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Search for "pyrimidines" in Full Text gives 99 result(s) in Beilstein Journal of Organic Chemistry.
When metal-catalyzed C–H functionalization meets visible-light photocatalysis
- Lucas Guillemard and
- Joanna Wencel-Delord
Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147
- , pyrimidines, and oximes (Figure 20). The mild arylation proceeded in good to excellent yields over 20 examples and worked with electron-deficient, electron-rich as well as relatively sterically hindered arylating reagents. The mechanism proposed by the authors is presented in Figure 21. First, the DG-assisted
Graphical Abstract
Figure 1: Concept of dual synergistic catalysis.
Figure 2: Classification of catalytic systems involving two catalysts.
Figure 3: General mechanism for the dual nickel/photoredox catalytic system.
Figure 4: General mechanisms for C–H activation catalysis involving different reoxidation strategies.
Figure 5: Indole synthesis via dual C–H activation/photoredox catalysis.
Figure 6: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 7: Oxidative Heck reaction on arenes via the dual catalysis.
Figure 8: Proposed mechanism for the Heck reaction on arenes via dual catalysis.
Figure 9: Oxidative Heck reaction on phenols via the dual catalysis.
Figure 10: Proposed mechanism for the Heck reaction on phenols via dual catalysis.
Figure 11: Carbazole synthesis via dual C–H activation/photoredox catalysis.
Figure 12: Proposed mechanism for the carbazole synthesis via dual catalysis.
Figure 13: Carbonylation of enamides via the dual C–H activation/photoredox catalysis.
Figure 14: Proposed mechanism for carbonylation of enamides via dual catalysis.
Figure 15: Annulation of benzamides via the dual C–H activation/photoredox catalysis.
Figure 16: Proposed mechanism for the annulation of benzamides via dual catalysis.
Figure 17: Synthesis of indoles via the dual C–H activation/photoredox catalysis.
Figure 18: Proposed mechanism for the indole synthesis via dual catalysis.
Figure 19: General concept of dual catalysis merging C–H activation and photoredox catalysis.
Figure 20: The first example of dual catalysis merging C–H activation and photoredox catalysis.
Figure 21: Proposed mechanism for the C–H arylation with diazonium salts via dual catalysis.
Figure 22: Dual catalysis merging C–H activation/photoredox using diaryliodonium salts.
Figure 23: Direct arylation via the dual catalytic system reported by Xu.
Figure 24: Direct arylation via dual catalytic system reported by Balaraman.
Figure 25: Direct arylation via dual catalytic system reported by Guo.
Figure 26: C(sp3)–H bond arylation via the dual Pd/photoredox catalytic system.
Figure 27: Acetanilide derivatives acylation via the dual C–H activation/photoredox catalysis.
Figure 28: Proposed mechanism for the C–H acylation with α-ketoacids via dual catalysis.
Figure 29: Acylation of azobenzenes via the dual catalysis C–H activation/photoredox.
Figure 30: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 31: Proposed mechanism for the C2-acylation of indoles with aldehydes via dual catalysis.
Figure 32: C2-acylation of indoles via the dual C–H activation/photoredox catalysis.
Figure 33: Perfluoroalkylation of arenes via the dual C–H activation/photoredox catalysis.
Figure 34: Proposed mechanism for perfluoroalkylation of arenes via dual catalysis.
Figure 35: Sulfonylation of 1-naphthylamides via the dual C–H activation/photoredox catalysis.
Figure 36: Proposed mechanism for sulfonylation of 1-naphthylamides via dual catalysis.
Figure 37: meta-C–H Alkylation of arenes via visible-light metallaphotocatalysis.
Figure 38: Alternative procedure for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 39: Proposed mechanism for meta-C–H alkylation of arenes via metallaphotocatalysis.
Figure 40: C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 41: Proposed mechanism for C–H borylation of arenes via visible-light metallaphotocatalysis.
Figure 42: Undirected C–H aryl–aryl cross coupling via dual gold/photoredox catalysis.
Figure 43: Proposed mechanism for the undirected C–H aryl–aryl cross-coupling via dual catalysis.
Figure 44: Undirected C–H arylation of (hetero)arenes via dual manganese/photoredox catalysis.
Figure 45: Proposed mechanism for the undirected arylation of (hetero)arenes via dual catalysis.
Figure 46: Photoinduced C–H arylation of azoles via copper catalysis.
Figure 47: Photo-induced C–H chalcogenation of azoles via copper catalysis.
Figure 48: Decarboxylative C–H adamantylation of azoles via dual cobalt/photoredox catalysis.
Figure 49: Proposed mechanism for the C–H adamantylation of azoles via dual catalysis.
Figure 50: General mechanisms for the “classical” (left) and Cu-free variant (right) Sonogoshira reaction.
Figure 51: First example of a dual palladium/photoredox catalysis for Sonogashira-type couplings.
Figure 52: Arylation of terminal alkynes with diazonium salts via dual gold/photoredox catalysis.
Figure 53: Proposed mechanism for the arylation of terminal alkynes via dual catalysis.
Figure 54: C–H Alkylation of alcohols promoted by H-atom transfer (HAT).
Figure 55: Proposed mechanism for the C–H alkylation of alcohols promoted by HAT.
Figure 56: C(sp3)–H arylation of latent nucleophiles promoted by H-atom transfer.
Figure 57: Proposed mechanism for the C(sp3)–H arylation of latent nucleophiles promoted by HAT.
Figure 58: Direct α-arylation of alcohols promoted by H-atom transfer.
Figure 59: Proposed mechanism for the direct α-arylation of alcohols promoted by HAT.
Figure 60: C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 61: Proposed mechanism for the C–H arylation of amines via dual Ni/photoredox catalysis.
Figure 62: C–H functionalization of nucleophiles via excited ketone/nickel dual catalysis.
Figure 63: Proposed mechanism for the C–H functionalization enabled by excited ketones.
Figure 64: Selective sp3–sp3 cross-coupling promoted by H-atom transfer.
Figure 65: Proposed mechanism for the selective sp3–sp3 cross-coupling promoted by HAT.
Figure 66: Direct C(sp3)–H acylation of amines via dual Ni/photoredox catalysis.
Figure 67: Proposed mechanism for the C–H acylation of amines via dual Ni/photoredox catalysis.
Figure 68: C–H hydroalkylation of internal alkynes via dual Ni/photoredox catalysis.
Figure 69: Proposed mechanism for the C–H hydroalkylation of internal alkynes.
Figure 70: Alternative procedure for the C–H hydroalkylation of ynones, ynoates, and ynamides.
Figure 71: Allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 72: Proposed mechanism for the allylic C(sp3)–H activation via dual Ni/photoredox catalysis.
Figure 73: Asymmetric allylation of aldehydes via dual Cr/photoredox catalysis.
Figure 74: Proposed mechanism for the asymmetric allylation of aldehydes via dual catalysis.
Figure 75: Aldehyde C–H functionalization promoted by H-atom transfer.
Figure 76: Proposed mechanism for the C–H functionalization of aldehydes promoted by HAT.
Figure 77: Direct C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 78: Proposed mechanism for the C–H arylation of strong aliphatic bonds promoted by HAT.
Figure 79: Direct C–H trifluoromethylation of strong aliphatic bonds promoted by HAT.
Figure 80: Proposed mechanism for the C–H trifluoromethylation of strong aliphatic bonds.
Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition
- Sivaraman Balasubramaniam,
- Sajith Vijayan,
- Liam V. Goldman,
- Xavier A. May,
- Kyra Dodson,
- Sweta Adhikari,
- Fatima Rivas,
- Davita L. Watkins and
- Shana V. Stoddard
Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59
- hydroxamic moieties [13][14][15], the non-availability of the central core modification stimulated our interest toward altering the central core to evaluate efficacy. We found particular interest in the replacement of the phenyl ring with diazine cores (pyridazines, pyrimidines and pyrazines) as their
Graphical Abstract
Figure 1: Chemical structures of the target diazine-based surrogates for the central core of panobinostat.
Figure 2: Docking pose for panobinostat and panobinostat derivatives in the HDAC8 receptor. (a) Overlay of al...
Figure 3: General building blocks for the visualized targets.
Scheme 1: Reaction conditions: a) MeOH, H2SO4 (5 drops), MS 4 Å (2 pieces), 68 °C, 8 h, 81%; b) DIBAL-H (1.2 ...
Scheme 2: Reaction conditions: a) boronic acid 15 (1.3 equiv), PdCl2(PPh3)2 (0.1 equiv), dioxane/H2O (3:1), Na...
Scheme 3: Reaction conditions: a) 5-bromo-2-chloropyrimidine (1 equiv), ethyl formate (1.5 equiv), THF (20 mL...
Scheme 4: Reaction conditions: a) boronic acid 15 (1.3 equiv), PdCl2(PPh3)2 (0.1 equiv), dioxane/H2O (8:2, Na2...
Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt
- Tobias Lucas,
- Jule-Philipp Dietz and
- Till Opatz
Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41
- Tobias Lucas Jule-Philipp Dietz Till Opatz Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10–14, 55128 Mainz, Germany 10.3762/bjoc.16.41 Abstract A synthesis of fluorinated pyrimidines under mild conditions from amidine hydrochlorides and the recently described
- heterocycles; fluorine; pyrazoles; pyrimidines; Introduction Due to its extremely widespread application in virtually all areas of synthetic organic chemistry, fluorine is considered a “magic” element. It confers metabolic stability and other unique properties to organic molecules and a large fraction of
- stage [15][16][17][18][19]. Fluorinated pyrimidines, pyrimidine analogues and pyrazoles [20][21] play a prominent role in several clinically important pharmaceuticals [22][23][24][25]. These compounds act against HIV or HIV-related diseases [26], such as opportunistic fungal infections, and represent
Graphical Abstract
Figure 1: The structures of 5-fluorouracil (1), 5-fluorocytosine (2), emtricitabine (3) and capecitabine (4).
Scheme 1: Synthesis of potassium (Z)-2-cyano-2-fluoroethenolate (8) by Dietz et al. [36].
Scheme 2: Scope of the cyclization reaction. All yields are those of the purified products. aNo further purif...
Scheme 3: Cyclization with phenylhydrazine (12a) to obtain the desired pyrazole 13a and the byproducts 13b an...
Ultrasonic-assisted unusual four-component synthesis of 7-azolylamino-4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines
- Yana I. Sakhno,
- Maryna V. Murlykina,
- Oleksandr I. Zbruyev,
- Anton V. Kozyryev,
- Svetlana V. Shishkina,
- Dmytro Sysoiev,
- Vladimir I. Musatov,
- Sergey M. Desenko and
- Valentyn A. Chebanov
Beilstein J. Org. Chem. 2020, 16, 281–289, doi:10.3762/bjoc.16.27
- 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines. Keywords: 5-amino-1H-pyrazole-4-carbonitrile; 3-amino-1,2,4-triazole; 7-azolylaminotetrahydroazolo[1,5-a]pyrimidines; heterocycle; multicomponent reaction; ultrasonication; Introduction Tetrahydropyrimidines are heterocycles of high pharmacological
- -pyrazole-4-carbonitrile with aromatic aldehydes and pyruvic acid or its esters under ultrasonication led to the formation of 4,5,6,7-tetrahydroazolo[1,5-a]pyrimidines 4a–u (Scheme 4) containing an azolylamino substituent in the 7-position via an unusual pseudo four-component reaction, rather than two
- ). In contrast to pyrazolyl-substituted pyrazolo[1,5-a]pyrimidine-7-carboxylic acids 4d–o, triazolyl-substituted derivatives 4p–u were unstable in protic solvents in the presence of water, and especially upon increasing the temperature gradually transformed into 7-hydroxytriazolo[1,5-a]pyrimidines 5a–f
Graphical Abstract
Scheme 1: Synthesis of tetrahydroazolopyrimidine derivatives.
