Gold-Catalyzed Cyclization of Alkynyl Heteroarenes with a Norbornene Bridge

Abstract

In this study, Au(III)-catalyzed cyclization reactions of alkynyl norbornene derivatives were developed to provide benzofused (hetero)arenes with substitutions at the benzocyclic ring. The combination of Au(OAc)3 and AgNTf2 allowed for the annulation of (hetero)arenes by intramolecular hydro(hetero)arylation followed by retro-Diels–Alder reactions to afford fully conjugated benzofused (hetero)arenes in higher yields as compared to the yield obtained using our previously developed Pd(OAc)2-catalyzed protocol. Furthermore, when Au(OAc)3 was replaced with AuCl3, (hetero)arenes with the norbornene bridge installed at the more electron-rich and sterically demanding position underwent a rearrangement to afford the corresponding regioisomeric products in a divergent manner. The result indicates that the rigid norbornene ring creates a steric effect, in addition to placing two reactive sites in proximity and serving as an acetylene synthon. This illustrates the importance of the steric effect in addition to the electronic effects of the catalyst and substrate on the rearrangement.

Homogeneous Gold Catalysis for Regioselective Carbocyclization of Alkynyl Precursors

“…Earlier this year, Joo et al . uncovered the Au(III)‐catalyzed carbocyclization of thienyl‐alkynes bridged by norbornene ring 4.36 under high temperature (Scheme 31, eq 2) [170] . Under the reaction condition, the norbornene serves as a masked olefin by eliminating cyclopentadiene via retro‐Diels‐Alder reaction.…”

“…Earlier this year, Joo et al uncovered the Au(III)catalyzed carbocyclization of thienyl-alkynes bridged by norbornene ring 4.36 under high temperature (Scheme 31, eq 2). [170] Under the reaction condition, the norbornene serves as a masked olefin by eliminating cyclopentadiene via retro-Diels-Alder reaction. Though the cyclization selectivity of this reaction follows 6-endo-dig regiochemistry, the positional selectivity varies with respect to the choice of anion in the gold catalyst.…”

Pyrazolopyridine Ligands in Transition-Metal-Catalyzed C–C and C–Heteroatom Bond-Forming Reactions

“…Later, it was found that Au(III) catalysts also enabled cyclization of the same substrates with rearrangements depending on the positions of substituents, suggesting the different nature of the palladium catalytic system that does not generate the corresponding rearrangement products. 29 In addition to utilizing 1-PzPy in Pd-catalyzed reactions, the Joo group prepared a series of its -extended derivatives, known as PzNPy ligands, and applied them to Pdcatalyzed aerobic C-H alkenylation reactions of (hetero)arenes (Scheme 8). 15,30 Inspired by the Rh-catalyzed annulation of N-aryl pyrazoles developed by Miura and co-Scheme 6 Pd-catalyzed addition of arylboronic acids to cyanoacetate derivatives using the L4 ligand followed by hydrolysis and decarboxylation (Adhikari, 2015).…”

“…Later, it was found that Au(III) catalysts also enabled cyclization of the same substrates with rearrangements depending on the positions of substituents, suggesting the different nature of the palladium catalytic system that does not generate the corresponding rearrangement products. 29…”