Synthesis of N-alkyl and N-aryl isoquinolones and derivatives via Pd-catalysed C–H activation and cyclization reactions

Abstract

Relatively less expensive Pd-catalysed oxidative coupling reactions for the preparation of N-alkyl and N-aryl substituted isoquinolones and their derivatives have been developed. A broad reaction scope has been demonstrated. In addition, studies of the reaction additives and mechanistic insights, as well as KIE studies for a better understanding of the reaction pathway, have been discussed.

Efficient Synthesis of Hydroxyl Isoindolones by a Pd‐Mediated CH Activation/Annulation Reaction

“…3) C À H oxidative addition: The deuterium-labeled competition reaction has revealed that the C À H bond cleavage is the turnover limiting step as we have observed a kinetic isotope effect (KIE) value of 3.0:1 (Scheme 6), which is different from the Rh-catalyzed transformation for which Kim has reported a KIE value of 1:1 for his hydroxyl isoindolone synthesis. In these cases of hydroxyl isoindolone synthesis, Pd-catalyzed C À H activation is irreversible, [16] whilst Rh-catalysis is reversible, [12,17] with the low KIE value. As we have observed the formation of amide 5 (was isolated in 21 % yield) during our reaction solvent screening (see the Supporting Information, Table S1, entry 1).…”

Cobalt(III)‐Catalyzed C−H Activation: Counter Anion Triggered Desilylative Direct ortho‐Vinylation of Secondary Benzamides

“…In these alkenylation reactions, use of alkynes as coupling partners offers a major advantage as alkynes can undergo a redox neutral process which does not require external oxidant. [4a] The amide is a weak coordinating group, which has been well explored as a directing group in CÀH activation reactions such as alkenylation, [2,3] annulations, [5] etc. [4] Generally, terminal alkynes are less compatible with many of the CÀH activation reactions.…”

“…[4] Generally, terminal alkynes are less compatible with many of the CÀH activation reactions. [5] However, under similar reaction conditions, it is challenging to terminate the reaction without cyclization to yield exclusively the olefin derivatives. [4a] The amide is a weak coordinating group, which has been well explored as a directing group in CÀH activation reactions such as alkenylation, [2,3] annulations, [5] etc.…”

ChemInform Abstract: Directed meta‐Selective Bromination of Arenes with Ruthenium Catalysts.

“…To explore the reaction pathway,wehave also carried out H/D exchange experiments.I nterestingly,w hen 3a-D 2 was treated with NBS under our standard conditions,u nlike Ackermann and Frosts results, [4] we did not observe any deuterium loss during the reaction, which is similar to the observations we had during our Pd-catalyzed reactions. [22] (Scheme 4) Surprisingly,w hen the cross-over H/D exchange experiment was carried out, we found that the Dh as shifted from 3a-D 5 to the structurally similar aryl pyridine 3d,which showed that deuterium was scrambling within the two molecules.T hese results indicate that during the C À H activation processes,t he Hi sv ery likely to be appearing as apossible ligand on the Ru metal center during the process up until the reductive elimination to give the Hb ack to the molecule.F urthermore,i ti sp ossible that the aryl pyridine was acting as acrucial ligand;aplausible intermediate 17 may form during the transformation, which could explain the H/D cross-over results.…”