The Witkop-Winterfeldt-Oxidation of Indoles

Abstract

In the early 1950s Witkop described in a series of papers that oxidation of indoles with a variety of oxidation reagents leads to the formation of quinolones. The mechanism of this reaction involves the oxidative cleavage of the 2,3-double bond of the indole moiety (Witkop-oxidation) followed by a Camps-cyclization forming the quinolone ring. Winterfeldt identified conditions which allow a one pot Witkop-oxidation/Camps-cyclization sequence and applied this strategy for the synthesis of pyrrolo[2,3-c]quinolones starting from 1,2,3,4-tetrahydro--carbolines. This review gives a comprehensive description of all described examples of this reaction including a definition of scope and limitations and a discussion of the mechanism of this transformation.

Breaking and Making of Rings: A Method for the Preparation of 4‐Quinolone‐3‐carb­oxylic Acid Amides and the Expensive Drug Ivacaftor

“…[9] A few years ago, an excellent compilation of the literature on WWO was published in a review article by Breinbauer. [10] Herein, we disclose a new method to produce the title compounds. Scheme 1.…”

Polystyrene Sulfonyl Chloride: A Highly Orthogonal Linker Resin for the Synthesis of Nitrogen‐Containing Heterocycles

“…Our intention to increase the diversity of the library by implementing the Witkop-Winterfeldt reaction on a solid phase for the first time was unaffected by these problems, and resulted in the scaffold-rearranging conversion of indoles into quinolones. [22] Indoles 12 were converted by ozonolysis into ketolactam intermediates 13, which were sequentially condensed selectively under basic conditions into g-quinolones 14 and cleaved from the resin as pyrrolo [3,2-b]quinolones 15. Such a simple detosylation reaction has not yet been reported for comparable sulfonamides, and benefits from the formation of an extended aromatic system as the driving force (Scheme 2, Table 2).…”

Polystyrolsulfonylchlorid – ein hochorthogonales Linkerharz für die Synthese von Stickstoffheterocyclen

“…Auf diese Weise wurde das Piperidonharz 10 mit einer Beladung von 1. 16 von Indolen zu Chinolonen, [22] an der festen Phase zu erhö-hen. Hierbei wurden die Indole 12 ozonolytisch zu Ketolactam-Intermediaten 13 gespalten, die folgend unter basischen Bedingungen zunächst selektiv zu g-Chinolonen 14 kondensiert und darauf als Pyrrolo[3,2-b]chinolone 15 vom Harz abgespalten wurden.…”

“…Auf diese Weise wurde das Piperidonharz 10 mit einer Beladung von 1. 16 von Indolen zu Chinolonen, [22]…”