Oldřich Paleta

Preparation of bis(polyfluoroalkyl)cyclopentadienes, new highly fluorophilic ligands for fluorous biphase catalysis

Abstract Bis[2-(perfluoroalkyl)ethyl]cyclopentadienes were synthesized from lithium [2-(perfluoroalkyl)ethyl]cyclopentadienides and 2-(perfluoroalkyl)ethyl triflates as mixtures of four regioisomers, structure of which was determined by 1H and 13C NMR spectroscopy. 2-(Perfluoroalkyl)ethyl triflates are useful fluorinated building blocks that can be employed in the synthesis of functionalised polyfluorinated substances.

Synthesis, fluorophilicities and regioisomer composition of ferrocenes and rhodium complexes based on bis(polyfluoroalkylated) cyclopentadienes

Abstract Ferrocenes and rhodium(I) carbonyl complexes were synthesized from lithium bis[2-(perfluoroalkyl)ethyl]cyclopentadienides and ferrous chloride–THF complex or tetracarbonyldichlorodirhodium. Fluorophilicities of starting bis[2-(perfluoroalkyl)ethyl]cyclopentadienes and ferrocenes made there from were determined. Four regioisomers of bis[2-(perfluoroalkyl)ethyl]cyclopentadienes, three regioisomers of the corresponding ferrocenes and two regioisomers of the corresponding rhodium complexes were identified and their ratio determined by 1D and 2D NMR spectroscopy.

Chemistry of [(perfluoroalkyl)methyl] oxiranes. Regioselectivity of ring opening with O-nucleophiles and the preparation of amphiphilic monomers

Abstract The reactions of oxiranes RFCH2CH(–O–)CH2 (RF≡C4F9, C6F13, C8F17; 4a–4c) with a series of alkanols in the presence of a Lewis acid took place at the terminal carbon atom with complete regioselectivity. 2-Hydroxyethyl methacrylate and acrylate reacted similarly. The reaction with alkane diols was controlled to proceed with one or two molecules of the oxiranes chemoselectively. Non-regioselective, base-catalysed ring opening by methacrylic acid (83% terminal attack) was discussed on the basis of the hard and soft acids and bases (HSAB) concept. A convenient transformation of the oxiranes to the corresponding diols 13a–13c via dioxolane intermediates, and their conversion to bis-methacrylates, was accomplished with overall yields of 75%–79%. Thiourea converted the oxiranes into the corresponding thiiranes (15a–15c). The reactions afforded products generally in yields of 82%–98%.

Highly selective synthesis of [(perfluoroalkyl) methyl] oxiranes (by the addition of iodoperfluoroalkanes to allyl acetate)

Abstract Mixtures of regioisomeric adducts of monoiodoperfluoroalkanes R F -I (R F = C 4 F 9 , C 6 F 13 C 8 F 17 ) with allyl acetate, R F CH 2 CHICH 2 OAc ( 1a–1c ) and rearranged adducts R F CH 2 CH(OAc)-CH 2 I ( 2a–2c ), were converted chemoselectively to the corresponding oxiranes R F CH 2 CH(-O-)CH 2 ( 3a–3c ) in yields of 94–96% (total yields of the two-step synthesis starting from R F -I were 85–87%). The chemoselectivity of the oxirane formation appeared to be very dependent on the solvent used. Dependence on the reaction conditions on formation of byproducts R F CH=CHCH 2 OAc ( 4a–4c ) and R F CH=CHCH 2 OH ( 5a–5c ) in the epoxidation reaction was studied.

Methyl 3,3,3-trifluoropyruvate: an improved procedure starting from hexafluoropropene-1,2-oxide; identification of byproducts

Optimized laboratory-scale preparation of methyl 3,3,3-trifluoropyruvate (3, MTFP) has been developed starting from industrial hexafluoropropene-1,2-oxide (1, HFPO) via methyl 2,3,3,3-tetrafluoro-2-methoxypropanoate (2, MTPr), which was transformed to 3 using sulfuric acid with isolated yields up to 81%. Byproducts formed in the transformation of 2 to 3, viz. methyl trifluoroacetate (4, MTAc), methyl 3,3,3-trifluoropyruvate hydrate (5), methyl hemiacetal of trifluoropyruvate (6), a dimer of methyl 3,3,3-trifluoropyruvate hydrate (7, DimMTP), and methyl fluorosulfate (8, Sulf) were identified and their amounts determined under various experimental conditions. Potential reaction pathways leading to the formation of the byproducts are discussed.

