Gennady I. Borodkin

First application of ionic liquids in electrophilic fluorination of arenes; Selectfluor™ (F-TEDA-BF4) for “green” fluorination

The NF fluorinating agent F-TEDA-BF4 dication salt (Selectfluor™) 1 dissolves in imidazolium-based ionic liquids [emim][OTf] 7, [emim][BF4] 8, [bmim][PF6] 9 and [bmim][BF4] 10 (assisted by sonication), providing a convenient medium for fluorination of arenes under essentially acid-free conditions in a simple set-up (no volatile solvent; simple extraction of the aromatics without aqueous work-up), from which the ionic liquid can be easily recycled and reused. Comparative studies in [emim][OTf] 7 with anisole as substrate show that 1 is superior to NFTh-BF4 (Accufluor®) 2 and that the N-fluoropyridinium salt NFPy-B2F74 is least effective. The scope of the reaction has been surveyed. Substrate selectivity (kmesitylene ∶ kdurene = 10) measured in competitive experiments in 7 is clearly indicative of a conventional polar mechanism. Substrate selectivity measured without the ionic liquid in MeCN solvent is also indicative of a polar mechanism but exhibits lower magnitude (kmesitylene ∶ kdurene = 6). Addition of dicyclohexano-24-crown-8 to the fluorination reaction mixture (1 and anisole) in 7 reduced the conversion but did not change the isomer distribution. AM1 minimization was used to model the complexation of 1 with this crown. With reactive aromatics optimal fluorination yields in ionic liquids (using 1 equivalent of the NF reagent) are around 50% (higher for naphthalene). A key control experiment suggests that the free base (produced upon transfer-fluorination) could complex to unreacted 1 (generating a bulky dimer complex which may be ineffective for fluorine transfer) in competition to N-protonation.

Interaction of anisole and thioanisole with the nitrosonium cation: π-vs. n-complex formation

1 H, 13C and 15N NMR studies and the results of MINDO/3 calculations show the interaction between anisole, thioanisole and the nitrosonium cation to result in the formation of π- and n-complexes, respectively.

Exploratory study of the reaction of bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor™ reagent) with diaryl sulfoxides: novel routes to Ar2SF2 and Ar2SF(OTf) via sulfoxide activation

Abstract Neither bis(2-methoxyethyl)aminosulfur trifluoride (Deoxofluor™ reagent) nor HF/pyridine alone can fluorinate diaryl sulfoxides. S-fluorination can be effected by activating the sulfoxide via protonation with HF/pyridine (70:30) to form sulfoxonium ions in equilibrium which are then S-fluorinated in situ with Deoxofluor™ to give Ar2SF2 compounds. Conversions depend strongly on steric factors and the reactions require the use of excess Deoxofluor™ and HF/pyridine. NMR data for the resulting diarylsulfur difluorides are gathered and discussed. Sulfoxide activation via diaryl (trifloxy) sulfonium triflate generated in situ from Ar2SO with triflic anhydride at low temperature represents another strategy for S-fluorination with Deoxofluor™ to generate Ar2S(OTf)F.

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

An efficient and operationally simple synthesis of 7-deuteropyrazolo[1,5-a]pyridine and 7-deutero-1,2,4-triazolo[1,5-a]pyridine derivatives using α-H/D exchange of 1-aminopyridinium cations in basic D2O followed by a 1,3-cycloaddition of acetylenes and nitriles is presented. A high regioselectivity and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium cations (R = H, Me, OMe).

Electrophilic reactivity and π-complexation studies in 1,8-naphthylene-bridged [3.2]paracyclophane with a cyclobutane calliper

The 1,8-naphthylene-bridged [3.2]paracyclophane 1, a novel syn-paracyclophane which is further rigidified via a cyclobutane calliper, reacts with 2.2 equivalents of Br2 in CCl4 in the dark to give the symmetrical dibromo derivative 2. Bromination with excess Br2 (6 equiv.) leads to further bromination at the 4-position of the naphthalene ring to give the tribromide 3. In contrast to [2.2]paracyclophane and naphthalene, compound 1 does not produce a persistent π-complex with NO+. Reaction of 1 with AgOTf results in cycloreversion to form a silver-complexed divinyl derivative 4 which could be decomplexed with excess 18-crown-6 to form 5. With tetracobalt dodecacarbonyl a metal π-complex on the exterior of the cyclophane unit was formed (6) with the cyclobutane ring remaining intact. NMR spectral features of the resulting products are examined. AM1 minimizations were used as a guide to structures and relative energies. The nitration, benzoylation, benzylation and ethylation of 1 were also studied.