Nucleophilic di- and tetrafluorination of dicarbonyl compounds

Article abstract of DOI:10.1021/jo0157674

Reactions of various diketo compounds with Deoxofluor [(CH₃OCH₂CH₂)₂NSF₃] have been investigated. When reacted with Deoxofluor, α-diketones, R₁COCOR₂ (R₁ = R₂

Full text of DOI:10.1021/jo0157674

J . Org. Chem. 2001, 66, 6263-6267
6263
Nu cleop h ilic Di- a n d Tetr a flu or in a tion of Dica r bon yl Com p ou n d s
Rajendra P. Singh, Utpal Majumder, and J ean’ne M. Shreeve*
Department of Chemistry, University of Idaho, Moscow, Idaho 83844-2343
jshreeve@uidaho.edu
Received May 17, 2001
Reactions of various diketo compounds with Deoxofluor [(CH3OCH2CH2)2NSF3] have been
investigated. When reacted with Deoxofluor, R-diketones, R1COCOR2 (R1 ) R2 ) Ph; R1 ) R2 )
4-Me-C6H4; R1 ) Ph, R2 ) Me; R1 ) Me, R2 ) Et) (1a -d ) formed difluoro derivatives (2a -d ) in the
presence of a catalytic amount of HF and/or tetrafluoro (3a -d ) products depending on the reaction
conditions and stoichiometry used. Reactions of â-diketones, R3COCH2COR4 (R3 ) R4 ) Ph; R3 )
R4 ) Me; R3 ) Me, R4 ) Ph) (4e-g), with Deoxofluor in the presence of a catalytic amount of HF
led to the formation of difluoroalkenones as a mixture of E (5e-g) and Z (6e-g) isomers in good
yield. Reaction of other diones, R5CO-X-COR6 (R5 ) R6 ) Ph, X ) -CHdCH-; R5 ) R6 ) Me, X )
-C6H4C6H4-; R5 ) R6 ) Ph, X ) -CH2CH2CH2-; R5 ) R6 ) Me, X ) -CH2CH2-) (7h -k ) with
Deoxofluor produced mainly difluoro products (8h -k ) with low yields of tertrafluoro derivatives
(9h -k ). Acyclic R-keto amides react poorly to give the corresponding difluoro derivatives, whereas
cyclic R-keto amides (10l-p ) react smoothly under very mild conditions to produce the corresponding
difluoro products (11l-p ) in >88% isolated yield.
In tr od u ction
ity of these species and relatively small size of the
trifluoromethyl group (only two and one-half times the
volume of a methyl group) lead to significant changes in
the chemistry of substituted compounds when compared
with their nonfluorinated analogues. The influence of a
fluorine atom or a fluorinated group in biologically active
molecules is often associated with increased lipophilic-
ity4,6 that these substituents impart giving rise to active
pharmaceutical and agrochemical compounds with im-
proved transport characteristics in vivo and facilitating
lower dose rates. While a wide variety of methods have
been developed for introducing difluoro groups into
organic compounds,7 the use of Deoxofluor as a nucleo-
philic difluoromethylating reagent is being explored.8,9
Utilization of Deoxofluor in the conversion of a simple
system such as aldehydes and ketones, into the corre-
sponding difluoro derivatives was reported recently,8,9 but
this methodology was not extended to polycarbonyl
compounds. Recently, we have reported the double nu-
Fluorine or a fluorinated group is a highly important
substituent in the field of organic chemistry, most often
bringing about some remarkable changes in the physical,
chemical and biological properties of new compounds/
materials that makes them suitable for diverse applica-
tions in the areas of materials science, agrochemistry,
and industry.1-5 The powerful electron-withdrawing abil-
* To whom correspondence should be addressed. Tel: 208-885-6215.
Fax: 208-885-9146.
(1) For the general applications of organofluorine compounds, see:
Organofluorine Chemistry: Principles and Commercial Applications;
Banks, R. E., Smart, B. E., Tatlow, J . C., Eds.; Plenum: New York,
1994.
(2) For the use of organofluorine compounds in medicinal and
biomedical chemistry, see: (a) Biomedical Frontiers of Fluorine
Chemistry; Ojima, I., McCarthy, J . R., Welch, J . T., Eds.; ACS
Symposium Series 639; American Chemical Society: Washington, DC,
1996. (b) Organic Chemistry in Medicinal Chemistry and Biomedical
Applications; Filler, R., Ed.; Elsevier: Amsterdam, 1993. (c) Welch, J .
T.; Eswaraksrishnan, S. Fluorine in Bioorganic Chemistry; J ohn Wiley
and Sons: New York, 1991. (d) Filler, R.; Kirk, K. Biological Properties
of Fluorinated Compounds. In Chemistry of Organic Fluorine Com-
pounds II: A Critical Review; Hudlicky, M., Pavlath, A. E., Eds.; ACS
Monograph 187; Americal Chemical Society: Washington, DC, 1995.
(e) Elliot, A. J . Fluorinated Pharmaceuticals. Chemistry of Organic
Fluorine Compounds II; ACS Monograph 187; Americal Chemical
Society: Washington, DC, 1995. (f) Sholoshonok, V. A., Ed. Enantio-
controlled Synthesis of Organo-Fluorine Compounds: Stereochemical
Challenge and Biomedical Targets; J ohn Wiley and Sons: 1999.
(3) For the use of of organofluorine compounds in agrosciences,
see: (a) Cartwright, D. Recent Developments in Fluorine-Containing
Agrochemicals. In Organofluorine Chemistry: Principles and Com-
mercial Applications; Banks, R. E., Smart, B. E., Tatlow, J . C., Eds.;
Plenum: New York, 1994. (b) Lang, R. W. Fluorinated Agrochemicals.
Chemistry of Organic Fluorine Compounds II; ACS Monograph 187;
American Chemical Society: Washington, DC, 1995.
(4) The ability of fluorine to change the properties of organic
molecules has been discussed extensively elsewhere. For example,
see: Smart, B. E. Characteristics of C-F systems. In Organofluorine
Chemistry: Principles and Commercial Applications; Banks, R. E.,
Smart, B. E., Tatlow, J . C., Eds.; Plenum: New York, 1994.
