Studies of nucleophilic attack on tris (pentafluorophenyl) phosphine and its oxides

The reaction of tris(pentafluorophenyl)phosphine [5] with the nucleophiles dimethyl formamide (DMF), hexamethylphosphoric triamide (HMPA), diethyl formamide (DEF), hexaethylphosphoric triamide (HEPA), hydrazine, N,N-dimethyl hydrazine (in presence and/or absence of KF), phenylhydrazine, ammonium hydroxide, formamide, aniline, sodium hydrogen sulfide, and hexaethylphosphorous triamide was investigated. The reaction of [5] with DMF and HMPA gave the same product, namely tris-[4-(N,N-dimethylamino)-2,3,5,6-tetrafluorophenyl]phosphine [12] but in higher yield in the case of HMPA. Compound (5] also reacted with DEF to give tris[4-(N,N-diethylamino)-2,3,5,6-tetrafluorophenyl] phosphine [14]. When [51 was treated with HEPA, it gave a mixture of bis(pentafluorophe~yl)-(N,N-diethylamino-tetrafluorophenyl)phosphine, pentafluorophenyl-bis-(N,N-diethylamino-tetrafluorophenyl)phosphine and tris (N,N-diethylamino-tetrafluorophenyl)phosphine. Treatment of [5] with aqueeus hydrazine solution in excess ethanol gave tris(4-hydrazo-2,3,4,6-tetrafluorophenyl)phosphine [1s1 in high yield while reaction with aqueous hydrazine led to C-P cleavage and production of tetrafluorophenyl hydrazine. With N,N-dimethyl hydrazine, [5] gave tris(4-N,N-dimethylhydrazine-2,3,5,6-tetrafluorophenyl) phosphine {20j. The latter could be obtained in higher yield and shorter reaction time, by the addition of KF. The reaction of compound {51 with phenylhydrazine in THF gave bis(pentafluorophe~yl)-4-S-phenylhydrazino- 2,3,5,6-tetrafluorophenyl phosphine [22] in low yield. Reaction of [5] with ammonium hydroxide in THF at high pressure in the presence of KF gave tris-~4-amino-2,3,5,6-tetrafluorophenyl)phosphine [25]. Similarly, formamide led to a mixture of (C6F4NHZ)3P, (C6F4NHZ)ZPC6FS, (C6F4NHZ)ZPC6F4NHCHO, and C6F4NHZP(C6Fs)(C6F4NHCHO). When [5] was treated with aniline, a mixture of mono-, di-, and tri-substituted products was obtained. Sodium hydrogen sulfide in ethylene glycol/ pyridine led to C-P cleavage and the isolation of pentafluorobenzene and tetrafluorothiophenol. Reaction of [5] and its oxide [35] with different alkoxides in the corresponding alcohols led mainly to C-P bond cleavage products, with the exception of one case where sodium methoxide was used in ether, and which led to tris-(4-methoxy-2,3,9,6-tetrafluorophenyl)phosphine [37]. On the basis of various spectroscopic data, it was concluded that the para position in compound [5] was generally the favoured site of attack.

(A) BODIPY as a versatile fluorophore (B) Synthesis of PNAs via Staudinger reaction

(A) In recent years, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophores have attracted considerable interest due to their unique photochemical properties. However detailed studies on the stability of BODIPY and analogues under acidic and basic conditions have been lacking. Thus the stability of a series of BODIPY analogues in acidic (di- and trichloroacetic acid) and basic (aqueous ammonium hydroxide) conditions was investigated using 11B NMR spectroscopy. Among the analogues tested, 4,4-diphenyl BODIPY was the most stable under the conditions used in the experiments. It was found that reaction of 4,4-dimethoxy BODIPY with dichloroacetic acid gave mixed anhydride 4,4-bis(dichloroacetoxy) BODIPY in good yields. Treatment of the latter mixed anhydride with alcohols such as methanol and ethanol in the presence of a base afforded corresponding borate esters, whereas treatment with 1,2-diols such as ethylene glycol and catechol in the presence of a base gave corresponding cyclic borate esters. Furthermore treatment of 4,4-difluoro-8-methyl-BODIPY with secondary amines in dihalomethane resulted in carbon–carbon bond formation at the meso-methyl position of BODIPY via Mannich-type reactions. The resulting modified BODIPY fluorophores possess high fluorescent quantum yields. Five BODIPY analogues bearing potential ion-binding moieties were synthesized via this Mannich-type reaction. Among these, the BODIPY bearing an aza-18-crown-5 tether was found to be selective towards copper (II) ion, resulting in a large blue shift in absorption and sharp fluorescent quenching, whereas aza-15-crown-4 analogue was selected towards fluoride ion, leading to effective florescent quenching and blue shift. (B) Peptide nucleic acids (PNA), as mimics of natural nucleic acids, have been widely applied in molecular biology and biotechnology. Currently, the preparation of PNA oligomers is commonly achieved by a coupling reaction between carboxyl and amino groups in the presence of an activator. In this thesis attempts were made towards the synthesis of PNA through the Staudinger ligation reactions between C-terminal diphenylphosphinomethanethiol thioesters and N-terminal α-azido PNA building blocks.