1.2- difluoro-aryl

Stereoselective Markovnikov addition of difluoro(aryl)-k3-bromane (25) to terminal acetylenes (24) has been reported, which gives rise to ( )-/3-fluoroalkenyl-k3-bromanes (26).41... 

Protein-tyrosine (PTP) inhibitors are potentially valuable pharmacological tools for studying cellular signal transduction and for therapeutic intervention. Derivatives of 1,1-difluoromethylphosphonic acid are known to be potent PTP inhibitors. An important method for synthesis of these compounds is fluorina-tion of acyl phosphonates by diethylaminosulfur trifluoride (DAST). This method allows synthesis of fcrf-butyl-protected difluoro(aryl)- or (naphthal-enyl)methylphosphonates, which under mildly acidic deprotection conditions afford desirable phosphonic acids [16, 39]. Acyl phosphonate fluorination by DAST has also been utilized for synthesis of a,a-(difluoroprop-2-ynyl)phos-phonates [14]. 

Aryl ketone hydra ones are oxidized and fluonnated by fluorine to give a mixture of mono and difluoro hydrocarbons [74] (equation 10)... 

Methyliodobenzene difluoride cleaves aryl dithioketals. The reactions are conducted in dichloromethane solutions at 0 °C to give gem-difluoro compounds in 65-90% yields [4 (equation 6)... 

Aryl and alkylxanthates are converted into difluoro(methylthw)methyl ethers with tetrabutylammonium dihydrogen trifluoride and Af-bromosuccinimide in... 

A solid-liquid phase-transfer technique is used to synthesize aryl difluoro-methyl sulfides and selenides thiophenols dissolved in an aromatic solvent are treated with solid sodium hydroxide in the presence of a catalytic amount of tris(3,6-dioxaheptyl)amine (TDA1) [49] This condensation proceeds by a carbene mechanism (equation 44)... 

Cyclocondensation of 2-iminopiperidine and 3-aryl-2-propynylnitriles afforded 4-aryl-2-imino-6,7,8,9-tetrahydro-22/-pyrido[l,2- ]pyrimidines <20000L3389, 2002W002/00629>. The minor isomers, 2-aryl-4-imino-6,7,8,9-tetrahy-dro-4/7-pyrido[l,2- ]pyrimidines could also be isolated in 2-30% yields from the reaction mixtures <20000L3389>. When the reactions were carried out in the presence of 2 equiv of NaHMDS, the product ratio was reversed. From the reaction mixture of 2-aminopyridine and perfluoro-2-methylpent-2-ene in MeCN, a 9 1 mixture of 2,4-difluoro-2-pentafluoroethyl-3-trifluoromethyl-477- and the isomeric 2,4-difluoro-4-pentafluoroethyl-3-trifluoromethyl-277-pyr-ido[l,2- ]pyrimidine (64%), and 2-pentafluoroethyl-3-trifluoromethyl-47/-pyrido[l,2- ]-pyrimidine-4-one (20%) was isolated <2000JFC(103)105>. 

DFDNB is the acronym for an aryl halide-containing compound having the structural names, l,5-difluoro-2,4-dinitrobenzene or l,3-difluoro-4,6-dinitrobenzene (Thermo Fisher). The reagent... 

The second-resolution approach relied on enzymatic resolution of acetate esters 62 (Scheme 4.7) (Hayakawa et ah, 1991). The sequence opened with the alkylation of 2,3-difluoro-6-nitrophenol (59) with l-acetoxychloro-2-propane (60) to deliver ether 61. Reduction of the nitro group of 61 gave an intermediate anihne that cyclized to give racemic benzoxazine 62 in 62% yield. A variety of lipases were then examined for the resolution. The best results arose from use of LPL Amano 3, derived from P. aeruginosa, which gave a ratio of 73 23 in favor of the desired (—)-enantiomer. Benzoylation of the enantiomerically-enriched mixture followed by chromatography of the aryl amides delivered enantiomerically pure 63. 

Benzo[4,5]furo[3,2- ]pyrrole 86 and benzo[4,5]thieno[3,2- ]pyrrole 87 were used for the synthesis of new constrained aryl-substituted 4,4-difluoro-4-bora-3a,4a-diaza-r-indacene (BODIPY) dyes 86 and 89 <2000JOC2900>. Their fluorescence characteristics were investigated and compared with the unconstrained systems published by Burghart and co-workers (Scheme 8) <199881276, 1999JOC7813>. 

