Direct Carbocyclization of Aldehydes with Alkynes:  Combining Gold Catalysis with Aminocatalysis

Abstract

A combination of gold(I) complexes and amine bases catalyzes the 5-exo-dig cyclization of formyl alkynes. This direct alpha-functionalization of aldehydes with unactivated alkynes does not involve the use of preformed enol equivalents.

A Critical Comparison: Copper, Silver, and Gold

“…34 The reaction often, in much the same way as do other enamine catalyses, requires quite high catalyst loadings of the secondary amine. 34 The reaction often, in much the same way as do other enamine catalyses, requires quite high catalyst loadings of the secondary amine.…”

Cooperative Copper(I) and Primary Amine Catalyzed Room‐Temperature Carbocyclization of Formyl Alkynes

“…We and others recently reported the carbocyclization of α‐disubstituted aldehydes onto nonactivated alkynes by merging aminocatalysis to indium11 or gold12 catalysis 13. Under such cooperative “metallo–organocatalysis” conditions,14 the metal catalyst allows the electrophilic activation of the alkyne moiety, whereas the nucleophilicity of the aldehyde is induced through the formation of an enamine.…”

Cooperative Catalysis with Metal and Secondary Amine: Synthesis of 2-Substituted Quinolines via Addition/Cycloisomerization Cascade

“…6-Hexyl [1,3]dioxolo [4,5-g]quinoline (3a): 85% yield; mp = 105-107°C; pale yellow solid; R f 0.50 (hexane/EtOAc = 80/20); 1 …”