Asymmetric Friedel–Crafts Alkylations of Indoles with Ethyl Glyoxylate Catalyzed by (S)‐BINOL‐Titanium(IV) Complex: Direct Access to Enantiomerically Enriched 3‐Indolyl(hydroxy)acetates

Abstract

Enantioselective Friedel-Crafts alkylation reactions of a variety of indoles with ethyl glyoxylate, catalyzed by a chiral (S)-BINOL-Ti(IV) complex (10 mol %), are reported. The corresponding ethyl 3-indolylA C H T U N G T R E N N U N G (hydroxy)acetates were formed in good yields and with high enantiomeric excess (up to 96 %). When methyl pyruvate or p-chlorophenylglyoxal was used, the bisindole compound was obtained in excellent yield. A possible mechanism is proposed.

Catalytic Functionalization of Indoles in a New Dimension

“…Shortly after, the reaction of variously substituted indoles with 72 d in the presence of catalytic amounts of binol/Ti(O i Pr) 4 complex 78 (10 mol %) was reported 89. After optimization of the reaction parameters, very high enantioselectivity were reached (up to 96 % ee ); however, the method appeared to be limited to the glyoxylate derivative 72 d .…”

Catalytic Enantioselective Arylation of Glyoxylate with Arylsilanes: Practical Synthesis of Optically Active Mandelic Acid Derivatives

“…While several synthetic methods for these compounds have been developed to date,2–5 the catalytic enantioselective Friedel–Crafts (F‐C) alkylation reaction of glyoxylate6 with aromatic or heteroaromatic rings is one of the most attractive and useful methods for their practical synthesis 7. 8 On the catalytic enantioselective F‐C alkylation reaction using chiral Cu7a,d or Ti7b,c catalysts, high yield and enantioselectivity have been achieved to efficiently synthesize mandelic acid derivatives. However, these catalytic reactions proceed only with highly reactive substrates, such as N ‐methylated aniline, indoline, and indole derivatives, and hence limit their synthetic application.…”

Katalytische Funktionalisierung von Indolen in einer neuen Dimension

“…Kurz darauf wurde die Reaktion von verschiedenartig substituierten Indolen mit 72 d in Gegenwart von 10 Mol‐% Binol/Ti(O i Pr) 4 ( 78 ) beschrieben 89. Nach Optimierung der Reaktionsparameter wurden sehr hohe Enantiomerenüberschüsse erzielt (bis 96 % ee ), jedoch mit einer Beschränkung auf das Glyoxylatderivat 72 d .…”