Synthesis of dimethyl heterocyclic‐o‐dicarboxylates using dimethyl acetylenedicarboxylate

Dimethyl acetylenedicarboxylate (DMAD) is a very important and useful reagent for the preparation of dimethyl heterocyclic‐o‐dicarboxylates, which are key intermediates in the synthesis of fused pyridazine derivatives. The synthesis of thiopyranes by the Diels‐Alder reaction of dithiocarboxylate derivatives, synthesis of various cyclazines by [2 + 8] cycloaddition reactions, and synthesis of dimethyl pyrazolo[3,4‐b]pyridine‐5,6‐dicarboxylates and polycyclic heterocycles containing the 1,6‐naphthyridine ring system by the reaction of o‐aminonitrile compounds with DMAD are described here.     

Regioselectively Synthesis of Thiazolo[4,5‐a]acridines and Oxazolo[5,4‐a]thiazolo[5,4‐j]acridines via Multicomponent Domino Reactions

A regioselective three‐component reaction of aromatic aldehydes, 2‐hydroxy‐1,4‐naphthoquinone and benzo[d]thiazol‐5‐amine in HOAc under microwave irradiation has been developed. A series of new thiazolo‐fused benzo[h]acridines were synthesized with high chemical yields in this one‐pot reaction. The resulting thiazolo‐fused acridines were employed to further react with aldehydes and ammonium acetate to give polycyclic‐fused oxazolo[5,4‐a]thiazolo[5,4‐j]acridines. The present synthesis shows several advantages, such as operational simplicity, fast reaction rates, which makes it a useful and attractive process of library generation for drug discovery.     

Total Synthesis of Gambierol by Using Oxiranyl Anions

Gambierol was isolated as a neurotoxin from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus and classified as a member of the polycyclic ether family of marine toxins. The structure consists of a ladder‐shaped trans‐fused octacyclic ring system that includes 18 stereogenic centers, two 1,3‐diaxial dimethyl‐substituted tetrahydropyranyl rings, and a partially conjugated triene side chain. The total synthesis of gambierol has been achieved by utilizing an oxiranyl anion strategy in an iterative manner. Synthetic highlights of this route include direct carbon–carbon formation on epoxides, sulfonyl‐assisted 6‐endo cyclization, and an expansion reaction of the tetrahydropyranyl rings to oxepanes to forge the polycyclic architecture of the target molecule.     

One‐Pot Three‐Component Synthesis of 6H‐chromeno[4,3‐b] or Cyclopenta[b]furo[3,2‐f]quinoline Derivatives

Two series of furo[3,2‐f ]quinoline‐2‐carboxylate were obtained via a three‐component reaction of aldehydes, 5‐aminobenzofuran‐2‐carboxylate, and 4‐hydroxy‐2H‐chromen‐2‐one or cyclopentane‐1,3‐dione in DMF under catalyst‐free condition in high yields. This one‐pot three‐component reaction provided an efficient method for the synthesis of fused polycyclic heterocycles for bioactive screening.     

A Stepwise Annulation for the Transformation of Cyclic Ketones to Fused 6 and 7‐Membered Cyclic Enimines and Enones

The efficient construction of functionalized polycyclic structures is an important objective in organic synthesis. Herein, we disclose a three‐step “[2 + n]” annulation method for the transformation of cyclic ketones to fused enimines and enones. The method relies on the Suzuki coupling reaction and the amide reductive alkenylation reaction. A series of fused bicyclic (6/6, 6/7, 8/7) and tricyclic (6/6/6; 6/6/7, 6/5/7) ring systems bearing an α,β‐enimine or an α,β‐enone functionality have been synthetized in good overall yields.     

One‐Pot Synthesis of Fused Pyrroles through a Key Gold‐Catalysis‐Triggered Cascade

A two‐step, one‐pot synthesis of fused pyrroles is realized by firstly condensing an N‐alkynylhydroxammonium salt with a readily enolizable ketone under mild basic conditions and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction involving a facile initial [3.3]‐sigmatropic rearrangement of the gold‐catalysis product, that is, an N,O‐dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields.     

The cyclization of vicinal 1-amino-2-acylvinylated derivatives of aromatic amines

A general method for the synthesis of substituted fused polycyclic compounds containing a 4-alkylamino or 4-dialkylaminopyridine cycle has been proposed. The method includes the addition of primary or secondary amines to vicinal (acylethynyl)arylamines followed by the cyclization of the adducts under acidic or basic catalysis conditions. Various aminonaphthoquinolinediones and aminoquinolines have been prepared in high yields by this method.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1423–1429, August, 1993.     

