Annelated indoles

Synthesis of [d]-annelated indoles by thermal electrocyclic reactions 95MI7. 

The cycloaddition reactions of 3-vinylindoles with acetylenic esters have been extensively studied. The reaction products generally obtained are [Z ]-annelated indoles, but Michael adducts can be isolated, depending on the substituents on the vinylindole (87HCA1419) (Scheme 1). 

Pyrroles, H.M.L. Davies. Synthesis of Porphyrins with Exocy-clic Rings from Cycloalkenopyrroles, T.D. Lash. Palladium-Catalyzed Coupling Reactions of Indoles, A.R. Martin and Q. Zheng. Cycloaddition Reactions of Indole Derivatives, U. Pindur. Transition-Metal Mediated Synthesis of Carbazole Derivatives, H. J. Knoiker. Synthesis of [b]-Annelated Indoles by Thermal Electrocyclic Reactions, S. Hibino and E. Sugi-no. Total Synthesis of (-) and ent (-) Duocarmycin SA, D.L. Boger. Index. I... 

Other novel and noteworthy investigations concerning Diels-Alder reactions of nitroso dienophiles are on the one hand directed to novel accesses to these dienophiles [358] on the other hand, synthetical approaches to nortropanes [359, 360], pyrrolocastanospermine analogs [361] and novel annelated indoles [362] have been developed basing on this powerful preparative tool. 

The scope of the aryl bromide moiety and the enol triflate fragment has revealed that this sequential amination is relatively broad and leads to various substituted and annelated indole derivatives 114-122 in good to excellent yields (Scheme 42). 

The use of quinone monoketals in the reaction with an exocyclic enaminoester is a new variation150. It is not a typical Nenitzescu reaction since an enamine anion is used. Tricyclic intermediates are obtained, which nevertheless formally give typical Nenitzescu products in high yield and regioselectively (equation 58). In this way annelated indoles of mitomycin type become accessible. 

Indigo derivatives, synthesis and application of 88YGK681. Indole-2-carboxylic acid, chemistry of 87YGK1171. Indolo-2,3-quinodimethanes and their analogues in synthesis of [b]-annelated indoles 89CRV1681. 

Vinylindoles, Diels-Alder reactions as a route to annelated indoles 88H(27)1253. 

Pindur U, Lemster T. Advances in marine natural products of the indole and annelated indole series chemical and biological aspects. Curr. Med. Chem. 2001 8 1681-1698. 

Researchers from Solvay reported a series of 1,7-annelated indole derivatives of ondanse-... 

From a series of 1,7-annelated indole derivatives, cilansetron [(-)-162j was selected for further pharmacologicalprofilingboth in vitro and in vivo (Table 14.14) (454). In the RVN and Gpl, cilansetron [pA, 9.94 (RVN) 7.80 (Gpl)] is about 10-fold more potent than ondansetron [pA, 8.99 (RVN) 6.80 (Gpl)]. In the von Bezold-Jarisch reflex test (BJR) in unrestrained conscious rats, cilansetron (ED = 26 jLLg/kg, p.o.) is orally active at a dose 6 times lower than that of ondansetron (ED =165 ptg/kg, p.o.). Solvay announced Phase III studies for cilansetron for the treatment of diarrhea-predominant irritable bowel syndrome, in July 2001 (455). 

The Diels-Alder cycloadditions of both 2-vinylindoles and 3-vinylindoles are very attractive methods for preparing [b]annelated indoles to serve as lead substances and as building blocks for alkaloids. Pindur and coworkers [84] have extensively studied the vinylindole Diels-Alder chemistry. 

Several aspects of the reactivity of annelated indoles have been discussed in CHEC-I, mainly in Volume 4. However, the spectroscopic properties of these systems have not been previously detailed. 

The physical and spectroscopic data of several linear and angular annelated indoles have been described in detail in the period from the mid-1980s to the mid-1990s. The heterocyclic ring system... 

Orf/io-quinodimethanes have been used in numerous S3mthetic applications for the construction of various polycyclic ring systems found in structurally complex target molecules, via [4+2] Diels-Alder type cycloadditions. In this context, indolo-2,3-quinodimethanes have become increasingly useful as synthetic precursors to a variety of interesting [6]annelated indoles, carbazoles, and alkaloids [111]. 

Pindur U (1988) New Diels-Alder reactions with vinylindoles. A regio- and StereocontroUed access to annellated indoles and derivatives. Heterocycles 27 1253-1268... 

Pindur U, Erfanian-Abdoust H (1989) Indolo-2,3-quinodimethanes and stable cyclic analogs for regio- and stereocontrolled syntheses of [b]-annelated indoles. Chem Rev 89 1681-1689... 

One-pot intramolecular reaction between trialkyl-( 1 -methyl-2-indolyl)borate and allylpalladium intermediate has been reported [20]. This. simultaneous 1,2-alkylmigration from boron to carbon provides a novel pathway to afford [i>]-an-nelated indole derivatives in 10-56% yields (Scheme 32.8). Trialkylindolylbo-rate 14 is generated in situ by the hydroboration of diene 13 with 9-BBN in THF followed by treatment with 2-lithio-1 -methylindole. The THF solution ofborate 14 containing 10 mol% of Pd(Ph3P)4 was heated under reflux for 1-3 h to afford [fc]-annelated indole 15 [20]. 

There are no precedents of such use of the 1,2-alkyl migration, a very common sequence in organoborane chemistry [23], for intramolecular cyclization. Ishikura and Terashima have further developed [24] a novel one-pot procedure for [a]-annelated indoles via cyclic trialkyl(indol-2-yl)borate as a key intermediate (Scheme 32.10). 

The results for the construction of [a]-annelated indoles are summarized in Table 32.4 [24]. 

Table 32.4 Formation of [a]-annelated indole 22 from indole 20 [24]... 

Synthesis of [6]-annelated indoles by thermal electrocyclic reactions 95MI7. Transition metal-mediated syntheses of carbazole derivatives 95MI6. Vilsmeier-Haack and Friedel-Crafits reactions, bromination, debromination, debenzylation in indole series and their synthetic application 99YZ35. 

Also nitrenes, generated from the allenyl azides 99, undergo the [2+1] cycloaddition reaction to give the annelated indole derivatives 100. ... 

Heating of the 2-(allenyl)phenyl azides 79 at 110 °C gave a mixture of the cyclopent-annelated indoles 80 and 81 °. ... 

Pindur, U., and H. Erfanian-Ardoust Indole 2,3 quinodimethanes and stable cyclic Analogues for Regio- and Stereocontrolled Syntheses of [b]-Annelated Indoles. Chem. Rev. 89, 1681 (1989). 

Pindur U., Kim M.H., Rogge M., and etc. New Diels-Alder reactions of (E/Z)-2 -methoxy-substituted 3-vinylindoles with carbo- and heterodieno-philes region- and stereoselective access to [b]-annelated indoles and functionalized or [a]-annelated carbazoles . -J. Org. Chem., 1992, v. 57, Jib 3, p. 910-915. 

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