(5) For recent discussions on the controversial topic of fluorine
hydrogen bonds, see: (a) O’Hagan, D. O.; Rzepa, H. S. J . Chem. Soc.,
Chem. Commun. 1997, 645. (b) Dunitz, J . D.; Taylor, R. Eur. Chem. J .
1997, 3, 89-92. (c) Howard, J . A. K.; Hoy, V. J .; O’Hagan, D. O.; Smith,
G. T. Tetrahedron 1996, 52, 12613-12622.
(6) Organofluorine Chemicals and Their Industrial Applications;
Banks, R. E., Ed. Ellis Harwood Ltd.: Chichester, 1979. (b) Welch, J .
T. Tetrahedron 1987, 43, 3123-3197.
(7) For general discussion on the synthesis of organofluorine com-
pounds, see: (a) Olah, G. A.; Prakash, G. K. S.; Chambers, R. D.
Synthetic Fluorine Chemistry; Wiley and Sons: New York, 1992. (b)
Furin, G. G. Synthetic Aspects of the Fluorination of Organic Com-
pounds; Harward Academic Publisher: London, 1991. (c) Furin, G. G.
Introduction of Fluorine by N-F Compounds. Methods of Organic
Chemistry (Houben-Weyl) Organo-Fluorine Compounds; Georg Thieme
Verlag: Stuttgart, New York, 1999; pp 432-499. (d)Taylor, S. D.;
Kotoris, C. C.; Hum, G. Tetrahedron 1999, 55, 12431-12477. (e)
McClinton, M. A.; McClinton, D. A. Tetrahedron 1992, 48, 6555-6666.
(f) Rozen, S. Chem. Rev. 1996, 96, 1717-1736. (g) Wilkinson, J . A.
Chem. Rev. 1992, 92, 505-519. (h) Rozen, S.; Mishani, E. J . Chem.
Soc., Chem. Commun. 1994, 2081. (i) Rozen, S.; Mishani, E.; Bar-haim,
A. J . Org. Chem. 1994, 59, 2918. (j) Middleton, W. J .; Bingham, E. M.
J . Org. Chem. 1980, 45, 2883-2887. (k) Rozen, S.; Lerman, O.; Kol,
M.; Hebel, D. J . Org. Chem. 1985, 50, 4753-4758.
(8) (a) Lal, G. S.; Pez. G. P. US Patent 6 080 886, 2000. (b) Lal, G.
S.; Pez, G. P.; Pesaresi, R. J .; Projonic, F. M.; Chen, H. J . Org. Chem.
1999, 64, 7048-7054. (c) Lal, G. S.; Labach, E.; Evans, A. J . Org. Chem.
2000, 65, 4830-4832.
(9) Lal, G. S.; Pez, G. P.; Pesaresi, R. J .; Projonic, M. J . Chem. Soc.,
Chem. Commun. 1999, 215-216.
10.1021/jo0157674 CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/18/2001

6264 J . Org. Chem., Vol. 66, No. 19, 2001
Singh et al.
Sch em e 1
Sch em e 2
cleophilic trifluoromethylation reactions of various diketo
compounds with Me3SiCF3 to achieve the corresponding
bis(trifluoromethylated) compounds.10 In our continuing
efforts to perfluoroalkylate organic compounds nucleo-
philically,11 we have extended the scope of Deoxofluor by
utilizing it to introduce two or four fluorine atoms into
the organic backbone of molecules.
reaction conditions gave only the difluoro compound (2c)
in 88% yield whereas the formation of a tetrafluoro
derivative (3c) was observed in trace amounts by GCMS.
Not unexpectedly, with 1-phenyl-1,2-propanedione (1c)
the carbonyl group vicinal to phenyl was the only reactive
one under the conditions used. Reactivity of 2,3-pentane-
dione(1d ) was also tested under similar reaction condi-
tions and the formation of a mixture of difluoro (2d ) and
tetrafluoro (3d ) products was observed but in low yields
(Scheme 1). They were characterized as a mixture by
NMR using 19F NMR, CH3CF2COCH2CH3 gave rise to a
quartet at δ -100.81 with J ) 19.5 Hz whereas CH3-
COCF2CH2CH3 showed a triplet at δ -109.59 with J )
17 Hz. The tetrafluoro product, CH3CF2CF2CH2CH3, gave
two multiplets centered at δ -96.66 and δ -133.41.
Rea ction of Deoxoflu or w ith â-Dik eton es. Both
symmetrical and unsymmetrical â-diketones were found
to be more reactive with Deoxofluor than R-diketones.
Interestingly, the products obtained were the vicinal
difluoroenones that were isolated in good yields as
mixtures of E and Z isomers. It has been observed that
after the formation of the vicinal difluoroenone, the
reaction proceeds further to produce the tetrafluoro
derivatives of the corresponding difluoroenone in low
yield. Reaction of dibenzoylmethane (4e) with 3 equiv of
Deoxofluor at 25 °C for 5 h gave the vicinal difluoroenone
(5e, 6e) as a mixture of E and Z isomers in a ratio of
∼1:1 in 80% yield (Scheme 2). The tetrafluoro derivative,
of the E isomer of the type PhCFdCFCF2Ph, was isolated
in 10% yield. The earlier synthesis to prepare vicinal
difluoroenone compounds (5e, 6e) using DAST [(bis-
(diethylamino)sulfur trifluoride] as a fluorinating reagent
with dibenzoylmethane as substrate was not very useful
where only minor amounts of the desired products were
reported; however, somewhat better results were ob-
tained with 4f.17 Under similar reaction conditions,
acetylacetone (4f) with Deoxofluor gave a mixture of E
and Z isomers of vicinal difluoroenone (5f, 6f) in the ratio
of ∼1:1 in 72% yield (Scheme 2). A much shorter period
is required for the completion of the reaction, but using
DAST as a fluorinating reagent, 48-64 h reaction time
has been reported with the formation of the products in
40-60% yield.17 When an unsymmetrical â-diketone such
as 1-benzoylacetone (4g) was used as the substrate, the
formation of two different vicinal difluoroenones and their
corresponding E and Z isomers were observed. These
observations showed that the reactivity of aryl and alkyl
â-diketones with Deoxofluor are very similar. All of the
â-diketone reactions occurred without the addition of HF
or a substance which would permit generation of HF in
situ.
