Ichikawa indole synthesis

The starting difluorostyrenes were synthesized in three steps from trifluoroethyl tosylate, and an Organic Synthesis preparation is available [3]. Trifluorostyrene 3 was converted to difluoromethyleneindoline 4 with sodium hydride (equation 2) and to 3-trifluoromethylindoline 5 with DBU [4, 5]. On treatment of 4 (R =R =H) with Af-iodosuccin-imide (EtjN-HF, CH CI, -10 °C), bromine (CCl, rt), and Nal (TMSCl, H O, rt), indoles 6-8 are formed, respectively, each in excellent yield. 

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, iJd. 

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The Ichikawa indole synthesis is the base-induced 5-endo-trig cycUzation of nrtfto-amino-p,p-difluorostyrenes 1 to 2-fluoroindoles 2 (Scheme 1, equation 1) [1-3]. The method is applicable to indolines, which can be oxidized to indoles [4, 5]. This nice chemistry exploits the inherent favorable conversion of a difluorinated sp carbon to an sp carbon, which then expels fluoride to give the aromatic indole. Ichikawa also applied this method to the preparation of 2-fluoiobenzo[fc]furans and 2-fluorobenzo[h]thiophenes [1, 2]. 

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