Palladium‐Nanoparticles‐Catalyzed Oxidative Annulation of Benzamides with Alkynes for the Synthesis of Isoquinolones

Abstract

A novel method to synthesize isoquinolones via oxidative annulation of N‐alkoxy benzamides and alkynes using binaphthyl‐stabilized palladium nanoparticles (Pd‐BNP) as catalyst has been developed. This methodology affords various isoquinolone derivatives in good to excellent yields with high regioselectivities in the presence of air as oxidant. N‐Methoxybenzothioamide was also found to undergo oxidative annulation with alkyne successfully and provided a sulfur analogue of isoquinolones in moderate yields. The Pd‐BNP catalyst was easily recovered and reused up to four times without any apparent agglomeration.magnified image

Isoquinolone Syntheses by Annulation Protocols

“…The formation of N-alkyl-, aryl-, or alkoxy-substituted isoquinolones by the oxidative [4 + 2] cyclocondensation of secondary benzamides with internal alkynes with selective cleavages of C-H and N-H bonds has been achieved using other transition-metal catalyst systems, such as nickel [61,62], iron [63] complexes as catalysts, and heterogeneous catalyst of palladium-nanoparticles [64], Pd/C [65,66].…”

N‐Methoxybenzamide: A Versatile Directing Group for Palladium‐, Rhodium‐ and Ruthenium‐Catalyzed C−H Bond Activations

“…This methodology affords various isoquinolone conjugates in good yield with high regioselectivity using air as an oxidant. Some representative examples are shown in Scheme …”

Isoquinolone Synthesis via Zn(OTf)2-Catalyzed Aerobic Cyclocondensation of 2-(1-Alkynyl)-benzaldehydes with Arylamines

“…Alkyne annulation is an important and efficient method for the synthesis of various heterocyclic compounds with high atom utilization [1][2][3][4][5][6][7][8][9][10]. Isoquinolones are one of the interesting and important nitrogen-heterocyclic compounds with versatile biological and physiological activities [11,12], and over the past decades, transition-metal-catalyzed isoquinolone formation through intermolecular annulation with the use of alkyne as one of the reaction partners has been well developed [13][14][15][16][17][18][19][20][21][22][23][24][25][26]. Among the different protocols for achieving this goal, the synthetic strategies starting from 2-(1-alkynyl)benzaldehydes are the most interesting due to their high atom utilization [15,21] (Scheme 1).…”