An Environmentally Friendly Synthetic Method of 1,2-Dihydroisoquinoline Frameworks via Three-Component Reaction with o-Alkynylbenzaldehydes, Primary Amines, and Pronucleophiles

Abstract

Three-component reactions with ortho-alkynylbenzaldehydes, primary amines, and pronucleophiles (Nu-H), such as CHCl3, proceeded to give 1,2-dihydroisoquinoline derivatives in good to high yields in the absence of any catalysts under mild reaction conditions.

Computational Analysis on the Dual Reactivity of Conjugated “Ene-Ene-Yne” Systems

“…Treatment of 26 with pronucleophiles (Nu-H) both with and without catalysts has resulted in pericyclic reactivity. [35][36][37][38] In situ generation of the imine via the condensation of 14 and aniline in the presence of CHCl 3 as the pronucleophile afforded a 91% yield of 28 (Nu ) CCl 3 ) after 48 h in the presence of only molecular sieves. 35 The cyclization can be catalyzed by Ag, Au, or In salts, which activate the alkyne and stabilize the resulting zwitterions.…”

Tandem imination/annulation of γ- and δ-ketoalkynes in the presence of ammonia/amines

“…Copper(I)-catalyzed domino fourcomponent coupling-cyclization using 2-ethynylbenzaldehydes, paraformaldehyde, secondary amine, and t-BuNH 2 in DMF leads to direct and efficient formation of 3-(aminomethyl)isoquinolines in good to high yields [24]. Moreover, a concise synthesis of 1,2-dihydroisoquinolines was established via three-component reactions of 2-alkynylbenzaldehydes, amines and various nucleophiles or pronucleophiles in the absence of a catalyst [25] or in the presence of carbophilic Lewis acid catalysts such as AgOTf [26], In(OTf) 3 , or AuClPPh 3 /AgNTf 2 [27] and Cu(I) or Pd(II) salts [28] CuSO 3 / C 12 H 25 SO 3 Na [29] and Mg(ClO 4 ) 2 /Cu(OTf) 2 [30] (Scheme 9).…”

Rhodium(II)‐Catalyzed and Thermally Induced Intramolecular Migration of N‐Sulfonyl‐1,2,3‐triazoles: New Approaches to 1,2‐Dihydroisoquinolines and 1‐Indanones

“…[4] Variations of 6-endo-dig cyclizationofp reformed or in situ-generated ortho-alkynylaryl aldimines and other strategies including the Larock dihydroisoquinolines ynthesis have been developed for the seconda pproach. [5,6] On the other hand, intramolecular Friedel-Crafts reaction [7] and Nazarov cyclization [8] are frequently used fort he synthesis of indanones. Moreover, severalo ther methods includingR h I -catalyzed isomerization have also been developed.…”