Enantioselective Copper(II)/Box‐Catalyzed Synthesis of Chiral β³‐Tryptophan Derivatives

Abstract

β‐Amino acids and their derivatives are important building blocks for the preparation of various bioactive compounds and materials. We developed a highly efficient method for the synthesis of β3‐tryptophan derivatives based on enantioselective Friedel‐Crafts alkylation of indoles with phthaloyl‐protected aminomethylenemalonate in the presence of chiral Cu()OTf2/iPrBox complex as a catalyst. A wide range of indoles with electron‐donating and electron‐withdrawing substituents gave the desired products in high yields (up to 99 %) and excellent enantioselectivities (up to 99 % ee). In the case of pyrrole the Friedel‐Crafts product was obtained in up to 90 % yield and up to 82 % ee.

Catalytic C3 aza-alkylation of indoles

“…These catalytic complexes were exploited in the works by Zhou, 62 Fu 63 and Beletskaya. 64 Zhou and Fu considered two similar catalysts to promote the reaction between indole and tosyl-protected aryl imines (Scheme 15a). They obtained C3-alkylation with high yields and enantioselectivities (up to 96%), and with only a limited formation of the bis-indolyl by-product, that could be furtherly suppressed lowering the temperature.…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…Beletskaya et al described asymmetric Friedel-Crafts reactions of indoles with arylidene malonates 41 in the presence of magnesium iodide [43] and with phthaloyl-protected aminomethylenemalonate 43 in the presence of Cu(OTf) 2 [44]. The processes were catalyzed by PyBox [43] or iPrBox [44], respectively (Scheme 16).…”

“…Beletskaya et al described asymmetric Friedel-Crafts reactions of indoles with arylidene malonates 41 in the presence of magnesium iodide [43] and with phthaloyl-protected aminomethylenemalonate 43 in the presence of Cu(OTf) 2 [44]. The processes were catalyzed by PyBox [43] or iPrBox [44], respectively (Scheme 16). The asymmetric reaction of indoles with α,β-unsaturated carbonyl compounds 45 (enones) was carried out using three similar catalytic systems (Scheme 17) [45][46][47].…”

Recent achievements in copper catalysis for C–N bond formation

“…Among the principal investigations in the field of the copper-mediated amination [7][8][9][10][11][12] and amidation [13,14] in last 15 years more specialized reviews can be cited [15,16]. Our own interest in the copper-catalyzed reactions exceeds the frames of purely Ullmann reactions due to a wide scope of various catalytic transformations promote by this metal and cover the following aspects: formation of C(sp 2 ) -P bonds [17][18][19], arylation with iodonium salts [20], formation of C-S and C-C bonds in the reactions with alkynes [21,22], use of the chiral Cu(II) complexes in the asymmetric addition reactions catalyzed by optically active Lewis acids [23][24][25][26], application of the heterogeneous copper catalysts like copper nanoparticles (CuNPs) [27] and copper-containing MOFs [28]. Our attention was also drawn by the Cu(I)-catalyzed Sonogashira coupling [29,30], formation of C-N bonds under the conditions of Chan-Lam-Evans reaction [31] or in the presence of poly(ethylene) glycols [32], the synthesis of polycyclic compounds [33].…”