Chiral Phosphoric Acid Catalyzed Asymmetric Friedel–Crafts Alkylation of Indole with 3‐Hydroxyisoindolin‐1‐one: Enantio­selective Synthesis of 3‐Indolyl‐Substituted Isoindolin‐1‐ones

Abstract

Chiral phosphoric acids have been proven to be effective organocatalysts for the asymmetric Friedel-Crafts alkylation of indoles with 3-hydroxyisoindolin-1-ones. The corresponding products were obtained in excellent chemical yields (up to 99 %) with moderate to excellent enantioselectivities (up to

Enantioselective Pictet–Spengler reactions of isatins for the synthesis of spiroindolones

“…Several instances have been reported previously where the 3,3′-substitution on the chiral phosphoric acid catalyst has been shown to reverse the sense of enantioselection. 10,13 …”

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

“…28 Gratifyingly, the enantiomeric excess could be enhanced to 92e99% in some cases by a single recrystallization of product. As described before, the BINOLphosphoric acid catalyst initiates the iminium formation and creates a chiral environment via close ion pairing between the iminium and the phosphate species.…”

Enantioselective Reactions of N‐Acyliminium Ions Using Chiral Organocatalysts

“…[83] Zhou et al reported the first intermolecular alkylation of indole with 3-hydroxyisoindolin-1-one in the presence of chiral H 8 -BINOL phosphoric acid (Scheme 15). [84] Under optimized reaction conditions, the unprotected indole reacted with 3-hydroxyisoindol-1-one (R 1 = H) 61 in the presence of chiral H 8 -BINOL phosphoric acid 62 (5 mol %) to afford the 3-substituted isoindoline-1-one 63 in 99 % yield and 83 % ee. The enantiomeric excess of 63 could be increased up to 99 % after a single recrystallization from methanol.…”