Cadogan cyclization

Sequential Suzuki-Miyaura cross-couplings and Cadogan cyclizations were developed under microwave dielectric heating conditions to access a variety of 2-substituted carbazoles and other fused heterocyclic systems (Scheme 13). The use of microwave irradiation not only minimized the proto-... 

Davies reported that carbazoles 39 were obtained from 2-nitrobiphenyls 38, which are the same substrates in Cadogan cyclization, via the palladium-catalyzed reductive cyclization under carbon monoxide (70 psi) as a reductant (Scheme 23.16) [23]. Amide and chloride groups were tolerated, leading to the corresponding carbazoles. Carbon dioxide is the only stoichiometric by-product, which is an advantage over Cadogan cyclization. 

Timari et al. described a total synthesis of furostifoline (224) starting from commercial o-cresol (1133). The key steps in this approach are the Suzuki coupling to the o-nitrobiaryl 1139 and subsequent Cadogan s reductive cyclization via a nitrene intermediate (692). 

Reaction of the TMS-nitro compound 1496 and the indole carboxaldehyde 1497 with a catalytic amount of TBAF led to the desired alcohol 1498, which, on further treatment with TFAA, followed by elimination of the corresponding trifluoroacetate with DBU, afforded the frans-stilbene 1499. Reductive cyclization of 1499 under Cadogan-Sundberg conditions afforded the bisindole 1500. Finally, condensation of 1500 with (dimethylamino)acetaldehyde diethyl acetal led to tjipanazole D (359) in 71% yield (796) (Scheme 5.255). 

An easy access to thieno[2,3-fc]indolc was found by Miyaura and coworkers [12] using a microwave-enhanced cross-coupling reaction in combination with a microwave-assisted Cadogan reductive cyclization. The authors [13] stated that then-method is very useful in minimizing the proto-deboronation in the cross-coupling reaction, and enhances the rate of reductive cyclization in a dramatic manner. 

Cadogan et al. performed a reductive cyclization of o-nitro-diphenyl sulfide (14) to phenothiazines (9) using triethyl phosphite. In the case of unsubstituted phenothiazine, the yield was 54%. 

CADOGAN - CAMERON WOOD Cyclization Synthesis of indoles, pyrroles and others N-heterocycles by cyclization of nitro compounds with trialkyl phosphite. 

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 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... 

The Cadogan reaction refers to the deoxygenation of o-nitrostyrenes 1 or o-nitrostilbenes with trialkyl phosphite or trialkylphosphine and subsequent cyclization of the resulting intermediate nitrene 2 to form indoles 3. The reductive cyclization protocol has also been exploited to prepare a variety of A -containing heterocyclic compounds including carbazoles, indazoles, benzimidazole, benzotriazoles, anthranils, phenazines, phenothiazines, quinolines, and related compounds. 

In 1962, Prof. John I. G. Cadogan at University of St. Andrews observed that aromatic C-nitroso compounds were readily deoxygenated by triethyl phosphite. Carbazoles were prepared from 2-nitrosdb ary s in this fashion albeit in low yields. Later on that year, he published an article titled Reduction of Nitro Compounds by Triethyl Phosphite A New Cyclization Reaction in the journal Proceedings of the Chemical Society In the paper, Cadogan described that 2- /7robiaryIs were also readily deoxygenated by... 

Cadogan himself further extended the scope of the Cadogan reaction. As early as in 1965, he already prepared carbazoles, indoles, indazoles, thiazoles and related compounds. In 1966, he synthesized phenothiazine (21) and anthranil 23, respectively, employing the reductive cyclization of nitrocompounds by triethyl phosphite. ... 

Merlic took advantage of the Cadogan reaction to make bisindoles. Thus cyclization of fra 5 -stilbene 38 with triethyl phosphite resulted in unsymmetrical 2,2 -bisindolyl 39 in modest yield. 

The first relevant report of a selective cyclization toward the (Cy 5) radical from a diallylic substrate was made in 1964 by Brace in the free radical chain reaction of 1,6-heptadiene (Scheme 25, X = CHj) with 1-iodoperfluoropropane initiated by AIBN. Further work, mainly by this author, confirmed (Scheme 25) the high selectivity toward formation of the (Cy 5) radical, in complete agreement with the results obtained with the 5-hexenyl radical (Sections II. 1 and III.1). Thus all reports, particularly in the polymerization area, that assumed formation of (Cy6) compounds must be regarded as suspect For instance, Cadogan and Hey reported the formation of a Cy5/Cy6 mixture by radical-initiated addition of various addenda to ethyl diallylacetate (X = CHCOjEt) but had to recognize later that the two compounds were in fact the two stereoisomeric (Cy5) compounds. 

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