Radical-induced reaction of monoiodo- and diiodo-perfluoroalkanes with allyl acetate: telomer and rearranged products, mass-spectral distinguishing of regioisomers

Abstract The radical reaction of monoiodoperfluoroalkanes R F I (R F = C 4 F 9 , C 6 F 13 , C 8 F 17 ) and diiodoperfluoroalkanes I-Q-I (Q = C 4 F 8 , C 6 F 12 ) with allyl acetate initiated by peroxidic initiators is described. Under the reaction conditions employed, the conversion of both R F I and IQI was complete in most cases. The reactions of R F I also yielded some 2:1 telomers which are new compounds which have been characterized. In certain cases, the telomers were isolated in preparative yield up to 34%. Both 1:1 adducts [R F CH 2 CHICH 2 OCOCH 3 , (2a-c) ] and 2:1 telomers (5a-c) underwent subsequent thermal rearrangement [formation of R F CH 2 CH(OCOCH 3 )CH 2 I, (3a-c) , and telomers (6a-c) , respectively] at elevated temperatures. In the reaction of diiodides IQI, monoadducts [CH 3 COOCH 2 CHICH 2 QI, (9a,b) ] and diadducts [(CH 3 COOCH 2 CHICH 2 ) 2 Q (10a,b)] were formed, but no telomeric and rearranged products were found under the reaction conditions employed. On the other hand, isolated mono- (9) and di-adducts (10) underwent a similar rearrangement to the compounds 2a-c and 5a-c at elevated temperatures. Regioisomeric primary and rearranged products could be distinguished by mass spectrometry in which characteristic signals for a series of compounds with different R F groups were found.

Investigation of new acyloxy derivatives of cholic acid and their esters as drug absorption modifiers

Skin penetration enhancers are used in the formulation of transdermal delivery systems for drugs that are otherwise not sufficiently skin-permeable. Intestinal absorption promoters/enhancers are used as excipients in oral formulations of poorly oral-bioavailable drugs. Series of fourteen acyloxy derivatives of 5β-cholic acid as potential drug absorption modifiers was generated by multistep synthesis. The synthesis of all newly prepared compounds is presented here. Structure confirmation of all generated compounds was accomplished by (1)H NMR, (13)C NMR, IR and MS spectroscopy methods. All the prepared compounds were analyzed using RP-TLC, and their lipophilicity (R(M)) was determined. The hydrophobicity (logP) and solubility (logS) of the studied compounds were also calculated using two commercially available programs. All the target compounds were tested for their in vitro transdermal penetration activity and as potential intestinal absorption enhancers. The anti-proliferative activity of all the final compounds was also assessed against the human cancer cell lines: T-lymphoblastic leukemia cell line and the breast adenocarcinoma cell line. Their cytotoxicity was also evaluated against the normal human skin fibroblast cells. Two compounds showed anti-proliferative effect on cancer cells without affecting the growth of normal cells, which should be promising in potential development of new drugs. Most of the target compounds showed minimal anti-proliferative activity (IC(50)>37 μM), indicating they would have low cytotoxicity when administered as chemical absorption modifiers. The relationships between the lipophilicity and the chemical structure of the studied compounds as well as the relationships between their chemical structure and enhancement effects are discussed in this article.

Radical additions to fluoro-olefins. Photochemical mono-fluoroalkylation and sequential bis-fluoroalkylation of oxolane

Oxolane was fluoroalkylated by its photoadditions under atmospheric pressure. Monofluoro-alkylations were carried out with hexafluoropropene (1) and perfluorovinyl ethers C,F,&[ CF( CF,)CF,O] .-CF=CF2 (2-4, n = O-2) by direct photoexcitation of the olefins to give high yields of addition products 9-12 (Sl-94%). The reactions were completely regioselective at the oxolane molecule and almost completely regioselective (93-99%) at the double bond of fluoro-oletins; no bis-fluoroalkylated oxolanes were detected. The completely selective

Low-temperature 19F NMR spectroscopy of 1-fluoro-1-lithioethenes: Stability, shifts and unexpected coupling constants

Abstract Half-lives and fluorine atom shifts of stabilized 1-fluoro-1-lithioethenes bearing hydrogen, fluorine, phenyl, and/or dimethylphenylsilyl groups in the β-positions have been determined by a low-temperature 19 F NMR spectroscopy. Some 1-fluoro-1-lithioethenes displayed an exceptionally low value of the trans - 3 J FF coupling constant. Stereoselectivity of carbenoid formation, as well as an effect of configuration on the stability is discussed.

Photochemical synthesis of fluoroalkanols based on tetrafluoroethylene

Abstract The conditions of the photochemical synthesis of fluoroalkanols H(C 2 F 4 ) n C(OH)R 1 R 2 (n = 1, 2) by the reaction of tetrafluoroethylene with alcohols in the presence of photoinitiators and sensitisers are described. The reaction is initiated by UV radiation and is performed under atmospheric pressure. The yields of alkanols were 0.1-0.39 mol using 250 W UV lamp after 6-8 hours and 73-82 % relatively to the converted tetrafluoroethylene.