Chiral Brønsted Acid Directed Iron‐Catalyzed Enantioselective Friedel–Crafts Alkylation of Indoles with β‐Aryl α′‐Hydroxy Enones

Abstract

A cooperative catalytic system established by the combination of an iron salt and a chiral Brønsted acid has proven to be effective in the asymmetric Friedel-Crafts alkylation of indoles with beta-aryl alpha'-hydroxy enones. Good to excellent yields and enatioselectivities were observed for a variety of alpha'-hydroxy enones and indoles, particularly for the beta-aryl alpha'-hydroxy enones bearing an electron-withdrawing group at the para position of the phenyl ring (up to 90 % yield and 91 % ee). The proton of the chiral Brønsted acid, the Lewis acid activation site, as well as the inherent basic site for the hydrogen-bonding interaction of the Brønsted acid are responsible for the high catalytic activities and enantioselectivities of the title reaction. A possible reaction mechanism was proposed. The key catalytic species in the catalytic system, the phosphate salt of Fe(III), which was thought to be responsible for the high activity and good enantioselectivity, was then confirmed by ESIMS studies.

Iron Catalysis in Organic Synthesis

“…209 The method provided 3-alkylated indoles in high yields and good enantioselectivities. The best results were obtained with arylenones bearing electronwithdrawing groups at the para-position of the aromatic substituent.…”

Insights into mesoporous metal phosphonate hybrid materials for catalysis

“…30,31 Moreover, it is probable to mimic the basic principles of natural enzymatic catalysis, wherein weak interaction such as electrostatic interaction and hydrogen bonding between the functional groups at fixed distances influence the reactivity of the catalysts. 32,33 Mesoporous organosilicas and organofunctionalized mesoporous silicas have been dedicated as efficient heterogeneous catalysts through the introduction of metal sites and organometallic ligands and post-modification. However, their further potency towards practical applications are prohibited by the high price of the organosilicane reagents and the unfavourable synthesis strategy that leads to the inferior distribution of catalytic sites and even sacrifice of porosity, which may be due to the incompatibility between the metal sites and organosilica networks.…”

Mesoporous Core–Shell Fenton Nanocatalyst: A Mild, Operationally Simple Approach to the Synthesis of Adipic Acid

“…Preparation of g-Al 2 O 3 : Self-assembled g-Al 2 O 3 nanomaterials were synthesized by employing our previous procedure. [24] In this typical synthesis, ammonium chloride (2.0 g, 37.4 mmol, E. Merck, 98.9 % GR) was added to 20 mL of an aqueous solution of sodium salicylate (1.6 g, 10 mmol, E. Merck, 99.5 %). The solution was stirred for 15 min.…”

“…For oxide materials at all pH values, there are large numbers of negative, neutral, or positive surface sites. [24] Measurement of the zeta potential showed that the surface charge of the self-assembled g-Al 2 O 3 is positive in Millipore water and negative in Millipore water at pH 8 (Supporting Information Figure S1). The zeta potentials of this material are + 6.97 and À32.7 mV in Millipore water and in Millipore water at pH 8, respectively.…”