Indoles with nitroalkenes

Scheme 57 Friedel-Crafts alkylation of indoles with nitroalkenes...

A series of chiral C2-symmetric tridentate bis(oxazoline) 110, 112 and bis(thiazoline) 111, in which a diphenylamine unit links the two chiral ox-azolines, was used for a more practical and efficient catalytic asymmetric alkylation of indoles with nitroalkenes (Scheme 31) [104], The alkylation of indole with frarzs-P-nitrostyrene in toluene at room temperature has been accomplished with 110d-Zn(OTf)2 or 113-Zn(OTf)2 as the catalyst. The obtained results show that the NH group in ligands 110-112 is crucial. Indole... 

The simply obtainable thiourea compounds 142-145 were the first organo-catalysts for the catalytic conjugate addition of indoles with nitroalkenes to yield optically active 2-indolyl-l-nitro derivative as 2.R-50 in fairly good yields and enantioselectivity. The simple thiourea-based organo catalyst 145 could be easily accessed in both enantiomeric forms from the commercially available materials. At the same time, the extremely simple methodology has proved the new approach useful for the synthesis of optically active target... 

Lin JH, Zhang CP, Zhu ZQ et al (2009) A novel pyrrohdinium ionic liquid with 1,1,2,2-tetra-fluoro-2-(l,l,2,2-tetrafluoroethoxy)ethanesulfonate anion as a recyclable reaction medium and efficient catalyst for Friedel-Crafts alkylations of indoles with nitroalkenes. J Fluorine Chem 130 394-398... 

Friedel-Crafts alkylation of indole with nitroalkenes was also effected by chiral phosphoric acid 21i (Equation 10.42) [88]. 

Herrera, R.P., Sgarzani, V, Bemardi, L. and Ricci, A. (2005) Catalytic enantioselectiveFriedel-Crafts alkylation of indoles with nitroalkenes by using a simple thiourea organocatalyst. Angewandte Chemie - International Edition, 44, 6576-6579. 

In 2011, Wan and co-workers developed bis-sulfonamide diamines as a new type of ligands for the Cu-catalyzed AFC alkylation of indoles with nitroalkenes. Ligand screening revealed that 141 was the optimal ligand. In the presence of 5 mol% Cu(OTf)2 and 141 in PhCFj, the AFC reaction of indoles with various aromatic nitroalkenes occurred smoothly to afford the corresponding products in excellent yields (88-99%) and enantioselectivity (88-97% ee) (Scheme 6.62). The reaction was not sensitive to air and moisture. 

In 2010, Wang and co-workers developed a new, efficient combinatorial catalyst, generated in situ by mixing Schiff base 146, Zn(OTf)2, and an achiral monodentate N ligand in a 1 1 3 ratio, for the AFC alkylation of indoles with nitroalkenes (Scheme 6.66). 

Other organometallic reagents such as Pt and Rh complexes are also found to be compatible catalysts in the AFC reactions. Song and co-workers reported the synthesis of the cationic pincer Pt" aqua complex 150 derived from a chiral bis(imidazolinyl)phenyl ligand. With 5 mol% of Pt complex 150 in toluene, the AFC alkylation of indoles with nitroalkenes proceeded to afford a variety of nitroalkylated indoles in good yields (up to 81%) with moderate to good enantioselectivity (up to 83% ee) (Scheme 6.68). 

In 2005, Ricci and coworkers published the first organocatalytic enantio-selective Friedel-Crafts allylation of indoles with nitroalkenes utilising simple thiourea 66. In general, moderate yields and enantioselectivities were observed for this difficult transformation, utilising 20 mol% catalyst... 

NitroaUCBnes. Organocatalytic enantioselective reaction of indoles with nitroalkenes appeared recently using chiral sulfonyl vicinal diamine 13 or chiral thiourea 14 as catalysts, which improved the electrophihcity of nitroalkene by double... 

This phosphoric acid derived from (i )-BINOL was also applied by Akiyama et al. as an organocatalyst to promote the highly enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes, generating the corresponding Friedel-Crafts adducts with high yields and excellent enantioselectivities of up to 94% ee for a broad range of substrates in the presence of 3-A molecular sieves (Scheme 10.2). ... 

Itoh, J. Fuchibe, K. Akiyama, T. Chiral Phosphoric Acid Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with Nitroalkenes Cooperative Effect of 3 A Molecular Sieves. Angew. Chem. Int. Ed. 2008, 47, 4016-4018. 

Hirata, T. Yamanaka, M. DFT Study of Chiral-Phosphoric-Acid-Catalyzed Enantioselective Friedel-Crafts Reaction of Indole with Nitroalkene Bifunctionality and Substituent Effect of Phosphoric Acid. Chem. Asian J. 2011, 6, 510-516. 

Ricci et al studied a series of thiourea catalysts for the Friedel-Crafts alkylation of aromatic and heteroaromatic compounds with nitroalkenes. They have succeeded in developing the Friedel-Crafts alkylation of indoles with nitroalkenes for the first time by means of a novel thiourea catalyst (13) (Scheme 2.48) [101]. The authors proposed the bifunctional nature of the thiourea catalyst, where thiourea activates the nitro group and at the same time the free alcoholic function interacts with the indole proton through a weak hydrogen bond, directing the attack of the incoming nucleophile on the Si face of the nitroalkene (Figure 2.18). 

The enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes is one of the most important carbon-bond-forming reactions for the preparation of biologically active compounds, such as indole alkaloids [39], Although several chiral catalysts have been investigated for the reaction, the enantioselectivities are not always satisfactory. Akiyama and coworkers developed a highly enantioselective Friedel-Crafts reaction of nitroalkenes 77 with indoles 75 using chiral phosphoric acid Ih (Scheme 11.21) [40]. They found that the addition of molecular... 

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