Ruthenium-Catalyzed Redox-Neutral [4 + 1] Annulation of Benzamides and Propargyl Alcohols via C–H Bond Activation

Abstract

Internal alkynes have been used widely in transition-metal-catalyzed cycloaddition reactions, in which they generally serve as two-carbon reaction partners. Herein, we report ruthenium(II)-catalyzed redox-neutral [4 + 1] annulation of benzamides and propargyl alcohols, in which propargyl alcohols act as one-carbon units. This synthetic utility of propargyl alcohols led to a series of potentially bioactive Nsubstituted quaternary isoindolinones with moderate to high yields under mild conditions. Without the requirement for an external metal oxidant, this title transformation is compatible with various functional groups, which further underscores its synthetic utility and versatile applicability. In addition, preliminary mechanism experiments have been conducted and a plausible mechanism is proposed.

Rhodium(III)-Catalyzed Redox-Neutral [3+3] Annulation of N-nitrosoanilines with Cyclopropenones: A Traceless Approach to Quinolin-4(1H)-One Scaffolds

“…Similarly, several formal [3+2] annulations between N-nitrosoanilines and diazo compounds [29] as well as propargyl alcohols [30] utilizing the N−nitroso group as an internal oxidant have been reported to prepare diversified indole scaffolds, in which the substrate involving the N−nitroso group seems to be an excellent synthon to build these intriguing privileged structures via a C-H bond activation and further annulation cascade. Therefore, in continuation of our recent efforts on transition-metal-catalyzed C-H annulations for the construction of heterocyclic scaffolds [31][32][33][34][35][36], we surprisingly found a new redox-neutral [3+3] annulation of N-nitrosoanilines with cyclopropenones [37][38][39] to generate a different substituted quinolin-4(1H)-one scaffold (Scheme 1c), which is a desirable privileged structure for further drug discovery. However, coincidentally, a similar work was reported by Cheng [40] after our work was finished and ready to submit.…”

Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions

“…Similarly to their work with rhodium, [47] Liu [67] reported a ruthenium catalyzed formal [4+1] annulation of propargyl alcohol derivatives with N ‐ethoxy benzamides by means of C−H functionalization reaction (Scheme 23). In comparison to the rhodium catalyzed method the overall isolated yields are very close to each other and the reaction with the ruthenium catalyst is operated at slightly lower temperature, not to mention the price difference between rhodium and ruthenium complexes.…”

C–H Functionalization of Aromatic Amides

“…In 2017, Liu's group reported a ruthenium‐catalyzed specific [4+1] annulation of aromatic amides and propargyl alcohols affording moderate to good yields (Scheme ) . The results reveal that the properties of para ‐substituents in the aromatic amides have an effect on the yield.…”