Feldman indole synthesis

There is a structural limitation to the Feldman indole ring synthesis. Thus, o-methyltosylanilide (7) failed to afford 

Despite the aforementioned obstacles that would need to be overcome or suppressed, the Feldman indole synthesis is a very promising novel route to 2-substituted indoles. 

Indole Ring Synthesis From Natural Products to Drug Discovery, First Edition. Gordon W. Gribble. 2016 John WQey Sons, Ltd. Published 2016 by John Wiley. Sons, Ltd. 

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The Feldman indole synthesis describes the reaction between lithiated 7V-phenyl-p-toluenesulfonamide (1) and phenyl(propynyl)iodonium triflate (2) to form indole 3 (Scheme 1, equation 1) [1, 2], The lithiated species 1 was generated from the corresponding tosylanilide with n-butyllithium (THF, -78 °C). Applications are limited thus far to the synthesis of indoles shown in equation 2. 

Scheme 2 Proposed Mechanism for the Feldman Indole Synthesis...

The mechanism of this interesting intermolecular indole synthesis as suggested by Feldman is depicted in Scheme 2 and presumably involves vinyl carbene 6 that cyclized to A-tosylindole [2]. The method is applicable to the synthesis of pyrroles and dihydropyrroles. 

The unique reactivity pattern of alkynyl iodonium salts discussed in Sections II,A.2 and II,D,la can also serve as two-carbon conjunctive reagents in the synthesis of pyrroles, dihydropyrroles, and indoles. Feldman et al. found that combination of alkyl or aralkyl tosylamide anions 101 with phenyl(propynyl)iodonium triflate (102) furnishes the corresponding dihydropyrroles 103 (95JOC7722) (Scheme 28). 

Further applications to preparations of nitrogen-containing heterocycles such as pyrroles (83,84) and indoles (85) by Feldman and co-workers [Eqs. (17), (18)] made these reactions more important and useful for natural product synthesis [66,67]. 

Chiral indole-2-sulfoxides have been employed by Feldman and Karatjas for asymmetric spirooxindole synthesis [70]. In one example, treatment of 115 with triflic anhydride initiated a Pummerer-type cyclization of the silyl enol ether side chain onto C3 (Scheme 30). Sequential hydrolysis of the resulting thioimidate intermediate with aqueous HgCl2 afforded the spirocyclohexanone functionalized oxindole 116 in modest yield and enantioselectivity at —78°C (33, 67% ee). Improved selectivity (58, 86% ee) was observed at lower reaction temperature (-110°C). 

Feldman, K.S. and Ngernmeesri, P. (2005) Dragmaddin E synthesis studies. Preparation of a model cycloheptannelated indole fragment Org Lett, 7, 5449-5452. 

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