Olah's Reagent Research Articles

The double halofluorination reaction of alkynes using trihaloisocyanuric acids and Olah's reagent

A simple and efficient method to produce a CF2 group vicinal to a CX2 group (X = chlorine or bromine) through double halofluorination reaction of alkynes using trihaloisocyanuric acid as halogenating agent and Pyridine.(HF)x (Olah's reagent) as fluoride source is presented. The alkynes used were 1-hexyne, 3-hexyne, phenylacetylene, 1-phenyl-1-butyne, and diphenylacetylene, obtaining, mainly, the desired products in 30–88 % yields. Among the trihaloisocyanuric acids studied, the tribromoisocyanuric acid gave the best yields and the most selective reactions, while trichloroisocyanuric acid, although the most reactive, had less selectivity in the reactions studied, giving in some cases several by-products.

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents.

For nucleophilic monofluorination, amine/HF reagents such as Et3 N⋅3HF, Pyr⋅9HF (Olah's reagent) and similar combinations belong to the most frequently used fluoride sources, whereupon the selectivity of these reagents can be very different depending of its acidity, the nucleophilicity of the fluoride equivalent, and the structure of the particular substrate. These reagents can be used safely in ordinary chemistry laboratories for nucleophilic substitution reactions by fluoride at sp3 -hybridized carbon centers. For ring opening reactions of epoxides, the regio- and stereoselectivity is very much depending of the nature of the epoxide and the acidity of the HF reagent favoring either SN 1 or SN 2 type reactions. Similarly, the outcome of halofluorination and similar reactions with sulfur or seleno electrophiles can be controlled by the particular combination of the electrophile and the fluoride source. Examples for the application of these reaction types for the synthesis of fluorine-containing analogues of natural products or biologically relevant compounds are in the focus of this personal account.

H-F bond insertions into α-diazo carbonyl compounds.

A reaction for H-F bond insertion into α-diazo carbonyl compounds is reported. The protocol describes a simple reaction setup employing commercially available HF·pyr (Olah reagent) as the fluorine source. The method is rapid and practical, and allows access to a broad range of α-fluorinated carbonyl compounds in generally good yields.

Fluorination of α-diazo-γ-lactams with the Olah reagent

A series of N-aryl α-fluoro-γ-lactams were successfully prepared by hydrofluorination of diazo counterparts with the Olah reagent in moderate yields. This approach was also applied to bromofluorination with N-bromosuccinimide as electrophilic bromine source.

Hydrogen Bonding: Regulator for Nucleophilic Fluorination.

The recent advances in nucleophilic fluorination, regulated through hydrogen bonding interactions are summarized. Two main categories of fluorine nucleophiles are discussed. Alkali-metal fluorides are widely used in various fluorination transformations because they are inexpensive and safe nucleophilic fluorine sources. But the non-controllable nucleophilicity and strong basicity of some of them cause undesired side reactions, which led to the introduction of hydrogen bonding to fine tune their nucleophilicity and basicity. In contrast, an HF-based fluorine nucleophile, HF/DMPU, is in some aspects superior to the conventional HF/pyridine (Olah's reagent) or HF/Et3 N because of the higher hydrogen bond basicity of DMPU. It has been used in several nucleophilic fluorinations such as fluorination of alkynes, fluoro-Prins reaction and fluorination of aziridines.

Synthesis and Preferred Conformations of All Regio‐ and Diastereoisomeric Methyl 2,3‐Fluorohydroxyalkanoates

AbstractSelective syntheses of enantiopure regio‐ and diastereomeric methyl 2,3‐fluoro‐hydroxyalkanoates via four different routes employing two types of fluorination reagents are reported. The anti‐ and syn‐3‐fluoro‐2‐hydroxyalkanoates 1 and 3 were prepared by treating the corresponding epoxides with Olah's reagent (Py·9HF). Cyclic sulfates prepared from the enantiomeric diols were ring‐opened with TBAF to give the anti‐ and syn‐2‐fluoro‐3‐hydroxyalkanoates 2 and 4. Thestereochemical analysis was performed mainly by NMR spectroscopy. Applying DFT/B3LYP and SCS‐MP2 quantum chemical methods, the coupling constants and relative energies of conformers were calculated. Solvent effects were considered using the COSMO continuum model.

ChemInform Abstract: A Synthesis of (S)-α-(fluorodiphenylmethyl)alkylamines by HF-Pyridine Treatment of 4-Alkyl-5,5-diphenyl-oxazolidinones.

