Photochemical Synthesis of Indoles and Carbazoles

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. 

The final section in this chapter illustrates relatively little explored—even rare— photochemical indole ring syntheses, but these reactions are deserving of exposure in the book. 

Suginome and coworkers discovered the novel [3+2] regioselective photoaddilion of 2-amino-1,4-naphthoquinones with electron-rich alkenes to afford lH-benz[/] indole-4,9-diones (Schane 16, equation 1) [112]. Likewise, amino-1,4-benzoquinones with alkenes gave lH-indole-4,7-diones (equation 2). If the initial photoproducts could not indolize by loss of alcohoL then the corresponding dihydro compounds were isolated. Parker and Mindt found that qui-none monoimides were smoothly photocyclized to the respective 5-hydroxyindoles (equation 3) [113]. 

As we saw briefly in Chapter 53, the photochemical version of the Graebe-Ullmann carbazole-carboUne synthesis can be an excellent route to these heterocycles. Similar to this benzotriazole reaction is the photolysis of aryl azides to give carbazoles and related fused indoles. 

Although the techniques of photochemistry may be inconvenient, especially for large-scale synthesis, the remarkable indole syntheses shown in this chapter—many of which have no nonphotochemical counterpart— shonld not be ignored by the organic chemist seeking to prepare a target indole or carbazole. 

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The most reliable method for generating nitrenes is the thermal or photochemical elimination of nitrogen from azides. An alternative method which is useful for indole and carbazole synthesis is the deoxygenation of aromatic nitro compounds with trivalent phosphorus compounds. Triethyl phosphite is the most commonly used reagent, though more reactive compounds may be useful in special cases (B-79MI30600). 

Some additional examples are depicted in Scheme 2, such as a convenient synthesis of 1 l f-benzo[a]carbazole (equation 1) [34], synthesis of A-substituted carbazoles (equations 2 and 3) [18, 35], and the use of AA -diarylsul-fonamides (equation 4) to construct ellipticine precursors [36,37]. Interestingly, photolysis of 2-cyanodiphenylamine (254nm, EtOH, MeCN) afforded carbazole in 87% yield, but a similar photochemical reaction of 2-aminophenyl-acetylene gave only a trace of indole (l%-2%) [38]. 

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