Sundberg indole synthesis

In this chapter we will see that aryl azides, like aryl nitro compounds, can form aryl nitrenes, or nitrene equivalents, under suitable conditions, leading to indoles. 

A tabulation of selected apphcadons of the Sundberg indole synthesis appears in Table 1 [20-26, 28, 29]. In contrast to Entry 4, the corresponding (Z)-o-azidocinnamoni-triles in refluxing toluene gave the respective tetrazolo[l,5-fl] 

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

As we saw with the early work of Smith and others, the pyrolysis of ortfto-azidobiphenyls is a powerful route to carbazoles. A recent synthesis of 2,7-dinitrocarbazole 

Mohna and coworkers synthesized 2-(2-azidoethyl) indole by thermolysis of both ( )- [54] and (Z)-4-(2- 

The Cadogan reaction refers to the deoxygenation of o-nitrostyienes 1 or o-nitrostilbenes with trialkyl phosphite or trialkylphosphine and subsequent cycliza-tion of the resulting intermediate nitrene 2 to form ii oles 3. The Sundberg indole synthesis refers to the synthesis of indoles 3 via either thermolysis or irradiation of o-azidostyrene 4 via the intermediacy of nitrene 2. 

Example 1, SOderberg s modified conditions to prepare indole  

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 49, Springer International Publishing Switzerland 2014 

Base-catalyzed intramolecular condensation of a 2-acetamido acetophenone (1) to a 2-(and possibly 3)-substituted-quinolin-4-ol (2), a 4-(and possibly 3)-substituted-quinolin-2-ol (3), or a mixture. 

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The previously unknown 2-nitroindoles have been conveniently prepared from o-nitroben-zaldehyde via the Sundberg indole synthesis fEq 10 61 ... 

The Sundberg indole synthesis using aromatic azides as precursors of nitrenes has been used in synthesis of various indoles. Some kinds of aryl azides are readily prepared by SNAr reaction of aromatic nitro compounds with an azide ion. For example, 2,4,6-trinitrotoluene (TNT) can be converted into 2-aryl-4,6-dinitroindole, as shown in Eq. 10.60.83... 

The Cadogan-Sundberg indole synthesis, often known as the Cadogan reaction, refers to the deoxygenation of o-nitrostyrenes or o-nitrostilbenes... 

Thankfully, some of the conventional and modem indole synthesis methods do apply to make azaindoles. They include the Larock reaction, Mori-Ban indole synthesis, Bartoli indole synthesis, Batcho-Leimgmber indole synthesis, and Cadogan-Sundberg indole synthesis. 

This reaction can be traced back to the initial work of Cadogan for the preparation of car-bazole by the reductive cyclization of aromatic nitro compounds with triethyl phosphite. This reaction was then extended by Sundberg to the fornnation of indoles by the treatment of o-nitrostyrene with triethyl phosphite or the formation of indolines from the o-alkyl nitrobenzenes. Thus the formation of indole from the reduction of o-nitfostyrenes is referred to as the Cadogan-Sundberg indole synthesis." ... 

The Cadogan-Sundberg indole synthesis involves the insertion of phosphorus atom to the N=0 double bond of the nitro group followed by the cleavage of triethyl phosphate to give IV-hydroxyl indole. Subsequently, the IV-hydroxyl indole was reduced by a second triethyl phosphite to afford indole as shown here. 

The reductive cyclization of 6>-nitrostryene (i.e., the Cadogan-Sundberg indole synthesis) has been improved by the transition metal catalyzation, selenium-based reductive cyclization, or hydrogen/Raney nickel reduced cyclizationJ... 

Other references related to the Cadogan-Sundberg indole synthesis are cited in the... 

Table 1 Early Applications of the Cadogan-Sundberg Indole Synthesis...

Scheme 8 The Cadogan-Sundberg Indole Synthesis Applied to Carbazoles...

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