Microwave-assisted Fischer indolization

A microwave-assisted Fischer indole synthesis under solvent-free conditions with Montmorillonite K10 clay modified with zinc chloride was employed in a key step of the synthesis of analogues of the cytostatic natural product, Sempervirine (Scheme 3.6)8. A dedicated laboratory microwave synthesizer was utilised. 

A microwave-assisted version of the Fischer indole synthesis was described by reaction of the hydrazone 179 [119]. The reaction was carried out on Mont-morillonite KIO doped with ZnCl2 giving reasonable yields of compound... 

However, the Fischer indole synthesis met with failure under classical heating conditions, using a variety of solvents and catalysts. The authors then explored ZnCl2-mediated microwave-assisted cyclization in a domestic microwave oven using the full irradiation power of c.a. 1500 W. The cyclization was found to proceed smoothly in DMF in a mere 9 min and the iso-Meridianins were isolated in good yields. 

As in other areas of organic synthesis, microwave irradiation has been adapted in Fischer indolizations (Table 3) [70-77], Whereas montmorillonite KSF worked well as reported for entries 1 to 3 [70], it utterly failed as reported for entries 4 to 5 [71], Entry 9 represents a novel decarboxylation of indole-2-carboxylic acids during microwave heating [73], For entries 10 and 11, yields are invariably higher under microwave conditions than with conventional heating, and the former represents an excellent synthesis of y-carbolines [74], Entries 12 to 15 feature propyl phospho-nic acid cyclic anhydride (T3P) as a mild water scavenger [75], Kremsner and Kappe have studied microwave-assisted organic synthesis in near-critical water at 300 °C,... 

The cyclic pyrido[3,2,l-jk]carbazoles 18 have been synthesized through microwave-assisted domino Fischer indole reaction/intramolecular cycHzation of phenylhydrazine hydrochloride 16 and 2-(3-oxo-l,3-diarylpropyl)-l-cyclohexanones 17 [25]. After optimizing the process, the best results were obtained by running the reaction in water at 140°C for 15 min (Scheme 12.6). The reaction showed a very good scope with 30 examples of pyrido[3,2,ljk]carbazoles 18 in excellent chemical yields (90-96%). 

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