Cadogan-Sundberg indole synthesis

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

It is generally accepted that the mechanism of this trialkyl phosphite deoxygenation of nitroarenes involves initial transformation to the nitrosoarene and trialkyl phosphate followed by a second deoxygenation to the corresponding nitrene. Support for this pathway is seen by the fact that noatching aryl azides afforded similar product ratios under thermolysis conditions [10-12], Indeed, prior to the work of Cadogan and Sundberg, several workers described indole 

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. 

The range of indoles synthesized via the Cadogan-Sundberg method is enormous, as summarized in Table 2 

Several modifications of the original Cadogan-Sundberg triethyl phosphite reaction conditions have been reported. 

and Guner presented theoretical evidence to suggest (equation 3) [80]. 

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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...

On the other hand, 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 Since the Sundberg indole synthesis and the Cadogan reaction share the common intermdiate nitrene, they are sometimes grouped together as the Cadogan-Sundberg indole synthesis. 

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