Isoquinolinium Ylides Research Articles

Cascade Synthesis of Pyrrolo[1,2-a]quinolines and Pyrrolo[2,1-a]isoquinolines via Formal [3 + 2]-Cycloaddition of Push-Pull Nitro Heterocycles with Carbonyl-Stabilized Quinolinium/Isoquinolinium Ylides.

Various substituted pyrrolo[1,2-a]quinolines and pyrrolo[2,1-a]isoquinolines were synthesized in good to high yields by the Et3N-mediated reaction of push-pull 3-nitrobenzofurans or 1-Ts-/1-Ms-3-nitroindoles and precursors of carbonyl-stabilized quinolinium and isoquinolinium ylides as 1,3-dipole equivalents. These transformations proceed in a one-pot manner starting with the formal [3 + 2]-cycloaddition stage, which is accompanied by double dearomatization of both quinoline/isoquinoline and benzofuran/indole moieties, followed by ring-opening of cyclic intermediate formed and nitrous acid elimination sequence. [3 + 2]-Cycloadducts were isolated as the final products in cases of impossibility or difficulty of their enolization. The present protocol was successfully extended to 3-nitro-4H-chromene derivatives as push-pull dipolarophile component. Finally, using the method of competing reactions, the reactivity of the starting compounds was compared with each other.

Annulation Reactions of Isoquinolinium Ylides with Sulfamate-Derived Cyclic Imines toward Polycyclic 1,3-Benzoxazepine Heterocycles

AbstractA dearomatization-guided and (3+2) cycloaddition-triggered annulation reaction of in situ formed isoquinolinium ylides with sulfamate-derived cyclic imines is reported, offering a cogent synthesis of tetracyclic 1,3-benzoxazepine frameworks in high yields. The protocol features successive ring-forming and ring-breaking events in a cascade fashion and is also scalable.

Chiral π-Cu(ii)-catalyzed site-, exo/endo-, and enantioselective dearomative (3 + 2) cycloadditions of isoquinolinium ylides with enamides, dienamides, and a trienamide.

Here, we report a highly effective dearomative (3 + 2) cycloaddition reaction between isoquinolinium ylides and α,β-enamides, α,β-γ,δ-dienamides, or an α,β-γ,δ-ε,ζ-trienamide, which is catalyzed by a chiral π-Cu(ii) complex (1-10 mol%) and proceeds in a site-selective, exo/endo-selective, and enantioselective manner. The (3 + 2) cycloaddition involving the α,β-enamides proceeds with high exo-selectivity and enantioselectivity. This method is applicable to various substrates including α-substituted, α,β-disubstituted, or β,β-disubstituted α,β-enamides, which are compounds with an intrinsically low reactivity. This method provides synthetic access to pyrroloisoquinoline derivatives with up to three chiral carbon centers, including those featuring fluorine and trifluoromethyl groups, as well as quaternary carbon centers. The (3 + 2) cycloaddition involving α,β-γ,δ-dienamides proceeds with high γ,δ-site-selectivity and enantioselectivity, whereby the exo/endo-selectivity depends on the substrates and ligands. Remarkably, the (3 + 2) cycloaddition of δ-phenyl-α,β-γ,δ-dienamide proceeds with high α,β-site-selectivity, exo-selectivity, and enantioselectivity. In a manner similar to the reaction with the α,β-γ,δ-dienamides, α,β-γ,δ-ε,ζ-trienamide furnishes a (3 + 2) cycloadduct with good ε,ζ-site-selectivity, endo-selectivity, and enantioselectivity.

New reactions of 3,4‐dihydro‐6,7‐dimethoxyisoquinoline ylide with nitrile derivatives

AbstractNovel examples for dipolar cycloaddition of isoquinolinium ylides to nitriles leading to new imidazo[2,1‐a]isoquinolines were described and the potential of this reaction in synthetic chemistry was explored. As a by‐product of this research, a number of N‐substituted, 3,4‐dihydro‐1H‐isoquinoline‐1‐carbonitriles were synthesized by a simple, efficient reaction of a series of isoquinolinium bromides and ethyl cyanoformate in the presence of triethylamine.

