Synthesis of fluorine analogs of protoporphyrin potentially useful for diagnosis and therapy of cancer. IV. Synthesis of (trifluorovinyl)vinyl- and (1-chloro-2,2-difluorovinyl)vinyldeuteroporphyrins.

Trifluoro or chlorodifluoro analogs of protoporphyrin, the compounds in the title, were synthesized for use in the diagnosis and therapy of cancer. 3- Or 8-acetyldeuteroporphyrin dimethyl esters (2 and 3) were iodinated with iodine in the presence of potassium carbonate to the corresponding iodo compounds (5 and 6). The iodo compounds (5 and 6) were treated with bis(trifluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)-palladium to give trifluorovinyl derivatives (7 and 8) in good yields. Reduction of the acetyl group of 7 and 8 with sodium borohydride afforded the corresponding hydroxyethyl derivatives (9 and 10). Compounds (9 and 10) were dehydrated with methanesulfonyl chloride and triethylamine to give (trifluorovinyl)vinyldeuteroporphyrin dimethyl esters (11 and 12). Treatment of 5 and 6 with bis(1-chloro-2,2-difluorovinyl)zinc in the presence of tetrakis(triphenylphosphine)palladium, followed by similar reactions as above gave (1-chloro-2,2-difluorovinyl)-vinyldeuteroporphyrin dimethyl esters (17 and 18).     

The synthesis and structural characterisation of an homologous series of group 14 1-chloro-2,2-difluorovinyl compounds

A series of group 14 1-chloro-2,2-difluorovinyl compounds Ph₃E(CClCF₂) (E=Ge, Sn, Pb) has been prepared using the low temperature reactions of 1-chloro-2,2-difluorovinyllithium (LiCClCF₂), generated in situ from CF₃CH₂Cl (HCFC-133a) and n-butyllithium. These new materials have been fully characterised, including for E=Ge and Sn, by single crystal X-ray studies. This is the first time that any main-group 1-chloro-2,2-difluorovinyl compounds have been crystallographically studied.     

Indium-Catalyzed C−F Bond Transformation through Oxymetalation/β-Fluorine Elimination to Access Fluorinated Isocoumarins

Fluorinated heterocycles have attracted much attention in the pharmaceutical and agrochemical industries. Many strategies have already been developed to achieve the synthesis of fluorinated heterocycles. Formidable challenges remain, however, in the synthesis of fluorinated isocoumarin derivatives that are among the most alluring structural motifs. Herein, the indium-catalyzed C−F bond transformation of 2-(2,2-difluorovinyl) benzoates is reported, which are readily accessible compounds, to give a diverse array of fluorinated isocoumarins. The present reaction proceeds smoothly using inexpensive reagents: a catalytic amount of indium salt in the presence of zinc salt. A theoretical calculation of potential energy profiles showed that the reaction consists of oxymetalation with the elimination of alkyl halide and the β-fluorine elimination.     

<Emphasis Type="Italic">N</Emphasis>-(2-chloro-1,2-difluorovinyl) derivatives of azoles

Reactions of N-(2,2-dichloro-1,1,2-trifluoroethyl)-substituted azoles with zinc, magnesium, butyllithium, and tris(diethylamino)phosphine were studied, and optimal conditions for the preparation of the corresponding N-(2-chloro-1,2-difluorovinyl) derivatives were found [tris(diethylamino)phosphine, chlorotrimethylsilane]. Some reactions of the obtained unsaturated fluorinated compounds with sulfur-centered nucleophiles were examined.     

Direct vinylation and difluorovinylation of arylboronic acids using vinyl- and 2,2-difluorovinyl tosylates via the Suzuki-Miyaura cross coupling

General reaction conditions were developed for the Pd(0)-catalyzed Suzuki-Miyaura coupling reaction of aryl boronic acids with a simple electrophilic vinylation reagent, vinyl tosylate, providing access to styrene derivatives in good yields. The easily accessible vinyl tosylate represents a stable and less toxic alternative to the vinyl halides and the triflate/nonaflate derivatives. Furthermore, this methodology was expanded to provide a facile and straightforward approach for the introduction of a gem-difluorovinyl substituent onto an aromatic ring using the similar and also readily available 2,2-difluorovinyl tosylate as the electrophilic complement.     

The nucleophilic addition reactions of difluorovinyl tosylates with O- and S-nucleophiles

A series of O- and S-nucleophiles reacted with 2,2-difluorovinyl tosylate 1 regiospecifically with the nucleophiles attacking at the terminal CF₂ carbon at room temperature, affording α,α-difluoroethyl ethers or thioethers in moderate to good yields.     

