Oxidation and hydrogenation of benzo[g]isoquinolines

The oxidation of methyl-substituted (in the pyridine and benzene rings) benzo[g]isoquinolines to substituted 2-azaanthraquinones was realized. It was established that the pyridine ring is partially reduced to give 1,2,3,4-tetrahydrobenzo[g]isoquinolines in the hydrogenation of benzo[g]isoquinolines in the presence of rhenium heptasulfide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 517–519, April, 1979.     

CuI-catalyzed domino reactions for the synthesis of benzoxazine-fused isoquinolines under microwave irradiation

A small library of benzoxazine-fused isoquinolines has been synthesized under microwave irradiation (MW) via CuI-catalyzed domino reactions of o-alkynyl aldehydes and amines having embedded nucleophiles. This strategy offers a operationally simple, environmentally acceptable route to synthesize benzoxazine-fused isoquinolines in moderate to good yields. All new compounds were characterized by ¹H NMR, ¹³C NMR, infrared, and high-resolution mass spectrometry techniques.     

First total syntheses of the 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines annoretine and litebamine

We describe here the first total synthesis of the two natural 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines, annoretine and litebamine, from [2-(2-styrylphenyl)ethyl]methylcarbamic acid ethyl esters. The key steps were the Bischler-Napieralski cyclization to form the isoquinoline unit and photocyclization of the resulting 2-methyl-5-styryl-3,4-dihydro-2H-isoquinolin-1-ones to 2-methyl-3,4-dihydro-2H-naphtho[2,1-f]isoquinolin-1-ones.     

Enantioselective iridium-catalyzed hydrogenation of 3,4-disubstituted isoquinolines

Reining in the outliers: An efficient approach for enantioselective hydrogenation of 3,4-disubstituted isoquinolines was successfully developed. When isoquinolines are treated with [Ir(cod)Cl](2) /(R)-synphos in the presence of 1-bromo-3-chloro-5,5-dimethyl-hydantoin (BCDMH), the chiral 3,4-disubstituted tetrahydroisoquinoline derivatives are obtained with ee?values as high as 96?% (see scheme; cod=1,5-cyclooctadiene).     

A convenient procedure for the synthesis of fused fluoro isoquinolines

A base-promoted conversion of ortho-trifluoromethyl benzyl derivatives of NH-heterocycles into a respective fluorinated isoquinolines (38-57% isolated yields) is reported. The reaction is general for the benzylated derivatives of the electron-rich NH-heterocycles and the respective derivatives of pyrazole. The outcome of the reaction could be explained by an intermediate formation of a highly reactive quinone methide species.     

Efficient syntheses of imidazolo[1,2-a]pyridines and -[2, 1-a]isoquinolines

2-Aminopyridines 1a-c and 1-aminoisoquinoline with 1-chloromethylbenzotriazole give 2-amino-1-[alpha-benzotriazol-1-ylmethyl]pyridinium chlorides 2a-c and 1-amino-2-(alpha-benzotriazol-1-ylmethyl)isoquinolinium++ + chloride 12, respectively. Compounds 2a-c and 12 react with aryl aldehydes 3a-h to afford imidazolo[1,2-a]pyridines 7a-k and imidazolo[2, 1-a]isoquinolines 13a,b in good yields.     

Copper-catalyzed tandem synthesis of [1,2,3]triazolo[5,1-a]isoquinolines and their transformation to 1,3-disubstituted isoquinolines

2-Azido-3-(2-iodophenyl)acrylates react with terminal alkynes in the presence of a copper(II) catalyst without ligands to give a wide range of [1,2,3]triazolo[5,1-a]isoquinolines in good yields. These compounds favor expulsion of N₂ in refluxed acetic acid to form 1,3-disubstituted isoquinolines. The procedure is simple, economical, and efficient.     

A new route for isoquinolines catalyzed by palladium

3-Bromopyridine-4-carbaldehyde is tethered with suitably electron withdrawing group substituted alkenes via Heck coupling followed by aldol reaction in dioxane at 150 °C under a catalytic system of Pd(OAc)₂/PPh₃/NaOAc to afford the corresponding isoquinolines in good yields.     

Synthesis of substituted isoquinolines by electrophilic cyclization of iminoalkynes

The tert-butylimines of o-(1-alkynyl)benzaldehydes and analogous pyridinecarbaldehydes have been cyclized under very mild reaction conditions in the presence of I(2), ICl, PhSeCl, PhSCl, and p-O(2)NC(6)H(4)SCl to give the corresponding halogen-, selenium-, and sulfur-containing disubstituted isoquinolines and naphthyridines, respectively. This methodology accommodates a variety of iminoalkynes and affords the anticipated heterocycles in moderate to excellent yields. Monosubstituted isoquinolines and naphthyridines have been synthesized by the metal-catalyzed ring closure of these same iminoalkynes. The silver-catalyzed ring closure is highly effective in cyclizing aryl-, alkenyl-, and alkyl-substituted iminoalkynes at 50 degrees C.     

Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines

The development of the first asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl]₂ and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans-tetrahydroisoquinolines in good yield with high levels of enantioselectivity. Directing group studies demonstrate that the hydroxymethyl functionality at the C1 position is critical for hydrogenation to favor the trans-diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable trans-selectivity.

trans-Selective asymmetric hydrogenation of 1,3-disubstituted isoquinolines.     

Synthesis of substituted isoquinolines via Pd-catalyzed cross-coupling approaches

Palladium complexes incorporating ligands based on a 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phosphaadamantanyl scaffold were used to catalyze the arylation of ethyl cyanoacetate, malononitrile, and various ketones. The products from these reactions can be elaborated to substituted β-arylethylamines and used in microwave-assisted Pictet-Spengler reactions. The protocol developed is suitable for the synthesis of libraries of substituted isoquinolines.     

Highly efficient synthesis of isoquinolines via nickel-catalyzed annulation of 2-iodobenzaldimines with alkynes: evidence for dual pathways of alkyne insertion

[reaction: see text] A wide range of substituted isoquinolines were synthesized via a highly efficient nickel-catalyzed annulation of the tert-butyl imines of 2-iodobenzaldehydes and various alkynes; examination of the regiochemistry of isoquinolines synthesized indicates that there are two different alkyne insertion pathways for the catalytic reactions.     

One-pot two-step tandem reactions for selective synthesis of pyrrolo[2,1-a]isoquinolines and dihydro-, tetrahydro-derivatives

A sequential one-pot two-step tandem reaction for selective and efficient synthesis of pyrrolo[2,1-a]isoquinoline and its dihydro- and tetrahydro-derivatives has been developed. The tandem reactions of isoquinoline, α-halogenated methylene compounds, aromatic aldehydes, and cyanoacetamide firstly give tetrahydropyrrolo[2,1-a]isoquinolines as main products. The corresponding pyrrolo[2,1-a]isoquinolines and dihydropyrrolo[2,1-a]isoquinolines can be obtained directly by controlling oxidation with DDQ. The mechanism of this tandem reaction involved the 1,3-dipolar cycloaddition of isoquinolinium ylide as the key step. A unique elimination of the amido group preferring to the cyano group has been observed.     

Gold(III) chloride-catalyzed three-component reaction: a facile synthesis of alkynyl derivatives of 1,2-dihydroquinolines and isoquinolines

Gold(III) chloride is found to be an effective catalyst for the addition of alkynes on activated quinoline/isoquinolines to produce a series of alkynyl-substituted 1,2-dihydroquinolines and isoquinolines in a single-step operation. The easy availability of starting materials, convenient synthetic procedure, operational simplicity, and high regioselectivity makes this strategy very useful for the preparation of enyne derivatives of aza-aromatic compounds.     

Synthesis of isoquinolines and naphthyridines by electrophilic ring closure of iminoalkynes

Substituted isoquinolines and naphthyridines have been prepared in good to excellent yields by the reaction of iminoalkynes with a variety of electrophiles under mild reaction conditions. Reaction: see text.     

Photochemical synthesis of benz[h]isoquinolines

The synthesis of benz[h]isoquinolines has been achieved using a highly convergent photochemical method. The approach presented provides ready access to biologically active compounds and building blocks not readily available through other methods.     

Cyclopalladated imines in synthesis 2 : a new synthesis of isoquinolines

Reaction of cyclopalladated arylimines with acrylonitrile, followed by thermolysis gives isoquinolines by an electrocyclic ring forming process and a subsequent eliminative aromatisation step.     

Current approaches to the synthesis of pyrrolo[2,1-a]isoquinolines (microreview)

Chemistry of Heterocyclic Compounds - This microreview considers methods for the synthesis of pyrrolo[2,1-a]isoquinolines, published from year 2014 until 2018.     

The synthesis of indolo- and pyrrolo[2,1-a]isoquinolines

The synthesis of fused isoquinolines from N-benzyl protected indoles and pyrroles is described. For example, treatment of t-butyl-2-(2-formyl-3,4-dihydro-1-naphthalenyl)-3-methyl-1H-indole-1-carboxylate with KOBu^t in DMF provided 14-methyl-8-phenylbenzo[h]indolo[2,1-a]isoquinoline in good yield. Analogous N-benzylpyrrole precursors could similarly be cyclized to give pyrrolo[2,1-a]isoquinolines.     

Novel synthesis of isoquinolines using isobenzofuran-nitrile Diels-Alder reactions

[reaction: see text] The synthesis of isoquinolines through coupling of 2-alkynylbenzaldehyde derivatives with beta-cyanocarbene complexes has been examined. The reaction involves formation of an isobenzofuran followed by intramolecular Diels-Alder reaction with the nitrile, a process with limited precedent. The unique success of this process in this system has been attributed to deoxygenation of the initial adduct to form the isoquinoline ring system.