A Two-Step Approach to a Hexacyclic Lamellarin Core via 1,3-Dipolar Cycloaddition of Isoquinolinium Ylides to Nitrostilbenes.

The 1,3-dipolar cycloaddition reaction of isoquinolinium ylides to nitrostilbenes provides an approach to 1,2-diarylpyrrolo[2,1-a]isoquinolinium-3-carboxylates and then to a complete hexacyclic lamellarin core.

Unprecedented access to functionalized pyrrolo[2,1-a]isoquinolines from the domino reaction of isoquinolinium ylides and electrophilic benzannulated heterocycles.

We have come across an unexpected reaction between electrophilic indoles and isoquinolinium methylides for accessing functionalized pyrrolo[2,1-a]isoquinolines. The reaction was found in general to yield the products in good yields. We also observed the formation of S-S-bridged bis-pyrrolo[2,1-a]isoquinolines from the reaction of 3-nitro benzothiophene and isoquinolinium methylides.

Correction: Copper-catalyzed direct C–H phosphorylation of N-imino isoquinolinium ylides with H-phosphonates

Correction for ‘Copper-catalyzed direct C–H phosphorylation of N-imino isoquinolinium ylides with H-phosphonates’ by Xin-Chen Zhan et al., Org. Chem. Front., 2019, 6, 1453–1457.

A multi-component reaction for the synthesis of pyrido [1,2-b] isoquinoline derivatives via the [3 + 2] cycloaddition reaction between alkynes and in situ generated isoquinolinium ylides.

An efficient and one-pot tandem procedure for the synthesis of fused ethanopyrido [1,2-b] isoquinoline derivatives from ninhydrin, proline and alkynes has been developed. This strategy exhibits an unprecedented [3 + 2] cycloaddition reaction between alkynes and isoquinolinium ylide (1,3 dipole) generated in situ from proline and ninhydrin. This newly developed methodology features simple operation and is metal free. In this methodology overall three new C-C bonds, two C-N bonds, and three new rings are formed in a single step process.

Copper-catalyzed direct C–H phosphorylation of N-imino isoquinolinium ylides with H-phosphonates

A new and efficient method for the synthesis of phosphorus-containing isoquinoline skeletons via copper-catalyzed direct C–H phosphorylation of isoquinoline N-amides with H-phosphonates has been described.

A [3 + 2]–[4 + 2]–[3 + 2] cycloaddition sequence of isoquinolinium ylide

A unique [3 + 2]–[4 + 2]–[3 + 2] cycloaddition sequence of isoquinolinium ylide is investigated to afford polycyclic compounds with ten stereogenic centers.

Synthesis and crystal structures of three novel benzimidazole/benzoindolizine hybrids

Abstract Three benzoindolizine derivatives, 1, 2, and 3, were obtained via 1,3-dipolar cycloaddition. The reaction of 1-(2′-benzimidazolylmethyl)isoquinolinium ylides with dimethyl acetylenedicarboxylate gave a mixture of pyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (1) and 1,10b-dihydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (2) derivatives containing a benzimidazole moiety. The reaction of this isoquinolinium N-ylide with dimethyl maleate gave an unexpected 2,3-dihydropyrrolo[2,1-a]isoquinoline-1,2-dicarboxylate (3). The structures of all reported compounds have been examined by X-ray crystallography, mass spectrometry, and NMR spectroscopy.

Polar [3 + 2] cycloaddition of isatin-3-imines with electrophilically activated heteroaromatic N-ylides: Synthesis of spirocyclic imidazo[1,2-a]pyridine and isoquinoline derivatives

A new synthesis of spiro[imidazo[1,2-a]pyridine-2,3′-indoline]-2′-ones 3a-f and spiro[imidazo[1,2-a]isoquinoline-2,3′-indolin]-2′-ones 5a-d, respectively by polar [3+2] cycloaddition reactions of isatin-3-imines with pyridinium and isoquinolinium ylides which are derived from 2-bromoacetophenone, 2,4′-dibromoacetophenone or methyl bromoacetate is described. These cycloaddition reactions consist of the nucleophilic attack of the heteroaromatic N-ylides on isatin-3-imine derivatives. The salient features of these processes include operational simplicity, high yields, and easily accessible starting materials. In addition, Density Functional Theory (DFT) calculations at the M06–2X/6–31+G(d) level have been performed to investigate the possible transition states and products. The theoretical results are in good agreement with the experimental findings and show that the product 3a is the most stable product and is formed through a kinetically feasible pathway.

