Nitroolefins, indole

Several iodine-catalyzed organic transformations have been reported. Iodine-catalyzed reactions are acid-induced processes. Molecular iodine has received considerable attention because it is an inexpensive, nontoxic and readily available catalyst for various organic transformations under mild and convenient conditions. Michael additions of indoles with unsaturated ketones were achieved in the presence of catalytic amounts of iodine under both solvent-free conditions and in anhydrous EtOH (Scheme 19) [85,86]. l2-catalyzed Michael addition of indole and pyrrole to nitroolefins was also reported (Scheme 20) [87]. 

Conjugate addition of indole to nitroolefins was carried out by thermal heating in a sealed tube or by addition of indolyl magnesium iodide or microwave irradiation. The results indicated that the microwave technique is most efficient with respect to time and yield (Scheme 26) [97]. 

Aluminum salen complexes have been identified as effective catalysts for asymmetric conjugate addition reactions of indoles [113-115]. The chiral Al(salen)Cl complex 128, which is commercially available, in the presence of additives such as aniline, pyridine and 2,6-lutidine, effectively catalyzed the enantioselective Michael-type addition of indoles to ( )-arylcrolyl ketones [115]. Interestingly, this catalyst system was used for the stereoselective Michael addition of indoles to aromatic nitroolefins in moderate enantiose-lectivity (Scheme 36). The Michael addition product 130 was easily reduced to the optically active tryptamine 131 with lithium aluminum hydride and without racemization during the process. This process provides a valuable protocol for the production of potential biologically active, enantiomerically enriched tryptamine precursors [116]. 

Chiral bis-sulfonamides 162-163 are a new group of organo catalysts for the enantioselective Friedel-Crafts alkylation of indoles to nitroolefins. The hy-... 

Jorgensen and co-workers employed chiral bis-sulfonamide catalyst 27, a proven ligand for metal-based asymmetric catalysis, for the Friedel-Crafts alkylations of N-methylindoles (24) using -substituted nitroolefins [52]. Using optimized conditions, 2 mol% 27 gave the desired indole alkylation products of substituted aryl and heteroaryl nitroolefins in moderate to high yields (20-91%) and moderate enantiopurities (13-63% ee Scheme 6.3). Aliphatic -substitution... 

Whereas cyclic secondary enaminones and nitroolefins mainly yield indoles in which the enamine nitrogen is incorporated into the heterocyclus (equation 242), linear tertiary a-ketoenamines are shown to react with nitroolefines at low temperature under kinetic control to give 1,2-oxazine N-oxides as [4 + 2]-cycloadducts, followed by retro-Diels-Alder reaction or rearrangement under thermodynamic control which leads diastereo-selectively to aminocyclopentenes. The reaction is called [3 + 2]-carbocyclization, apparently because the ketoenamine is reacting as a 1,3-dipole. The products are hydrolysable to polysubstituted nitrocyclopentanones with retained configuration325 (equation 243). 

Possible coordination of the thiourea catalyst with not only nitroolefin but also indole through the thiourea hydrogen atom and the hydroxyl oxygen atom, respectively, in the transition state are supposed (Figure 9.9). 

Table 9.13 Thiourea catalysed Michael reaction of nitroolefins with indole...

With respect to nitroolefins as electrophiles, indoles [335-337], 4,7-dihydroindoles [338], pyrroles [339], and naphthols [340] have been nsed with success in the reaction employing different chiral bifunctional organocatalysts. Scheme 2.118 shows... 

Scheme 2.118 Asymmetric Friedel-Ciafts eilkylation of indoles with nitroolefins...

Keywords 2-Ethynylanilines, sulfonyl azide, nitroolefins, CuBr, 1,4-dioxane, room temperature, one-pot three-compOTient reaction, polysubstituted indoles... 

To a stirred mixture of p-toluenesulfonyl azide (3 0.30 mmol, 1.2 equiv), nitroolefin (2, 0.25 mmol, 1.0 equiv), and CuBr (0.025 mmol, 10 mol %) in anhydrous 1,4-dioxane (0.5 mL) was added a solution of 2-ethynylaniline (1 0.25 mmol, 1.0 equiv) in 1,4-dioxane (0.5 mL) at room temperature under nitrogen atmosphere. Triethylamine (104 pL, 0.75 mmol, 3.0 equiv) was tehn slowly added by syringe. The whole mixture was thereafter stirred vigorously until completion of the reaction (monitored by TLC, 3-5 h). Upon completion of the reaction, the reaction mixture was quenched with saturated ammonium chloride solution (3.0 mL) the mixture was stirred for additional 10 min and extracted with ethyl acetate (3 x 3.0 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuum. The crude product was purified using flash column chromatography (EtOAc/ -hexane, 1 3) to obtain polysubstituted indoles 4. All the products were characterized by their spectral studies. 

Chen, Z., Zheng, D., and Wu, J. (2011). A facile route to polysubstituted indoles via three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin. Org. Lett., 13, 848-851. 

Three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin also could lead to polysubstituted indole derivatives in moderate to good yields with CuBr catalyst. The reaction conditions are extremely mild and various polysubstituted indoles were obtained successfully. Initially, a triazole intermediate was formed from alkyne and sulfonyl azide in the presence of CuBr and triethy-lamine. It could convert into reactive ketenimine by the ring-opening rearrangement. Subsequently intramolecular nucleophilic addition, intermolecular Michael addition, and tautomerization could lead to the desired polysubstituted indoles [49] (Scheme 8.20). 

Scheme 8.20 Polysubstituted indole derivatives synthesis via three-component reaction of 2-ethynylaniline, sulfonyl azide, and nitroolefin.

Scheme 35.5 F-C alkylation between indoles and nitroolefins with phosphoric acid as catalyst.

The use of phosphoric acid ml-lGd for the catalysis of a tandem double F-C reaction gave rise to fluorene derivatives (up to 96% ee) by the reaction between indoles and 2-formylbiphenyl derivatives [74]. Vinyl indole derivatives combined with a,P-unsaturated aldehydes gave rise to functionalized tetrahydrocarbazoles with two or more stereocenters via an intermolecular triple cascade process by means of secondary amine 7a catalysis [75]. Catalyst 7a also promoted a quadruple F-C/Michael/Michael/aldol condensation reaction between indoles, acrolein, and aromatic nitroolefins (Scheme 35.19) [76]. This work provides a straightforward... 

Although heterocycUc ortho-quinodimethanes (oQDMS) have been studied extensively to design Diels-Alder reactions for the synthesis of complex indole alkaloids for more than 30 years, asymmetric catalysis of the Diels-Alder reaction of nitroolefins 32 or methylene-indolinones 39 with in situ generated heterocyclic... 

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