Scheme 2: Various multicomponent reactions involving pyruvic acids (pyruvates) and different α-aminoazoles.
Scheme 3: Synthesis of 4-arylamino-substituted tetrahydroquinolines.
Scheme 4: Ultrasound-assisted multicomponent reactions of 3-amino-1,2,4-triazole or 5-amino-1H-pyrazole-4-car...
Scheme 5: Synthesis of 3-cyano-7-(4-methoxyphenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acid (7)....
Scheme 6: Proposed reaction mechanism.
Figure 1: Alternative structures A and B for the tetrahydroazolopyrimidines 4.
Figure 2: Molecular structure of ethyl 5-(4-bromophenyl)-3-cyano-7-((4-cyano-1H-pyrazol-5-yl)amino)-4,5,6,7-t...
Figure 3: Chains of 4g molecules in the crystal phase.
Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction
- Renata Kaczmarek,
- Dariusz Korczyński,
- James R. Green and
- Roman Dembinski
Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1
- common framework for materials with potent biological properties [6][7][8][9][10]. Modification on this site of the nucleobase usually does not interfere with Watson–Crick base pairing. For example, C-5-modified pyrimidines are well tolerated by commercial polymerases [11][12]. Alkynyl modifications not
Graphical Abstract
Scheme 1: Preparation of (2'-deoxy)-5-alkynyluridines 2 and 3, their dicobalt hexacarbonyl derivatives 4 and 5...
Figure 1: Structures of nucleosides 6 and 7, products of the Nicholas reaction.
A green, economical synthesis of β-ketonitriles and trifunctionalized building blocks from esters and lactones
- Daniel P. Pienaar,
- Kamogelo R. Butsi,
- Amanda L. Rousseau and
- Dean Brady
Beilstein J. Org. Chem. 2019, 15, 2930–2935, doi:10.3762/bjoc.15.287
- from lactone to 20% (Scheme 2). Due to the interest in the potential preparation of pyrimidines from β-ketonitriles and guanidine [18], we wanted to test the general applicability of this method for access to a variety of alkyl and aryl-substituted β-ketonitriles (as summarized in Table 1). When we
- the synthesis of glycomimetic products from sugar lactones, and for the synthesis of various pyrimidines. Proposed retrosynthesis of the free diol 1. Preparation of O-unprotected, trifunctionalized synthons from lactones. Preparation of a variety of β-ketonitriles. Supporting Information Supporting
Graphical Abstract
Scheme 1: Proposed retrosynthesis of the free diol 1.
Scheme 2: Preparation of O-unprotected, trifunctionalized synthons from lactones.
An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent
- Nicky J. Willis,
- Elliott D. Bayle,
- George Papageorgiou,
- David Steadman,
- Benjamin N. Atkinson,
- William Mahy and
- Paul V. Fish
Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271
- air- and moisture-stable. The scope of published substrates includes chlorination of 7H-pyrrolo[2,3-d]pyrimidines and we wished to see if we could extend the scope to include sulphur containing heterocycles such as thieno[3,2-d]pyrimidines (e.g., 6). It was also important to explore if 12 would
Graphical Abstract
Figure 1: Chemical structure of Notum inhibitor LP-922056 (1).
Scheme 1: Synthesis of LP-922056 (1). Reagents and conditionsa: (a) (COCl)2 (3.3 equiv), DMF, CH2Cl2, 55 °C ,...
Scheme 2: Chlorination of 6 with N-chlorosuccinimide (NCS). Reagents and conditions: (a) NCS (1.2 equiv), AcO...
Scheme 3: Improved synthesis of 5. Reagents and conditions: (a) NaOMe (5 equiv), 1,4-dioxane, 0 °C then rt, 1...
Figure 2: Concentrations of 1 in mouse following oral administration (p.o.) at 10 mg/kg.
Scheme 4: Preparation of amides 17. Representative reagents and conditionsa: (a) HBTU (1.1 equiv), iPr2NEt (2...
In water multicomponent synthesis of low-molecular-mass 4,7-dihydrotetrazolo[1,5-a]pyrimidines
- Irina G. Tkachenko,
- Sergey A. Komykhov,
- Vladimir I. Musatov,
- Svitlana V. Shishkina,
- Viktoriya V. Dyakonenko,
- Vladimir N. Shvets,
- Mikhail V. Diachkov,
- Valentyn A. Chebanov and
- Sergey M. Desenko
Beilstein J. Org. Chem. 2019, 15, 2390–2397, doi:10.3762/bjoc.15.231
- -dihydrotetrazolo[1,5-a]pyrimidine derivatives. Under similar conditions using 4,4,4-trifluoroacetoacetic ester 5-hydroxy-4,5,6,7-tetrahydrotetrazolo[1,5-a]pyrimidines are obtained. The analogous reaction with acetylacetone requires scandium(III) triflate as catalyst. The antioxidant activity of selected compounds
- was assayed with 1,1-diphenyl-2-picrylhydrazyl. Keywords: 5-aminotetrazole; antioxidant activity; 1,3-dicarbonyl compounds; multicomponent synthesis; tetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines and their partially hydrogenated derivatives are known for their interesting
- biological properties. They have been reported to have anticancer [1], antimicrobial [2][3] and antioxidant [3] activities and to act as inhibitors of hepatitis B virus [4]. The dihydro derivatives of tetrazolo[1,5-a]pyrimidines belong to a bit special kind of dihydropyrimidines due to the strong electron
Graphical Abstract
Scheme 1: Three synthetic approaches to dihydrotetrazolo[1,5-a]pyrimidines.
Scheme 2: Three-component reaction of 1, 7a,b and 8a–d in water.
Figure 1: Molecular structure of 9a according to X-ray data. Displacement ellipsoids are shown at the 50% pro...
Scheme 3: Three-component reaction of 5-aminotetrazole (1) with formaldehyde (7a) and acetylacetone (10).
Scheme 4: a) Three-component reaction of 5-aminotetrazole (1) with acetaldehyde (7b) and ethyl 4,4,4-trifluor...
Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage
- Gagandeep Kour Reen,
- Ashok Kumar and
- Pratibha Sharma
Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165
- halide substituent in the product which was successfully overcome by this protocol along with the synthesis of pyrazines and pyrimidines in high yield (Scheme 3). Furthermore, easy functionalization of the products from the viewpoint of reactive halide made them valuable synthons. Molecular oxygen used
- derivatives have been reported by the group of R. K. Reddy [113]. The protocol offered an open air, ligand- and base-free methodology with an extension towards the synthesis of imidazo[1,2-a]pyrazines/pyrimidines and benzo[d]imidazo[2,1-b]thiazoles. For this reaction, they have synthesized the respective
Graphical Abstract
Figure 1: Various drugs having IP nucleus.
Figure 2: Participation percentage of various TMs for the syntheses of IPs.
Scheme 1: CuI–NaHSO4·SiO2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 2: Experimental examination of reaction conditions.
Scheme 3: One-pot tandem reaction for the synthesis of 2-haloimidazopyridines.
Scheme 4: Mechanistic scheme for the synthesis of 2-haloimidazopyridine.
Scheme 5: Copper-MOF-catalyzed three-component reaction (3-CR) for imidazo[1,2-a]pyridines.
Scheme 6: Mechanism for copper-MOF-driven synthesis.
Scheme 7: Heterogeneous synthesis via titania-supported CuCl2.
Scheme 8: Mechanism involving oxidative C–H functionalization.
Scheme 9: Heterogeneous synthesis of IPs.
Scheme 10: One-pot regiospecific synthesis of imidazo[1,2-a]pyridines.
Scheme 11: Vinyl azide as an unprecedented substrate for imidazo[1,2-a]pyridines.
Scheme 12: Radical pathway.
Scheme 13: Cu(I)-catalyzed transannulation approach for imidazo[1,5-a]pyridines.
Scheme 14: Plausible radical pathway for the synthesis of imidazo[1,5-a]pyridines.
Scheme 15: A solvent-free domino reaction for imidazo[1,2-a]pyridines.
Scheme 16: Cu-NPs-mediated synthesis of imidazo[1,2-a]pyridines.
Scheme 17: CuI-catalyzed synthesis of isoxazolylimidazo[1,2-a]pyridines.
Scheme 18: Functionalization of 4-bromo derivative via Sonogashira coupling reaction.
Scheme 19: A plausible reaction pathway.
Scheme 20: Cu(I)-catalyzed intramolecular oxidative C–H amidation reaction.
Scheme 21: One-pot synthetic reaction for imidazo[1,2-a]pyridine.
Scheme 22: Plausible reaction mechanism.
Scheme 23: Cu(OAc)2-promoted synthesis of imidazo[1,2-a]pyridines.
Scheme 24: Mechanism for aminomethylation/cycloisomerization of propiolates with imines.
Scheme 25: Three-component synthesis of imidazo[1,2-a]pyridines.
Figure 3: Scope of pyridin-2(1H)-ones and acetophenones.
Scheme 26: CuO NPS-promoted A3 coupling reaction.
Scheme 27: Cu(II)-catalyzed C–N bond formation reaction.
Scheme 28: Mechanism involving Chan–Lam/Ullmann coupling.
Scheme 29: Synthesis of formyl-substituted imidazo[1,2-a]pyridines.
Scheme 30: A tandem sp3 C–H amination reaction.
Scheme 31: Probable mechanistic approach.
Scheme 32: Dual catalytic system for imidazo[1,2-a]pyridines.
Scheme 33: Tentative mechanism.
Scheme 34: CuO/CuAl2O4/ᴅ-glucose-promoted 3-CCR.
Scheme 35: A tandem CuOx/OMS-2-based synthetic strategy.
Figure 4: Biomimetic catalytic oxidation in the presence of electron-transfer mediators (ETMs).
Scheme 36: Control experiment.
Scheme 37: Copper-catalyzed C(sp3)–H aminatin reaction.
Scheme 38: Reaction of secondary amines.
Scheme 39: Probable mechanistic pathway.
Scheme 40: Coupling reaction of α-azidoketones.
Scheme 41: Probable pathway.
Scheme 42: Probable mechanism with free energy calculations.
Scheme 43: MCR for cyanated IP synthesis.
Scheme 44: Substrate scope for the reaction.
Scheme 45: Reaction mechanism.
Scheme 46: Probable mechanistic pathway for Cu/ZnAl2O4-catalyzed reaction.
Scheme 47: Copper-catalyzed double oxidative C–H amination reaction.
Scheme 48: Application towards different coupling reactions.
Scheme 49: Reaction mechanism.
Scheme 50: Condensation–cyclization approach for the synthesis of 1,3-diarylated imidazo[1,5-a]pyridines.
Scheme 51: Optimized reaction conditions.
Scheme 52: One-pot 2-CR.
Scheme 53: One-pot 3-CR without the isolation of chalcone.
Scheme 54: Copper–Pybox-catalyzed cyclization reaction.
Scheme 55: Mechanistic pathway catalyzed by Cu–Pybox complex.
Scheme 56: Cu(II)-promoted C(sp3)-H amination reaction.
Scheme 57: Wider substrate applicability for the reaction.
Scheme 58: Plausible reaction mechanism.
Scheme 59: CuI assisted C–N cross-coupling reaction.
Scheme 60: Probable reaction mechanism involving sp3 C–H amination.
Scheme 61: One-pot MCR-catalyzed by CoFe2O4/CNT-Cu.
Scheme 62: Mechanistic pathway.
Scheme 63: Synthetic scheme for 3-nitroimidazo[1,2-a]pyridines.
Scheme 64: Plausible mechanism for CuBr-catalyzed reaction.
Scheme 65: Regioselective synthesis of halo-substituted imidazo[1,2-a]pyridines.
