A siniplc synthesis of 4-, 5-. 6-. and 7-hydroxy-and -methoxyindoles via cyanoalkylation of 0-protected nitrophenols hy vicarious nuclcophilic substitution of hydrogen. followcd by catalytic hydropcnation of thc (2-nitroaryl)acctonitnlcs obtained is des-
crihcd.Hydroxy-and methoxyindoles are key starting materials in the synthesis of a great variety of natural products and biologically important compounds. Thus, there is a great and continuous interest in methods of synthesis of these compounds. However, in spite of numerous papers'), no general and simple method, applicable to the synthesis of all isomeric hydroxy-and alkoxyindoles without a substituent in position 2, was hitherto reported. The R e i~s e r t~,~) and the Batcho-Leimgruber5) methods, which are most frequently used for this purpose, require as starting materials appropriate methylnitrophenol derivatives which are often difficult to obtain.Another general method to synthesize such indole derivatives consists in the reductive cyclization of (2-nitroary1)-acetonitriles6). This method has however limited value, since the syntheses of these starting materials are troublesome and specific for particular isomers.In our previous papers we have described a new general method for the introduction of a-functionalized alkyl substituents into nitroaromatic rings7). This method, named "Vicarious Nucleophilic Substitution of Hydrogen (VNS)" consists in the reaction of nitroarenes with carbanions containing leaving groups at the carbanionic center and offcrs an easy access to many valuable nitroarene derivatives, inter alia, to the appropriate (2-nitroaryl)a~etonitriles*,~). Availability of these nitriles makes the indole synthesis via these intermediates a useful and versatile method.As an exemplification of this approach we present here a general method of synthesis of 4-, 5-, 6-, and I-hydroxy-and -alkoxyindoles and their derivatives based on the VNS reaction of 0-protected nitrophenols with acetonitrile derivatives yielding (2-nitrophenyl)acetonitriles, followed by catalytic hydrogenation of the latter which results in the formation of the corresponding indoles.Mononitrophenols are unable to enter directly the VNS reaction, since under strongly basic conditions they exist in form of nitrophenolate anions unable to produce anionic o adducts with carbanions. Protection of the hydroxy group via methylation or benzylation affords the corresponding ethers which react readily according to the VNS scheme. Nevertheless, alkoxy groups somewhat deactivate the nitroaromatic ring toward the nucleophilic attack, thus, the most easily available cyanomethylating agent -chloroacetonitrile -does not react with alkoxynitroarenes satisfactorily, due to its instability in basic media. In our hands the most convenient cyanomethylating agent for the reaction with nitrophenol derivatives was (4-ch1orophenoxy)-acetonitrile (10) readily available via reaction of 4-chlorophenol with chloroacetonitrile.
In the reaction of dimethyl phosphite anion with I-nitronaphthalene, nucleophilic substitution of hydrogen takes place according to a redox stoicheiometry, giving substituted dimethyl naphthalenephosphonates and benzazepines; other bicyclic nitroarenes react in a similar way. Hz), 128.3 (d), 129.0 (s), 132.2 (d), 135.9 (d,Jcp 221.8 Hz), 141.7 (d, Jcp 2.9 Hz), and 163.4 (d, Jcp 21.5 Hz).53.1 (dq, Jcp 5.8 Hz), 53.7 (4) ,126.7 (d), 126.9 (d) ,127.5 (dd, Jcp 22.9
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