Enantioselective Friedel−Crafts Alkylation Reactions Catalyzed by a Chiral Nonracemic C₂-Symmetric 2,2‘-Bipyridyl Copper(II) Complex

Abstract

Enantioselective Friedel-Crafts alkylation reactions of a series of substituted indoles with methyl trifluoropyruvate, catalyzed by a chiral nonracemic C(2)-symmetric 2,2'-bipyridyl copper(II) triflate complex, are described. The corresponding 3,3,3-trifluoro-2-hydroxy-2-indole-3-yl-propionic acid methyl esters were formed in good yield and in high enantiomeric excess (up to 90%). This is the first report of the use of a chiral nonracemic 2,2'-bipyridyl ligand in catalytic and enantioselective Friedel-Crafts alkylation reactions. The structural characterization of a copper(II) chloride complex of the chiral 2,2'-bipyridyl ligand by X-ray crystallography is also presented. [reaction: see text]

The Asymmetric Formal Hetero‐Diels–Alder Reaction of Methyl (E)‐4‐Aryl‐2‐oxo‐3‐butenoates Catalyzed by [Sc(OTf)3/pybox] Complexes

“…Such coordination increases the reactivity of the substrate, and the use of asymmetric catalysts may induce enantioselectivity in the reactions. [9,10] Moreover, the Friedel-Crafts reaction has found many applications in both aromatic and heterocyclic systems (especially with indoles), [11][12][13][14][15][16][17] and all these reactions have been asymmetrically performed by using box [18] and pybox [19] based chiral catalysts. Their absolute configuration was then related to that of 7 by stereospecific isomerization and/or desilylation reactions.…”

Domino Reactions Involving Catalytic Enantioselective Conjugate Additions

“…Replacement of the aryl substituent by a simple methyl group resulted in the formation of a mixture of diastereomers (4 : 1) with low enantioselectivity. The same chromanes have previously been prepared using copper-based catalysts, but with a considerably lower yield and ee-values [31].…”

“…Recently, Shibasaki reported on the three-component assembly of allenic esters 29 with ketones 28 and alkyl-Zn derivatives in the presence of copper acetate and the bidentate phosphane Difluorophos (31), that led to the formation of highly functionalized δ-lactones 30 with good to excellent yield and ee-values (Scheme 8.7) [14].…”

Copper(II) Trifluoromethanesulfonate

“…17 The active copper(II) catalyst was generated in situ. The corresponding 3,3,3-trifluoro-2-hydroxy-2-indolyl-propionic acid methyl esters were formed in good yield (up to 79%), and in up to 90% enantiomeric excess (eq 18).…”