Resu lts a n d Discu ssion s
Deoxofluor was found to be a very useful reagent8,9 for
introducing a difluoro or terafluoro moiety in organic
molecules using a single-step reaction. During the course
of our research in the area of nucleophilic perfluoroalkyl-
ation, it was realized that the use of Deoxofluor with di
and polycarbonyl systems could provide a straightforward
route to the syntheses of the corresponding tetrafluoro
and polyfluorinated compounds in a single step. To study
the chemistry of Deoxofluor with dicarbonyl compounds,
various substrates were selected in which the two car-
bonyl units often are located in different chemical
environments. This chemistry is described as follows.
Rea ction of Deoxoflu or w ith r-Dik eton es. The
reactions of R-diketones with Deoxofluor are very much
dependent on the nature of the substituents vicinal to
the keto functionalities. For example, the reaction of
benzil (1a ) with 3 equivalents of Deoxofluor at 60 °C for
24 h, in the presence of a catalytic amount of HF
(generated by adding a drop of ethanol time to time), gave
the corresponding tetrafluoro derivative (3a ) in 75% yield
with concomitant formation of the corresponding difluoro
product (2a ) in trace amounts as determined by GCMS
(Scheme 1). The earlier syntheses of 3a reported in the
literature result in either low yields12 or require the use
of elemental fluorine,13 xenon difluoride,14 or bromine
monofluoride.15 When Deoxofluor, which is a thermally
stable, easy-to-handle liquid, is used as a fluorinating
reagent, reactions are easily controlled. Under similar
reaction conditions, the reaction of 4,4′-dimethylbenzil
(1b) with Deoxofluor produced the tetrafluoro product
(3b) in 72% yield. This material is an useful additive to
decrease the viscosity of liquid crystal compounds.16
Formation of 2b was observed in trace amounts.
With some of the substrates, selectivity is often ob-
served. For example, the reaction of 1-phenyl-1,2-pro-
panedione (1c) with excess Deoxofluor under similar
(10) Singh, R. P.; Leitch, J . M.; Twamley, B.; Shreeve, J . M. J . Org.
Chem. 2001, 66, 1436-1440.
(11) Singh, R. P.; Shreeve, J . M. Tetrahedron 2000, 56, 7613-7633
and references therein.
(12) (a) Chentao, Y.; Prakash, G. K. S. J . Org. Chem. 1994, 59,
6493-6494. (b) Kremlev, M. M.; Maznyi, I. S.; Sereda, S. V.; Yagupol’skii,
Y. L. Zh. Org. Khim. 1992, 28, 982-986.
(13) (a) McEwen, W. E.; Guzikowski, A. P.; Wolf, A. P. J . Fluorine
Chem. 1984, 25, 169-193. (b) Merritt, R. F. J . Org. Chem. 1967, 32,
4124-4126.
In general, the reactions of â-diketones with DAST as
a fluorinating reagent were similar However, with DAST
(14) Gregorcic, A.; Zupan, M. J . Org. Chem. 1979, 44, 4120-4122.
(15) Rozen, S.; Brand, M. J . Org. Chem. 1986, 51, 222-225.
(16) Seiji, S.; Osamu, Y.; Takahashi, M.; Hidemasa, K.; Katsutoshi,
M. J pn. Kokai Tokkyo Koho, J P 05331084, 1993.
(17) Asato, A. E.; Liu, R. S. H. Tetrahedron Lett. 1986, 27, 3337-
3340.

Di- and Tetrafluorination of Dicarbonyl Compounds
J . Org. Chem., Vol. 66, No. 19, 2001 6265
Sch em e 3
Sch em e 4
Sch em e 5
the yield of the vicinal difluoroenone from â-diketones
was found to be low (40-60%) and reaction required 48-
64 h to reach completion.17 Since the structures of DAST
and Deoxofluor are very similar, the reaction mechanism
of vicinal difluoroenone formation from â-diketones with
Deoxofluor would be expected to be essentially identical
to that of DAST18,19 (Scheme 3). It is well-known that
â-diketones exist as an equilibrium mixture of keto and
enol forms. The enol form of the â-diketone reacts with
Deoxofluor to replace the hydroxyl proton eliminating HF
and forming the intermediate X. Intramolecular fluorine
transfer generates the R-fluorinated species Y that reacts
in its enol form with Deoxofluor to produce an expected
intermediate Z. Migration of fluorine to the â-carbon and
elimination of (MeOCH2CH2)2NS(O)F gave the R,â-di-
fluoroenone as a mixture of E and Z isomers as the final
product.
Rea ction of Deoxoflu or w ith Oth er Dion es. The
diones where the two keto groups are separated by two
methylene spacers or an aromatic moiety were also
examined and their reactivity was found to be sluggish
at 25 °C. However, when the reaction was carried at 60
°C for 24 h in the presence of a catalytic amount of HF
(generated by adding a drop of ethanol from time to time),
the difluoro products were obtained in moderate yields.
These were slowly converted into the corresponding
tetrafluoro products but in low yield. For example, in the
presence of a catalytic amount of HF in dichloromethane
at 60 °C, the reaction of trans-1,2-dibenzoylethylene (7h )
with 3 equiv of Deoxofluor gave the difluoro compound
(8h ) in 66% and the tetrafluoro product (9h ) in 10%
yields. Reaction with 4,4′-diacetylbiphenyl (7i) was es-
sentially analogous at 60 °C with three equivalents of
Deoxofluor to produce mainly the difluoro derivative (8i)
in 72% yield. Formation of the tetrafluoro compound (9i)
was observed in ∼10% yield. Reaction of 1,3-dibenzoyl-
propane (7j) with Deoxofluor produced the corresponding
difluoro product (8j) in 65% yield and the tetrafluoro
product (9j) in traces as detected by GCMS. Acetonylace-
tone (7k ) under similar reaction conditions produced
mainly the difluoro product (8k ) in 62% yield (Scheme
4).
of a catalytic amount of HF, PhCF2CONEt2 was found
in 20% yield based on GCMS. The yield of the product
did not change even after 3 days at reflux. A similar lack
of reactivity was observed when 1-(N-morpholino)-2-
phenylethane-1,2-dione was used as a substrate. On the
other hand, cyclic R-keto amides such as 10l react with
3 equiv of Deoxofluor in the presence of a catalytic
amount of HF at room temperature for 8 h to give 11l in
90% isolated yield. Under identical reaction conditions,
10m -p led to the formation of the corresponding difluoro
amides (11m -p ) in >90% isolated yields (Scheme 5).