Combination of Pyridinium and Isoquinolinium Ylides with Phenylisocyanate and Isothiocyanates: Synthesis, Characterisation, and X-Ray Crystal Structures of Mesoionic Monosubstituted 3-Oxo-Propanamides or Thioamides

Pyridinium ylides derived from 2-bromoacetophenone or methyl bromoacetate have been reacted with phenylisocyanate, phenyl- or methylisothiocyanate to afford mesoionic monosubstituted 3-oxo-propanamides or thioamides, via self-protonation of the intermediate N-anion. A similar reaction under the same conditions of isoquinolinium ylides with phenylisocyanate or phenyisothiocyante also produced the corresponding mesoionic compounds. In order to establish the exact structure of the mesoionic compounds, single crystal X-ray structures were obtained for three of the pyridinium ylides.

Cu(OTf)2-promoted efficient synthetic route towards glycospiro-pyrrolo[2,1-a]isoquinolines

A simple, convenient and efficient protocol for the construction of an array of glycospiro-pyrroloisoquinolines using isoquinolinium ylide and a carbohydrate-derived exocyclic olefin in the presence of Cu(OTf)2–Et3N catalytic system is described. Isoquinoline and alkylbromoacetates/2-bromoacetophenones were employed to generate the azomethine ylides in the presence of Et3N in refluxing toluene and subsequent exposure to the olefin led to the desired isoquinoline derivatives.

ChemInform Abstract: One‐Pot Two‐Step Synthesis of 1‐(Ethoxycarbonyl)indolizines via Pyridinium Ylides.

AbstractThe reaction of readily prepared pyridinium and isoquinolinium ylides with arylidene‐malonates is investigated.

ChemInform Abstract: Efficient Synthesis of Novel Tetrahydropyrrolo[3′,4′:3,4]pyrrolo[2,1‐a]isoquinoline Derivatives via a Simple and Convenient MCR in Aqueous Micellar System.

AbstractA facile synthesis of the title compounds (16 examples) is completed by 1,3‐dipolar cycloaddition of isoquinolinium ylides to phenyl maleimide derivatives.

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.

ChemInform Abstract: Regio- and Stereoselectivity in Reactions of Isoquinolinium Ylides with Unsaturated Nitriles.

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Synthesis of Benzoindolizine Derivatives by Reaction of Trimethyl Phosphite, Dialkyl Acetylenedicarboxylates and Isoquinolinium or Quinolinium Bromides

The reactive 1:1 adduct produced by the addition of trimethyl phosphite to dialkyl acetylenedicarboxylates protonated by isoquinolinium or quinolinium bromides to afford isoquinolinium or quinolinium ylides and vinyl phosphonium bromides. 1,3-Dipolar cycloaddition reaction between isoquinolinium or quinolinium ylides and vinyl phosphonium bromides, followed by elimination of dimethyl phosphite and subsequent air-oxidation led to benzoindolizine derivatives in good yields.

Microwave-Assisted Multicomponent Synthesis of Aza-, Diaza-, Benzo-, and Dibenzofluorenedione Derivatives

A microwave procedure was efficiently applied to the synthesis of a series of heteropolycyclic compounds with known or potential biological activities. Antitumor amide 3was obtained in a few minutes and with high yields through a solventless, one-pot cyclization, followed by treatment with the suitable amine. This method was also used to access tetracyclic aza-compounds 5/6, where their selective formation as N,N-syn and N,N-anti regioisomers was investigated under a solventless condition, or by changing the solvent, in the presence of solid supports and a catalytic amount of ecofriendly metal salts. Thermal access to similar polycyclic compounds recently reported under conventional heating by using the preformed pyridinium or isoquinolinium ylides was improved in this instance by microwave irradiation and extended to the synthesis of diaza-esters. In any case, the one-pot, three-component cyclization was more atom-efficient than the N-ylide sequence.