Abstract Treatment of enantiomerically pure (S)-4-alkyl-5,5-diphenyl-oxazolidinones, themselves derived from appropriate amino acids, with HF–pyridine (Olah's reagent) generated a range of (S)-α-(fluorodiphenylmethyl)alkylamines. These compounds represent a novel range of fluorinated chiral amines.

A synthesis of ( S)-α-(fluorodiphenylmethyl)alkylamines by HF–pyridine treatment of 4-alkyl-5,5-diphenyl-oxazolidinones

Treatment of enantiomerically pure ( S)-4-alkyl-5,5-diphenyl-oxazolidinones, themselves derived from appropriate amino acids, with HF–pyridine (Olah's reagent) generated a range of ( S)-α-(fluorodiphenylmethyl)alkylamines. These compounds represent a novel range of fluorinated chiral amines.

Regioselectivity of the ring opening of propene oxides bearing electron-withdrawing substituents at the methyl group with Olah's reagent

The regiochemistry of the hydrofluorination of terminal epoxides with Olah's reagent (Py·9HF) is dependent on the electron-withdrawing character of the β-substituents. Phenoxy ethers with different substitution patterns of the aromatic ring and several N-heterocycles were examined as β-substituents.

Selective electrolytic fluorinations in 70% HF/30% pyridine

The selective fluorination of compounds containing benzylic hydrogen atoms was accomplished by electrolysis in a mixture of 70% HF and 30% pyridine (Olah's reagent) using a square wave alternating current (1.76–2.75 V, 0.02–0.05 Hz) and Pt electrodes. This method can be used in the laboratory to prepare conveniently gram-size quantities of monofluorinated products. An ion radical mechanism has been proposed.

Synthesis of monofluorinated C 4-building blocks based on methallyl chloride

Halofluorination of methallyl chloride using N-halosuccinimides in combination with triethylamine trishydrofluoride (Et 3N·3HF) gave in each case more than 98% of the Markovnikov products and <2% of the regioisomers in good yield. The formal addition of methanesulfenyl fluoride with the combination of dimethyl(methylthio)sulfonium fluoroborate (DMTSF) and Et 3N·3HF gave a 94:6 mixture of both regioisomers. Only small phenylsulfenyl fluorination of methallyl chloride has been observed when treated with N-phenylthiophthalimide (NPTP) and Olah's reagent. With benzenesulfenyl chloride, 1,3-dichloro-2-methyl-2-(phenylthio)propane is formed which on treatment with Olah's reagent at 0 °C or with Et 3N·3HF at 60 °C rearranges to 1,2-dichloro-2-methyl-2-(phenylthio)propane. Treatment of 1,3-dichloro-2-methyl-2-(phenylthio)propane with silver fluoride in methylene chloride at −30 °C gave 1-chloro-2-fluoro-2-methyl-3-(phenylthio)propane which was also obtained by reaction of 1-bromo-3-chloro-2-fluoro-2-methylpropane with thiophenolate. Chlorofluorination of methallylphenylthio ether using NCS/Et 3N·3HF failed, while corresponding reactions with NBS or NIS and Et 3N·3HF gave mainly the bromo- or iodo-fluorides with Markovnikov orientation in 61% or 35% yields. Related halofluorinations of methallylphenyl ether gave the halofluorides in good yield. All attempts to obtain chromanes or thiochromanes bearing a 3-fluorine substituent by cyclization of these halofluorinated ethers or thio ethers failed using different Lewis acids. However, the benzyl protected o-allylphenol which was bromofluorinated with NBS/Et 3N·3HF in good yield gave on catalytic hydrogenation over Pd/C the 3-fluoro-2 H-chromane in nearly quantitative yield.

High regioselectivity in the alternative cleavage of terminal epoxides with different sources of nucleophilic fluoride

The ring-opening of epoxides derived from esters of 10-undecenoic acid using Olah's reagent yields predominantly the 10-fluoro-1 1-hydroxy derivatives, while the other regio isomers are obtained predominantly with mixtures of triethylamine trishydrogen fluoride and other amines. The best yields and best regioselectivity for the 11-fluoro-10-hydroxy compound, however, are found in conversion of the epoxide with potassium hydrogen difluoride/18-crown-6 in DMF.