With DAST, 11m was obtained in 95% yield.7j In both
R-keto amides only the R-keto group was found to be
reactive. This likely arises from deactivation of the
carbonyl vicinal to the nitrogen atom by the donation of
the lone pair of electrons from the nitrogen to the
carbonyl carbon, thus reducing its electrophilic character.
In summary, in an effort to synthesize both difluoro
and tetrafluoro derivatives, we have studied the reactions
of R, â, and γ dicarbonyl compounds with Deoxofluor.
With R-ketodiones, the products formed varied as a
function of the substitutent groups. For example, in the
case of benzil, the tetrafluoro product was achieved
whereas when one phenyl group was replaced with
methyl (1-phenyl-1,2-propanedione), the difluoro product
was the major one even in the presence of excess
Deoxofluor. This difference in products may arise from
a decrease in the electrophilicity of the carbonyl group
alpha to the methyl group. The reaction of â-diketones
such as dibenzoylmethane or 2,4-pentanedione with
Deoxofluor under mild conditions led to the formation of
the vicinal difluoroenone as a mixture of E and Z isomers.
In diones where the two carbonyl groups are separated
by at least two or more bonds, the reaction was found to
be slow and only a single carbonyl group was found to
be fluorinated. Acyclic R-ketoamides with Deoxofluor
reacted poorly whereas cyclic ones gave the corresponding
difluoro products in very good yield. This is in agreement
with the results obtained when AcOF was used as an
electrophilic fluorinating agent with nonbenzylic acyclic
enones.7k In both the cases, only the R-keto group of the
amide was found to result in the corresponding difluoro
amide. In general, with Deoxofluor reactions with various
substrates appear to occur more rapidly and often give
superior yields compare to DAST.
Rea ction of Deoxoflu or w ith Acyclic a n d Cyclic
r-Ketoa m id es. Initially the reactions of acyclic R-keto
amides, such as PhCOCONEt2, were carried out with 3
equiv of Deoxofluor. After 24 h at reflux, in the presence
(18) Hudlicky´, M. Fluorine Chemistry for Organic Chemists; Oxford
University Press: New York, 2000; pp 45-46.
(19) Hudlicky´, M. Fluorination with Diethylaminosulfur Trifluoride
and Related Aminofluorosulfuranes. Org. React. 1988, 35, 513-637
and references therein.

6266 J . Org. Chem., Vol. 66, No. 19, 2001
Singh et al.
133.3, 134.9,138.8, 145.5 (dd, J ) 250 Hz, J ) 45 Hz), 154.4
(J ) 250 Hz, J ) 45 Hz), 194.5. MS (EI) m/z (species, rel int)
244 (M+, 64), 243 (M+ - H, 82), 167 (M+ - Ph, 2), 105 (PhCO+,
100), 77 (Ph+, 59).
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were performed under dry
nitrogen atmosphere. Diketo compounds were obtained from
Aldrich and were used as received. Deoxofluor was a gift from
Air Products. Products were purified by flash chromatography
using a mixture of diethyl ether and pentane as an eluent.
1H, 19F, and 13C NMR spectra were recorded in CDCl3 on a
spectrometer operating at 200, 188, and 50 MHz, respectively.
Chemical shifts are reported in ppm relative to the appropriate
(Z)-2,3-Diflu or o-1,3-d ip h en yl-2-p r op en -1-on e
Yield: 38%. Viscous liquid. IR (film): 3062, 1651, 1493, 1448,
1325, 1277, 1184, 1100, 977, 881, 847, 766, 717, 692, 658 cm-1
(6e).
.
1H NMR (CDCl3) δ: 7.2-7.9.0 (m, 10H). 19F NMR (CDCl3) δ:
-108.56 (d, 1F, J ) 8 Hz), -139.92 (d, 1F, J ) 8 Hz). 13C NMR
(CDCl3) δ: 128.2, 128.4, 128.8 (d, J ) 3 Hz), 128.9 (d, J ) 3
Hz), 129.4 (d, J ) 4 Hz), 131.2, 133.5, 135.7, 143.1 (dd, J )
258 Hz, J ) 18 Hz), 155.1 (J ) 258 Hz, J ) 18 Hz), 188.4. MS
(EI) m/z (species, rel int): 244 (M+, 62), 243 (M+ - H, 91), 167
(M+ - Ph, 3), 105 (PhCO+, 100), 77 (Ph+, 70). HRMS: calcd
for C15H10F20 244.0700, found 244.0712.
1
standard, CFCl3 for 19F and TMS for H and 13C NMR spectra.
IR spectra were recorded using NaCl plates for neat liquids
and KBr pellets for solids. Mass spectra were measured on
an electron impact 70 ev spectrometer and high-resolution
mass spectra (HRMS) were obtained using a suitable mass
spectrometer.
(E)-1,2,3,3-Tetr aflu or o-1,3-diph en ylpr open e. Yield: 10%.
1H NMR (CDCl3) δ: 7.1-7.7 (m, 10H). 19F NMR (CDCl3) δ:
-97.25 (d, 1F, J ) 23.5 Hz), -97.34 (d, 1F, J ) 23.5 Hz),
-148.35 (doublet of triplet, 1F, J ) 129 Hz, J ) 24 Hz),
-161.33 (doublet of triplet, 1F, J ) 129, 17 Hz). MS (EI) m/z
(species, rel int): 266 (M+, 100), 246 (M+ - HF, 15), 188 [M+
- (Ph + H), 47], 169 [M+ - (Ph + HF), 29], 127 (PhCF2+, 65),
77 (Ph+, 20). HRMS: calcd for C15H10F4 266.0719, found
266.0733.
