Enantioselective Merger of Aminocatalysis with π‐Lewis Acid Metal Catalysis: Asymmetric Preparation of Carbo‐ and Heterocycles

Abstract

The metallo‐organocatalyzed enantioselective synthesis of various five‐membered carbo‐ and heterocyclic structures through the merger of aminocatalysis with the catalytic indium(III) or copper(I) activation of α‐disubstituted formyl alkynes is described. The use of indium trichloride associated with the (R)‐1,1′‐bis‐(2‐naphthylamine) ligand led to encouraging results with up to 85:15 enantiomeric ratio. After a careful examination of several other strategies, the best synergic catalytic system, which combines a chiral copper(I) complex with cyclohexylamine, afforded the enantioselective preparations of cyclopentane, indane, and pyrrolidine scaffolds with moderate to excellent control of the all‐carbon quaternary stereogenic centers created through such cyclization processes.

Intriguing mechanistic labyrinths in gold(i) catalysis

“…More recently, gold( i ) catalysis has also been combined with strong oxidants, 111 organocatalysts, 112 palladium, nickel or rhodium, 113 and photoredox reactions 114 leading to a completely new set of interesting transformations.…”

Enamine/Transition Metal Combined Catalysis: Catalytic Transformations Involving Organometallic Electrophilic Intermediates

“…Furthermore, within this topic, Ratovelomanana-Vidal, Michelet and coauthors have been very fruitful and developed several chemical transformation employing alkynes as substrates, and various metals integrated with enamine catalysis providing various carbocyclic products. Here, they successfully employed Indium catalyst [47–49], copper catalyst [50–52], and iron catalyst [53]. However, it was not until 2012 that they demonstrated an enantioselective version of the chemical transformation, providing the chiral cyclopentanes 52 in moderate-to-high yields and ee (Scheme 11) [52].…”

Synergy, Compatibility, and Innovation: Merging Lewis Acids with Stereoselective Enamine Catalysis

“…Moderate enantiomeric excesses (up to 70 % ee) were obtained in this reaction and so the same authors examined the use of enantiopure BINAM (BINAM = 1,1'-binaphthyl-2,2'-diamine) and InCl 3 in the same reaction. [52] With cyclohexylamine as an organocatalyst, the copper(I) complex could be efficiently replaced by indiumA C H T U N G T R E N N U N G (III) chloride. This generated a mild catalytic system, thus allowing room temperature preparation of a large range of carbo-and heterocyclic rings.…”

“…The chiral copper(I) complex activates the alkynyl residue, thereby triggering attack of the ( E )‐enamine formed in situ, through a chair‐like transition state. Moderate enantiomeric excesses (up to 70 % ee ) were obtained in this reaction and so the same authors examined the use of enantiopure BINAM (BINAM=1,1′‐binaphthyl‐2,2′‐diamine) and InCl 3 in the same reaction 52. With cyclohexylamine as an organocatalyst, the copper(I) complex could be efficiently replaced by indium(III) chloride.…”