ates 74 were generated from the corresponding diazonium tetrafluoroborates with sodium iodide in acetone and cyclised to the indoles 75. 6 The cyclisation onto a vinyl bromide allow a wider variety of indoles to be constructed than the analogous radical cyclisation onto a triple bond. Vinyl bromides are als substituted indoles shown in Scheme 37. 7 This reaction is rationalised as involving BnNH2 an aryne intermediate; after cyclisation the aryllithium species 18-54% is intercepted by electrophiles such as benzaldehyde and ethyl hloroformate. Kuehm-Caubere and co-workers have also described an efficient synthesis of 2-substituted indoles by Scheme 35 arynic cyclisation. The aryl imines 76 derived from methyl ketones gave the indoles 77 in the presence of the complex base An electrochemical method, involving the use of a redox flow derived from sodamide and sodium tert-butoxide. cell, has provided an efficient synthesis of l-alkylaminoindoles from the nitroamines 68. 3-Cyano-1-hydroxyindoles have been prepared od yield by base catalysed cyclisation of the aromatic nitro compounds 69. In concentrated hydrochloric tion requires the 2-methyl substituent and occurs only in the presence of concentrated acids, indicating that a tertiary carbo cation intermediate is involved 10 The known"lateral lithi- ation"of the methyl group of Boc-protected o-toluidines has Bu' Li(3. 3 mol been applied to the synthesis of ethyl indole-2-carboxylates by quenching the anion with diethyl oxalate; the reaction allows the preparation of indole esters bearing a range of substituents In t the six-membered ring 1 New examples of base catalysed reactions which lead to formation of the indole C2-C3 bond include the cyclisation of the succinimide 72 to the indole 7312 and the intramolecular addition of benzyl sulfones to imines and carbodiimides NHR CO2 Me 3-Methylindoles can be prepared from propargylanilines prop-2-ynylanilines) by the. new and conceptually simple method illustrated in Scheme 38.19 There are several con- straints on the method which were established experimentally Palladium catalysed cyclisation reactions are increasingly the trialkylsilyl group and the nitrogen protecting group were mportant methods for the formation of the C3-C3a bond of chosen in order to be stable to methanesulfonic acid, the cyclis- indoles. The methodology illustrated in Scheme 9 for the con- ing agent, and the position at which the cation cyclises must struction of hydroxybenzofurans has also been applied to be sufficiently activated by ring substituents. Another acid indole synthesis as has the solid phase intramolecular Heck catalysed cyclisation procedure which leads to indoles unsubsti reaction. A simple condensation-cyclisation procedure, tuted in the five-membered ring, is the reaction of anilines with shown in Scheme 36, is the palladium catalysed reaction of triethanolamine in the presence of tin() chloride and 2-iodoanilines with ketones. Related cyclisations of pre- ruthenium catalyst formed enamines to 2-trifluoromethylindole-3-carboxylic acid esters have been described. 115 A new indole synthesis makes use of radical cyclisation for OMe TIPS the construction of the c3--c3a bond. The radical intermedi Meo NH R The indoloquinone 79 has been synthesised by a route in which the key step is intramolecular 1, 3-dipolar addition of the azomethine ylide 78. The 1, 3-dipole was generated from an N-methyloxazolium salt by ring opening with cyanide. A novel 2856 J Chem. Soc. Perkin Trans.1999. 2849-28662856 J. Chem. Soc., Perkin Trans. 1, 1999, 2849–2866 An electrochemical method, involving the use of a redox flow cell, has provided an efficient synthesis of 1-alkylaminoindoles from the nitroamines 68. 108 3-Cyano-1-hydroxyindoles have been prepared in good yield by base catalysed cyclisation of the aromatic nitro compounds 69. 109 In concentrated hydrochloric acid 4-amino-2-methylbenzofurans 70 are converted in high yield into the isomeric 4-hydroxy-2-methylindoles 71. The reac￾tion requires the 2-methyl substituent and occurs only in the presence of concentrated acids, indicating that a tertiary carbo￾cation intermediate is involved.110 The known “lateral lithi￾ation” of the methyl group of Boc-protected o-toluidines has been applied to the synthesis of ethyl indole-2-carboxylates by quenching the anion with diethyl oxalate; the reaction allows the preparation of indole esters bearing a range of substituents in the six-membered ring.111 New examples of base catalysed reactions which lead to formation of the indole C2–C3 bond include the cyclisation of the succinimide 72 to the indole 73 112 and the intramolecular addition of benzyl sulfones to imines and carbodiimides.113 Palladium catalysed cyclisation reactions are increasingly important methods for the formation of the C3–C3a bond of indoles. The methodology illustrated in Scheme 9 for the con￾struction of hydroxybenzofurans has also been applied to indole synthesis 29 as has the solid phase intramolecular Heck reaction.30 A simple condensation–cyclisation procedure, shown in Scheme 36, is the palladium catalysed reaction of 2-iodoanilines with ketones.114 Related cyclisations of pre￾formed enamines to 2-trifluoromethylindole-3-carboxylic acid esters have been described.115 A new indole synthesis makes use of radical cyclisation for the construction of the C3–C3a bond. The radical intermedi￾Scheme 35 Scheme 36 ates 74 were generated from the corresponding diazonium tetrafluoroborates with sodium iodide in acetone and cyclised to the indoles 75. 116 The cyclisation onto a vinyl bromide allows a wider variety of indoles to be constructed than the analogous radical cyclisation onto a triple bond. Vinyl bromides are also used as precursors in the synthesis of 3,4-disubstituted indoles shown in Scheme 37.117 This reaction is rationalised as involving an aryne intermediate; after cyclisation the aryllithium species is intercepted by electrophiles such as benzaldehyde and ethyl chloroformate. Kuehm-Caubère and co-workers have also described an efficient synthesis of 2-substituted indoles by arynic cyclisation. The aryl imines 76 derived from methyl ketones gave the indoles 77 in the presence of the complex base derived from sodamide and sodium tert-butoxide.118 3-Methylindoles can be prepared from propargylanilines (prop-2-ynylanilines) by the new and conceptually simple method illustrated in Scheme 38.119 There are several con￾straints on the method which were established experimentally: the trialkylsilyl group and the nitrogen protecting group were chosen in order to be stable to methanesulfonic acid, the cyclis￾ing agent, and the position at which the cation cyclises must be sufficiently activated by ring substituents. Another acid catalysed cyclisation procedure which leads to indoles unsubsti￾tuted in the five-membered ring, is the reaction of anilines with triethanolamine in the presence of tin() chloride and a ruthenium catalyst.120 The indoloquinone 79 has been synthesised by a route in which the key step is intramolecular 1,3-dipolar addition of the azomethine ylide 78. 121 The 1,3-dipole was generated from an N-methyloxazolium salt by ring opening with cyanide. A novel Scheme 37 Scheme 38