Mo2F4(PR3)4 compounds and a comparison of their properties with those of other Mo2X4(PR3)4 compounds. A new synthetic route to metal fluorides by the reaction of alkyl species with Olah's reagent

The syntheses of Mo 2 F 4 (PMe 3 ) 4 (1) and Mo 2 F 4 (PMe 2 Ph) 4 (2) from of the reaction Mo 2 Me 4 (PR 3 ) 4 with Olah's reagent (py.xHF) proceed in high yields with the liberation of methane gas. Compound 1 crystallizes in space group I43m, with a=10.8138 (4) A, V=1264.5 (2) A 3 , and Z=2. The molybdenum atoms are disordered over three positions; principal bond distances are Mo(1)-Mo(1)'=2.110 (5) A, Mo(1)-P(1)=2.444 (3) A, and Mo(1)-F(1)=2.105 (2) A

Synthesis of monofluorinated compounds from methallyl chloride

Monofluorinated organic compounds gain an important position as biologically active substances or intermediates for synthesis of such compounds. However, the selective introduction of one fluorine substituent is sometimes difficult. Triethylamine tris-hydrofluoride (Et 3N,3HF) in combination with different electrophiles are effective systems for monofluorination of olefins [1–3]. The halofluorination [1] of methallylchloride ( 1) gives mainly the corresponding Markovnikov addition products 2 and some traces of anti-Markovnikov orientated compounds 3, while the bromofluorination of allyl chloride gave both regioisomers in a 4:1 ratio [4]. When using the combination dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF)/ Et 3N,3HF [2] a mixture of mainly 2 (XSMe), some 3 (XSMe) and some amount of 4 (RMe) has been isolated. ▪ The fluorosulfenylation, however, was not realized using phenylsulfenyl chloride in combination with Et 3N,3HF; 1,3-dichloro-2-methyl-2-phenylthio-propane ( 5) was formed which is rearranged to 4 (RPh) using Olah's reagent (−78°C to 0°C) or Et 3N,3HF (16h, 60°C). Treatment of 5 with AgF in dichloro-methane at −30°C gave the desired fluorinated compound 2 (XSPh).

Transannular oxygen participation in halofluorination reactions of 9-oxabicyclo[6.1.0]non-4-ene[1

The transannular O-heterocyclization of 9-oxabicyclo[6.1.0]non-4-ene in halofluorination reactions using N-halosuccinimides and triethylamine tris-hydrofluoride or Olah's reagent, respectively, yields endo, endo-2-halo-6-fluoro-9-oxabicyclo[3.3.1.]nonane as the main product and endo,endo-2-halo-5-fluoro-9-oxabicyclo[4.2.1.]nonane as the minor compound by halonium assisted epoxide ring participation.

Different selectivities in fluorination reactions using Olah's reagent or Et 3N/3HF

Different selectivities in fluorination reactions using Olah's reagent or Et 3N/3HF

Conformational analysis using torsion angle notation : attempted prediction and interpretation of the steric course of the cleavage reaction between bicyclic aziridines and hydrogen fluoride in pyridine solution

Dynamic conformational analysis of the cleavage of methyl-substituted 7-aza bicyclo [4.1.0] heptanes by Olah's reagent (30 wt % of pyridine in hydrogen fluoride), using the torsion angle notation, allows structural and conformational prediction of the 2-fluoro cyclohexylamine products. Consequently, a mechanism for the cleavage is proposed.

Reactions of cyclooctene compounds with fluorinating agents

A comparative study of the reactivity of 9-oxabicyclo[6.1.0] non-4-ene compared to the corresponding aziridine shows trans- opening of the epoxide with the almost neutral fluorinating reagent (Et 3N, 3HF) but no reaction with the aziridine. With Olah's reagent double bond participation is observed in the reaction of the epoxide while a stereoselective addition of HF to the double bond without participation of the aziridine ring takes place with 9-azabicyclo[6.1.0]non-4-ene under the same conditions.

Synthesis of a fluorinated analog of the sex pheromone of the processionary moth thaumetopoea. pityocampa(denis and schiff.)

The synthesis of ( E )-13-fluorohexadec-13-en-11-ynyl acetate 1 , a fluorinated analog of the sex pheromone of the processionary moth Thaumetopoea pityocampa is described. The synthetic scheme involves epoxidation of the double bond, regioselective opening of the oxirane ring with Olah's reagent, tosylation of the resulting fluorohydrin and dehydrotosylation. Structural features of the intermediate diastereomeric fluorohydrins 4a and 4b and tosylates 5a and 5b are also discussed on the basis of their 1H and 19F NMR spectra.

Different selectivities in bromofluorination reactions using N-bromosuccinimide/triethylamine tris hydrofluoride or Olah's reagent

A new reagent is used for bromofluorination. Its selectivity is compared with that of a known one in the competition between normal 1,2-addition and transannular π-cyclisation of cycloalka-1,5-dienes 1 and 5.