Scheme 66: Synthesis of 2-phenylimidazo[1,2-a]pyridines.
Scheme 67: Synthesis of diarylated compounds.
Scheme 68: CuBr2-mediated one-pot two-component oxidative coupling reaction.
Scheme 69: Decarboxylative cyclization route to synthesize 1,3-diarylimidazo[1,5-a]pyridines.
Scheme 70: Mechanistic pathway.
Scheme 71: C–H functionalization reaction of enamines to produce diversified heterocycles.
Scheme 72: A plausible mechanism.
Scheme 73: CuI-promoted aerobic oxidative cyclization reaction of ketoxime acetates and pyridines.
Scheme 74: CuI-catalyzed pathway for the formation of imidazo[1,2-a]pyridine.
Scheme 75: Mechanistic pathway.
Scheme 76: Mechanistic rationale for the synthesis of products.
Scheme 77: Copper-catalyzed synthesis of vinyloxy-IP.
Scheme 78: Regioselective product formation with propiolates.
Scheme 79: Proposed mechanism for vinyloxy-IP formation.
Scheme 80: Regioselective synthesis of 3-hetero-substituted imidazo[1,2-a]pyridines with different reaction su...
Scheme 81: Mechanistic pathway.
Scheme 82: CuI-mediated synthesis of 3-formylimidazo[1,2-a]pyridines.
Scheme 83: Radical pathway for 3-formylated IP synthesis.
Scheme 84: Pd-catalyzed urea-cyclization reaction for IPs.
Scheme 85: Pd-catalyzed one-pot-tandem amination and intramolecular amidation reaction.
Figure 5: Scope of aniline nucleophiles.
Scheme 86: Pd–Cu-catalyzed Sonogashira coupling reaction.
Scheme 87: One-pot amide coupling reaction for the synthesis of imidazo[4,5-b]pyridines.
Scheme 88: Urea cyclization reaction for the synthesis of two series of pyridines.
Scheme 89: Amidation reaction for the synthesis of imidazo[4,5-b]pyridines.
Figure 6: Amide scope.
Scheme 90: Pd NPs-catalyzed 3-component reaction for the synthesis of 2,3-diarylated IPs.
Scheme 91: Plausible mechanistic pathway for Pd NPs-catalyzed MCR.
Scheme 92: Synthesis of chromenoannulated imidazo[1,2-a]pyridines.
Scheme 93: Mechanism for the synthesis of chromeno-annulated IPs.
Scheme 94: Zinc oxide NRs-catalyzed synthesis of imidazo[1,2-a]azines/diazines.
Scheme 95: Zinc oxide-catalyzed isocyanide based GBB reaction.
Scheme 96: Reaction pathway for ZnO-catalyzed GBB reaction.
Scheme 97: Mechanistic pathway.
Scheme 98: ZnO NRs-catalyzed MCR for the synthesis of imidazo[1,2-a]azines.
Scheme 99: Ugi type GBB three-component reaction.
Scheme 100: Magnetic NPs-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 101: Regioselective synthesis of 2-alkoxyimidazo[1,2-a]pyridines catalyzed by Fe-SBA-15.
Scheme 102: Plausible mechanistic pathway for the synthesis of 2-alkoxyimidazopyridine.
Scheme 103: Iron-catalyzed synthetic approach.
Scheme 104: Iron-catalyzed aminooxygenation reaction.
Scheme 105: Mechanistic pathway.
Scheme 106: Rh(III)-catalyzed double C–H activation of 2-substituted imidazoles and alkynes.
Scheme 107: Plausible reaction mechanism.
Scheme 108: Rh(III)-catalyzed non-aromatic C(sp2)–H bond activation–functionalization for the synthesis of imid...
Scheme 109: Reactivity and selectivity of different substrates.
Scheme 110: Rh-catalyzed direct C–H alkynylation by Li et al.
Scheme 111: Suggested radical mechanism.
Scheme 112: Scandium(III)triflate-catalyzed one-pot reaction and its mechanism for the synthesis of benzimidazo...
Scheme 113: RuCl3-assisted Ugi-type Groebke–Blackburn condensation reaction.
Scheme 114: C-3 aroylation via Ru-catalyzed two-component reaction.
Scheme 115: Regioselective synthetic mechanism.
Scheme 116: La(III)-catalyzed one-pot GBB reaction.
Scheme 117: Mechanistic approach for the synthesis of imidazo[1,2-a]pyridines.
Scheme 118: Synthesis of imidazo[1,2-a]pyridine using LaMnO3 NPs under neat conditions.
Scheme 119: Mechanistic approach.
Scheme 120: One-pot 3-CR for regioselective synthesis of 2-alkoxy-3-arylimidazo[1,2-a]pyridines.
Scheme 121: Formation of two possible products under optimization of the catalysts.
Scheme 122: Mechanistic strategy for NiFe2O4-catalyzed reaction.
Scheme 123: Two-component reaction for synthesizing imidazodipyridiniums.
Scheme 124: Mechanistic scheme for the synthesis of imidazodipyridiniums.
Scheme 125: CuI-catalyzed arylation of imidazo[1,2-a]pyridines.
Scheme 126: Mechanism for arylation reaction.
Scheme 127: Cupric acetate-catalyzed double carbonylation approach.
Scheme 128: Radical mechanism for double carbonylation of IP.
Scheme 129: C–S bond formation reaction catalyzed by cupric acetate.
Scheme 130: Cupric acetate-catalyzed C-3 formylation approach.
Scheme 131: Control experiments for signifying the role of DMSO and oxygen.
Scheme 132: Mechanism pathway.
Scheme 133: Copper bromide-catalyzed CDC reaction.
Scheme 134: Extension of the substrate scope.
Scheme 135: Plausible radical pathway.
Scheme 136: Transannulation reaction for the synthesis of imidazo[1,5-a]pyridines.
Scheme 137: Plausible reaction pathway for denitrogenative transannulation.
Scheme 138: Cupric acetate-catalyzed C-3 carbonylation reaction.
Scheme 139: Plausible mechanism for regioselective C-3 carbonylation.
Scheme 140: Alkynylation reaction at C-2 of 3H-imidazo[4,5-b]pyridines.
Scheme 141: Two-way mechanism for C-2 alkynylation of 3H-imidazo[4,5-b]pyridines.
Scheme 142: Palladium-catalyzed SCCR approach.
Scheme 143: Palladium-catalyzed Suzuki coupling reaction.
Scheme 144: Reaction mechanism.
Scheme 145: A phosphine free palladium-catalyzed synthesis of C-3 arylated imidazopyridines.
Scheme 146: Palladium-mediated Buchwald–Hartwig cross-coupling reaction.
Figure 7: Structure of the ligands optimized.
Scheme 147: Palladium acetate-catalyzed direct arylation of imidazo[1,2-a]pyridines.
Scheme 148: Palladium acetate-catalyzed mechanistic pathway.
Scheme 149: Palladium acetate-catalyzed regioselective arylation reported by Liu and Zhan.
Scheme 150: Mechanism for selective C-3 arylation of IP.
Scheme 151: Pd(II)-catalyzed alkenylation reaction with styrenes.
Scheme 152: Pd(II)-catalyzed alkenylation reaction with acrylates.
Scheme 153: A two way mechanism.
Scheme 154: Double C–H activation reaction catalyzed by Pd(OAc)2.
Scheme 155: Probable mechanism.
Scheme 156: Palladium-catalyzed decarboxylative coupling.
Scheme 157: Mechanistic cycle for decarboxylative arylation reaction.
Scheme 158: Ligand-free approach for arylation of imidazo[1,2-a]pyridine-3-carboxylic acids.
Scheme 159: Mechanism for ligandless arylation reaction.
Scheme 160: NHC-Pd(II) complex assisted arylation reaction.
Scheme 161: C-3 arylation of imidazo[1,2-a]pyridines with aryl bromides catalyzed by Pd(OAc)2.
Scheme 162: Pd(II)-catalyzed C-3 arylations with aryl tosylates and mesylates.
Scheme 163: CDC reaction for the synthesis of imidazo[1,2-a]pyridines.
Scheme 164: Plausible reaction mechanism for Pd(OAc)2-catalyzed synthesis of imidazo[1,2-a]pyridines.
Scheme 165: Pd-catalyzed C–H amination reaction.
Scheme 166: Mechanism for C–H amination reaction.
Scheme 167: One-pot synthesis for 3,6-di- or 2,3,6-tri(hetero)arylimidazo[1,2-a]pyridines.
Scheme 168: C–H/C–H cross-coupling reaction of IPs and azoles catalyzed by Pd(II).
Scheme 169: Mechanistic cycle.
Scheme 170: Rh-catalyzed C–H arylation reaction.
Scheme 171: Mechanistic pathway for C–H arylation of imidazo[1,2-a]pyridine.
Scheme 172: Rh(III)-catalyzed double C–H activation of 2-phenylimidazo[1,2-a]pyridines and alkynes.
Scheme 173: Rh(III)-catalyzed mechanistic pathway.
Scheme 174: Rh(III)-mediated oxidative coupling reaction.
Scheme 175: Reactions showing functionalization of the product obtained by the group of Kotla.
Scheme 176: Mechanism for Rh(III)-catalyzed oxidative coupling reaction.
Scheme 177: Rh(III)-catalyzed C–H activation reaction.
Scheme 178: Mechanistic cycle.
Scheme 179: Annulation reactions of 2-arylimidazo[1,2-a]pyridines and alkynes.
Scheme 180: Two-way reaction mechanism for annulations reaction.
Scheme 181: [RuCl2(p-cymene)]2-catalyzed C–C bond formation reaction.
Scheme 182: Reported reaction mechanism.
Scheme 183: Fe(III) catalyzed C-3 formylation approach.
Scheme 184: SET mechanism-catalyzed by Fe(III).
Scheme 185: Ni(dpp)Cl2-catalyzed KTC coupling.
Scheme 186: Pd-catalyzed SM coupling.
Scheme 187: Vanadium-catalyzed coupling of IP and NMO.
Scheme 188: Mechanistic cycle.
Scheme 189: Selective C3/C5–H bond functionalizations by mono and bimetallic systems.
Scheme 190: rGO-Ni@Pd-catalyzed C–H bond arylation of imidazo[1,2-a]pyridine.
Scheme 191: Mechanistic pathway for heterogeneously catalyzed arylation reaction.
Scheme 192: Zinc triflate-catalyzed coupling reaction of substituted propargyl alcohols.
One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion
- Christina Görgen,
- Katharina Boden,
- Guido J. Reiss,
- Walter Frank and
- Thomas J. J. Müller
Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136
- ][51][52], pyrimidines [48][49], and 5-acylpyrazoles [48][49]. The latter 5-acylpyrazole arose after work-up from the three-component AA–cyclocondensation synthesis employing Boc-hydrazine as a binucleophilic hydrazide substrate. Based on our attempts to isolate potential 1,5-diacylpyrazole precursors
Graphical Abstract
Figure 1: Selected anticancer active 3,5-diaryl-1-acylpyrazoline (left) and xanthine oxygenase inhibitors (ce...
Figure 2: Selected 1-acyl-5-hydroxypyrazolines with analgesic (left, center) and antibacterial activity (cent...
Scheme 1: Glyoxylation–alkynylation (GA) and activation–alkynylation (AA) synthesis of alkynediones in a one-...
Scheme 2: Consecutive three-component synthesis to give 5-benzoyl-3-phenyl-1H-pyrazole (6a) after alkaline de...
Figure 3: ORTEP plot of 5-benzoyl-3-phenyl-1H-pyrazole (6a) (thermal ellipsoids at 30% probability); the dire...
Scheme 3: Cyclization of 1,4-diphenylbut-3-yne-1,2-dione (3a) and Boc-hydrazine (4a) to give intermediate 5a.