Rea ction of r-Dik eton es w ith Deoxoflu or . In a typical
experiment, R-diketones (2 mmol) (1a -c) were dissolved in
dichloromethane (5 mL), Deoxofluor (6 mmol) was added at
room temperature and followed by the addition of 2 drops of
ethanol (to generate a catalytic amount of HF). The reaction
mixture was heated at 60 °C for 24 h. Reaction was quenched
by the slow addition of aqueous NaHCO3 solution until
effervescence was complete. The dichloromethane layer was
separated and dried over anhydrous MgSO4. It was filtered
and removal of solvent afforded the product.
(E)-3,4-Diflu or o-3-p en ten -2-on e (5f).17 Yield: 39%. Vis-
cous liquid. 1H NMR (CDCl3) δ: 2.0-2.3 (m, 6H). 19F NMR
(CDCl3) δ: -116.55 (broad multiplet, 1F, J ) 129 Hz), -163.33
(broad doublet, 1F, J ) 127 Hz) [lit.17 -117.70 (broad, 1F, J )
130 Hz), -162.90 (broad, 1F, J ) 128 Hz)]. MS (EI) m/z
1,1,2.2-Tet r a flu or o-1,2-d ip h en ylet h a n e (3a ).12a Yield:
75%. Colorless solid. Mp 115 °C. IR (film): 1449, 1255, 1145,
1
1078, 933, 878, 751, 696, 657 cm-1. H NMR (CDCl3) δ: 7.3-
7.5 (m, 10H). 19F NMR (CDCl3) δ: -112.26 (s, 4F). 13C NMR
(CDCl3) δ: 116 (t, J C-F ) 251.5 Hz), 126.8, 126,9, 127.0, 127.2,
127.5, 128.0, 130.8. MS (EI) m/z (species, rel int): 254 (M+,
12), 235 (M+ - F, 1), 215 (M+ - HF2, 1), 127 (PhCF2+, 100),
77 (Ph+, 17). HRMS: calcd for C14H10F4 254.0719, found
254.0704.
(species, rel int) 120 (M+, 35), 105 (M+ - Me, 30), 77 (M+
-
COMe, 24), 43 (MeCO+, 100).
(Z)-3,4-Diflu or o-3-p en ten -2-on e (6f).17 Yield: 33%. Vis-
cous liquid. 1H NMR (CDCl3) δ: 2.0-2.3 (m, 6H). 19F NMR
(CDCl3) δ: -99.83 (q, 1F, J ) 18 Hz), -151.24 (m, 1F) (lit.17
-99.95 (q 1F, J ) 19 Hz), -151.20 (m, 1F). MS (EI) m/z
2,2-Diflu or o-2-ph en yl-acetoph en on e (2a).15 Yield is trace
as detected by MS. MS (EI) m/z (species, rel int) 232 (M+, 1),
213 (M+ - F, 1), 194 [(M+ - 2F, 1), 127 (PhCF2+, 10), 105
(PhCO+, 100), 77 (Ph+, 53).
(species, rel int): 120 (M+, 32), 105 (M+ - Me, 38), 77 (M+
-
COMe, 20), 43 (MeCO+, 100).
(E)-2,3-Diflu or o-1-p h en yl-2-bu ten -1-on e (5g).17 Yield:
25% (based on GCMS). 19F NMR (CDCl3) δ: -118.48 (doublet
of quartet, 1F, J ) 128 Hz, 17 Hz), -159.58 (quartet of doublet,
1F, J ) 128 Hz, 6.5 Hz). MS (EI) m/z (species, rel int): 182
(M+, 41), 181 (M+ - H, 24), 162 (M+ - Me, 5), 105 (PhCO+,
100), 77 (Ph+, 93).
1,1,2.2-Tetr a flu or o-1,2-bis(4-m eth ylph en yl)eth a n e (3b).
Yield: 72%. Colorless solid. Mp: 130-131 °C. IR (film): 3050,
1450, 1261, 1140, 1078, 929, 875, 750, 696 cm-1 1H NMR
.
(CDCl3) δ: 3.34 (s, 6H), 7.0-7.5 (m, 8H). 19F NMR (CDCl3) δ:
-111.56 (s, 4F). 13C NMR (CDCl3) δ: 116 (t, J CF ) 251.5 Hz),
126.8, 126,9, 127.0, 127.2, 127.5, 128.0, 130.8. MS (EI) m/z
(Z)-2,3-Diflu or o-1-p h en yl-2-b u t en -1-on e (6g).17 Yield:
1
30%. Viscous liquid. H NMR (CDCl3) δ: 2.36 (dd, 3H, J ) 20
(species, rel int): 282 (M+, 10), 263 (M+ - F, 1), 243 (M+
-
Hz, J ) 4.5 Hz), 7.3-8.0 (m, 5H). 19F NMR (CDCl3) δ: -99.16
(q, 1F, J ) 20 Hz), -146.36 (broad singlet, 1F, J ) 7 Hz). MS
(EI) m/z (species, rel int): 182 (M+, 57), 181 (M+ - H, 33), 167
(M+ - Me, 6), 163 (M+ - F, 3), 162 (M+ - HF, 8), 105 (PhCO+,
100), 77 (Ph+, 95).
HF2+, 1], 228 [M+ - (HF2+ + Me), 1], 141 (MeC6H4CF2+, 100).
Anal. Calcd for C16H14F4: C, 68.06; H, 5.00. Found: C, 67.92;
H, 4.89.
1,1-Diflu or o-1-p h en ylp r op a n on e (2c). Yield: 88%. Vis-
cous liquid. IR (film): 1747, 1450, 1361, 1262, 1128, 1090,
Rea ction of Oth er Dik eton es w ith Deoxoflu or . Reac-
tions of 7h -k with Deoxofluor were carried out under condi-
tions identical to those used for 1a -c.
1067, 969, 939, 762, 695 cm-1
.
