Synthesis Of Isoquinolines Research Articles

ChemInform Abstract: Synthesis of Isoquinolines via Rh(III)‐Catalyzed C—H Activation Using Hydrazone as a New Oxidizing Directing Group.

AbstractAn efficient method for the synthesis of highly substituted isoquinolines by a Rh(III)‐catalyzed hydrazone directed ortho C—H bond activation and annulation without an external oxidant is described.

ChemInform Abstract: Synthesis of Triazolo Isoquinolines and Isochromenes from 2‐Alkynylbenzaldehyde via Domino Reactions under Transition‐Metal‐Free Conditions.

We describe two simple straightforward syntheses of triazolo isoquinolines (3) and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2-(alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6-endo cyclization domino sequence. In yet another strategy, the synthon 1 was condensed with nitromethane followed by electrophilic iodo cyclization of the resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene derivatives. The salient feature of the above two strategies involves formation of the corresponding heterocycles under metal-free conditions in good yields.

Efficient Synthesis of Isoquinolines via Rh(III)-Catalyzed Oxidative Annu­lation of Picolinamides with Alkynes

An efficient synthesis of isoquinolines via Rh(III)-catalyzed oxidative annulation of picolinamides with alkynes using Cu(OAc)2 as an oxidant has been developed. The scope of the reaction was studied with a selection of various picolinamides and alkynes, and the desired isoquinolines were obtained in good to excellent yields.

Practical Synthesis of A Macrocyclic HCV Protease Inhibitor: A High-Yielding Macrolactam Formation

A practical synthesis of a macrocyclic HCV protease inhibitor, MK-1220, is described. The key features are a new synthesis of the trisubstituted isoquinoline, Sonogashira fragment coupling, and a high-yielding, 18-membered macrolactam formation.

ChemInform Abstract: Recent Development of Broensted Acid‐Promoted Synthesis of Quinoline, Isoquinoline and Carboline Derivatives

AbstractReview: 63 refs.

ChemInform Abstract: Rh(III)‐Catalyzed Synthesis of Multisubstituted Isoquinoline and Pyridine N‐Oxides from Oximes and Diazo Compounds.

AbstractThis is the first Rh‐catalyzed method for the synthesis of isoquinoline and pyridine N‐oxides with an arylic or vinylic C—H activation as cyclization‐initiating step.

Rhodium(III)‐Catalyzed CH Activation and Indole Synthesis With Hydrazone as an Auto‐Formed and Auto‐Cleavable Directing Group

An efficient, practical, and external-oxidant-free indole synthesis from readily available aryl hydrazines was developed, by using hydrazone as a directing group for Rh(III)-catalyzed C-H activation and alkyne annulation. The hydrazone group was formed by in situ condensation of hydrazines and C=O source, whereas its N-N bond was served as an internal oxidant, for which we termed it as an auto-formed and auto-cleavable directing group (DG(auto)). This method needs no step for pre-installation and post-cleavage of the directing group, making it a quite easily scalable approach to access unprotected indoles with high step economy. The DG(auto) strategy was also applicable for isoquinoline synthesis. In addition, synthetic utilities of this chemistry for rapid assembly of π-extended nitrogen-doped polyheterocycles and bioactive molecules were demonstrated.

Rhodium-Catalyzed Synthesis of Isoquinolines and Indenes from Benzylidenehydrazones and Internal Alkynes

A new route is presented for the selective assembly of isoquinolines and indenes by rhodium-catalyzed tandem cyclization of benzylidenehydrazones with internal alkynes. This method involves the selective cleavage of the N-N bond and the C═N bonds and is dependent on the substituents of the benzylidenehydrazone.

Mn(II)/O2-promoted oxidative annulation of vinyl isocyanides with boronic acids: synthesis of multi-substituted isoquinolines.

An efficient manganese(II)/O2-promoted oxidative radical cascade reaction was developed for the modular synthesis of multi-substituted isoquinolines from easily accessible vinyl isocyanides and boronic acids.

Synthesis of isoquinolines via visible light-promoted insertion of vinyl isocyanides with diaryliodonium salts.

A synthetic strategy for multi-substituted isoquinoline derivatives has been developed using visible light-promoted vinyl isocyanide insertion with diaryliodonium salts at room temperature. The methodology presented here represents the first example of isoquinoline synthesis via somophilic isocyanide insertion.

Efficient synthesis of isoquinolines and pyridines via copper(i)-catalyzed multi-component reaction

A wide range of 3-substituted isoquinolines, steroidal pyridines, 5,6-dihydrobenzo[f]isoquinolines and 1,6-naphthyridine were synthesized in good yield via a ligand-free copper-catalyzed three-component reaction of β-halovinyl/aryl aldehyde, aromatic/aliphatic terminal alkyne and tert-butylamine/benzamidine in DMF under microwave irradiation. A catalyst-free reaction of ortho-alkynyl aryl/vinyl aldehydes with benzamidine under microwave irradiation also provided the 3-substituted isoquinoline and substituted pyridine derivatives in excellent yield.

