Enantioselective and Regioselective Friedel–Crafts Alkylation of Pyrroles with Nitroalkenes Catalyzed by a Tridentate Schiff Base–Copper Complex

Abstract

On a (pyr)role: A mild and highly efficient catalytic system has been developed for the asymmetric Friedel–Crafts alkylation of pyrroles with nitroalkenes (see scheme). High yields, and excellent enantioselectivities and regioselectivities were obtained for a broad range of substrates. The synthetic utility of this methodology and mechanistic studies involving a novel, negative, nonlinear effect are also presented.

Synthesis of diN-Substituted Glycyl-Phenylalanine Derivatives by Using Ugi Four Component Reaction and Their Potential as Acetylcholinesterase Inhibitors

“…( S )-Ethyl-2-Amino-3-Phenylpropionate: This compound was prepared following the methodology reported by Guo et al [30]. SOCl 2 (5.88 mL) was added dropwise at 0 °C to a suspension of L-phenylalanine 1 (4.46 g, 27.0 mmol) in 50 mL ethanol.…”

Recent Advances in Metal‐ and Organocatalyzed Asymmetric Functionalization of Pyrroles

“…From the optimization of the reaction condition, it was revealed that the reaction of 5 mol% of chiral ligand L10, 5 mol% of CuBr 2, and 10 mol% of piperidine when dissolved in diethyl ether at room temperature for 1 hour, deliver the homochiral dimer C-23 as blue solid (Scheme 27). [87] This complex (C-23) was then dissolved in toluene or aqueous toluene and effectively catalyzed the subsequent Friedel-Crafts alkylation of pyrroles to nitroolefins. Various α-functionalized pyrrole products 70, bearing tertiary stereogenic centers were achieved in high yield and excellent enantioselectivity.…”

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,…”

“…Du [49][50][51][52][53] developed an efficient catalyst containing bisoxazolines and bisimidazolines-Zn(OTf) 2 . Wang reported the involvement of a dimeric Cu II coordination cluster (CC) and piperidine as a catalyst for reactions between aromatic nitroalkenes and ortho-substituted indoles [41]. However, some of the reported protocols have drawbacks such as high catalyst loading, long reaction time, the need for additives, low temperature (0 to −20 • C) and multi-step designed ligands, thus limiting their practical applications.…”

“…Catalysts 2016, 6, 140 2 of 9 nitroalkenes and ortho-substituted indoles [41]. However, some of the reported protocols have drawbacks such as high catalyst loading, long reaction time, the need for additives, low temperature (0 to −20 °C) and multi-step designed ligands, thus limiting their practical applications.…”