Figure 4: Ellipsoid plot of 1-Boc-5-benzoyl-5-hydroxypyrazoline 5a.
Scheme 4: Model reaction for optimizing the activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hyd...
Scheme 5: One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines 5.
Figure 5: ORTEP plot and dimer of compound 5r (thermal ellipsoids at 30% probability).
Steroid diversification by multicomponent reactions
- Leslie Reguera,
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Daniel G. Rivera
Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121
- epiandrosterone acetate, etc., all providing excellent yields of steroidal pyrimidines after 12 h of reaction at 90 °C (Scheme 13). The reaction sequence of this multicomponent protocol comprises the initial formation of the Biginelli product, followed by aromatization under air to furnish the heterocyclic ring
- strong oxidizing Jones reagent, because the oxidizing power of sulfuric acid was not enough to achieve oxidation. Interestingly, the use of microwave irradiation instead of classic heating allowed obtaining the Biginelli product in only 10 min, instead of 12 h as required for the synthesis of pyrimidines
- targeting steroid-fused pyrimidines, Boruah’s group developed a solid-phase MCR between 2-hydroxymethylene-3-ketosteroids, aromatic aldehydes and ammonium acetate [46]. As shown in Scheme 15, the reaction was carried out with steroid 49 and different aldehydes to furnish the set of compounds 50 in good to
Graphical Abstract
Figure 1: Structures of natural steroids of A) animal and B) plant origin.
Scheme 1: Synthesis of a steroidal β-lactam by Ugi reaction of a cholanic aldehyde [14].
Scheme 2: Synthetic route to steroidal 2,5-diketopiperazines based on a diastereoselective Ugi-4CR with an an...
Scheme 3: Multicomponent synthesis of a heterocycle–steroid hybrid using a ketosteroid as carbonyl component [18]....
Scheme 4: Synthesis of peptidomimetic–steroid hybrids using the Ugi-4CR with spirostanic amines and carboxyli...
Scheme 5: Synthesis of azasteroids using the Ugi-4CR with androstanic and pregnanic carboxylic acids [22].
Figure 2: Ugi-4CR-derived library of androstanic azasteroids with diverse substitution patterns at the phenyl...
Scheme 6: Synthesis of 4-azacholestanes by an intramolecular Ugi-4C-3R [26].
Scheme 7: Synthesis of amino acid–steroid hybrid by multiple Ugi-4CR using steroidal isocyanides [29].
Scheme 8: Synthesis of ecdysteroid derivatives by Ugi-4CR using a steroidal isocyanide [30].
Scheme 9: Stereoselective multicomponent synthesis of a steroid–tetrahydropyridine hybrid using a chiral bifu...
Scheme 10: Pd(II)-catalyzed three-component reaction with an alkynyl seco-cholestane [34].
Scheme 11: Multicomponent synthesis of steroid–thiazole hybrids from a steroidal ketone [36].
Scheme 12: Synthesis of cholanic pseudo-peptide derivatives by novel MCRs based on the reactivity of ynamide [37,38].
Scheme 13: Synthesis of steroid-fused pyrimidines and pyrimidones using the Biginelli-3CR [39,42,43].
Scheme 14: Synthesis of steroidal pyridopyrimidines by a reaction sequence comprising a 4CR followed by a post...
Scheme 15: Synthesis of steroid-fused pyrimidines by MCR of 2-hydroxymethylene-3-ketosteroids [46].
Scheme 16: Synthesis of steroid-fused naphthoquinolines by the Kozlov–Wang MCR using ketosteroids [50,51].
Scheme 17: Conjugation of steroids to carbohydrates and peptides by the Ugi-4CR [62,63].
Scheme 18: Solid-phase multicomponent conjugation of peptides to steroids by the Ugi-4CR [64].
Scheme 19: Solid-phase multicomponent conjugation of peptides to steroids by the Petasis-3CR [68].
Scheme 20: Synthesis of steroidal macrobicycles (cages) by multiple multicomponent macrocyclizations based on ...
Scheme 21: One-pot synthesis of steroidal cages by double Ugi-4CR-based macrocyclizations [76].
The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives
- Tilman Lechel,
- Roopender Kumar,
- Mrinal K. Bera,
- Reinhold Zimmer and
- Hans-Ulrich Reissig
Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61
- ammonium salts or with hydroxylamine hydrochloride afford pyrimidines PM or pyrimidine N-oxides PO with a highly flexible substitution pattern in good yields. The functional groups of these heterocycles also allow a variety of subsequent reactions to various pyrimidine derivatives. On the other hand, acid
- reactions are possible. Keywords: allenes; condensations; multicomponent reactions; oxazoles; pyrimidines; quinoxalines; Introduction Multicomponent reactions are known to create unique product skeletons in an atom economic, efficient and time saving fashion. In many cases, compounds bearing functional
- particular heterocyclic compounds. The synthesis of pyrimidines PM, pyrimidine N-oxides PO, oxazoles OX, 1,2-diketones DK and quinoxalines QU starting from β-ketoenamides KE is the topic of the present review. Review Scope of the LANCA three-component synthesis of β-ketoenamides The scope of the LANCA three
Graphical Abstract
Scheme 1: Discovery of the LANCA three-component reaction. The reaction of pivalonitrile (1) with lithiated m...
Scheme 2: Proposed mechanism of the LANCA three-component reaction to β-ketoenamides KE and pyridin-4-ol deri...
Scheme 3: One-pot preparation of pyridin-4-ols PY and their subsequent transformations to highly substituted ...
Scheme 4: Synthesis of β-ketoenamides KE by the LANCA three-component reaction of alkoxyallenes, nitriles and...
Scheme 5: β-Ketoenamides KE36–43 derived from enantiopure components.
Scheme 6: Bis-β-ketoenamides KE44–46 derived from aromatic dicarboxylic acids.
Scheme 7: Conversion of alkyl propargyl ethers E into aryl-substituted β-ketoenamides KEAr and selected produ...
Scheme 8: Condensation of LANCA-derived β-ketoenamides KE with ammonium salts to give 5-alkoxy-substituted py...
Scheme 9: Synthesis of PM31–35 from β-ketoenamides KE37, KE38, KE40, KE41 and KE78 obtained by method A (NH4O...
Scheme 10: Synthesis of bis-pyrimidine derivatives PM36, PM39 and PM40 from β-ketoenamides KE44–46 by method A...
Scheme 11: Functionalization of pyrimidine derivatives PM through selenium dioxide oxidations of PM5, PM9, PM15...
Scheme 12: Conversion of 2-vinyl-substituted pyrimidine PM7 into aldehyde PM50; (NMO = N-methylmorpholine N-ox...
Scheme 13: Deprotection of 5-alkoxy-substituted pyrimidines PM2, PM20 and PM29 and conversion into nonaflates ...
Scheme 14: Palladium-catalyzed coupling reactions of PM54 and PM12 giving rise to new pyrimidine derivatives P...
Scheme 15: Synthesis of pyrimidyl-substituted pyridyl nonaflate PM60.
Scheme 16: Condensation of LANCA-derived β-ketoenamides KE with hydroxylamine hydrochloride leading to pyrimid...
Scheme 17: Reactions of β-ketoenamides KE15 and KE7 with hydroxylamine hydrochloride leading to pyrimidine N-o...
Scheme 18: Structures of pyrimidine N-oxides PO30–33 derived from β-ketoenamides KE43, KE45, KE78 and KE80.
Scheme 19: Reduction of PO4 to PM5 and Boekelheide rearrangements of PO13, PO14, PO4 and PO30 to 4-acetoxymeth...
Scheme 20: Deprotection of 4-acetoxymethyl-substituted pyrimidine derivatives PM61 and PM63, oxidations to for...
Scheme 21: Synthesis of pyrimidinyl-substituted alkyne PM74 and conversion into furopyrimidine PM75 and Sonoga...
Scheme 22: Trifluoroacetic acid-promoted conversion of LANCA-derived β-ketoenamides KE into oxazoles OX and 1,...
Scheme 23: Conversion of β-ketoenamide KE79 into oxazole OX16 and transformation into 5-styryl-substituted oxa...
Scheme 24: Mechanisms of the formation of 1,2-diketones DK and of acetyl-substituted oxazole derivatives OX.
Scheme 25: Hydrogenolyses of benzyloxy-substituted β-ketoenamides KE52 and KE54 to 1,2-diketone DK14 and to di...
Scheme 26: Conversions of 2,4-dicyclopropyl-substituted oxazole OX7 into oxazole derivatives OX18–20 (PPA = po...
Scheme 27: Syntheses of vinyl and ethynyl-substituted oxazole derivatives OX21 and OX23 and their palladium-ca...
Scheme 28: Synthesis of C3-symmetric oxazole derivative OX28 and the STM current image of its 1-phenyloctane s...
Scheme 29: Condensation of 1,2-diketones DK with o-phenylenediamine to quinoxalines QU1–7 (CAN = cerium ammoni...
Scheme 30: The LANCA three-component reaction leading to β-ketoenamides KE and the structure of functionalized...
Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines
- Andrejs Šišuļins,
- Jonas Bucevičius,
- Yu-Ting Tseng,
- Irina Novosjolova,
- Kaspars Traskovskis,
- Ērika Bizdēna,
- Huan-Tsung Chang,
- Sigitas Tumkevičius and
- Māris Turks
Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41
- to increased fluorescence quantum yield (74%) in THF solution. The compounds exhibit low cytotoxicity and as such are useful for the cell labelling studies in the future. Keywords: 7-deazapurines; fluorescence; nucleophilic aromatic substitution; purines; push–pull systems; pyrrolo[2,3-d]pyrimidines
Graphical Abstract
Figure 1: Examples of fluorescent purine/7-deazapurine derivatives.
Scheme 1: General synthetic routes for the compounds 5, 7–9, 10 and 11. Method A: alkyl halogenide, MeCN or D...
Figure 2: 1H NMR spectra of compound 6b in CD3CN at different temperatures (300 MHz, c = 12.5 mg/mL); a, b, c...
Figure 3: Comparison of 1H NMR spectra of compounds 8a and 5 (300 MHz, CDCl3).
Figure 4: a) Experimental UV–vis absorption spectra (lines) with computed theoretical absorption bands (colum...
Figure 5: Photos of compound 8c (A and B) and compound 11c (C and D) in THF, CHCl3, DMSO, MeCN and MeOH befor...
Figure 6: a) Fluorescence spectra of compounds 8c (λexc = 360 nm) and 11c (λexc = 370 nm) in solvents of diff...
Figure 7: Energy diagram for the frontier molecular orbitals of compounds 8a, 8c, 11a and 11c.
Figure 8: Labeled MCF-7 cells using compound 9 (C,D) and unlabeled MCF-7 cells (A,B) in microscope (2 h, c(9)...
Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers
- Christian Schütz and
- Martin Empting
Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241
Graphical Abstract
Figure 1: The four quorum sensing systems in P. aeruginosa las, iqs, rhl, and pqs. Abbreviations: OdDHL, N-(3...
Figure 2: Schematic overview of the PQS biosynthesis and involvement of related metabolites and PqsE in virul...
Figure 3: Anthranilic acid (1) and derivatives thereof (2–4).
Figure 4: Crystal structure of 6-FABA-AMP in complex with PqsA.
Figure 5: Structures of substrate mimetic PqsA inhibitors.
Figure 6: Structures and characteristics of prominent classes of PqsD inhibitors.
Figure 7: Comparison of docking poses of three prototypic PqsD inhibitors: benzamidobenzoic acid derivative 12...
Figure 8: Structures and characteristics of hits against PqsD identified through different methods.
Figure 9: HHQ and PQS analogues as PqsD inhibitors and chemical probe used for screening.
