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Fluorination of substrates (I) with Selectfluor gives 2-mono-fluorobutynones (II) which undergo subsequent 5-endo-dig cyclization in the presence of a gold(I)-catalyst and silver triflate providing 2,5-diaryl-substituted 3-fluorofurans in high yields.

Furans substituted with halogens at the beta carbon, which is less prone to electrophilic reactions compared to an alpha position, are important intermediates for accessing highly substituted furans. The regioselectivity of the introduction of a halogen plays an important role in their preparation. This review summarizes efforts for the synthesis of β-halofurans (but not benzofurans) as sorted by halogen (iodo, bromo, chloro, and fluoro). This article provides general reaction schemes that were confirmed with multiple examples and are sometimes applicable to other halogens, and selected reactions specific to a particular substrate and a halogen.

Reactions of 5-p-tolylethynyl-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolylethynyl-2′-deoxyuridine with Co2(CO)8 in THF gave 5-p-tolC2[Co2(CO)6]-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolC2[Co2(CO)6]-2′-deoxyuridine (92 and 66%).

[1317-39-1] Cu2O (MW 143.08) InChI = 1S/2Cu.O InChIKey = BERDEBHAJNAUOM-UHFFFAOYSA-N (weak base; activates halides towards nucleophilic substitution;1 forms carbenoid intermediates from diazo compounds2 and radicals from arenediazonium salts;3 activates isocyanides towards 1,1-addition4) Physical Data: mp 1235 °C; d ∼6 g cm−3. Solubility: insol most organic solvents; slightly sol quinoline and benzonitrile;1a variously sol acids (salt formation, in some cases disproportionation to Cu0 and CuII). Form Supplied in: red to brown powder; widely available. Typical impurities: Cu, CuO,5 NaCl,5 stabilizers (e.g. gelatine,5 oil, zinc stearate), moisture.5 For reactions in anhydrous media the reagent is vacuum-dried before use. Preparative Methods: since reactions involving Cu2O are heterogeneous, they may critically depend on the particle size.6b An active preparation is obtained by reduction of CuII solutions7 but may suffer deactivation at high reaction temperatures1a octahedral,54 cubic,55, 56 thread/wire,56 tube/rod,57 crystalline,58 amorphous,59 or poly(vinyl alcohol) coated60 nanoparticles can be prepared. Handling, Storage, and Precautions: Cu2O is incompatible with alkynes, diazonium salts, and diazo compounds. Copper compounds are moderately toxic.

Reactions of (η5-C5Me5)Re(NO)(PPh3)(C⋮CC⋮CR) (R = Me, H) and (t-BuO)3W⋮W(O-t-Bu)3 give (t-BuO)3W⋮CR and the title complex (79−76%), which crystallizes from toluene as a solvated tert-butoxy-bridged dimer. The NMR, IR, and crystallographic properties establish dominant Re−C⋮C−C⋮W as opposed to +ReCCCW- character.

5-Endo-dig cycloisomerization of 1,4- and 1,2,4- mostly aryl-substituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride etherate (10 mol %) in dichloromethane at room temperature gave 2,5-di- and 2,3,5-trisubstituted furans in high yields (85-97%). DSC studies confirmed that a solely thermal process does not take place. A relevant catalytic process, employing mu-oxo-tetranuclear zinc cluster Zn4(OCOCF3)6O, yielded bicyclic furopyrimidine nucleosides, when starting from acetyl-protected 5-alkynyl-2'-deoxyuridines (85-86%). Furopyrimidine was deprotected or simultaneously converted into pyrrolopyrimidine nucleoside. The time/concentration dependence for the reaction of 1-phenyl-4-(4-methylphenyl)butynone to 2-(4-methylphenyl)-5-phenylfuran displayed first-order kinetics with the rate dependent on catalyst concentration. The plot of ln k(obs) versus ln[ZnCl2] indicated first-order cycloisomerization, as referred to ZnCl2 concentration, using both NMR and UV-vis reaction monitoring. The crystal structure of propyl furopyrimidine nucleoside (orthorhombic, P2(1)2(1)2(1), a/b/c = 5.684(2)/6.682(2)/36.02(2) A, Z = 4) shows C2'- endo deoxyribose puckering, and the base is found in the anti position in crystalline form.

5-(4-Bromophenyl)-3-iodo-2-(4-methylphenyl)furan 2-(4-Bromophenyl)oxirane 4-Ethynyltoluene Lithium diisopropylamide 1-(4-Bromophenyl)-4-methylphenyl)but-3-yn-1-ol Chromium trioxide 1-(4-Bromophenyl)-4-methylphenyl)but-3-yn-1-one N-Isosuccinamide Keywords: electrophilic cyclization; iodosuccinamide; halofurans; unsymmetrical iodofurans; hydriotic acid; sonogashira coupling-addition-cyclocondensation; one-pot; safety; waste disposal

Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231.

5-Endo-dig cycloisomerization of 1,4-di- and 1,2,4-trisubstituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride (10 mol %) in dichloromethane at room temperature (22 °C) provides 2,5-di- and 2,3,5-trisubstituted furans in high yields (85−97%).

