Alkali‐Metal Promoted Chemo‐ and Regioselective Cycloisomerization Reactions to (Z)‐3‐Alkylideneisoindolin‐1‐ones: Unusual Positive Role of H₂O

Abstract

An alkali‐metal promoted cycloisomerization reaction of 2‐alkynylbenzamides is described for the synthesis of useful (Z)‐3‐alkylideneisoindolin‐1‐one derivatives in modest to good yields and excellent chemo‐ and regioselectivity. Superstoichiometric amounts of water was found to be crucial for this reaction, and no transition‐metal salts are necessary. This synthetically green protocol proceeds efficiently with 100% atom economy and tolerates a diverse number of functional groups.

Tin(II) triflate Catalysed Synthesis of 3‐Methyleneisoindolin‐1‐ones

“…Tan et al . have developed a Na 2 CO 3 promoted cycloisomerization of 2‐alkynylbenzamides synthesis of useful ( Z )‐3‐alkylideneisoindolin‐1‐one derivatives . Although several elegant approaches have been developed for the synthesis of 3‐methylene isoindolinones, there is still a prerequisite to establish a method which overcomes the shortcomings associated with previously reported methods such as fewer substrate scope, low functional group tolerance, lack of generality and harsh reaction conditions.…”

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.…”

Base-Promoted 5-exo-dig Cyclization of o-Alkynylamides or 2-En-4-ynamides with CO2 toward Fully Substituted Acrylates

“…For example, Mehta and Qiu independently reported the halo-amination of 2-(1-alkynyl)­benzamides toward a series of halo-containing heteroisoindolin-1-ones . Alternatively, intramolecular nucleophilic addition of nitrogen or oxygen anions to 2-ethynylarenes to generate vinyl anions, followed by protonation, could generate a series of alkylidene­isoindolinone products . In continuation of our efforts in CO 2 fixation, we envisioned that the in situ generated vinyl anions could undergo nucleophilic addition of CO 2 to furnish 2-(3-oxoisoindolin-1-ylidene)­acetic acids bearing the tetrasubstituted vinyl fragments.…”

“…Based on the above results and some relative studies, − a mechanism has been proposed in Scheme . First, with the assistance of base, compound 1 is deprotonated into amide anion A .…”