization on the C-2 position of the indole when a 3-acylindole was subjected to these oxidative cyclization conditions. 

An alternative to SO2 expulsion is via the intermediate tetrathiacyclophane, generated by oxidative cyclization of a tetrathiol, which upon desulfurization afforded the dithiacyclophane <01JA4704>. Subsequent methylation with (MeO)2CHBF4, followed by the Stevens rearrangement gave the ring-contracted, Ws-thiomethyl ether that was S-methylated and subjected to a Hofmann elimination affording 3, which is in a 1 20 equilibrium with 4. 

Cyclization of iodopyiidinyl aUyl ethers derived fom dihalopyridines and sodium aUyUc oxides leads to formation of furo[2,3-fc]pyridines 292, furo[3,2-c]pyiidines 293, and furo[2,3-c]pyridines 294 by a Heck mode of reaction (Scheme 101). In the reaction sequences, the initial step in the preparation of iodopyridine aUyl ethers involves regioselective lithiation of 3-fluoro, 2-fluoro-, and 4-chloropyridines with LDA. Subsequently, the lithiated species are treated with iodine as electrophile. A variety of iodopyiidinyl ethers have been prepared from dihalopyridines and sodium aUyhc oxides and subjected to the Pd-catalyzed cyclization reactions with formation of the furoannulated pyridine products. When the allyl groups carry a 2-substituent as in stracture 295, hydridopaUadium elimination is prevented. Instead, sodium formate reductive elimination of the palladium substituent gives the product 296. The isomeric structures 297 and 298 are available similarly. ... 

In order to elucidate the mechanism of this reaction, a substrate probe was designed. Diastereomerically pure indole 140 was synthesized and subjected to the aerobic oxidative cyclization (Scheme 9.20). Annulated indole 141 was produced as a single diastereomer. The outcome of this reaction strongly suggested a mechanism involving initial palladation of the indole, followed by alkene insertion and )3-hydride elimination (an intramolecular Fujiwara-Moritani reaction). If the reaction proceeded by alkene activation followed by nucleophilic attack of the indole, then the opposite diastereomer would have been observed. This experiment confirmed that an oxidative Heck reaction pathway was operative in this aerobic indole annulation. 

In 2006, Lu and coworkers [53] described a method for the synthesis of carbazoles using the palladium(ll)-catalysed oxidative Heck reaction (Scheme 9.25). Indole 177 was subjected to catalytic Pd(OAc)2 and 2.1equiv of benzoquinone to afford carbazole 178 in 88% yield. Because the alkene is 1,1-disubstituted, a 5-exo cyclization mode (as seen in Ferreira and Stoltz s [48] indole annulation) is unproductive, and a 6-endo cyclization ultimately occurs. The putative intermediate is then believed to be oxidized to the aromatic carbazole by the excess benzoquinone. When indole 179, featuring a terminal alkene, was treated with these oxidative conditions, a mixture of products from 6-endo cyclization (180) and 5-exo cyclization (and subsequent isomerization and [3+2] cycloaddition, 181) was observed. A variety of substituted carbazoles were obtained by this palladium(n)-catalysed oxidative cyclization. 

In the deuterium-hydrogen crossover experiment, enyne 23 was subjected to a mixed atmosphere of D2 and H2 or an atmosphere of DH (Scheme 11). In both cases, no crossover products were observed, which is in agreement with hemolytic hydrogen activation. It also indicates that oxidative cyclization took place prior to hemolytic hydrogen activation. 

However, when 1,2-DAB 155a and benzaldehyde 252a were subjected to the oxidative cyclization conditions (Cho et al. 2012, 2013) used for benzoxazole and benzothiazole synthesis in the presence of a catalytic amount of NaCN, the expected benzimidazole 261 was not obtained (Scheme 2.35, Eq. 1). Instead, the corresponding imine was obtained as the major product along with an unexpected product in a slightly lower yield than the amount of NaCN used (Scheme 2.35, Eq. 2). When a stoichiometric amount of NaCN was used under the same conditions, the unexpected 3-phenyl 2-aminoquinoxaIine 262a was obtained as the major product (Scheme 2.35, Eq. 3) (Cho et al. 2014). 

The application of the one-pot conditions to (Z,Z)-substrate 199 was not as clean as the reactions of either 195 or 197 (Scheme 53). By subjecting 199 to a stepwise sequence where aminohydroxylation was followed by cyclization, the authors were able to conclude that the problematic step for the use of 199 was the oxidative cyclization to 201 rather than the aminohydroxylation to 200. Similar problems were found for the (Z, )-diene that corresponds to 199. 

Nitrogen nucleophiles in proximity to (T) -cyclohexa-l,3-diene)iron complexes have been often subjected to oxidative cyclization. Tetrahydro-l -pyrrolo[l,2-o]indoles... 

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