Diversity‐oriented Construction of Chromanone‐fused Polycyclic Pyrrolidinyl‐dispirooxindoles

Achieved herein is a novel diversity‐oriented one‐pot multicomponent synthesis of polycyclic pyrrolidinyl‐dispirooxindoles 3 . The key pyrrolidine forming reaction is the 1,3‐dipolar cycloaddition event of isatylidenyl‐chromanones 2 with azomethine ylides (thermally generated in situ from isatins and proline or thioproline). Products bearing four consecutive stereocenters consist of two oxindole moieties and a pyrrolidinyl core, including vicinal spiroquaternary stereocenters fused in one ring structure, were smoothly obtained in high yields (up to 89% yield) with good diastereoselectivity (up to >20:1). Valuable feature of this method was the design of new hybrid architectures for biological screenings through creating molecular diversity and complexity by means of the generation of several bonds and rings in a single operation. In particular, their biological activity against human leukemia cells K562 and normal L929 cells have been evaluated. These results suggested changes of this chromanone group could obviously impact the activity, and a chromanone group located in the polycyclic pyrrolidinyl‐dispirooxindoles is beneficial for the activity. What is more, the results also indicated that chromanone‐fused polycyclic pyrrolidinyl‐dispirooxindoles 3 have selective cytotoxicity against cancer cells K562 compared with normal cells L929.     

Synthesis of Enantioenriched Indolines by a Conjugate Addition/Asymmetric Protonation/Aza‐Prins Cascade Reaction

A conjugate addition/asymmetric protonation/aza‐Prins cascade reaction has been developed for the enantioselective synthesis of fused polycyclic indolines. A catalyst system generated from ZrCl₄ and 3,3′‐dibromo‐BINOL enables the synthesis of a range of polycyclic indolines in good yields and with high enantioselectivity. A key finding is the use of TMSCl and 2,6‐dibromophenol as a stoichiometric source of HCl to facilitate catalyst turnover. This transformation is the first in which a ZrCl₄?BINOL complex serves as a chiral Lewis‐acid‐assisted Brønsted acid.     

Cascade synthesis of fused polycyclic dihydropyridines by Ni–Zn–Fe hydrotalcite (HT) immobilized on silica-coated magnetite as magnetically reusable nanocatalyst

Research on Chemical Intermediates - An efficient ecofriendly approach has been developed for one-pot multicomponent synthesis of fused polycyclic dihydropyridine (DHP) derivatives. Tandem...     

Palladium‐Catalyzed Synthesis of Phenanthridine/Benzoxazine‐Fused Quinazolinones by Intramolecular CH Bond Activation

A highly efficient synthesis of phenanthridine/benzoxazine‐fused quinazolinones by ligand‐free palladium‐catalyzed intramolecular C?H bond activation under mild conditions has been developed. The C?C coupling provides the corresponding N‐fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.     

Synthesis of New Schiff Bases and Polycyclic Fused Thiopyranothiazoles Containing 4,6‐Dichloro‐1,3,5‐Triazine Moiety

New aromatic aldimines, isatine substituted ketimines based on (4,6‐dichloro‐1,3,5‐triazin‐2‐yl)‐hydrazine scaffold and polycyclic fused thiopyranothiazoles formed using hetero‐Diels‐Alder reactions starting from 4‐thioxo‐2‐thiazolidinones and 5‐norbornene‐2,3‐dicarboxylic acid triazino‐derivatives synthetic approach is described. The application of condensation and cyclocondensation reactions of N‐nucleophiles and carbonyl agents for synthesis a number of biologically active triazine derivatives is reported. Screening of anticancer activity in vitro yielded the most active compounds 3a , 8b , and 8f for different cell lines.     

Applications of Microwaves in the Synthesis of Polycyclic Six-Membered N,N-Heterocycles

The development of new strategies for the synthesis of polycyclic heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in the synthesis of six-membered polycyclic heterocyclic compounds containing two nitrogen atoms is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of six-membered polycyclic N,N-heterocycles.     

Enantioselective gold-catalyzed synthesis of polycyclic indolines

The synthesis of architecturally complex polycyclic fused indolines is achieved in a chemo-, regio-, and stereodefined manner, via an enantioselective gold-catalyzed cascade hydroindolination/iminium trapping synthetic sequence. Highly functionalized tetracyclic fused furoindolines (2) and dihydropyranylindolines (4) are synthesized in moderate to good yields and enantiomeric excesses of up to 87%.     