19F NMR (CDCl3) δ: -107.00
1
(s, 2F); H NMR (CDCl3) δ 2.29 (t, 3H, J ) 1.7 Hz), 7.3-7.6
(m, 5H). 13C NMR (CDCl3) δ: 24, 115.8 (t, J CF ) 252 Hz), 125.5
(t, J ) 6 Hz), 128.8, 131.0, 131.8 (t, J CCF ) 25.2 Hz), 197 (t,
J CCF ) 32.6 Hz). MS (EI) m/z (species, rel int): 170 (M+, 14),
155 (M+ - Me, 1), 127 (PhCF2+, 100), 77 (Ph+, 12), 43 (CH3-
CO+, 85).
tr a n s-4,4-Diflu or o-1,4-d ip h en yl-2-b u t en e-1-on e (8h ).
Yield: 66%. Viscous liquid. IR (film): 2970, 1680, 1638, 1597,
1450, 1329, 1285, 1257, 1188, 1043, 1015, 963, 773, 694 cm-1
.
19F NMR (CDCl3) δ: -95.14 (d, 2F, J ) 10.5 Hz). 1H NMR
(CDCl3) δ: 7.00 (t, 1H, J ) 10.5 Hz), 6.99 (triplet of doublets,
1H), 7.25-8.0 (m, 9H). 13C NMR (CDCl3) δ: 118.8 (t, J ) 239
Hz), 125.3 (t, J ) 6 Hz), 127.2 (t, J ) 7 Hz), 128.7, 128.8, 128.9,
130.5 (t, J ) 2 Hz), 189.2. MS (EI) m/z (species, rel int): 258
(M+, 6), 238 (M+ - HF, 2), 131 (M+ - PhCF2, 36), 127 (PhCF2,
13), 105 (PhCO+, 100), 77 (Ph+, 40). HRMS: calcd for C16H12F2O
258.0856, found 258.0849.
1,1,2,2-Tetr a flu or o-1-p h en ylp r op a n e (3c).13a Yield is
trace as detected by MS. MS (EI) m/z (species, rel int): 192
(M+, 14), 177 (M+ - CH3, 1), 173 (M+ - F, 1), 127 (PhCF2
,
+
100), 77 (Ph+, 18).
Rea ction of â-Dik eton es w ith Deoxoflu or . In a typical
experiment, â-diketones (2 mmol) (4d -f) were dissolved
dichloromethane (5 mL) Deoxofluor (6 mmol) was added at
room temperature. The reaction mixture was stirred at 25 °C
for 5 h. The workup procedure was identical to that used for
1a -c.
tr a n s-1,4-Dip h en yl-1,1,4,4-t et r a flu or o-2-b u t en e (9h ).
Yield: 10%. Viscous liquid. 19F NMR (CDCl3) δ: -93.86 (d, J
) 4 Hz). 1H NMR (CDCl3) δ: 7.2-7.5 (m, 2H). MS (EI) m/z
(species, rel int): 280 (M+, 10), 260 (M+ - HF, 1), 241 [M+
-
(E)-2,3-Diflu or o-1,3-d ip h en yl-2-p r op en -1-on e
(5e).
(HF + F), 2], 153 (M+ - PhCF2, 40), 133 [M+ - (PhCF2 + HF),
32], 127(PhCF2, 100), 77 (Ph+, 16).
Yield: 42%. Viscous liquid. IR (film): 3060, 1685, 1597, 1495,
1448, 1348, 1273, 1175, 1136, 1099, 1029, 918, 845, 793, 767,
717, 688 cm-1. 1H NMR (CDCl3) δ 7.4-8.0 (m, 10H). 19F NMR
(CDCl3) δ -136.01 (d, 1F, J ) 129 Hz), -154.93 (d, 1F, J )
129 Hz). 13C NMR (CDCl3) δ 127.1 (d, J ) 8 Hz), 127.2 (d, J )
8 Hz), 128.4, 128.8 (d, 2 Hz), 129.0, 129.9, 131.3 (d, J ) 2 Hz),
4-Acetyl-4′-(1,1-d iflu or oeth yl)bip h en yl (8i). Yield: 72%.
Colorless solid. Mp: 149 °C. IR (film): 2965, 1677, 1395, 1174,
1122, 910, 820, 730 cm-1
.
19F NMR (CDCl3) δ: -87.75 (q, 2F,
1
j ) 18 Hz). H NMR (CDCl3) δ: 1.90 (t, 3H, J ) 18 Hz), 2.63
(s, 3H), 7.5-7.7 (m, 8H). 13C NMR (CDCl3) δ: 25.9 (t, J ) 29.5

Di- and Tetrafluorination of Dicarbonyl Compounds
J . Org. Chem., Vol. 66, No. 19, 2001 6267
Hz), 26.6, 121.1 (t, J ) 237 Hx), 125.2 (6 hz), 127.2, 127.3,
128.9, 136.2, 137.9 (t, J ) 26.5), 141.2, 144.7, 197.62. MS (EI)
Rea ction of r-Keto Am id es w ith Deoxoflu or . In a
typical experiment, R-ketoamides (2 mmol) (10l-p ) were
dissolved in dichloromethane (5 mL), and Deoxofluor (6 mmol)
was added at room temperature followed by the addition of 2
drops of ethanol (to generate a catalytic amount of HF). The
reaction mixture was stirred at room temperature for 8 h.
Reaction was quenched by the slow addition of aqueous
NaHCO3 solution until the effervescence was completed. The
dichloromethane layer was separated, dried over anhydrous
MgSO4, and removed under reduced pressure.
m/z (species, rel int): 260 (M+, 38), 245 (M+ - Me, 100), 225
(M+ - (Me + HF), 3], 152 (C6H4C6H4+, 37), 2], 65 (MeCF2
,
+
10), 43 (MeCO+, 18). Anal. Calcd for C16H14F2O: C, 73.82; H,
5.42. Found: C, 73.69; H, 5.47.
4,4′-Bis(1,1-Diflu or oet h yl)b ip h en yl (9i). Yield: 10%.
Colorless solid. Mp: 140 °C. IR (film) 2964, 1390, 1296, 1261,
1166, 1016, 912, 819, 731 cm-1 19F NMR (CDCl3) δ: -112.55
.
