Enhanced Efficiency of Thiourea Catalysts by External Brønsted Acids in the Friedel–Crafts Alkylation of Indoles

Abstract

A novel study on the influence of external Brønsted acids on thiourea catalysts in the asymmetric Friedel-Crafts alkylation of indoles with nitroalkenes is reported. The final 3-substituted indole derivatives were synthesized with better results because of cooperative effects between the chiral thiourea and a Brønsted acid additive (1a·HA). The effects of diverse

Dianhydrohexitols: new tools for organocatalysis. Application in enantioselective Friedel-Crafts alkylation of indoles with nitroalkenes

“…With D-and L-mandelic acid, no match or mismatch effect was observed and the chirality of the acid has no influence on the enantioselectivity; the same major isomer being formed (entries 4 and 5). Similar results have been found by Herrera et al 40 This fact showed that chirality was preferentially controlled by the thiourea catalyst. The additive acids only activated the thiourea moiety rather than participating itself into the transition state.…”

“…Recently, Herrera and co-workers reported that external Brønsted acids could enhance the efficiency of thiourea catalyst. 40 So we envisioned that higher enantioselectivity and reactivity might be achieved by using a suitable additive acids thus, we started to investigate the use of acid additives in this reaction.…”

“…[31][32][33][34][35][36][37][38][39][40][41] The indole skeleton is considered to be one of the most useful moieties in pharmaceutical chemistry. [42][43] …”

Highly Efficient Tetranuclear ZnII2LnIII2 Catalysts for the Friedel–Crafts Alkylation of Indoles and Nitrostyrenes

“…For the reaction between indole and β-nitrostyrene, various catalytic systems have been proposed. These include hydrogen-bond-based compounds [11][12][13][14][15][16] such as thiourea [11,14,15,[17][18][19][20], phosphoric acid [16], silanediols [21,22], sulfamic acid [23] and 2,6-bis(amido)benzoic acid [24]; metal based compounds [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] such as Al III [25,39], Cu II [26][27][28][29][30]41], Zn II [31][32][33][34][35]40,…”

A Cooperative Ternary Catalysis System for Asymmetric Lactonizations of α‐Ketoesters

“…[20] Consistent with this proposed mode of binding, no change by 1 H NMR spectroscopy was observed when calcium methoxide and 1,3-diphenylthiourea were mixed alone in toluene-d 8 , implying that calcium is likely not activating the HBD. [21] ESI mass spectrometry revealed a mass corresponding to the catalyst–substrate complex (NHC B + enal), but no mass corresponding to any co-catalyst adducts. [18b, 22] Observation of this intermediate also suggests that the pendent silyl ether of NHC B remains silylated under the reaction conditions.…”