Sodium dithionite initiated addition of CF2Br2 to β-pinene and reactions of the adduct: Synthesis and the reactivity of new 1,1-difluorodienes

Sodium dithionite effectively promotes the addition of dibromodifluoromethane to the exocyclic double bond of β-pinene. The reaction proceeded in a MeCN/H₂O system to give almost quantitatively an adduct, 1-(2-bromo-2,2-difluoroethyl)-4-(2-bromoisopropyl)-cyclohexene, as the sole product. On treatment of the adduct with 2,2,6,6-tetramethylpiperidine elimination of HBr only from the (CH₃)₂CHBr group occurred to give a mixture of regioisomeric dienes, while treatment with 50% KOH under phase transfer catalysis conditions or with K₂CO₃ in DMF resulted in total dehydrobromination to give trienes possessing an exocyclic CHCF₂ group. Surprisingly, the main course of the reactions of the adduct with DBU (1,8-diazabicyclo[5.4.0]undece-7-ene) and also with t-BuOK in THF was elimination of HBr only from the CH₂CF₂Br group to afford 1-(2,2-difluorovinyl)-4-(2-bromoisopropyl)cyclohexene as the main product. Catalytic hydrogenation of the adduct followed by treatment with DBU afforded a conjugated diene, 1-(2,2-difluorovinyl)-4-isopropylcyclohexene. Compounds bearing the CHCF₂ group are new 1,1-difluorodienes which readily reacted with 4-phenyl-3H-1,2,4-triazoline-3,5-dione to give cycloadducts, derivatives of triazolo[1,2-α]cinnoline.     

Heck-type 5-endo-trig cyclizations promoted by vinylic fluorines: Ring-fluorinated indene and 3H-pyrrole syntheses from 1,1-difluoro-1-alkenes

Arylpalladium or aminopalladium species bearing a 2,2-difluorovinyl group undergo an unusual 5-endo alkene insertion followed by β-fluorine elimination. These processes provide a facile access to ring-fluorinated five-membered carbocyclic and heterocyclic compounds starting from an o-(3,3-difluoroallyl)phenyl trifluoromethanesulfonate and 3,3-difluoroallyl ketone O-pentafluorobenzoyloximes. In both systems, the two vinylic fluorine atoms are essential for Heck-type 5-endo-trig cyclizations.     

Dehydrodimerization of iodobenzenes to iodinated biaryls

The molybdenum pentachloride-mediated oxidative coupling of iodo-substituted electron rich benzenes without the loss of the iodo-substituents is reported. The presented methodology is an environmentally friendly alternative to known thallium(III)- and lead(IV)-reagents. Even 2,2',6,6'-tetraiodobiphenyl derivatives are easily accessible.     

对环芳烷二氯化产物组成的GC—MS表征

对环芳烷([2,2]Paracyclophane,简称PCP）是指苯环对位桥联的化合物,PCP及其氯代PCP的重要用途是通过升华、裂解、聚合等步骤沉积于物体表面形成聚合膜,该聚合膜具有透湿和透气小、抗化学腐蚀和抗辐射等优良性能[1,2].     

Synthesis of gem-dihaloenynes and butatrienes from gem-dihalovinyl derivatives

gem-Dihaloenynes were synthesized in high yields from 1,1,4,4-tetrahalo-1,3-butadienes through the Fritsch-Buttenberg-Wiechell (FBW) rearrangement mediated by an organolithium compound. Butatriene derivatives could be obtained efficiently via an organolithium-mediated reaction of o-halo-(2,2-dihalovinyl)benzenes.     

Rhodium-catalyzed reactions of dithiols and 1,4-bis(bromomethyl)benzenes leading to enantioenriched dithiaparacyclophanes

We have achieved the first catalytic enantioselective synthesis of planar-chiral dithiaparacyclophanes by means of cationic rhodium(I)/(S)-BINAPHANE complex-catalyzed reactions of dithiols and 1,4-bis(bromomethyl)benzenes. The present method represents the first example of asymmetric synthesis of planar-chiral cyclophanes through catalytic enantioselective construction of the ansa chains.     

Intramolecular cyclotrimerization of triynes catalyzed by N-heterocyclic carbene-CoCl2/Zn or -FeCl3/Zn

[reaction: see text] Triynes 1 could effectively be cyclotrimerized to annulated benzenes 2 by treatment with a catalytic amount of zinc powder, N-heterocyclic carbene, and CoCl(2) or FeCl(3).     