Figure 10: Structure of PqsD-targeting biofilm inhibitor derived from linezolid.
Figure 11: Fragment-based PqsE-inhibitors 24–26.
Figure 12: PqsE co-crystal structures. (A) native product 2-ABA; (B–D) hit fragments 24–26.
Figure 13: Structurally diverse PqsBC-inhibitors 27–30.
Figure 14: Native PqsR ligand HHQ (31) which is converted into PQS (32) by PqsH and synthetic inhibitors 33 an...
Figure 15: Quinazolinone inhibitor 36 (QZN).
Figure 16: Crystal structure of QZN (36) in complex with PqsRCBD.
Figure 17: Structures of best fitting compounds 37–40 obtained from docking studies.
Figure 18: Initial hit 21 and optimized compound 42 (M64).
Figure 19: Co-crystal structure of M64 (42) with PqsRLBD.
Figure 20: M64 (42) as the starting point for further optimization leading to 43, which was further modified a...
Figure 21: Hit fragments from the benzamide (47–48) and oxadiazole class (49–51).
Figure 22: Structures of dual inhibitors 52–55.
Figure 23: Sulfonyl pyrimidines 56–58 acting as dual PqsD/PqsR inhibitors.
Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry
- Michael K. Bogdos,
- Emmanuel Pinard and
- John A. Murphy
Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179
- oxidant (Scheme 22) [67]. Heterocycles in drugs are not only restricted to five-membered rings. Pyridines, pyrazines, pyrimidines, pyridazines are all common functional groups in biologically active compounds. Liu et al. have published the visible light-catalysed oxidation of dihydropyrimidines (DHPMs
Graphical Abstract
Figure 1: Depiction of the energy levels of a typical organic molecule and the photophysical processes it can...
Figure 2: General catalytic cycle of a photocatalyst in a photoredox organocatalysed reaction. [cat] – photoc...
Figure 3: Structures and names of the most common photocatalysts encountered in the reviewed literature.
Figure 4: General example of a reductive quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocata...
Figure 5: General example of an oxidative quenching catalytic cycle. [cat] – photocatalyst, [cat]* – photocat...
Scheme 1: Oxidative coupling of aldehydes and amines to amides using acridinium salt photocatalysis.
Figure 6: Biologically active molecules containing a benzamide linkage.
Scheme 2: The photocatalytic reduction of amino acids to produce the corresponding free or protected amines.
Scheme 3: The organocatalysed photoredox base-mediated oxidation of thiols to disulfides.
Scheme 4: C-Terminal modification of peptides and proteins using organophotoredox catalysis.
Scheme 5: The reduction and aryl coupling of aryl halides using a doubly excited photocatalyst (PDI).
Figure 7: Mechanism for the coupling of aryl halides using PDI, which is excited sequentially by two photons.
Scheme 6: The arylation of five-membered heteroarenes using arenediazonium salts under organophotoredox condi...
Scheme 7: The C–H (hetero)arylation of five-membered heterocycles under Eosin Y photocatalysis.
Scheme 8: The C–H sulfurisation of imidazoheterocycles using Eosin B-catalyzed photochemical methods.
Scheme 9: The introduction of the thiocyanate group using Eosin Y photocatalysis.
Scheme 10: Sulfonamidation of pyrroles using oxygen as the terminal oxidant.
Scheme 11: DDQ-catalysed C–H amination of arenes and heteroarenes.
Scheme 12: Photoredox-promoted radical Michael addition reactions of allylic or benzylic carbons.
Figure 8: Proposed mechanistic rationale for the observed chemoselectivities.
Scheme 13: The photocatalytic manipulation of C–H bonds adjacent to amine groups.
Scheme 14: The perylene-catalysed organophotoredox tandem difluoromethylation–acetamidation of styrene-type al...
Figure 9: Examples of biologically active molecules containing highly functionalised five membered heterocycl...
Scheme 15: The [3 + 2]-cycloaddition leading to the formation of pyrroles, through the reaction of 2H-azirines...
Figure 10: Proposed intermediate that determines the regioselectivity of the reaction.
Figure 11: Comparison of possible pathways of reaction and various intermediates involved.
Scheme 16: The acridinium salt-catalysed formation of oxazoles from aldehydes and 2H-azirines.
Scheme 17: The synthesis of oxazolines and thiazolines from amides and thioamides using organocatalysed photor...
Figure 12: Biologically active molecules on the market containing 1,3,4-oxadiazole moieties.
Scheme 18: The synthesis of 1,3,4-oxadiazoles from aldehyde semicarbazones using Eosin Y organophotocatalysis.
Scheme 19: The dimerization of primary thioamides to 1,2,4-thiadiazoles catalysed by the presence of Eosin Y a...
Scheme 20: The radical cycloaddition of o-methylthioarenediazonium salts and substituted alkynes towards the f...
Scheme 21: The dehydrogenative cascade reaction for the synthesis of 5,6-benzofused heterocyclic systems.
Figure 13: Trifluoromethylated version of compounds which have known biological activities.
Scheme 22: Eosin Y-catalysed photoredox formation of 3-substituted benzimidazoles.
Scheme 23: Oxidation of dihydropyrimidines by atmospheric oxygen using photoredox catalysis.
Scheme 24: Photoredox-organocatalysed transformation of 2-substituted phenolic imines to benzoxazoles.
Scheme 25: Visible light-driven oxidative annulation of arylamidines.
Scheme 26: Methylene blue-photocatalysed direct C–H trifluoromethylation of heterocycles.
Scheme 27: Photoredox hydrotrifluoromethylation of terminal alkenes and alkynes.
Scheme 28: Trifluoromethylation and perfluoroalkylation of aromatics and heteroaromatics.
Scheme 29: The cooperative asymmetric and photoredox catalysis towards the functionalisation of α-amino sp3 C–...
Scheme 30: Organophotoredox-catalysed direct C–H amidation of aromatics.
Scheme 31: Direct C–H alkylation of heterocycles using BF3K salts. CFL – compact fluorescent lamp.
Figure 14: The modification of camptothecin, demonstrating the use of the Molander protocol in LSF.
Scheme 32: Direct C–H amination of aromatics using acridinium salts.
Scheme 33: Photoredox-catalysed nucleophilic aromatic substitution of nucleophiles onto methoxybenzene derivat...
Scheme 34: The direct C–H cyanation of aromatics with a focus on its use for LSF.
Synthesis of pyrazolopyrimidinones using a “one-pot” approach under microwave irradiation
- Mark Kelada,
- John M. D. Walsh,
- Robert W. Devine,
- Patrick McArdle and
- John C. Stephens
Beilstein J. Org. Chem. 2018, 14, 1222–1228, doi:10.3762/bjoc.14.104
- [3,4-b]pyridines, pyrazolo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidinones [12][13][14][15][16][17][18]. The majority of methods used in the generation of the pyrazolo[1,5-a]pyrimidinones employ a two-step process, which first requires the synthesis and isolation of the intermediate 5-aminopyrazoles
Graphical Abstract
Figure 1: Bioactive pyrazolo[1,5-a]pyrimidinones.
Scheme 1: Synthesis of 5-aminopyrazoles. Reaction conditions: ketonitrile (2.0 mmol, 1.0 equiv), hydrazine (2...
Scheme 2: One-pot synthesis of pyrazolo[1,5-a]pyrimidinones. aReaction conditions: ketonitrile (0.9 mmol, 1.0...
Figure 2: X-ray crystal structure of pyrazolo[1,5-a]pyrimidinone 3m with ellipsoids at 50% probability.
Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides
- Kartik Temburnikar and
- Katherine L. Seley-Radtke
Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65
- feature (hetero)aryl aromatic groups such as 9-deazapurines, pyrimidines, pyridines and phenyl groups connected by a C–C bond to a sugar (or sugar mimic) as shown in Figure 4 [30][45][46][47][50][54][55][56][57]. The change in the nature of the glycosidic bond is accompanied by i) increased hydrolytic
Graphical Abstract
Figure 1: Structural components of nucleic acids. Shown is the monomeric building block of nucleic acids. Cha...
Figure 2: Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leavin...
Figure 3: Structural modifications to nucleobase-sugar connectivity. The O–C–N bond between nucleobase and su...
Figure 4: Examples of natural and synthetic C-nucleosides. Pseudouridine and formcycin are among several natu...
Figure 5: Synthetic approaches to C-nucleosides. A. Two common strategies for C-nucleoside synthesis involve ...
Figure 6: Steroselective C-nucleoside synthesis using D-ribonolactone. A. Nucleophilic substitution of D-ribo...
Figure 7: Synthesis of C1'-substituted 4-aza-7,9-dideazaadenine C-nucleosides [63-65,69,70]. A. Reaction of D-ribonolacton...
Figure 8: Pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides. A series of sugar- and nucleobase-substit...
Figure 9: Synthesis of 1',2'-cyclopentyl C-nucleoside [73]. Functional groups at C1' and C2' were installed and e...
Figure 10: Anti-influenza C-nucleosides mimicking favipiravir riboside [74]. A. Structure of favipiravir and its r...
Figure 11: Alternative method for synthesis of 2'-substituted C-nucleosides [75]. A. Synthesis of C2'-substituted ...
Figure 12: Synthesis of carbocyclic C-nucleosides using cyclopentanone [53]. A. Nucleophlic substitution on cyclop...
Figure 13: Synthesis of carbocyclic C-nucleosides via Suzuki coupling [53]. A. Synthesis of OTf-cyclopentene that ...
5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines
- Ranjana Aggarwal and
- Suresh Kumar
Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15
- extensively employed as useful synthons in designing and constructing a plethora of fused pyrazoloazines of potential synthetic and medicinal interest viz pyrazolo[3,4-b]pyridines 7 [18], pyrazolo[1,5-a]pyrimidines 8 [19], pyrazolo[3,4-d]pyrimidines 9 [20][21], pyrazolo[3,4-b]pyrazines 10 [22], pyrazolo[5,1-c
- spiropyrazolo[3,4-b]pyridines 63 and 64 starting from 5-aminopyrazole (R = H, R1 = Me, 16), isatin 54 and α-cyanoacetic ester 62 or 15 in aqueous-mediated reaction in presence of NaCl. Regioisomeric pyrazolo[1,5-a]pyrimidines 65 were not formed in any of the tried reaction conditions. An increase in the amount
- ). Synthesis of pyrazolo[1,5-a]pyrimidines Pyrazolo[1,5-a]pyrimidines, structural isomers of pyrazolo[3,4-b]pyridines, are of interest because they constitute an important class of heterocycles which display biological and pharmacological activities and are useful precursors in the synthesis of many
Graphical Abstract
Figure 1: Selected examples of drugs with fused pyrazole rings.
Figure 2: Typical structures of some fused pyrazoloazines from 5-aminopyrazoles.
Scheme 1: Regiospecific synthesis of 4 and 6-trifluoromethyl-1H-pyrazolo[3,4-b]pyridines.
Scheme 2: Synthesis of pyrazolo[3,4-b]pyridine-6-carboxylates.
Scheme 3: Synthesis of 1,4,6-triaryl-1H-pyrazolo[3,4-b]pyridines with ionic liquid .
Scheme 4: Synthesis of coumarin-based isomeric tetracyclic pyrazolo[3,4-b]pyridines.
Scheme 5: Synthesis of 6-substituted pyrazolo[3,4-b]pyridines under Heck conditions.
Scheme 6: Microwave-assisted palladium-catalyzed synthesis of pyrazolo[3,4-b]pyridines.
Scheme 7: Acid-catalyzed synthesis of pyrazolo[3,4-b]pyridines via enaminones.
Scheme 8: Synthesis of pyrazolo[3,4-b]pyridines via aza-Diels–Alder reaction.
