Rhodium‐Catalyzed Dual C−H Activation for Regioselective Triple Annulation of Enaminones: Access to Polycyclic Naphthopyran Derivatives

Abstract

Rh‐catalyzed C−H activation of arenes for oxidative annulations with alkynes stands out as a protocol for polycyclic scaffolds. This perspective drives us to disclose herein a rhodium catalyzed regioselective triple annulation of enaminones with hydroxyl‐alkynoates via double C−H functionalization for polycyclic naphtho‐pyran scaffolds. Secondary coordination of OH in alkynoate dictated the regioselectivity. Initial lactonization occurred chemoselectively on to enamine part via carbo rhodation followed by reductive elimination. This protocol was scalable and has shown high functionality tolerance. KIE studies were done to get insight in to the mechanism, and some downstream transformations were achieved to show the synthetic potential of the method.

Synthesis of Indenone-Fused Pyran Derivatives from Aryl Enaminones and Cyclopropenones through Unsymmetrical Relay C–H Bond Activation and Double C–C/C–O Bond Formation

“…Based on the results presented above and previous reports, , a plausible mechanism accounting for the formation of 3aa is proposed in Scheme . Initially, C–H bond metalation occurs with 1a to furnish intermediate I .…”

“…As an important class of synthetic intermediates, enaminones are not only easily obtainable but also highly versatile in reactivity . Very recently, their synthetic utility has been extended to CHA reactions. , In these reactions, various alkyne and alkene derivatives were used as coupling partners (CPs) to generate functionalized carbocyclic products. For example, Zhu et al reported the reactions of aryl enaminones with alkynes to afford functionalized naphthalenes (Scheme a) .…”

Construction of Rings via Metal‐Catalyzed C−H Annulation with Unsymmetrical Internal Alkynes: Selectivity and Applications

“…Along this line, they developed a triple C−H annulation of enaminones with hydroxyl alkynoates, with the in situ generated fused naphthol, which could assist further C−H annulation, leading to PAHs (Scheme 46–2). [30b] …”

Pd-Catalyzed Sequential Electrophilic Cyclization/Selective C–H Annulation Cascade: Synthesis of Isoxazole-Phthalimide-Fused Poly-Heterocyclics

“…Surprisingly, the incipient alkenyl-palladium intermediate could not be molded for successive activation of C–H bonds in spite of its availability at a reachable distance on both sides (Scheme e, Ar 1 & Ar 2 ). With our persistent interest in the combined alkyne/C–H activation, we herein reveal the tactic of annulating maleimides in succession to isoxazole formation by successfully transporting the Pd center from C-4 to the C–H bond of arene. Despite the availability of similar aryl groups at equidistance, the annulation occurred regioselectively at the C–H of Ar 1 .…”