Miscellaneous Oxidative Cyclizations

Several oxidative cyclizations to form the indole ring not involving a familiar name reaction are covered in this chapter. 

The versatile reagents phenyliodine (III) bis (trifluoro-acetate) (PIFA) and phenyliodine (III) diacetate (PIDA) have found additional utility in the oxidative cyclization of suitable substrates to indoles. Zhao and colleagues used 

Indole Ring Synthesis From Natural Products to Drug Discovery, First Edition. Gordon W. Gribble. 2016 John Wiley Sons, Ltd. Published 2016 by John Wiley Sons, Ltd. 

Jenekhe and coworkers found that DDQ converts anthrazo-line 7 to heptacyclic bis(indolo[l,2-a]quinolone) 8 (equation 3) [19]. Youn and Jang used DDQ to convert Af-Ts-2-alkenylanilines into indoles via, it is proposed, a radical cation generated by SET (equation 4) [20]. In the case of p,p-disubstituted 2-alkenylanilines, the 2,3-disubstituted indole product is derived from a C-2 to C-3 aryl migration via a phenonium ion (equation 5). 

Unlike their polar species counterparts, carlxx ations and carbanions, radicals did not play a major role in organic synthesis until recent times. But now they feature prominently in all aspects of organic chemistry, including indole ring synthesis. 

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A few other miscellaneous cyclizations are worthy of mention. o-Substituted benzene derivatives of general structure 382 (X = O, S or NH) undergo oxidative cyclization on irradiation to give the corresponding heterocyclic system (383),402 Similar behavior is exhibited by a thioamide [Eq. (102)]. Nonoxidative photoeyclization... 

Miscellaneous reactions which involve the cyclization of one component to an aziridine by a polar reaction include the electrochemical oxidative cyclization of / -(p-toluenesulfonyl) aminomalonates to 2,2-bis(carbomethoxy)-JV-(p-toluenesulfonyl)aziridines <88CL1065> and the bromonium ion-mediated cyclization of JV-propargyl acetamides to 2-(2-bromoalkylidene)aziridines... 

Miscellaneous ring closure reactions involving carbon-carbon bond formation are shown in Scheme 72 and 73. An oxidation-cyclization-oxidation process was effected by PCC to convert alcohols 197 to 4-piperidones 198 <04JOC3226>. Intramolecular alkylation was used to covert chiral enaminone 199 to 200, a key intermediate in the total synthesis of lepadin alkaloids... 

Miscellaneous reactions. Cyclization accompanies oxidation of an allene moiety as a result of the participation of an internal nitrogen nucleophile. "... 

MISCELLANEOUS REACTIONS OF DIHYDROPYRIDINES Additional tests for net hydride transfers initiated by single-electron transfer include the use of substrates in which such pathways would necessarily involve readily ring-opened cyclopropylmethyl or readily cyclized 5-hexenyl radicals. Products from these radical reactions are not formed in NAD+/ NADH dependent enzymic reductions or oxidations (Maclnnes et al., 1982, 1983 Laurie et al., 1986 Chung and Park, 1982). Such tests have also been applied in non-enzymic reductions. Thus cyclopropane rings in cyclopropyl 2-pyridyl ketones, or imines of formylcyclopropane (van Niel and Pandit, 1983, 1985 Meijer et al., 1984) survive Mg+2 catalysed reduction by BNAH or Hantzsch esters but are opened by treatment with tributylin hydride. 

Besides processes (1) and (2), the reader should be aware that nucleophilic attacks on alkynes are treated in other chapters of this book, dealing with rearrangements, cyclizations, polyacetylenes, cyclic acetylenes and perhaps others. A number of publications overlap with ours in different ways and at different levels -. They treat individual alkynes or families " , e.g. acetylene, diacetylenes , acetylene dicarboxylic esters haloacetylenes , alkynyl ethers and thioethers > ynamines , fluoro-alkynes ethynyl ketpnes , nitroalkynes , etc. synthetic targets, e.g. pyrazoles , if-l,2,3-triazoles , isothiazoles , indolizines S etc. reagents, e.g. nitrones , lithium aluminium hydride , heterocyclic A -oxides - , azomethine ylids - , tertiary phosphorus compounds , miscellaneous dipolar nucleophiles - , etc. The reader will appreciate that all of these constitute alternate entries into our subject. 

Miscellaneous Reactions of Oxirans.—The first successful enzymatic cyclization of a non-natural squalene has been disclosed. (18Z)-Oxidosqualene (188), which does not possess the naturally occurring a -trans stereochemistry, was caused to cyclize, in the presence of 2,3-epoxysqualene sterol cyclase, to (205)-epinorlanosterol (189). The polyene oxide (190) underwent an uncommon tricyclization in CH2CI2 containing Bp3-OEt2 to form the cw-fused A/B-ring 18-nor-steroid (191) (25%) this compound was found to be identical with a material derived by treatment of a naturally occurring steroid with BF3. 

The quindoline 224may be prepared by the condensation of indoxyl-2-carboxylic acid with 6-aminopiperonaldehyde in the presence of hydrochloric acid, when decarbo lation and cyclization take place. Nitric acid oxidation of 224 gave an unstable nitrodicarboxylic acid which decarboxylated readily to a nitromonocarboxylic acid formulated as 8-nitro-3-carboline-3-carboxylic acid (225). g. Miscellaneous Methods, A variety of methods lead to benz-carboline derivatives. Only a few of the more unusual ones will be... 

Miscellaneous Processes. A versatile synthetic route to the pyrrolophenanthridone alkaloids has been developed that involves a palladium-mediated cyclization of iV-benzoyl indolines, then 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (DDQ)-promoted oxidation of the resulting dihydropyrrolophenanthridones. Related processes have been exploited in an elegant total synthesis of the marine alkaloid (+)-dragmacidin F and in the preparation of biologically relevant indoles. 202.203... 

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