Scheme 9: Synthesis of macrocyclane fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 10: Three-component synthesis of 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine derivatives.
Scheme 11: Ultrasonicated synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-diones.
Scheme 12: Synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine] derivatives under conventional heating co...
Scheme 13: Nanoparticle-catalyzed synthesis of pyrazolo[3,4-b]pyridine-spiroindolinones.
Scheme 14: Microwave-assisted multicomponent synthesis of spiropyrazolo[3,4-b]pyridines.
Scheme 15: Unexpected synthesis of naphthoic acid-substituted pyrazolo[3,4-b]pyridines.
Scheme 16: Multicomponent synthesis of variously substituted pyrazolo[3,4-b]pyridine derivatives.
Scheme 17: Three-component synthesis of 4,7-dihydropyrazolo[3,4-b]pyridines and pyrazolo[3,4-b]pyridines.
Scheme 18: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanediones.
Scheme 19: Ultrasound-mediated three-component synthesis of pyrazolo[3,4-b]pyridines.
Scheme 20: Multicomponent synthesis of 4-aryl-3-methyl-1-phenyl-4,6,8,9-tetrahydropyrazolo [3,4-b]thiopyrano[4...
Scheme 21: Synthesis of 2,3-dihydrochromeno[4,3-d]pyrazolo[3,4-b]pyridine-1,6-diones.
Scheme 22: FeCl3-catalyzed synthesis of o-hydroxyphenylpyrazolo[3,4-b]pyridine derivatives.
Scheme 23: Ionic liquid-mediated synthesis of pyrazolo[3,4-b]pyridines.
Scheme 24: Microwave-assisted synthesis of pyrazolo[3,4-b]pyridines.
Scheme 25: Multicomponent synthesis of pyrazolo[3,4-b]pyridine-5-carbonitriles.
Scheme 26: Unusual domino synthesis of 4,7-dihydropyrazolo[3,4-b]pyridine-5-nitriles.
Scheme 27: Synthesis of 4,5,6,7-tetrahydro-4H-pyrazolo[3,4-b]pyridines under conventional heating and ultrasou...
Scheme 28: L-Proline-catalyzed synthesis of of pyrazolo[3,4-b]pyridine.
Scheme 29: Microwave-assisted synthesis of 5-aminoarylpyrazolo[3,4-b]pyridines.
Scheme 30: Microwave-assisted multi-component synthesis of pyrazolo[3,4-e]indolizines.
Scheme 31: Synthesis of fluoropropynyl and fluoroalkyl substituted pyrazolo[1,5-a]pyrimidine.
Scheme 32: Acid-catalyzed synthesis of pyrazolo[1,5-a]pyrimidine derivatives.
Scheme 33: Chemoselective and regiospecific synthesis of 2-(3-methylpyrazol-1’-yl)-5-methylpyrazolo[1,5-a]pyri...
Scheme 34: Regioselective synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
Scheme 35: Microwave-assisted synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidine carboxylates.
Scheme 36: Microwave and ultrasound-assisted synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
Scheme 37: Base-catalyzed unprecedented synthesis of pyrazolo[1,5-a]pyrimidines via C–C bond cleavage.
Scheme 38: Synthesis of aminobenzothiazole/piperazine linked pyrazolo[1,5-a]pyrimidines.
Scheme 39: Synthesis of aminoalkylpyrazolo[1,5-a]pyrimidine-7-amines.
Scheme 40: Synthesis of pyrazolo[1,5-a]pyrimidines from condensation of 5-aminopyrazole 126 and ethyl acetoace...
Scheme 41: Synthesis of 7-aminopyrazolo[1,5-a]pyrimidines.
Scheme 42: Unexpected synthesis of 7-aminopyrazolo[1,5-a]pyrimidines under solvent free and solvent-mediated c...
Scheme 43: Synthesis of N-(4-aminophenyl)-7-aryloxypyrazolo[1,5-a]pyrimidin-5-amines.
Scheme 44: Base-catalyzed synthesis of 5,7-diarylpyrazolo[1,5-a]pyrimidines.
Scheme 45: Synthesis of 6,7-dihydropyrazolo[1,5-a]pyrimidines in PEG-400.
Scheme 46: Synthesis of 7-heteroarylpyrazolo[1,5-a]pyrimidine-3-carboxamides.
Scheme 47: Synthesis of 7-heteroarylpyrazolo[1,5-a]pyrimidine derivatives under conventional heating and micro...
Scheme 48: Synthesis of N-aroylpyrazolo[1,5-a]pyrimidine-5-amines.
Scheme 49: Regioselective synthesis of ethyl pyrazolo[1,5-a]pyrimidine-7-carboxylate.
Scheme 50: Sodium methoxide-catalyzed synthesis of 3-cyano-6,7-diarylpyrazolo[1,5-a]pyrimidines.
Scheme 51: Synthesis of various pyrazolo[3,4-d]pyrimidine derivatives.
Scheme 52: Synthesis of hydrazinopyrazolo[3,4-d]pyrimidine derivatives.
Scheme 53: Synthesis of N-arylidinepyrazolo[3,4-d]pyrimidin-5-amines.
Scheme 54: Synthesis of pyrazolo[3,4-d]pyrimidinyl-4-amines.
Scheme 55: Iodine-catalyzed synthesis of pyrazolo[3,4-d]pyrimidinones.
Scheme 56: Synthesis of ethyl 6-amino-2H-pyrazolo[3,4-d]pyrimidine-4-carboxylate.
Scheme 57: Synthesis of 4-substituted-(3,6-dihydropyran-4-yl)-1H-pyrazolo[3,4-d]pyrimidines.
Scheme 58: Synthesis of 1-(2,4-dichlorophenyl)pyrazolo[3,4-d]pyrimidin-4-yl carboxamides.
Scheme 59: Synthesis of 5-(1,3,4-thidiazol-2-yl)pyrazolo[3,4-d]pyrimidine.
Scheme 60: One pot POCl3-catalyzed synthesis of 1-arylpyrazolo[3,4-d]pyrimidin-4-ones.
Scheme 61: Synthesis of 4-amino-N1,C3-dialkylpyrazolo[3,4-d]pyrimidines under Suzuki conditions.
Scheme 62: Microwave-assisted synthesis of pyrazolo[3,4-b]pyrazines.
Scheme 63: Synthesis and derivatization of pyrazolo[3,4-b]pyrazine-5-carbonitriles.
Scheme 64: Synthesis of 2-thioxo-pyrazolo[1,5-a][1,3,5]triazin-4-ones.
Scheme 65: Synthesis of 2,3-dihydropyrazolo[1,5-a][1,3,5]triazin-4(1H)-one.
Scheme 66: Synthesis of pyrazolo[1,5-a][1,3,5]triazine-8-carboxylic acid ethyl ester.
Scheme 67: Microwave-assisted synthesis of 4,7-dihetarylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 68: Alternative synthetic route to 4,7-diheteroarylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 69: Synthesis of 4-aryl-2-ethylthio-7-methylpyrazolo[1,5-a][1,3,5]triazines.
Scheme 70: Microwave-assisted synthesis of 4-aminopyrazolo[1,5-a][1,3,5]triazine.
Scheme 71: Synthesis of pyrazolo[3,4-d][1,2,3]triazines from pyrazol-5-yl diazonium salts.
Scheme 72: Synthesis of 2,5-dihydropyrazolo[3,4-e][1,2,4]triazines.
Scheme 73: Synthesis of pyrazolo[5,1-c][1,2,4]triazines via diazopyrazolylenaminones.
Scheme 74: Synthesis of pyrazolo[5,1-c][1,2,4]triazines in presence of sodium acetate.
Scheme 75: Synthesis of various 7-diazopyrazolo[5,1-c][1,2,4]triazine derivatives.
Scheme 76: One pot synthesis of pyrazolo[5,1-c][1,2,4]triazines.
Scheme 77: Synthesis of 4-amino-3,7,8-trinitropyrazolo-[5,1-c][1,2,4]triazines.
Scheme 78: Synthesis of tricyclic pyrazolo[5,1-c][1,2,4]triazines by azocoupling reaction.
Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications
- Mattias Bood,
- Sangamesh Sarangamath,
- Moa S. Wranne,
- Morten Grøtli and
- L. Marcus Wilhelmsson
Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7
- small modifications to nucleobases, such as the 8-vinyldeoxyadenosine [21], has led to the introduction of fluorescence. Considering the differences in the structures of purines and pyrimidines, adenine is unique amongst the natural bases as it offers several sites for modifications: C2, C8, the C6
- pyrimidines, only the C5 and C6 positions are available for modifications without directly perturbing the base-pairing properties. The subtle differences between the nucleobases within a class could lead one to believe that the chemistry developed for modifications of adenine would translate easily to guanine
- found to be general for a large set of 4-hydroxy-5-(o-aminoarylthio)pyrimidines [39]. The mechanism was thought to proceed via protonation of a pyrimidine ring nitrogen which activates it to nucleophilic attack by an unprotonated anilino nitrogen on the positive C4 of the pyrimidine ring which carries
Graphical Abstract
Figure 1: a) Angles and unit vectors used to define the relative orientations of the donor and acceptor trans...
Figure 2: Notable recent examples of fluorescent base analogues. For cnA and dnA the attachment point to the ...
Scheme 1: Synthesis of the tricyclic cytosine aromatic core [39]. (a) Ethylene glycol, K2CO3, 120 °C, 1 h, 40%; (...
Scheme 2: Synthesis of protected tC and tCO deoxyribose phosphonates [41]. (a) Ac2O, pyridine, rt; (b) 2-mesityle...
Scheme 3: Synthesis of protected tCnitro deoxyribose phosphoramidite [14]. a) aq NaOH, 24 h, reflux; b) EtOH, HCl...
Scheme 4: Improved synthesis of tC and tC derivatives, where R = H, 7-MeO or 8-MeO [47]. a) H2NNH2 followed by H2O...
Scheme 5: Improved synthesis of tCO derivatives [47]. a) Ac2O, pyridine, 16 h, rt, 85%; b) PPh3, CCl4, DCM, 5 h, ...
Scheme 6: Synthesis of protected tCO ribose phosphoramidite [50]. a) MesSO2Cl, DIPEA, MeCN, 4 h, rt; b) 2-aminoph...
Scheme 7: Synthesis of protected deoxyribose qA [51]. a) N-(tert-Butoxycarbonyl)-2-(trimethylstannyl)aniline, (Ph3...
Scheme 8: Synthesis of protected deoxyribose qA for DNA SPS [53]. a) AcCl, MeOH, rt, 40 min; b) p-toluoyl chlorid...
Scheme 9: Synthesis of qA derivatives. a) EtI, Cs2CO3, DMF, 4 h, rt, 90%; b) HBPin, Pd(PPh3)4, Et3N, 1,4-diox...
Scheme 10: Synthesis of quadracyclic adenine base–base FRET pair. a) HCHO, NaOH, MeCN, H2O, 50 °C, 1 h; b) TBD...
Figure 3: Absorption and emission of tC (dashed line) and tCO (solid line) in dsDNA. The absorption below 300...
Figure 4: Spectral overlap between the emission of qAN1 (cyan) and the absorption of qAnitro (black) in dsDNA...
Figure 5: Example of typical FRET efficiency as a function of number of base pairs separating the donor and a...
Figure 6: FRET efficiency as a function of number of base pairs separating the donor (qAN1) and acceptor (qAn...
CF3SO2X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF3SO2Na
- Hélène Guyon,
- Hélène Chachignon and
- Dominique Cahard
Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272
- metals found in Langlois’ reagent could be responsible for reaction initiation. The scope was evaluated on pyridines, pyrroles, indoles, pyrimidines, pyrazines, phthalazines, quinoxalines, deazapurine, thiadiazoles, uracils, xanthenes and pyrazolino-pyrimidines (Scheme 35). The combination of previous
Graphical Abstract
Scheme 1: Trifluoromethylation of enol acetates by Langlois.