Photoinduced electron-transfer bicyclopropenyl-benzene rearrangements of 2,2',3,3'-tetraphenylbicyclopropenyls: a new mechanism via Dewar benzene

[reaction: see text] The 9,10-dicyanoanthracene-sensitized photoreaction of 1-methyl- and 1,1'-dimethyl-2,2',3,3'-tetraphenylbicyclopropenyl gives the corresponding benzene and Dewar benzene derivatives, indicating that their photoinduced electron-transfer bicyclopropenyl-benzene rearrangements proceed via Dewar benzenes.     

Pt- and Au-catalyzed oxidative cyclization of 2-ethenyl-1-(prop-2'-yn-1'-ol)benzenes to naphthyl aldehydes and ketones: catalytic oxidation of metal-alkylidene intermediates using H2O and H2O2

2-Ethenyl-1-(prop-2'-yn-1'-ol)benzenes was cyclized through catalytic oxidation with PtCl(2)/CO/H(2)O and PEt(3)AuCl/H(2)O(2); the metal-naphthylidene intermediates were identified and oxygenated with water and H(2)O(2), respectively; for the efficiency of cyclization, the Au catalytic system is superior to that of the PtCl(2)-catalysis because of its compatibility toward diverse alcohol substrates including both internal alkynes and terminal alkynes.     

N-Polyfluoroethyl and N-2-chlorodifluorovinyl derivatives of azoles

Reactions of tetrafluoroethylene, chlorotrifluoroethylene and 1,2-dichlorodifluoroethylene with N-potassium salts of imidazole, 2-methylbenzimidazole, 3,5-dimethylpyrazole, 1,2,4-triazole, and benzotriazole lead to the formation of the corresponding N-(1,1,2,2-tetrafluoroethyl), N-(2-chloro-1,1,2-trifluoroethyl), and N-(2-chloro-1,2-difluorovinyl) azoles. Treatment of N-(2-chloro-1,2-difluorovinyl) and N-(2-chloro-1,1,2-trifluoroethyl) derivatives of azoles with tetramethylammonium fluoride is a useful synthetic method for the preparation of heterocycles with 1,2,2,2-tetrafluoroethyl group attached to nitrogen.     

Direct coupling of benzene with olefin catalyzed by Pd(OAc)(2) combined with heteropolyoxometalate under dioxygen

The oxidative coupling reaction of benzenes with alkenes was successfully achieved by the Pd(OAc)(2)/molybdovanadophosphoric acid (HPMoV)/O(2) system. For example, the reaction of benzene with ethyl acrylate by the above catalytic system in acetic acid afforded ethyl cinnamate as a major product in satisfactory yield.     

Pd(OAc)2-catalyzed oxidative coupling reaction of benzenes with olefins in the presence of molybdovanadophosphoric acid under atmospheric dioxygen and air

The direct oxidative coupling reaction of benzenes with alkenes bearing an electron-withdrawing group was successfully achieved by the use of Pd(OAc)(2)/molybdovanadophosphoric acid (HPMoV) as the key catalyst under O(2) or air atmosphere. Thus, the reaction of benzene with ethyl acrylate under air (1 atm) assisted by Pd(OAc)(2)/HPMoV afforded ethyl cinnamate as a major product in satisfactory yield (74%). This catalytic system could be extended to the coupling reactions between various substituted benzenes and alkenes through the direct aromatic C-H bond activation. In the reaction of benzene with ethyl acrylate under O(2) (1 atm), the best turn-over number (TON) of Pd(OAc)(2) reached was 121. This reaction provides a green route to cinnamate derivatives, which are important precursors of a variety of pharmaceuticals.     

Microwave-assisted, Ir-catalyzed aromatic C–H borylation

One-step conversions of 1,3-disubstituted benzenes to aryl boronates and 2,6-disubstituted pyridines to heteroaryl boronates are described. Microwave heating was used for all reactions. [(COD)Ir(μ-OMe)]₂ and 4,4′-di-tert-butyl-2,2′-bipyridine were used as catalysts, in methyl tert-butyl ether. Acceleration of the rate of reaction was remarkable compared with that of same reaction under conventional heating conditions.     

β,β-二氟乙烯基化合物制备方法研究进展

近年来,随着β,β-二氟乙烯基类化合物的广泛应用,其合成方法的研究也越来越多.详细介绍了卤代二氟醋酸盐、卤代二氟甲烷、双膦酸盐、有金属参与、双三氟甲基汞和二异丙基胺基锂和二氟甲基芳环砜等法制备β,β-二氟乙烯的研究进展,同时对其反应机理作了相应阐述.