This method can be applied to introduce CF, and CF3 groups at oxygen and nitrogen atoms in various molecules. oe,a-Difluoro ethers are prepared from O-alkyl(aryl) carbothioales in moderate to good yields by reaction with tetrabutylammonium dihydrogen trifluoride and /V-bromosuccinimide or /V-iodosuccinimide,64 or with bromine trifluoride.65... 

Ethylene dithioacetals of benzophenone and its 4-fluoro-, 4-bromo-, 4,4 -difluoro-, 4,4 -dichlo-ro-, and 3,5-dimethyl-substituted analogs react with sulfuryl chloride or sttlfuryl chloride fluoride in hydrogen fluoride/ pyridine at — 78 C to room temperature to give the corresponding geminal difluorides in 85-90% yield. The reaction is, however, not applicable to dialkyl or alkyl aryl ketones as they undergo chlorination under these conditions.73... 

The second product in this reaction, the difluorotris(perfluoroalkyl)-A5-phosphane, does not dissolve in aryl fluorides and, because of its greater density, forms a lower layer which can be easily separated. In this way the difluoro-A5-phosphanes are regenerated almost quantitatively and can be used in the synthesis many times. An example is the decomposition of 4-nitrobenzene-diazonium trifluorotris(heptafluoropropyl)phosphate at 87 C which provides l-fluoro-4-ni-trobenzene in 82% yield and difluorotris(heptafluoropropyl)-A5-phosphane in quantitative yield.6 This method is a convenient modification of the Balz-Schiemann reaction (see Section 26.1.3.). 

When present, water competes with fluoride to give phenols together with aryl fluorides for example, AT-(3-fluoro-4-hydroxy-5-aminophcnethyl)trifluoroacetamide gives, after in situ photochemical fluorodediazoniation (vide infra), 7V-(3,5-difluoro-4-hydroxyphenethyl)tri-fluoroacetamidc (67 %) and Af-(3-fluoro-4,5-dihydroxyphcnethyl)trifluoroacetamide(34%).251... 

Alkoxy-trifluoro- ElOb, 221 (CS-SR - CF3) Amino-trifluoro- ElOb, 221 (CS-SnR CF3) Aryl-difluoro-phenylthio- ElOb,. 220 (H -> F SAr - F) Aryloxy-trifluoro- ElOb, 22l (CS-C1 - CF3)... 

Hy droxy aryl) alky nes. Phenyl 1, l-difluoro-2,2-dichloroethyl ethers (1) are prepared from phenols with 1 in aqueous KOH/CH2Cl2 catalyzed by Bu4NOH (—90% yield). These ethers on treatment with BuLi (4 equiv.) rearrange to o-acetylenic phenols (a), which are usually isolated as acetylenic silanes (2) in 70-80% yield. 

The 5,7-diaryl-2-fluoro-4/7-l,3-diazepines have been synthesized from 3-aryl-substituted 277-azirines and difluoro-carbene (Scheme 13). The reaction involves isomerization of azirinium ylide into a 2-aza-l,3-diene, which undergoes [4+2] cycloaddition with the starting azirine, followed by ring expansion and dehydrofluorination <2006TL639>. 

The following give abnormal results when treated with chlorosulphonic acid alone, preferably at 50 °C for 30-60 minutes fluorobenzene (4,4 -difluoro-diphenylsulphone, m.p. 98 °C) iodobenzene (4,4 -diiododiphenylsulphone, m.p. 202 °C) o-dichlorobenzene (3,4,3, 4 -tetrachlorodiphenylsulphone, m.p. 176 °C) and o-dibromobenzene (3,4,3, 4 -tetrabromodiphenylsulphone, m.p. 176— 177 °C). The resulting sulphones may be crystallised from glacial acetic acid, toluene or ethanol, and are satisfactory for identification of the original aryl halide. In some cases sulphones accompany the sulphonyl chloride they are readily separated from the final sulphonamide by their insolubility in cold 6 m sodium hydroxide solution the sulphonamides dissolve readily and are reprecipitated by 6 m hydrochloric acid. 

Adcock, W. and Kok, G.B., Polar substituent effects on 19F chemical shifts of aryl and vinyl fluorides a fluorine-19 nuclear magnetic resonance study of some l,l-difluoro-2-(4-substituted-bicyclo[2,2,2]oct-l-yl)ethenes, J. Org. Chem., 50, 1079, 1985. 

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