Scheme 2: Trifluoromethylation of (het)aryl enol acetates.
Scheme 3: Mechanism for the trifluoromethylation of enol acetates.
Scheme 4: Oxidative trifluoromethylation of unactivated olefins and mechanistic pathway.
Scheme 5: Oxidative trifluoromethylation of acetylenic substrates.
Scheme 6: Metal free trifluoromethylation of styrenes.
Scheme 7: Synthesis of α-trifluoromethylated ketones by oxytrifluoromethylation of heteroatom-functionalised ...
Scheme 8: Catalysed photoredox trifluoromethylation of vinyl azides.
Scheme 9: Oxidative difunctionalisation of alkenyl MIDA boronates.
Scheme 10: Synthesis of β-trifluoromethyl ketones from cyclopropanols.
Scheme 11: Aryltrifluoromethylation of allylic alcohols.
Scheme 12: Cascade multicomponent synthesis of nitrogen heterocycles via azotrifluoromethylation of alkenes.
Scheme 13: Photocatalytic azotrifluoromethylation of alkenes with aryldiazonium salts and CF3SO2Na.
Scheme 14: Copper-promoted intramolecular aminotrifluoromethylation of alkenes with CF3SO2Na.
Scheme 15: Oxytrifluoromethylation of alkenes with CF3SO2Na and hydroxamic acid.
Scheme 16: Manganese-catalysed oxytrifluoromethylation of styrene derivatives.
Scheme 17: Oxytrifluoromethylation of alkenes with NMP/O2 and CF3SO2Na.
Scheme 18: Intramolecular oxytrifluoromethylation of alkenes.
Scheme 19: Hydrotrifluoromethylation of styrenyl alkenes and unactivated aliphatic alkenes.
Scheme 20: Hydrotrifluoromethylation of electron-deficient alkenes.
Scheme 21: Hydrotrifluoromethylation of alkenes by iridium photoredox catalysis.
Scheme 22: Iodo- and bromotrifluoromethylation of alkenes by CF3SO2Na/I2O5 or CF3SO2Na / NaBrO3.
Scheme 23: N-methyl-9-mesityl acridinium and visible-light-induced chloro-, bromo- and SCF3 trifluoromethylati...
Scheme 24: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na / TBHP by Lipshutz.
Scheme 25: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/TBHP reported by Lei.
Scheme 26: Carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/(NH4)2S2O8.
Scheme 27: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/K2S2O8 reported by Wang.
Scheme 28: Metal-free carbotrifluoromethylation of N-arylacrylamides with CF3SO2Na/PIDA reported by Fu.
Scheme 29: Metal-free cascade trifluoromethylation/cyclisation of N-arylmethacrylamides (a) and enynes (b) wit...
Scheme 30: Trifluoromethylation/cyclisation of N-arylcinnamamides: Synthesis of 3,4-disubstituted dihydroquino...
Scheme 31: Trifluoromethylation/cyclisation of aromatic-containing unsaturated ketones.
Scheme 32: Chemo- and regioselective cascade trifluoromethylation/heteroaryl ipso-migration of unactivated alk...
Scheme 33: Copper-mediated 1,2-bis(trifluoromethylation) of alkenes.
Scheme 34: Trifluoromethylation of aromatics with CF3SO2Na reported by Langlois.
Scheme 35: Baran’s oxidative C–H trifluoromethylation of heterocycles.
Scheme 36: Trifluoromethylation of acetanilides and anilines.
Scheme 37: Trifluoromethylation of heterocycles in water.
Scheme 38: Trifluoromethylation of coumarins in a continuous-flow reactor.
Scheme 39: Oxidative trifluoromethylation of coumarins, quinolines and pyrimidinones.
Scheme 40: Oxidative trifluoromethylation of pyrimidinones and pyridinones.
Scheme 41: Phosphovanadomolybdic acid-catalysed direct C−H trifluoromethylation.
Scheme 42: Oxidative trifluoromethylation of imidazopyridines and imidazoheterocycles.
Scheme 43: Oxidative trifluoromethylation of imidazoheterocycles and imidazoles in ionic liquid/water.
Scheme 44: Oxidative trifluoromethylation of 8-aminoquinolines.
Scheme 45: Oxidative trifluoromethylation of various 8-aminoquinolines using the supported catalyst CS@Cu(OAc)2...
Scheme 46: Oxidative trifluoromethylation of the naphthylamide 70.
Scheme 47: Oxidative trifluoromethylation of various arenes in the presence of CF3SO2Na and sodium persulfate.
Scheme 48: Trifluoromethylation of electron-rich arenes and unsymmetrical biaryls with CF3SO2Na in the presenc...
Figure 1: Trifluoromethylated coumarin and flavone.
Scheme 49: Metal-free trifluoromethylation catalysed by a photoredox organocatalyst.
Scheme 50: Quinone-mediated trifluoromethylation of arenes and heteroarenes.
Scheme 51: Metal- and oxidant-free photochemical trifluoromethylation of arenes.
Scheme 52: Copper-mediated trifluoromethylation of arenediazonium tetrafluoroborates.
Scheme 53: Oxidative trifluoromethylation of aryl- and heteroarylboronic acids.
Scheme 54: Oxidative trifluoromethylation of aryl- and vinylboronic acids.
Scheme 55: Oxidative trifluoromethylation of unsaturated potassium organotrifluoroborates.
Scheme 56: Oxidative trifluoromethylation of (hetero)aryl- and vinyltrifluoroborates.
Scheme 57: Copper−catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 58: Iron-mediated decarboxylative trifluoromethylation of α,β-unsaturated carboxylic acids.
Scheme 59: Cu/Ag-catalysed decarboxylative trifluoromethylation of cinnamic acids.
Scheme 60: I2O5-Promoted decarboxylative trifluoromethylation of cinnamic acids.
Scheme 61: Silver(I)-catalysed denitrative trifluoromethylation of β-nitrostyrenes.
Scheme 62: Copper-catalysed direct trifluoromethylation of styrene derivatives.
Scheme 63: Transition-metal-free synthesis of β-trifluoromethylated enamines.
Scheme 64: I2O5-mediated iodotrifluoromethylation of alkynes.
Scheme 65: Silver-catalysed tandem trifluoromethylation/cyclisation of aryl isonitriles.
Scheme 66: Photoredox trifluoromethylation of 2-isocyanobiphenyls.
Scheme 67: Trifluoromethylation of potassium alkynyltrifluoroborates with CF3SO2Na.
Scheme 68: N-trifluoromethylation of nitrosoarenes with CF3SO2Na (SQ: semiquinone).
Scheme 69: Trifluoromethylation of disulfides with CF3SO2Na.
Scheme 70: Trifluoromethylation of thiols with CF3SO2Na/I2O5.
Scheme 71: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/CuCl/DMSO.
Scheme 72: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/(EtO)2P(O)H/TMSCl.
Scheme 73: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PPh3/N-chlorophthalimide.
Scheme 74: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 75: Electrophilic trifluoromethylsulfenylation by means of CF3SO2Na/PCl3.
Scheme 76: Trifluoromethylsulfenylation of aryl iodides with in situ generated CuSCF3 (DMI: 1,3-dimethyl-2-imi...
Scheme 77: Pioneering trifluoromethylsulfinylation of N, O, and C-nucleophiles.
Scheme 78: Trifluoromethylsulfinylation of (1R,2S)-ephedrine (Im: imidazole; DIEA: N,N-diisopropylethylamine).
Scheme 79: Trifluoromethylsulfinylation of substituted benzenes with CF3SO2Na/CF3SO3H.
Scheme 80: Trifluoromethylsulfinylation of indoles with CF3SO2Na/P(O)Cl3.
Scheme 81: Trifluoromethylsulfinylation of indoles with CF3SO2Na/PCl3.
Scheme 82: Formation of triflones from benzyl bromides (DMA: dimethylacetamide).
Scheme 83: Formation of α-trifluoromethylsulfonyl ketones, esters, and amides.
Scheme 84: Allylic trifluoromethanesulfonylation of aromatic allylic alcohols.
Scheme 85: Copper-catalysed couplings of aryl iodonium salts with CF3SO2Na.
Scheme 86: Palladium-catalysed trifluoromethanesulfonylation of aryl triflates and chlorides with CF3SO2Na.
Scheme 87: Copper-catalysed coupling of arenediazonium tetrafluoroborates with CF3SO2Na.
Scheme 88: Synthesis of phenyltriflone via coupling of benzyne with CF3SO2Na.
Scheme 89: Synthesis of 1-trifluoromethanesulfonylcyclopentenes from 1-alkynyl-λ3-bromanes and CF3SO2Na.
Scheme 90: One-pot synthesis of functionalised vinyl triflones.
Scheme 91: Regioselective synthesis of vinyltriflones from styrenes.
Scheme 92: Trifluoromethanesulfonylation of alkynyl(phenyl) iodonium tosylates by CF3SO2Na.
Scheme 93: Synthesis of thio- and selenotrifluoromethanesulfonates.
A novel synthetic approach to hydroimidazo[1,5-b]pyridazines by the recyclization of itaconimides and HPLC–HRMS monitoring of the reaction pathway
- Dmitry Yu. Vandyshev,
- Khidmet S. Shikhaliev,
- Andrey Yu. Potapov,
- Michael Yu. Krysin,
- Fedor I. Zubkov and
- Lyudmila V. Sapronova
Beilstein J. Org. Chem. 2017, 13, 2561–2568, doi:10.3762/bjoc.13.252
- derivatives, there is great interest in imidazo[1,5-annelated]diazines due to their diverse pharmacological actions and bioisosterism with imidazo[4,5-d]pyrimidines (purines). The presence of a bridgehead nitrogen atom is a common structural motif of these heterocyclic systems. For example, compounds with the
- imidazo[1,5-a]pyrazine structure show inhibitory activity against kinases BTK [1], MEK [2], ACK1 [3], mTORC1(2) [4], c-Src [5], growth factor IGF-1R [6] and act as the antagonists of Hedgehog pathway dependent malignancies [7]. Imidazo[1,5-a]pyrimidines are inhibitors of the bone morphogenic protein [8
- ], antitumor agents [9], and are stimulators of guanylate cyclase [10], whereas imidazo[1,5-c]pyrimidines demonstrate anti-infectious effects in the treatment of brucellosis [11], etc. However, the chemistry, medicinal chemistry and pharmacology of imidazo[1,5-b]pyridazines, with the imidazole ring connected
Graphical Abstract
Scheme 1: Intramolecular cyclization of 3-(aminomethyl)pyridazines and related compounds (route A). Condition...
Scheme 2: Heterocyclization of 1-aminoimidazoles with 1,3-dicarbonyl or α,β-unsaturated carbonyl compounds (r...
Scheme 3: Heterocyclization of 1-aminoimidazoles with structural transformation of dielectrophilic reagents (...
Scheme 4: Recyclization of N-arylitaconimides 1 with 1,2-diaminobenzimidazole (2).
Scheme 5: Possible synthetic routes of the interaction of itaconimides 1 with diaminoimidazole 4.
Scheme 6: 1H,13C-HMBC correlations: the most significant correlations for imidazopyridazine 9d and possible f...
