Gold-Catalyzed Formal [4 + 2] Cycloaddition of 5-(Ethynylamino)pent-2-yn-1-yl Esters to 1,2,3,5-Tetrahydrobenzo[g]quinolines

Abstract

A synthetic method to prepare 1,2,3,5-tetrahydrobenzo[ g]quinolines efficiently that relies on gold(I)-catalyzed cycloisomerization of 5-(ethynylamino)pent-2-yn-1-yl esters at room temperature under atmospheric conditions is described. The proposed reaction mechanism presents a unique instance of an in situ formed allenic ester and gold keteniminium species to undergo a formal [4 + 2] cycloaddition pathway.

(Z)-γ-Alkylidenebutenolide Synthesis through Au(I)-Catalyzed 1,3-Acyloxy Migration and the Carbonyl–Ene Reaction

“…Although the formation of 3,4unsubstituted (Z)-γ-alkylidenebutenolides from terminal alkynes and (Z)-3-bromopropenoic acid was achieved in Lu's bimetal-catalyzed Sonogashira coupling and 5-exo-dig hydrocarboxylation, the scope of starting materials limited molecular diversity. 4 Recent intermolecular lactonizations have also been attempted to generate (Z)-γ-alkylidenebutenolides, though issues on regioselectivity, stereoselectivity, as well as substrate flexibility are still encountered. 5−7 Accordingly, development of more general approaches to Z-configured γ-alkylidenebutenolides remains both essential and challenging.…”

“…Transitional-metal-catalyzed 1,3-acyloxy of propargyl esters, a class of functionalized alkyne compounds, provides an efficient means to access carbocyclic and heterocyclic ring systems . The in situ generated allenyl esters may perform as nucleophiles, electrophiles, dienophiles, and 1, n -dipoles in the cycloisomerization and cycloaddition reactions. Inspired by previous researchers, we envisioned a bimetal catalyzed/mediated synthesis of ( Z )-γ-alkylidenebutenolides (Scheme ).…”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…Chan and coworkers reported the efficient (32−89%) synthesis of benzo fused tetrahydroquinolines 264 by a formal intermolecular [4 + 2] cycloaddition of propargyl acetate tethered aryl ynamides 263 (Scheme 63). 131 This cascade transformation involves the initial Au-catalyzed rearrangement of the propargyl ester motif into an acyloxyallene 265 followed by its nucleophilic addition onto the Au-activated ynamide. The resulting carbocation 266 is then trapped by the pendant aromatic group to furnish the polycyclic structure of the final compound.…”

Gold-Catalyzed Homogeneous (Cyclo)Isomerization Reactions

“…An initial [3,3]-sigmatropic rearrangement of the acetate group and activation of the ynamide group would yield the keteniminium ion 51 which would experiment a formal [4+2]-cycloaddition yielding 52 . This protocol is efficient even in the presence of air and moisture, indicating the tolerance of the gold catalysts to diverse reaction conditions (Chen et al, 2018).…”