Reductive cyclization Subject

Some time ago, Holliman and co-workers illustrated a method for synthesizing polysubstituted phenazines by reductive cyclization of o-nitrodiphenylamine. However, the yield was poor when competitive cyclizations occurred <70CC1423>. Recently, Kamikawa and co-workers reported a more efficient method to synthesize phenazines using sequential aniline arylation, which was first introduced by Buchwald <97JOC1264>. Regioselective bromination of o-nitrodiphenylamine 226 with bromine in the presence of sodium bicarbonate yielded 227 which was subjected to the Buchwald conditions to provide the desired phenazine 228 and the eliminated product 229 <00TL355>. The former compound is a proposed intermediate for the synthesis of the radical scavenger benthocyanin A. 

Renaut et al. elaborated a synthetic route to linearly fused oxadiazoloquinazoles <2000S2009>. These authors reported that the Ar-oxide carbamate 361 can be subjected to ring closure to the unsaturated cyclized product 362 under fairly forcing conditions (220 °C, 0.1 Torr). Much milder reaction conditions are needed, however, to carry out a reductive cyclization treatment of 361 in ethanol in the presence of sodium borohydride (at 50°C) gave rise to the partially reduced product 363 in nearly quantitative yield. 

The 2-(0-nitrobenzenesulfonamido)alcohol 359 was obtained from 358 through a sequence of reactions, which was then subjected to oxidation with Dess-Martin periodinane to give the 2-(t>-nitrobenzenesulfonamido)ketone 360 in 84% yield (Scheme 74). Upon reductive cyclization with hydrogen and palladium over activated carbon, 360 gave the 1,2,5-benzothiazepine 361 <2004T3349>. 

Spirooxindoles, such as, for example ( )-coerulescine (101) have been prepared employing a sequence starting from 2-fluoronitrobenzene, which was initially subjected to treatment with the anion of dimethyl malonate, followed by decarboxylation and concomitant installation of the methylene group using formaldehyde in the presence of potassium carbonate to produce the intermediate 102 in good yield. This material readily underwent dipolar cycloaddition with the azomethine ylide generated from sarcosine and formaldehyde, followed by a reductive cyclization of adduct 103 to furnish the natural product 101 <02TL9175>. 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

The improvement results from using a catalytic transfer hydrogenation [113] for the reductive cyclization. The critical step of this method is the demethylation of the methyl acetal. This problem has been a main subject of a first review on the synthesis of benzoxazinoid aglucones [104]. 

Claasz generated the mercaptan in situ from the disulfide. Claasz also treated a-bromo esters with the thiol and subjected the adducts to reductive cyclization, which produced the benzothiazinones.127... 

In further applications, dithienylethene compounds have been tethered to P-cyclodextrin for photocontrolled uptake and release of a porphyrin <04CEJ1114>, whereas a cationic dithienylethene derivative has been subjected to electrochemical reductive cyclization <04AG(E)2812>. A dithienylethene containing a 1,10-phenanthroline unit and a rhenium(I) complex thereof has also been prepared and studied <04JA12734>. 

Reductive cyclization of ta-ethynyl a,P-unsaturated esters. The Lewis acid-catalyzed radical cyclization is subject to 1,3-asymmetric induction by the chiral moiety of the ester. Thus (-)-8-phenylmenthyl esters give mainly the 2-methylene-cycloalkylacetic esters of (R) configuration. 

Isomerized bromo derivatives of MBH adducts of isatin have been utilized to synthesize 3-spirocycloalkylindolones via reductive cyclization. Bromo derivative 4 as a mixture of ( )- and (Z)-isomers prepared from MBH adduct upon treatment with HBr embedded on silica gel under microwave irradiation has been subjected to reduction with NaBH4 at room temperature for 0.5 h (Scheme 4.2). Excellent yields of 3-spirocycloalkylindolones 5 were obtained, but with poor diastereoselectivities. 

Synthesis of 210 was started from preparation of chiral diamine 211 (Scheme 50) [172], In particular, D-serine methyl ester was converted to iV-benzyl derivative 212, which was transformed into carboxylic acid 212 using reaction with chloroacetyl chloride and subsequent hydrolysis. Carboxylic acid 212 was subjected to coupling with benzyl amine, reduction, reaction with ethyl oxalyl chloride and reductive cyclization to give bicyclic compound 213. Finally, 211 Two-step reduction of 213 led to the formation of diamine 211, which was isolated as dihydrochloride. Reaction of 211 with dichloro derivative 215 and then - hydrazine hydrate gave the product 216, which was coupled with carboxylic acid 217 and subjected to catalytic hydrogenation to give 210. 

Similarly to o-nitroarylacetic acids (vide supra Scheme 3), o-nitrocinnamic acids also underwent the reductive cyclization when subjected to the treatment with ammonium formate and zinc dust in supercritical CO2 [19]. In this case, concomitant hydrogenation resulted in the formation of 3,4-dihydroquinolones 30 ( heme 18). 

In a unique twist on the use of oxocarbenium reduction to generate tetrahydrofurans, Romo and Mitchell reported the generation of 2,5-cis- and 2,5-trani-tetra-hydrofurans from the reductive cyclization of ketones having a pendant p-lactone (Scheme 5) [8]. This reaction builds upon previously reported results from Mead et al. and leads to the stereospecific synthesis of highly substituted tetrahydrofurans [9]. For example, when a fi-p-lactone 13 was subjected to TESOTf and excess Et3SiH, they isolated 2,5-trans-tetrahydrofuran 14 in 82 % yield as a 14 1 mixture of dia-stereomers, while the corresponding yn-p-lactone 16 gave 2,5-cfr-tetrahydrofuran 17 in 78 % yield as a >19 1 mixture of diastereomers. The stereochemical outcome of these reactions is consistent with the Woerpel et al. model as depicted for the reduction of 15 and 18. 

Novi and coworkers124 have shown that the reaction of 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene with sodium benzenethiolate in dimethyl sulfoxide yields a mixture of substitution, cyclization and reduction products when subjected at room temperature to photostimulation by a sunlamp. These authors proposed a double chain mechanism (Scheme 17) to explain the observed products. This mechanism is supported by a set of carefully designed experiments125. The addition of PhSH, a good hydrogen atom donor, increases the percent of reduction products. When the substitution process can effectively compete with the two other processes, the increase in the relative yield of substitution (e.g., with five molar equivalents of benzenethiolate) parallels the decrease in those of both cyclization and reduction products. This suggests a common intermediate leading to the three different products. This intermediate could either be the radical anion formed by electron transfer to 2,3-bis(phenylsulfonyl)-l,4-dimethylbenzene or the a radical formed... 

Reaction sequence E removed an extraneous oxygen by Sml2 reduction and installed an oxygen at C(15) by enolate oxidation. The C(l) and C(15) hydroxy groups were protected as a carbonate in Step E-5. After oxidation of the terminal vinyl group, the C-ring was constructed by a Dieckmann cyclization in Step F-4. After temporary protection of the C(7) hydroxy as the MOP derivative, the (1-ketoestcr was subjected to nucleophilic decarboxylation by phenylthiolate and reprotected as the BOM ether (Steps F-5, F- 6, and F-7). 

Reduction of the newly introduced nitro moiety affords aniline 40. This is then subjected to the familiar condensation-cyclization sequence to give antimalarial... 

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