Cadogan reaction

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

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. 

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. ... 

Bose applied Cadogan s indazole synthesis and achieved an enhanced greener one-pot process using microwave. Thus Schiff base 24 was prepared by microwaving (400 W) a mixture of equivalent amounts of the aldehyde and the aniline. The Cadogan reaction was completed imder microwave as soon as the temperature reached 150 "C with excess of triethyl phosphate to afford indazole 25. 

Creenia and Horaguchi also explored the Cadogan reaction for the synthesis of a variety of W-containing heterocycles. With the aide of microwave, a less reactive and less toxic triphenylphosphine could be used in place of triethyl phosphite. For example, a one-pot, two-step synthesis of benzimidazole 26 was accomplished by microwaving (200 W) a mixture of... 

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. 

This and other reactions of NAA have been discussed by Cadogan (1971)... 

Cadogan and coworkers160 developed a fructose-derived l,3-oxazin-2-one chiral auxiliary which they applied in the Diels-Alder reactions of its iV-enoyl derivatives 246 with cyclopentadiene using diethylaluminum chloride as the Lewis acid catalyst. The reactions afforded mixtures of endo 247 and exo 248 (equation 68). The catalyst binds to the chiral dienophile in a bidentate fashion (co-ordination to both carbonyl groups). As a consequence, the dienophile is constrained to a rigid conformation which accounts for the almost complete diastereofacial selectivities observed. 

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). 

For reviews of reactions with these reagents, see Castro Org. React. 1983, 29, 1-162 Mackie, in Cadogan Organophosphorus Reagents in Organic Synthesis, Academic Press New York, 1979 pp. 433-466. 

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. 

Although it is known that free radicals add predominantly to the least substituted end of an olefinic double bond there is very little quantitative information on the relative rate of addition at the two positions in asymmetric olefins (Cadogan and Hey, 1954 Cvetanovid, 1963). The rotating cryostat has been used to examine this aspect for the case of the addition of hydrogen atoms to a variety of olefins deposited in a matrix of adamantane. The ratios of the rates of addition are given in Table 7, and for illustration the reaction with propylene is considered below. 

Alkyl nitrites have been used to effect nitrosation or diazotisation in aprotic solvents. Typically, arylamines react in benzene solution to give biaryls (Cadogan et al., 1966). Friedman and coworkers have examined the products from alkyl nitrites and amines in a number of solvents. No mechanistic study aimed at identifying the details of the nitrosation reaction was attempted rather the emphasis was on the intermediacy of a diazoalkane and subsequent reaction of carbocations (Friedman and Bayless, 1969 Friedman et al., 1969). 

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