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).

[reaction: see text] 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine monochloride/CH(2)Cl(2), at room temperature, in the absence of base, provides 3-halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).

Recent progress in synthetic approaches to the Mitsunobu reaction are reviewed. Efforts that have focused on the phase-switching modifications of phosphane, azodicarboxylate, and nucleophilic components are emphasized. An approach to product separation with fluorous compounds is reviewed in detail. Alternative reagents and recently introduced products are cited. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The conformation of a representative molecule of a new, potent class of antiviral-active modified nucleosides is determined. A bicyclic nucleoside, 3-(2'-deoxy-beta-D-ribofuranosyl)-6-(4-methylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one, shows C2'-endo and C3'-endo ribose conformations in solution (63:37, 37 degrees C; DMSO-d6), as determined by 1H NMR studies. The crystal structure of a 3',5'-di-O-acetyl-protected derivative (monoclinic, P21, a/b/c= 6.666(1)/12.225(1)/24.676(2) A, beta=90.24(1) degrees , Z=4) shows exclusively C2'-endo deoxyribose puckering. The base is found in the anti position both in solution and in crystalline form.

5-Endo-dig electrophilic cyclization of 5-alkynyl-2'-deoxyuridines with N-iodosuccinimide or N-bromosuccinimide in acetone at room temperature gives 3-(2'-deoxy-beta-D-ribofuranosyl)-5-halo-2,3-dihydrofuro[2,3-d]pyrimidin-2-ones that usually precipitate from the reaction mixture (86-74%).

Reactions of 5-p-tolylethynyl-2'-deoxyuridine and 3',5'-di-O-acetyl-5-p-tolylethynyl-2'-deoxyuridine with Co2(CO)8 in THF gave 5-p-tolC2[CO2(CO)6]-2'-deoxyuridine and 3',5'-di-O-acetyl-5-p-tolC2[CO2(CO)6]-2'-deoxyuridine (92 and 66%).

5-Exo-dig cyclocondensation of alk-3-yn-1-ones with hydrazines, in the presence of montmorillonite K-10, provides an effective method with a high atom economy for the synthesis of diversely 1,3,5-trisubstituted pyrazoles. The microwave-accelerated reaction proceeds in the absence of solvent and leads to 5-benzyl substituted pyrazoles with good yields (72-91%). The regiochemistry of the process was confirmed by the X-ray crystallographic structure determination of 1-(2-fluorophenyl)-5-(4-methylbenzyl)-3-phenyl-1H-pyrazole.

Reactions of 5-p-tolylethynyl-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolylethynyl-2′-deoxyuridine with Co2(CO)8 in THF gave 5-p-tolC2[Co2(CO)6]-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolC2[Co2(CO)6]-2′-deoxyuridine (92 and 66%).

Fluorous technology, a modern approach that exploits phase separation, is reviewed. Strategies towards organic synthesis are outlined and application examples given.

Efficient, general synthesis of oxophosphoranesulphenyl chlorides ABP(O)SCl 2 based on the reaction of phosphorus trimethylsilylthionoesters ABP(S)OSiMe3 7 with chlorinating agents is described.

A novel efficient synthesis of sym-monoselenopyrophosphates 3 based on the reaction of diphosphoryl diselenides 1 with dialkyltrimethylsilyl phosphites 2 is described.

A novel highly efficient synthesis of sym-tetra-alkyl monothio- and monoseleno-pyrophosphates (RO)2P(O)XP(O)(OR′)2(X = S,Se) based on the condensation of dialkoxyoxophosphorane-sulphenyl or -selenenyl chlorides (RO)2P(O)XCl (X = S,Se) with dialkyl trimethylsilyl phosphites (RO)2POSiMe3(9) is described. Remarkably selective reaction of a O,O′-dialkyl O″-trimethylsilyl selenophosphate (RO)2P(Se)OSiMe3(13) with sulphuryl dichloride in the presence of an equimolar amount of a phosphite (9) leads to the formation of sym-monoselenopyrophosphates in excellent yield. A new rearrangement in phosphorus chemistry, sym-monoselenopyraphosphates (11) to asym-monoselenopyrophosphates (12), has been observed.

The remarkably selective reaction of O,O,O-dialkyltrimethylsilylselenophosphates (1) in the presence of equimolar amounts of dialkyltrimethylsilyl phosphites (2) with sulphuryl chloride leading to tetra-alkyl symmetrical selenopyrophosphates (3) in excellent yields is reported.

The remarkably selective reaction of O,O,O-dialkyltrimethylsilylselenophosphates (1) in the presence of equimolar amounts of dialkyltrimethylsilyl phosphites (2) with sulphuryl chloride leading to tetra-alkyl symmetrical selenopyrophosphates (3) in excellent yields is reported.

Our recent work on ligand exchange in chlorophosphonium salts and chloro-phosphoranes as well as on the reactions of phosphorus pseudohalogens with PIII compounds resulted in the novel methods for the synthesis of various phosphorus and carboxylic acids anhydrides.