Unusual Reactivity of Isoquinolinones Generated by Silver-Catalyzed Cycloisomerizations of Imines Derived from ortho-Alkynylsalicylaldehydes

Abstract

8-Isoquinolinones derived from a silver-catalyzed cycloisomerization of in situ formed ortho-alkynylsalicylaldimines react with 1 equiv of acetylenedicarboxylate derivatives to give pyrano[2,3,4-ij]isoquinolines through a [4 + 2]-cycloaddition reaction. When 2 equiv of the alkyne are used, structurally complex benzo[de]chromenes are obtained through an intricate cascade process comprising unusual formal [4 + 2]-and [2 + 2]cycloadditions followed by several ring-opening and ring-closing processes. ■ RESULTS AND DISCUSSION Considering that imines 1 are easily formed from the corresponding aldehyde through a condensation reaction with appropriate amines, we started our investigation by studying the multicomponent reaction of ortho-alkynylsalicy-t1 laldehyde derivatives 3, anilines 4, and dimethyl acetylenedi-49 t1 carboxylate 5a (Table 1). Thus, when a 1:1:1 mixture of these 50 three reagents was dissolved in tetrahydrofuran in the presence 51 of 5 mol % of silver triflate and was heated at reflux for 3 h, it 52 was possible to gain the desired multicomponent coupling 53 products 6 in moderate yields (Table 1). As shown, different 54 substitution was allowed at the aldehyde 3 and aniline 4 but, 55 unfortunately, the reaction did not proceed with other alkynes 56 lacking the two electron-withdrawing groups. Structural

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

“…Using the developed reaction conditions wide range of isoquinoline derivatives were synthesized with good functional group tolerance (Scheme 215). [227] The present protocol represents a rare entry to pyrano fused isoquinolines which was later modified by Fernández et al [60b] . using Ag‐catalysis.…”

“…Under these reaction conditions pyrano[2,3,4‐ ij ]isoquinoline were isolated up to of 65% yields (Scheme 21). [60b] …”

Six-membered ring systems: with O and/or S atoms

“…Cascade annulative coupling reaction of 3,5-diarylisoxazoles with three equivalents of internal alkynes occurs in the presence of rhodium complex 13 and copper(II) acetate in 1,4-dioxane to deliver benzo[de]chromenes-bearing isoquinoline units (Scheme 20) (19S258). Isoquinolin-8-ones, formed via silver(I)-catalyzed cycloisomerization of o-alkynylsalicylaldimines formed in situ, react with one equivalent of acetylenedicarboxylates to provide pyridino[2,3-de]chromenes, while when reacted with two equivalents of the alkyne, complex benzo[de]chromene-type compounds are obtained (19JOC3184).…”

AgNTf2-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

“…As a powerful π-activator, silver can promote various reactions of alkynes in high efficiencies [3–8]. Generally speaking, the proceeding of these reactions involves the activation of alkyne bond by coordination of [Ag] and then the attacking of nucleophilic partners, followed by a protodemetalation step to form the alkene motif (Scheme 1, path a) [9–11]. However, the formation of a silver carbene intermediate, which could be generated usually from relevant diazo precursors [12–14], appears to be an unusual event in silver-mediated reactions of alkynes (Scheme 1, path b).…”