One-pot synthesis of isoquinoline and related compounds via Cu-mediated tandem cross-coupling and cyclization

One-pot synthetic strategy has been developed to access isoquinolines and its analogs via Cu-mediated tandem cross-coupling and cyclization in good yields under mild reaction conditions. A mixture of suitably substituted α-bromoaldehyde, terminal alkyne, and aq NH3 in CuI/1,10-phenanathroline catalytic system afforded the 3-substituted isoquinoline regio-selectively in good to excellent yields.

ChemInform Abstract: Rhodium‐Catalyzed Oxidative Coupling of Aryl Hydrazones with Internal Alkynes: Efficient Synthesis of Multisubstituted Isoquinolines.

AbstractThe title reaction proceeds through a tandem C—C/C—N bond forming process and a N—N bond cleavage.

Recent development of Brensted acid-promoted synthesis of quinoline, isoquinoline and carboline derivatives

Recent development of Brensted acid-promoted synthesis of quinoline, isoquinoline and carboline derivatives

Synthesis of Isoquinolines via Rh(III)-Catalyzed C–H Activation Using Hydrazone as a New Oxidizing Directing Group

An efficient and mechanistically interesting method for the synthesis of highly substituted isoquinolines by a Rh(III)-catalyzed hydrazone directed ortho C-H bond activation and annulation without an external oxidant is described. This reaction is accomplished via a C-C and C-N bond formation along with N-N bond cleavage.

4+2] vs [3+2] Annulations in the Nickel‐ and Cobalt‐Catalyzed Reaction of ortho‐Haloimines with Alkynes: Differential Reactivity towards the Synthesis of Isoquinolines and Aminoindenes

AbstractMetal‐catalyzed annulation reactions to synthesize carbo‐ and heterocycles have been an attractive field of research for many years. The development of new cyclization reactions utilizing readily available less expensive metal catalyst is one of the important tasks. In this regard, this review summerizes and discusses about nickel‐ and cobalt‐catalyzed [4+2] and [3+2] annulation reactions of ortho‐halo substituted imines and alkynes. Nickel complexes under suitable reaction conditions underwent [4+2] annulation to form six‐membered isoquinoline (salts) derivatives. However, cobalt complexes afforded aminoindenes via [3+2] annulation reactions. Both reactions proceed through a five membered metallacycle. The regioselective insertion of alkyne containing keto or ester groups into the metallacycle further demonstrates the difference in selectivity of these metal complexes.

Synthesis of Triazolo Isoquinolines and Isochromenes from 2-Alkynylbenzaldehyde via Domino Reactions under Transition-Metal-Free Conditions

We describe two simple straightforward syntheses of triazolo isoquinolines (3) and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2-(alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6-endo cyclization domino sequence. In yet another strategy, the synthon 1 was condensed with nitromethane followed by electrophilic iodo cyclization of the resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene derivatives. The salient feature of the above two strategies involves formation of the corresponding heterocycles under metal-free conditions in good yields.

ChemInform Abstract: Primary Amines as Directing Groups in the Ru‐Catalyzed Synthesis of Isoquinolines, Benzoisoquinolines, and Thienopyridines.

AbstractThe synthesis of the title compounds proceeds via the directed C‐H activation of several different substituted amines, followed by dehydrogenative coupling with internal alkynes.

Rh(III)-Catalyzed Synthesis of Multisubstituted Isoquinoline and Pyridine N-Oxides from Oximes and Diazo Compounds

Multisubstituted isoquinoline and pyridine N-oxides have been prepared by Rh(III)-catalyzed cyclization of oximes and diazo compounds via aryl and vinylic C-H activation. This intermolecular annulation involving tandem C-H activation, cyclization, and condensation steps proceeds under mild conditions, obviates the need for oxidants, releases N2 and H2O as the byproducts, and displays a broad substituent scope.

Synthesis of Functional Heterocycles <i>via</i> Tandem Reaction

Tandem reactions for efficient construction of nitrogen-containing heterocycles were developed. One-pot platinum(II)-catalyzed synthesis of indoles and isoquinolines has been achieved via isocyanates, which were derived from a Hofmann-type rearrangement of 2-alkynylbenzamides and 2-alkynylbenzylamides using a hypervalent iodine reagent. As an extension of this approach, trans-2,3-dihydro-4-quinolones were synthesized via acid-catalyzed intermolecular [2+2]-cycloaddition of aldehydes and carbamates, which were formed from nucleophilic addition of alcohols to isocyanate intermediates. Direct, efficient syntheses of the benzimidazo[2,1-a]isoquinoline ring system have been achieved with 2-bromoarylaldehydes, terminal alkynes, and 1,2-phenylenediamines by a microwave-accelerated tandem process in which a Sonogashira coupling, 5-endo cyclization, oxidative aromatization, and 6-endo cyclization can be performed in a single synthetic operation.