The Asymmetric Friedel‐Crafts Reaction of Indoles with Arylidenemalonates Catalyzed by MgI₂/PyBox Complexes

Abstract

A mild and efficient catalytic enantioselective addition of indoles to dimethyl arylidenemalonates using MgI2 and PyBOX ligands bearing halogen substituents has been elaborated. The reactions were conducted in DCM at low temperature generally providing high yields (up to 99%), while enantioselectivity was shown to be strongly dependent on the nature of substituents in arylidenemalonate and indole reaching 83% ee. The reactivity of arylidenemalonates under described conditions was found to be enough different from that in copper‐catalyzed Friedel‐Crafts alkylation.

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

“…The addition of pyrrole 10 a to substrate 2 led to product 11 a in high yield (90 %) and moderate enantioselectivity (55 % ee ) within 24 h. The reaction of N ‐methylpyrrole with 2 did not run to completion even after 48 h. In this instance, product 11 b was obtained in good yield (83 %), but with poor enantiomeric excess (12 % ee ). It is known that the enantioselectivity of Friedel‐Crafts asymmetric reactions of pyrroles is usually lower than indoles, for example, in the reaction with benzylidenemalonates and ethenetricarboxylates, probably because of the smaller size of pyrrole molecules. However, the use of more sterically hindered ligand t BuBox ( L3 ) instead of L2 allowed us to increase the enantioselectivity of the reaction with pyrrole 10 a to 82 %, albeit in slightly lower yield (80 %).…”

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].…”