(s, 2F). 1H NMR (CDCl3) δ: 3.20 (s, 3H), 6.87 (d, 1H, J ) 8
Hz), 7.16 (t, 1H, J ) 8 Hz), 7.4 - 7.6 (m, 2H). 13C NMR (CDCl3)
δ: 121.7 (t, J ) 237 Hz), 125.2 (t, J ) 6 Hz), 127.2, 137.5 (t,
J ) 27 Hz), 141.7. MS (EI) m/z (species, rel int): 282 (M+, 52),
1-P h en yl-3,3-d iflu or ooxin d ole (11l). Yield: 90%. Light
yellow solid. Mp: 89-90 °C. IR (film): 1759, 1619, 1501, 1469,
1376, 1300, 1126, 1085, 1033, 1001, 945, 840, 763, 700 cm-1
.
267 (M+ - Me, 100), 263 (M+ - F), 4), 247 (M+ - Me + HF,
19F NMR (CDCl3) δ: -110.85 (s, 2F). 1H NMR (CDCl3) δ: 6.8-
7.7 (m, 9H). 13C NMR (CDCl3) δ: 110.5 (t, J CF ) 248 Hz), 112.7,
124.3, 126.2, 128.9, 129.9, 132.6, 133.4, 144.2. MS (EI) m/z
(species, rel int): 245 (M+, 100), 216 [M+ - (CO + H), 31],
198 [M+ - (CO + F), 94], 77 (Ph+, 13). HRMS: calcd for
C14H9F2NO 245.0652, found 245.0661.
16), 152 [M+ - (2MeCF2), 4], 126 (C6H4CF2+ , 33), 65 (MeCF2
6). HRMS: calcd for C16H14F4 282.1032, found 282.1017.
,
+
5,5-Diflu or o-1,5-d ip h en ylp en ta n -1-on e (8j). Yield: 65%.
Viscous liquid. IR (film): 3000, 1685, 1597, 1450, 1325, 1269,
1179, 970, 761, 696 cm-1
.
19F NMR (CDCl3) δ: -95.55 (t, 2F,
1
J ) 14 Hz). H NMR (CDCl3) δ: 1.85 (m, 2H), 2.19 (m, 2H),
2.96 (t, 2H, J ) 7 Hz), 7.2 - 8.0 (m, 10H) 13C NMR (CDCl3) δ:
17.2 (t, J ) 4 Hz), 37.62, 28.2 (t, J ) 27.5 Hz), 123.0 (t, J )
238 Hz), 124 9 (t, J ) 6 Hz), 127.9, 128.4, 129.7, 133.1, 136.8,
199.2, 189.2. MS (EI) m/z (species, rel int): 274 (M+, 1), 254
(M+ - HF, 20), 234 (M+ - 2HF, 2), 127 (PhCF2+, 8), 105
(PhCO+, 100), 77 (Ph+, 35). Anal. Calcd for C17H16F2O: C,
74.44; H, 5.88. Found: C, 74.81; H, 5.95.
1-Meth yl-3,3-d iflu or ooxin d ole (11m ).7j Yield: 90%. Light
yellow solid. Mp: 89-90 °C. IR (film): 3060, 1758, 1622, 1473,
1381, 1350, 1251, 1114, 1076, 1022, 940, 856, 761, 698 cm-1
.
19F NMR (CDCl3) δ: -112.55 (s, 2F). 1H NMR (CDCl3) δ: 3.20
(s, 3H), 6.87 (d, 1H, J ) 8 Hz), 7.16 (t, 1H, J ) 8 Hz), 7.4-7.6
(m, 2H). 13C NMR (CDCl3) δ: 26.30, 109.4, 123.9, 124.6, 123.5,
143.9, 165.3. MS (EI) m/z (species, rel int): 183 (M+, 100), 168
(M+ - Me, 8), 164 (M+ - F, 5), 155 (M+ - CO, 27), 154 [M+
-
1,1,5,5-Tetr a flu or o-1,5-d ip h en ylp en ta n e (9j). Yield is a
trace as detected by GCMS. MS (EI) m/z (species, rel int): 296
(CO + H), 44], 136 [M+ - (CO + F), 20], 135 [M+ - (CO + F
+ H), 30]. HRMS: calcd for C9H7F2NO 183.0496, found
183.0504.
(M+, 17), 276 (M+ - HF, 20), 256 (M+ - 2HF, 1), 169 (M+
-
PhCF2, 2), 127 (PhCF2, 100), 77 (Ph+, 8).
1-Ben zyl-3,3-d iflu or ooxin d ole (11n ). Yield: 92%. Yellow
solid. Mp: 76-77 °C. IR (film): 1740, 1622, 1483, 1334, 1259,
5,5-Diflu or oh exa n -2-on e (8k ). Yield: 62%. Colorless liq-
1
uid. 19F NMR (CDCl3) δ: -92.83 (m, 2F). H NMR (CDCl3) δ:
1174, 1024, 901, 832, 792, 728 cm-1
.
19F NMR (CDCl3) δ:
2.01 (m, 4H), 2.62 (t, 3H, J ) 6.7 Hz), 2.65 (s, 3H). MS (EI)
m/z (species, rel int): 136 (M+, 2), 121 (M+ - Me, 6), 65
(MeCF2+, 13), 43 (MeCO+, 100).
1
-111.93 (s, 2F). H NMR (CDCl3) δ: 4.87 (s, 2H), 6.4-7.6 (m,
9H). 13C NMR (CDCl3) δ: 42.5, 110.2, (t, J CF ) 248 Hz), 123.8,
124.7, 127.2, 128.1, 129.0, 134.2, 149.3. MS (EI) m/z (species,
rel int) 259 (M+, 44), 239 (M+ - HF, 1), 168 (M+ - PhCH2,
20), 91 (PhCH2+, 100), 77 (Ph+, 2). Anal. Calcd for C15H11F2-
NO: C, 69.48; H, 4.28. Found: C, 69.56; H, 4.12.
