Carboxyl‐Directed Conjugate Addition of C−H Bonds to α,β‐Unsaturated Ketones in Air and Water

Abstract

A simple ruthenium‐catalyzed conjugate addition of C−H bonds to α,β‐unsaturated ketones directed by a removable carboxyl group was developed as an effective protocol to synthesize ortho‐alkylated benzoic acids in a greener manner. Without any additives, satisfactory to excellent yields of the targeted products were achieved in neat water, and the process characterizes in mild reaction conditions (in air and water), simple operations, and broad substrate scope. Noteworthy features of this method include mild reaction conditions (in air and water), operational simplicity and broad substrate scope. The versatility and utility of the addition products were demonstrated through further transformation into commonly inaccessible but highly useful motifs of meta‐substituted alkylbenzenes and 3‐substituted isochromanones.magnified image

Rhodium(III)‐Catalyzed C–H Alkylation/Nucleophilic Addition Domino Reaction

“…Subsequently, Wang demonstrated a three‐component catalytic carboxygenation through rhodium(III)‐catalyzed C–H activation . Inspired by these findings, and along with our previous studies,[6d], [7a], [7b], [8c], [8d] we became intrigued by developing a domino C–H addition reaction guided by synthetically useful coordinating groups. Herein, we report a mild rhodium(III)‐catalyzed C–H alkylation/aldol Domino reaction manifold with aryl oximes and pyrazoles under neutral reaction conditions (Scheme c).…”

“…The catalytic activation of otherwise inert C–H bonds has undergone explosive development in recent years, providing an expedient route for the conversion of abundant C–H bonds into the desired functional groups, Among them, transition‐metal‐catalyzed C–H alkylation has surfaced as a powerful tool for eco‐friendly C–C forming reaction due to its inherent step‐ and atom‐economy, as well as its environmentally‐benign fashion. Since Lewis/Smith as well as Murai highlighted the potential of ruthenium(0) catalysts for C–H/olefin addition, major advances in transition‐metal‐catalyzed C–H alkylation with C=C/C=X (X = O; N) bonds have been made on the basis of ruthenium(II), rhodium, cobalt, among others . Notable progress in alkenyl C–H bond or C(sp 3 )–H bond addition to α,β‐unsaturated acceptors was recently made by the aid of rhodium(III) catalyst.…”

Rhodium‐Catalyzed Annelation of Benzoic Acids with α,β‐Unsaturated Ketones with Cleavage of C−H, CO−OH, and C−C Bonds

“…For some heteroarenes, for example, thiophenes or furans, this reaction proceeds with concomitant decarboxylation . Hydroarylation pathways give rise to ortho ‐alkylated benzoates (Scheme b) . For maleimides, a decarboxylative variant is also known .…”

Divergent Syntheses of Spiroindanones and 2-Substituted 1-Indanones by Ruthenium-Catalyzed Tandem Coupling and Cyclization of Aromatic Acids with α,β-Unsaturated Ketones

“…In this context, coupling of aromatic acids and alkynes/alkenes represents a particularly useful contribution to isocoumarins/3,4-dihydroisocoumarins synthesis, while the reactions of benzoic acids with acrylates exclusively delivered phthalide derivatives through the sequence of ortho -olefination of carboxyl and subsequent Michael addition (Scheme , a) . Recently, we reported a ruthenium-catalyzed conjugate addition of C–H bonds to α,β-unsaturated ketones directed by a carboxyl (Scheme , b) . Inspired by this encouraging work, we envisioned that the enols formed via tautomeric transformation of ketones may attack the CO bond of carboxyls, leading to the formation of 1-indanones via a Dieckmann condensation reaction.…”