15N-Labelling and structure determination of adamantylated azolo-azines in solution
- Sergey L. Deev,
- Alexander S. Paramonov,
- Tatyana S. Shestakova,
- Igor A. Khalymbadzha,
- Oleg N. Chupakhin,
- Julia O. Subbotina,
- Oleg S. Eltsov,
- Pavel A. Slepukhin,
- Vladimir L. Rusinov,
- Alexander S. Arseniev and
- Zakhar O. Shenkarev
Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250
- -ones in acidic conditions occurs through the formation of the adamantyl cation. Keywords: adamantylation; azolo-1,2,4-triazines; J-coupling; 15N-labelled; NMR spectra; 1,2,4-triazolo[1,5-a]pyrimidines; Introduction The incorporation of an adamantyl moiety in bioactive molecules and analogues of
- this approach for the syntheses of 15N-labelled tetrazolo[1,5-b][1,2,4]triazines and tetrazolo[1,5-a]pyrimidines [25] starting from 15N-labelled 5-aminotetrazole. However, due to proton tautomerism, the use of single-labelled [2-15N]-5-aminotetrazole led to the formation of isotopomer mixtures, which
- JHN interactions with the H2 proton in the 1,2,4-triazolo[5,1-c][1,2,4]triazines 19-15N2, 20-15N2, and 21a,b-15N2 and the H2 and H6 protons in the 1,2,4-triazolo[1,5-a]pyrimidines 23-15N2 and 24-15N2 permitted the straightforward assignments of the labelled 15N atoms (see Scheme 2 and Scheme 3). The
Graphical Abstract
Figure 1: (A) Adamantylated azoles and derivatives of 1,2,4-triazolo[5,1-c][1,2,4]triazine with antiviral act...
Scheme 1: Synthesis and adamantylation of 15N-labelled 13-15N2 and JHN and JCN data confirming the structures...
Scheme 2: Synthesis and adamantylation of 15N-labelled 20-15N2 and JHN and JCN data confirming the structures...
Scheme 3: Synthesis and adamantylation of 15N-labelled 23-15N2 and JHN and JCN data confirming the structure ...
Scheme 4: Isomerization of 15a in the presence of tetrazolo[1,5-b][1,2,4]triazin-7-one 13-15N2 and isotopic e...
Figure 2: 1D 15N NMR spectra of 30–70 mM 13-15N2, 15a,b-15N2, 20-15N2, 21a,b-15N2, 23-15N2 and 24-15N2 in DMS...
Figure 3: Signals of the C1' and C6 atoms in the proton-decoupled 1D 13C NMR spectra of 30–42 mM 15a,b-15N2, ...
Figure 4: Detection and quantification of the 1H-15N spin–spin interactions in compound 15a-15N2 (DMSO-d6, 45...
Figure 5: ORTEP diagrams of the X-ray structures of compounds 15a-15N2 (a) and 15b-15N2 (b). For clarity, the...
Scheme 5: Mechanism of the isomerization of compounds 15a and 15b.
Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines
- Elisandra Scapin,
- Paulo R. S. Salbego,
- Caroline R. Bender,
- Alexandre R. Meyer,
- Anderson B. Pagliari,
- Tainára Orlando,
- Geórgia C. Zimmer,
- Clarissa P. Frizzo,
- Helio G. Bonacorso,
- Nilo Zanatta and
- Marcos A. P. Martins
Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237
- de Química de Heterociclos (NUQUIMHE), Department of Chemistry, Federal University of Santa Maria (UFSM), 97105-900, Santa Maria, RS, Brazil 10.3762/bjoc.13.237 Abstract An efficient synthesis methodology for a series of tetrazolo[1,5-a]pyrimidines substituted at the 5- and 7-positions from the
- CCl3, which leads to tetrazolo[1,5-a]pyrimidines in high regioselectivity with R at the 7-position of the heterocyclic ring; and (b) precursor compounds with R = aryl or methyl, which leads to a mixture of compounds, tetrazolo[1,5-a] pyrimidines (R in the 5-position of the ring) and 2-azidopyrimidines
- theory (DFT) for energetic and molecular orbital (MO) calculations. Keywords: 5-aminotetrazol; azide–tetrazole equilibrium; 2-azidopyrimidine; β-enaminones; tetrazolo[1,5-a]pyrimidine; trifluoromethylatedtetrazolo[1,5-a]pyrimidines; Introduction Tetrazolo[1,5-a]pyrimidines have attracted attention in
Graphical Abstract
Figure 1: Hydrogen coupling constants (3JH-H) of (a) H6–H7 for 3a and (b) H5–H6 for 5h.
Figure 2: LUMO coefficients for (a) β-enaminones 1a,h, and their (b) conjugated acids.
Figure 3:
(a) 1H and (b) 13C NMR spectra demonstrating the 3d![[Graphic 9]](/bjoc/content/inline/1860-5397-13-237-i9.svg?max-width=637&scale=1.18182)
4d equilibrium in DMSO-d6 at 25 °C.
Figure 4: ORTEP® [45] plot of 7a with thermal ellipsoids drawn at 50% probability level.
Figure 5: Tetrazolo[1,5-a]pyrimidine observed in solution (CDCl3 and DMSO-d6) and 2-azidopyrimidine observed ...
Figure 6: ORTEP® [45] plot of 8i with thermal ellipsoids drawn at 50% probability level.
Figure 7: Representation of the possible equilibrium existing between 6i, 7i, and 8i.
Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains
- Layal Hariss,
- Kamal Bou Hadir,
- Mirvat El-Masri,
- Thierry Roisnel,
- René Grée and
- Ali Hachem
Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208
- prepared in fair yields by the reaction of gem-difluoroenones with aminopyridines, -pyrimidines and -pyridazines. Condensed heterocycles of this type play an important role as key core structures of various bioactive compounds. Further, starting with a chloroimidazopyridazine derivative, Pd-catalyzed
- demonstrated also good anticancer properties [11][12], while imidazo[1,2-a]pyrimidines 2 are also known for their antituberculosis activity [13], and imidazopyridazine 3 acts as a sirtuin modulator [14]. On the other hand, the incorporation of fluorine or fluorinated groups into organic molecules has been
- [24]. Herein, we report the synthesis of imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazopyridazines with fluorinated side chains following an efficient strategy developed by Hajra et al. [25]. This methodology, developed for the synthesis of 3-aroylimidazopyridines, involves a copper
Graphical Abstract
Figure 1: Representative examples of bioactive imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, imidazopyr...
Scheme 1: Retrosynthetic scheme for the preparation of our target molecules A.
Scheme 2: Synthesis of enones 6 with a gem-difluoroalkyl side chain.
Scheme 3: Synthesis of 7a.
Figure 2: Structures of 7a and 7e by X-ray crystallography analysis.
Scheme 4: One-pot synthesis of 7a.
Mechanochemical synthesis of small organic molecules
- Tapas Kumar Achar,
- Anima Bose and
- Prasenjit Mal
Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186
- , benzimidazoles, pyrimidines, indoles, etc. [114][136][137][138][139]. Further improvements are in demand for the development of synthesis with solvent-less, time efficient, less byproducts, energy saving, easy handling procedures, etc. [112][140][141]. In 2016, Rousseau and co-workers reported a solvent-free
Graphical Abstract
Scheme 1: Mechanochemical aldol condensation reactions [48].
Scheme 2: Enantioselective organocatalyzed aldol reactions under mechanomilling. a) Based on binam-(S)-prolin...
Scheme 3: Mechanochemical Michael reaction [51].
Scheme 4: Mechanochemical organocatalytic asymmetric Michael reaction [52].
Scheme 5: Mechanochemical Morita–Baylis–Hillman (MBH) reaction [53].
Scheme 6: Mechanochemical Wittig reactions [55].
Scheme 7: Mechanochemical Suzuki reaction [56].
Scheme 8: Mechanochemical Suzuki–Miyaura coupling by LAG [57].
Scheme 9: Mechanochemical Heck reaction [59].
Scheme 10: a) Sonogashira coupling under milling conditions. b) The representative example of a double Sonogas...
Scheme 11: Copper-catalyzed CDC reaction under mechanomilling [67].
Scheme 12: Asymmetric alkynylation of prochiral sp3 C–H bonds via CDC [68].
Scheme 13: Fe(III)-catalyzed CDC coupling of 3-benzylindoles [69].
Scheme 14: Mechanochemical synthesis of 3-vinylindoles and β,β-diindolylpropionates [70].
Scheme 15: Mechanochemical C–N bond construction using anilines and arylboronic acids [78].
Scheme 16: Mechanochemical amidation reaction from aromatic aldehydes and N-chloramine [79].
Scheme 17: Mechanochemical CDC between benzaldehydes and benzyl amines [81].
Scheme 18: Mechanochemical protection of -NH2 and -COOH group of amino acids [85].
Scheme 19: Mechanochemical Ritter reaction [87].
Scheme 20: Mechanochemical synthesis of dialkyl carbonates [90].
Scheme 21: Mechanochemical transesterification reaction using basic Al2O3 [91].
Scheme 22: Mechanochemical carbamate synthesis [92].
Scheme 23: Mechanochemical bromination reaction using NaBr and oxone [96].
Scheme 24: Mechanochemical aryl halogenation reactions using NaX and oxone [97].
Scheme 25: Mechanochemical halogenation reaction of electron-rich arenes [88,98].
Scheme 26: Mechanochemical aryl halogenation reaction using trihaloisocyanuric acids [100].
Scheme 27: Mechanochemical fluorination reaction by LAG method [102].
Scheme 28: Mechanochemical Ugi reaction [116].
Scheme 29: Mechanochemical Passerine reaction [116].
Scheme 30: Mechanochemical synthesis of α-aminonitriles [120].
Scheme 31: Mechanochemical Hantzsch pyrrole synthesis [121].
Scheme 32: Mechanochemical Biginelli reaction by subcomponent synthesis approach [133].
Scheme 33: Mechanochemical asymmetric multicomponent reaction[134].
Scheme 34: Mechanochemical Paal–Knorr pyrrole synthesis [142].
Scheme 35: Mechanochemical synthesis of benzothiazole using ZnO nano particles [146].
Scheme 36: Mechanochemical synthesis of 1,2-di-substituted benzimidazoles [149].
Scheme 37: Mechanochemical click reaction using an alumina-supported Cu-catalyst [152].
Scheme 38: Mechanochemical click reaction using copper vial [155].
Scheme 39: Mechanochemical indole synthesis [157].
Scheme 40: Mechanochemical synthesis of chromene [158].
Scheme 41: Mechanochemical synthesis of azacenes [169].
Scheme 42: Mechanochemical oxidative C-P bond formation [170].
Scheme 43: Mechanochemical C–chalcogen bond formation [171].
Scheme 44: Solvent-free synthesis of an organometallic complex.
Scheme 45: Selective examples of mechano-synthesis of organometallic complexes. a) Halogenation reaction of Re...
Scheme 46: Mechanochemical activation of C–H bond of unsymmetrical azobenzene [178].
Scheme 47: Mechanochemical synthesis of organometallic pincer complex [179].
Scheme 48: Mechanochemical synthesis of tris(allyl)aluminum complex [180].
Scheme 49: Mechanochemical Ru-catalyzed olefin metathesis reaction [181].
Scheme 50: Rhodium(III)-catalyzed C–H bond functionalization under mechanochemical conditions [182].
Scheme 51: Mechanochemical Csp2–H bond amidation using Ir(III) catalyst [183].
Scheme 52: Mechanochemical Rh-catalyzed Csp2–X bond formation [184].
Scheme 53: Mechanochemical Pd-catalyzed C–H activation [185].
Scheme 54: Mechanochemical Csp2–H bond amidation using Rh catalyst.
Scheme 55: Mechanochemical synthesis of indoles using Rh catalyst [187].
Scheme 56: Mizoroki–Heck reaction of aminoacrylates with aryl halide in a ball-mill [58].
Scheme 57: IBX under mechanomilling conditions [8].
Scheme 58: Thiocarbamoylation of anilines; trapping of reactive aryl-N-thiocarbamoylbenzotriazole intermediate...
