Isoquinoline scaffold

Distinct functional groups with acidic hydrogens can also promote these transformations. For instance, benzoylnitromethane (208) or ethyl bromopyruvate (206) react with isoquinoline (6) and acetylenedicarboxylates via the same dipolar mechanism to generate a pyrrolo[2,l-a]isoquinoline scaffold. However, in these cases, after closure of the 5-membered ring, a double-bond formation via dehydrogenation or nitrous acid elimination yields the fully aromatic ring systems 207 and 209 (Scheme 28) [82, 183]. 

A one-pot 4-component Ugi reaction and Pd-catalyzed intramolecular Heck reaction was developed for the synthesis of two types of isoquinoline scaffolds illustrated in Scheme 37. In this approach an amine, an aldehyde, a carboxylic acid, and an isocyanide react to provide a diversity of a-acylamino amides 81 and 82 which undergo a Pd-catalyzed intramolecular Heck and double bond isomerization reaction to generate the isoquinoline products 83 and 84... 

The isoquinoline scaffold can be found in a wide variety of biologically active natural and synthetic compounds [31-38]. Particularly, isoquinolines having an additional nitrogen atom tethered by one carbon at the 3-position, including such isoquinoline alkaloids as quinocarcine [39—42], ecteinascidins 597 and 583 [43, 44], and 3-(2-pyridinyl)isoquinolines [45—47] constitute an important class of compounds with important biological activities (Fig. 2). 

Some results of previous studies on perfluoroalkylated isoquinolines were recently summarized by Petrov [7]. This chapter focuses on the syntheses, properties, and applications of ring-fluorinated isoquinolines (limited to compounds that retain the aromatic isoquinoline scaffold), starting from the historical background of earlier studies. Additionally, an overview of the syntheses of pyridine-ring-trifluoromethylated derivatives is also given. 

The deoxygenative methodology allows incorporating azole residues into azaaromatic scaffolds. Pyridine, quinoline, isoquinoline, azaindole, and pyrimidine N-oxides were converted to their a-triazole and a-diazole derivatives by treatment with the corresponding p-toluenesulfonylazoles and Hunig s base at elevated temperatures [119] or by treatment with sulfuryldiimidazole in nonpolar solvents at elevated temperatures [120]. 

N-Heterocychc scaffolds such as indolo[2,l-ii]isoquinohnes, pyrrolo[2,l-a] isoquinolines, and indolo/pyrrolo[2,l [l,6]naphthyridines are abundant in natural products and biologically active scaffolds, semiconductors, and luminescent materials. Verma and coworkers have described a rapid high yield synthesis of medicinally important indolo-, pyrrolo[2,l [l,6]naph-thyridines, and isoquinolines 89 via a copper-catalyzed tandem approach (2014TL(55)4724). This microwave-assisted protocol uses hydroxymethyl... 

This protocol allows the formation of two heterocyclic rings in a one-pot reaction through the electrophilic aimulation. Most importantly, these isoquinoline-fused benzimidazoles with a halo group are important scaffolds for the introduction of various functional groups and significant for dmg discovery. 

In this chapter, we try to highlight the various aspects, issues, and applications of this reaction in the syntheses of isoquinoline derivatives. The isoguinoline nucleus is often found as a scaffold in the alkaloid families with interesting biological and physiological activities. 

Pakomwit S, Krasivan M (2014) Convenient access to novel functionahzed pyrazino[l,2-h] isoquinohn-6-one and diazepino[l,2-h]isoquinolin-7-one scaffolds via the Cushman multi-component reaction followed by post-condensation. Tetrahedron Lett 55(14) 2299-2303. doi 10.1016/j.tetlet.2014.02.099... 

Olsen, C.A., Parera, N Alberido, F and Alvarez, M. (2005) 5,6-Dihydropyrrolo[2,l-b]isoquinolines as scaffolds for synthesis of lamellarin analogues. Tetrahedron Lett., 46,2041-2044. 

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