Gold and Carbene Relay Catalytic Enantioselective Cycloisomerization/Cyclization Reactions of Ynamides and Enals

Abstract

The combined use of gold as transition metal catalyst and N‐heterocyclic carbene (NHC) as organic catalyst in the same solution for relay catalytic reactions was disclosed. The ynamide substrate was activated by gold catalyst to form unsaturated ketimine intermediate that subsequently reacted with the enals (via azolium enolate intermediate generated with NHC) effectively to form bicyclic lactam products with excellent diastereo‐ and enantio‐selectivities. The gold and NHC coordination and dissociation can be dynamic and tunable events, and thus allow the co‐existence of both active metal and carbene organic catalysts in appreciable concentrations, for the dual catalytic reaction to proceed.

Multicatalysis protocol enables direct and versatile enantioselective reductive transformations of secondary amides

“…To tackle the abovementioned multiple challenges, a multicatalysis ( 57 – 60 ) approach was envisioned. The multicatalysis is an emerging strategy for developing unprecedented and challenging transformations that could not be achieved by a single catalytic system.…”

Recent Advances in Cooperative N-Heterocyclic Carbene Catalysis

“…The cooperative catalysis using NHC and gold catalyst was reported (Figure 5) [31]. When NHC precursor A8 (20 mol%), PPh 3 AuCl/AgPF 6 (10 mol%), and DABCO (25 mol%) were employed, the relay reaction of ynamide substrate 28 with enal 29 gave the bicyclic lactam 30 in 84% yield with 99% ee.…”

N‐Heterocyclic Carbene Organocatalysis: Activation Modes and Typical Reactive Intermediates

“…The unsaturated ketimine intermediate could subsequently react with enals (via azolium enolate intermediate generated with NHC) effectively to form bicyclic lactam products with excellent diastereo-and enantio-selectivities (Scheme 58). [86] The generation of the chiral enolate intermediates via NHC-catalyzed intramolecular redox reactions of α-haloaldehydes was disclosed by Bode's group in 2006. [87] In 2013, Enders and colleagues demonstrated an interesting formal [3+2] cycloaddition of NHC-bound azolium enolates with 2-nitrovinylindoles.…”