Thyagarajan indole synthesis

Additional examples of this fascinating chemistry are listed in Table 1 [9, 10]. For Entries 1-3, the initially formed m-chlorobenzoate product is methanolized to the methyl ether (not shown). Entry 3 represents an attractive synthesis of pyrrolo[3,2-d]pyrimidines [11]. Water is the nucleophile in Entry 4, not m-chlorobenzoate, in a sequence that provides pyrrolo[3,2-c]coumarins [12]. Entry 5 describes the preparation of pyrrolo[3,2-c] [1] benzothi-opyran-4-ones, which is a new ring system and where water has captured the intermediate 3-methylene-2-hydroxy indoline [13]. Entry 6 features the synthesis of pyrrolo[3,2-c]pyrones [14]. Entry 7 describes a similar rearrangement of A-alkyl-A-allenylmethylanihnes with magnesium monoperoxyphthalate (MMPP) to afford 2-vinylindoles [15], This reaction presumably follows the one described earlier, although none of the presumed intermediates could be isolated. 

Two reviews written by Majumdar are available that cover the aforementioned chemistry and other advances in the aromatic ort/to-Claisen and aza-Claisen rearrangements [16, 17], What characterizes the Thyagarajan indole syntheses are the very mild conditions (spontaneous) and the excellent yields. 

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. 

Ar= Ph, 2-CIPh, 4-CIPh, 2-MePh, 4-MePh, 4-BrPh, 4-N02Ph, 2,4-Cl2Ph 

Ar= Ph, 4-CIPh, 4-MePh, 2,4-Cl2Ph, 2,4-Me2Ph, 3,5-Me2Ph, 4-N02Ph 

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A summary of the applications of this rearrangement to indole synthesis by Makisumi and Takada is illustrated in Scheme 4. In the case of reactions involving cyanide (equation 3), when R=H, the 2-cyano-3-methylindoles are also isolated in 7%-9% yield resulting from nucleophilic attack at the C-2 indolenium ion formed by loss of hydroxide from 9. Likewise, the extensions of Thyagarajan s initial result to the synthesis of other indoles are shown in Scheme 5. 

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