A Novel Three-Component Reaction for the Diastereoselective Synthesis of 2H-Pyrimido[2,1-a]isoquinolines via 1,4-Dipolar Cycloaddition

Abstract

[reaction: see text] The 1,4-dipole derived from isoquinoline and DMAD has been shown to react readily with N-tosylimines resulting in the diastereoselective synthesis of 2H-pyrimido[2,1-a]isoquinoline derivatives.

Synthesis and solid-state supramolecular chemistry of a series of pyridinium-derived zwitterions

“…1,2 These reactions proceed via addition of the N-heterocycle to DMAD to form a dipolar intermediate, followed by subsequent reaction with a second equivalent of DMAD to produce a variety of heterocyclic compounds such as substituted quinolizones. Reactions including Huisgen cycloadditions, 6,[11][12][13][14] Morita-Baylis-Hillman type reactions (MBH), 15, 16 Diels-Alder reactions 3,17 and multi-component reactions [7][8][9][10] have all been known to employ these acetylene-derived zwitterions. In more recent research, the zwitterionic intermediate is most often produced en route to more complex heterocyclic compounds in multi-component reactions (MCR).…”

Design of Multi‐Component Reactions: From Libraries of Compounds to Libraries of Reactions

“…In the sixties Huisgen et al had trapped zwitter-ionic intermediate 4 with some reagents such as phenylisocyanate, diethyl mesoxalate, and dimethyl azodicarboxylate [45]. Subsequently, Nair et al have been expanding this chemistry for the last 5 years, which is reflected in the discovery of several new MCRs (Scheme 6) [46]. In this way, a new family of MCRs was developed on the basis of only one two-component reaction.…”

“…The algorithm based on the reorganization of an existing reaction (oligomerizations, MCRs) has obvious advantages over an empirical design, in which successful combinations of sub-reactions are created by a lucky chance. It has been discussed above that a reorganization of appropriate reactions was used for the creation of the new MCRs [37,46,47]. This approach can be improved with the simultaneous variations of several parameters in a multi-component system.…”

Isoquinoline-catalyzed reaction between 4-hydroxycoumarin or 4-hydroxy-6-methylpyran-1-one and dialkyl acetylene dicarboxylates: synthesis of coumarin and pyranopyrane derivatives

“…[5][6][7][8][9][10][11] These zwitterions intermediate can be trapped with a variety of electrophiles and proton donors, which is a novel protocol for the synthesis of heterocyclic compounds. [5][6][7][8][9][10][11][12][13] Trapping of the zwitterion formed by the addition of isoquinoline to dimethyl acetylenedicarboxylate (DMAD) with electrophiles such as isocyanates, 14 N-tosylimines, 15 quinines 16 and electrophilic styrenes, 17 has been recently used for the synthesis of different isoquinoline-fuzed heterocyclic systems. Reaction of electron-deficient acetylene esters with isoquinoline or quinoline has been also studied in the presence of organic acidic compounds.…”