P r ep a r a tion of Acyclic Am id es (10n -p ). In a typical
procedure, unprotected isatin (5 mmol) was dissolved in THF
(20 mL), and sodium hydride (5 mmol) was added at -20 °C.
The reaction mixture was warmed slowly to room temperature
and stirred for 3 h. To the mixture was added benzyl bromide
(5 mmol) dropwise at room temperature and the resulting
mixture stirred for 24 h. Methylene chloride (20 mL) was
added, and the solution was washed with water three times.
The dichloromethane layer was dried over magnesium sulfate
and filtered. The solvent was removed at reduced pressure.
N-Ben zylisa tin (10n ): Yield: 85%. Orange solid. Mp: 126-
127 °C. IR (film): 1735, 1612, 1467, 1350, 1177, 1093, 813,
N-Ben zyl-3,3-diflu or o-5-flu or ooxin dole (11o). Yield: 88%.
Yellow solid. Mp: 58-59 °C. IR (film): 3060, 1753, 1625, 1490,
1371, 1350, 1294, 1263, 1199, 1179, 1138, 1091, 1018, 972, 881,
820, 972, 756, 734, 698 cm-1 19F NMR (CDCl3) δ: -112.06 (s,
.
2F), -117.60 (s, 1F). 1H NMR (CDCl3) δ: 4.86 (s, 2H), 6.4-
7.7 (m, 8H). 13C NMR (CDCl3) δ: 44.0, 110.4 (t, J ) 248 Hz),
111.6, 111.8, 112.5, 113.1, 119.7, 120.2, 121.2 (t, J ) 8 Hz),
127.2, 128.2, 129.1, 133.9, 139.0, 156.9 (t, J ) 2.5 Hz), 161.8
(t, J ) 2.5 Hz), 165.2 (t, J ) 30 Hz). MS (EI) m/z (species, rel
int): 277 (M+, 19), 248 [M+ - (CO + H), 1], 186 (M+ - PhCH2,
2), 91 (PhCH2, 100). HRMS: calcd for C15H10F3NO 277.0714,
found 277.0699.
1
753, 695 cm-1. H NMR (CDCl3) δ: 4.91 (s, 2H), 6.5-7.7 (m,
9H). 13C NMR (CDCl3) δ: 44.0, 110.9, 117.7, 123.8, 125.4,
127.4, 128.1, 129.0, 134.5, 138.2, 150.7, 158.2, 183.2. MS (EI)
m/z (species, rel int): 337 (M+, 68), 180 [M+ - (COCO + H),
57], 146 (M+ - PhCH2,100), 91 (PhCH2+, 67) 77 (Ph+, 22). Anal.
Calcd for C15H11NO2: C, 75.94; H, 4.67. Found: C, 75.52; H,
4.47.
N-Ben zyl-3,3-diflu or o-5-tr iflu or om eth oxyoxin dole (11p).
Yield: 90%. Yellow solid. Mp: 85-86 °C. IR (film): 3067, 1759,
1628, 1489, 1371, 1292, 1261, 1182, 1059, 1020, 974, 895, 829,
N-Ben zyl-5-flu or oisa tin (10o). Yield: 80%. Yellow solid.
Mp: 130-133 °C. IR (film): 1737, 1620, 1483, 1330, 1264, 1171,
799, 699 cm-1 19F NMR (CDCl3) δ: -58.74 (s, 3F), -112.18 (s,
.
2F). 1H NMR (CDCl3) δ: 4.88 (s, 2H), 6.5-7.5 (m, 8H). 13C
NMR (CDCl3) δ: 44.1, 110.2 (t, J ) 248 Hz), 111.6, 116.5 (t, J
) 250 Hz), 118.6, 121.2 (t, J ) 8 Hz), 126.6, 127.2, 128.3, 129.1,
133.7, 141.9(t, J ) 2.5 Hz), 145.5, 165.0 (t, J ) 30 Hz). MS
(EI) m/z (species, rel int): 343 (M+, 14), 314 [M+ - (CO + H),
1], 252 (M+ - PhCH2, 2), 91 (PhCH2, 100). Anal. Calcd for
C16H10F5NO2: C, 55.97; H, 2.94. Found: C, 55.58; H, 2.81.
1019, 887, 825, 781, 696 cm-1 19F NMR (CDCl3) δ: -118.0 (s,
.
1F). 1H NMR (CDCl3) δ: 4.87 (s, 2H), 6.4-7.5 (m, 9H). MS
(EI) m/z (species, rel int): 255 (M+, 75), 198 [M+ - (2CO +
H), 48], 164 (M+ - PhCH2, 100), 108 [M+ - (2CO + PhCH2),
20], 91 (PhCH2, 80). Anal. Calcd for C15H10FNO2: C, 70.58;
H, 3.95. Found: C, 69.68; H, 3.93.
N-Ben zyl-5-tr iflu or om eth oxyisa tin (10p ). Yield: 82%.
Yellow solid. Mp: 100-102 °C. IR (film): 1740, 1622, 1483,
1334, 1259, 1174, 1024, 901, 832, 792, 728 cm-1 19F NMR
.
Ack n ow led gm en t. This work was supported by the
National Science Foundation (Grant No. CHE-9720365)
and by the Petroleum Research Fund, administered by
the ACS. We are grateful to Dr. G. Knerr for obtaining
high-resolution mass spectra. The generosity of Air
Products for the gift of Deoxofluor is deeply appreciated.
(CDCl3) δ: -58.74 (s, 3F). 1H NMR (CDCl3) δ: 4.88 (s, 2H),
6.5-7.5 (m, 9H). 13C NMR (CDCl3) δ: 44.5, 112.3, 118.6, 120.2
(q, J CF ) 298 Hz), 127.6, 128.5, 129.3, 131.2, 134.1, 145.5,
149.17, 158.1, 182.4. MS (EI) m/z (species, rel int): 321 (M+,
74), 264 (M+ - 3F, 29), 230 (M+ - PhCH2, 85), 91 (PhCH2,
100), 69 (CF3+, 27). Anal. Calcd for C16H10F3NO3: C, 59.82;
H, 3.14. Found: C, 59.50; H, 3.13.
J O0157674