Circumpentacene with Open-Shell Singlet Diradical Character

Circumacenes (CAs) are a distinctive type of benzenoid polycyclic aromatic hydrocarbons where an acene unit is completely enclosed by a layer of outer fused benzene rings. Despite their unique structures, the synthesis of CAs is challenging, and until recently, the largest CA molecule synthesized was circumanthracene. In this study, we report the successful synthesis of an extended circumpentacene derivative 1 , which represents the largest CA molecule synthesized to date. Its structure was confirmed by X-ray crystallographic analysis and its electronic properties were systematically investigated by both experiments and theoretical calculations. It shows a unique open-shell diradical character due to the existence of extended zigzag edges, with a moderate diradical character index (y₀=39.7 %) and a small singlet-triplet energy gap (ΔE_S-T=−4.47 kcal/mol). It exhibits a dominant local aromatic character with π-electrons delocalized in the individual aromatic sextet rings. It has a small HOMO–LUMO energy gap and displays amphoteric redox behavior. The electronic structures of its dication and dianion can be considered as doubly charged structures in which two coronene units are fused with a central aromatic benzene ring. This study provides a new route toward stable multizigzag-edged graphene-like molecules with open-shell di/polyradical character.     

Three-component cascade reaction synthesis of polycyclic 1,4-dihydropyridine derivatives in water

An efficient and straightforward synthesis of polycyclic 1,4-dihydropyridine derivatives has been developed by reacting heterocyclic ketene aminals (HKAs) with 1,3-cyclohexanedione derivatives and a number of substituted salicylaldehyde, respectively, via three-component cascade reactions in water. This strategy provides an efficient and environmentally friendly approach for easy access to various new fused polycyclic 1,4-dihydropyridine derivatives without the need of organic solvents in moderate to good yields.     

Synthesis of 1,2,3-triazole-fused heterocycles via Pd-catalyzed cyclization of 5-iodotriazoles

A convenient approach toward polycyclic frameworks containing fused 1,2,3-triazoles is described. The synthesis consists of a Cu-catalyzed cycloaddition and an intramolecular Pd-catalyzed direct arylation or Heck reaction, and affords the products in good to excellent yields.     

Polycyclic Six-Membered N-Heterocycles: Microwave-Assisted Synthesis

The development of new strategies for synthesis of polycyclic heterocycles has remained a highly attractive but challenging proposition. An overview of the application of microwave irradiation in nitrogen-containing six-membered polycyclic heterocyclic compounds synthesis is presented, focusing on the developments in the past 5–10 years. This contribution covers the literature concerning the total synthesis of N-heterocycles.     

Reactivity and stereoselectivity of oxazolopyridines with a ring‐junction nitrogen atom

The present study demonstrates a synopsis of the scientific researches reported on the different reactions of oxazolo[3,2‐a]pyridines, besides the preparation of significant fused heterocycles up till now. The different main sections that described the reactivity of the inspected analogues include stereoselective alkylation, reactions involved oxazolidine ring, synthesis of polycyclic systems, indole alkaloids, and alkyl amines. The stereochemical selectivity of oxazolopiperidone lactams is studied, in which the configuration of the stereocenter C8a and substituents at the C8 and C8a effect on the stereoselectivity. On the other hand, the synthetic consequence of the alkylation products provides diverse routes for the synthesis of substituted enantiopure piperidines that are used for the synthesis of natural products, for example, (?)‐rhazinilam, (+)‐eburnamonine, (+)‐aspidospermidine, indole alkaloids such as dihydrocleavamine, nor‐20‐epiuleine, (+)‐dasycarpidone, (+)‐uleine, indoloquinolizidine, (+)‐dihydrocorynantheine, (?)‐dihydrocorynantheol, and indolizines, eg, octahydroindolizines, monomorine I, (?)‐S‐coniceine, and (?)‐R‐coniceine.     

A cascade process toward the synthesis of fused polycyclic dihydropyridines

The synthesis of fused polycyclic dihydropyridines was achieved using a cascade process comprising a Suzuki coupling, a nucleophilic cyclization and a hydrogen migration. Several functional groups are tolerated in this reaction and the methodology could be applied with success to quinoline and isoquinoline derivatives.