Copper‐Catalyzed Stereoselective Domino Synthesis of (Z)‐3‐Methyleneisoindolin‐1‐one

Abstract

Stereoselective synthesis of (Z)‐3‐methyleneisoindolin‐1‐one has been achieved via intermolecular coupling of terminal alkynes and 2‐halobenzamide using a square pyramidal [Cu(DMAP)4I]I complex as catalyst within a short time. This cross coupling reaction features the use of unprotected 2‐halobenzamide to achieve excellent yield of corresponding isoindolin‐1‐ones with free NH group. The catalyst was also found to be equally active for N‐substituted 2‐halobenzamide, phenyl propiolic acids and silylated alkyne.

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

“…In 2018, Phukandescribed ad omino reactiono fu nprotected2 -halobenzamide andt erminal alkynes using as quare pyramidal [Cu(DMAP) 4 I]I complex as ac atalyst to yield the corresponding( Z)-3-methyleneisoindolinones with free NH group via cross-coupling reaction followed by 5-exo-dig cycloisomerization. [132] This methodology allows the use of ab road range of terminala lkynes. The authors also described the extension of this methodology to phenyl propiolic acid derivatives and silylated alkynes with N-protectedbromobenzamides to afford the products in good yield.…”

“…[127] As eries of Cu-catalyzed domino synthetic protocols for the synthesis of 3-methyleneisoindolinones startingf rom 2-halobenzamides and alkynes have been reported (Scheme 60). [128][129][130][131][132] In 2013, Zhang and co-workers reporteda stereoselective microwave assisted synthesis of (Z)-3-methyleneisoindolinone derivativesf rom N-substituted-2-bromobenz-amides and arylacetylenes using aC u(OAc) 2 •H 2 O/DBU catalyst. [128] Later,aCu-catalyzedd ecarboxylative cross-couplingo f N-substituted-2-halobenzamidesw ith aryl alkynyl carboxylic acids, followedb y5 -exo-dig heteroannulation, was reported by the Patel.…”

“…N‐Unprotected iodobenzamides were well tolerated, affording the substituted isoindolinones in high yield. In 2018, Phukan described a domino reaction of unprotected 2‐halobenzamide and terminal alkynes using a square pyramidal [Cu(DMAP) 4 I]I complex as a catalyst to yield the corresponding ( Z )‐3‐methyleneisoindolinones with free NH group via cross‐coupling reaction followed by 5‐ exo – dig cycloisomerization [132] . This methodology allows the use of a broad range of terminal alkynes.…”

Phosphazene Superbase-Mediated Regio- and Stereoselective Iodoaminocyclization of 2-(1-Alkynyl)benzamides for the Synthesis of Isoindolin-1-ones

“…Due to the medicinally privileged nature of the isoindolinone scaffold, several synthetic organic as well as medicinal researchers have reported various interesting approaches for the synthesis of the isoindolin-1-ones. − Also, various alkyne annulation reactions, such as metal-catalyzed annulations, − base mediated annulations, − aza-conjugate additions, , etc., have been extensively used for synthesizing a variety of isoindolinone derivatives.…”

Palladium/Copper-Catalyzed Denitrogenative Alkylidenation and ortho-Alkynylation Reaction of 1,2,3-Benzotriazin-4(3H)-ones

“…Particularly, 3-arylmethylene isoindolin-1-one has been recognized as a vital scaffold not only because of its remarkable biological activities but also as a useful intermediate for the synthesis of various alkaloids . The literature report reveals that transition-metal-catalyzed tandem alkynylation/cyclization reaction was perhaps one of the most frequently utilized strategies to synthesize 3-arylmethylene isoindolin-1-one derivatives in a highly stereoselective manner . In 2000, Kundu and his co-workers reported a palladium-catalyzed stereoselective synthesis of ( Z )-3-aryl­(alkyl)­idene isoindolin-1-ones using ortho -halo benzamides and terminal alkynes as substrates .…”