Reductive cyclization of o-nitrostyrenes

Several procedures have been explored for the reductive cyclization of o-nitrostyrenes. Triethyl phosphite accomplishes this transformation by deoxy- 

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Several investigators have developed the reductive cyclization of o-nitrostyrenes into an efficient synthesis of indoles. Thus, research by the groups of Watanabe [458, 459], Sbderberg [460, 461], and Cenini [462, 463] have established this reductive Pd-catalyzed AMieteroannulation reaction as a viable route to simple indoles and fused indoles (372) as shown below. Ohta... 

Later, an analogous Mo(VI)-catalyzed reductive cyclization of o-nitrostyrenes 198 was utilized by Arnaiz in the synthesis of multisubstituted indoles 199, possessing various functional groups (Scheme 9.71) [228]. Similarly to Cenini s report, the authors proposed a mechanism involving cyclization of a reactive nitrenoid like 195. 

Most ring syntheses of this type are of modern origin. The cobalt or rhodium carbonyl catalyzed hydrocarboxylation of unsaturated alcohols, amines or amides provides access to tetrahydrofuranones, pyrrolidones or succinimides, although appreciable amounts of the corresponding six-membered heterocycle may also be formed (Scheme 55a) (73JOM(47)28l). Hydrocarboxylation of 4-pentyn-2-ol with nickel carbonyl yields 3-methylenetetrahy-drofuranone (Scheme 55b). Carbonylation of Schiff bases yields 2-arylphthalimidines (Scheme 55c). The hydroformylation of o-nitrostyrene, subsequent reduction of the nitro group and cyclization leads to the formation of skatole (Scheme 55d) (81CC82). 

Seven- and eight-membered cycloalkenes are available by intramolecular coupling of allenes. The reductive cyclizations (requiring SnCh) of o-nitrostyrenes and o-nitrobenzylidenimines afford indoles and 2//-indazoles, respectively. 

The dinitrostyrene approach has also been applied to the preparation of 5,6,7-trimethoxyindole by reductive cyclization of 2-nitro-3,4,5-trimethoxy-) -nitrostyrene, obtained by the nitration of 3,4,5-trimethoxy-i -nitrostyrene in Ac O with fuming... 

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 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. 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

The Batcho indole synthesis involves the conversion of an o-nitrotoluene to a (3-dialkyl-amino-o-nitrostyrene with dimethylformamide acetal, followed by reductive cyclization to indoles. This provides a useful strategy for synthesis of substituted indoles (Eq. 10.49).63... 

Recently, Kraus and Maeda have reported an elegant synthesis of the important C-4 o-anisyl derivative 26 in racemic form.85 This route involves pyrrolidine ring synthesis with key steps being Michael addition of the enolate of dimethyl a-ketoglutarate 174 to nitrostyrene derivative 175 followed by cyclization of the adduct 176 under reductive conditions to hemiaminal 177 (Scheme 63). 

Sanz, Amaiz, and colleagues discovered that a dichlorodioxomolybdenum(VI) complex can reductively cyclize nitrobiphenyls to carbazoles and nitrostyrenes to indoles (Scheme 3, equations 1 and 2) [ 12]. The Mo-catalyzed cyclization was applied to the synthesis of 2-carbonyl indoles in one pot from o-nitrobenzaldehydes (equation 3) [12]. Waldvogel and colleagues used MoCl,/ TiCl to synthesize carbazoles via an oxidative cyclization of diaryl amines (equation 4) [13]. These conditions were superior to TiCl, FeClj, and Pd(OAc)j/HOAc. A Pauson-Khand reaction using Co(CO) was employed by Saito s team to prepare lff-pyrrolo[2,3-(>]indol-2-ones (equation 5) [8]. 

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