Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthryl) propionic acids by an effective combination of radical and organometallic chemistry

Article abstract of DOI:10.1021/jo048294k

(Chemical Equation Presented) Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)-propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a - c as key intermediates. Thus, ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction of 6a - c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization of the resulting β-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a - c with butyllithium followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyllithium for 10 seconds at -110°C and subsequent addition of the suitable pyruvate to the lithiated intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained by site-selective metalation of 1,3- difluorophenanthrene 28 and the bromophenanthrene 24, respectively, with LDA followed by quenching of the metalated intermediates with the suitable alkyl pyruvate. Fluorination of the above α-hydroxypropionates with DAST, followed by the alkaline hydrolysis, allowed the expected 2-(phenanthryl) propionic acids 1-5 to be obtained in satisfactory overall yields.

Full text of DOI:10.1021/jo048294k

Regioselectively Nucleus and/or Side-Chain Fluorinated
2-(Phenanthryl)propionic Acids by an Effective Combination of
Radical and Organometallic Chemistry
Giacomo Ricci and Renzo Ruzziconi*
Dipartimento di Chimica, Universita` di Perugia, Via elce di sotto 8, I-06123 Perugia, Italy
ruzzchor@unipg.it
Received September 25, 2004
Regioselectively nucleus and/or side-chain fluorinated 2-(phenanthr-1-yl)- and 2-(phenanthr-2-yl)-
propionic acids 1-5 were prepared using phenanthren-1(2H)-ones 6a-c as key intermediates. Thus,
ethyl 2-(fluorophenanthryl)propionates 11 were obtained in good yields by Reformatsky reaction
of 6a-c with ethyl 2-bromopropionate followed by dehydratation and DDQ-promoted aromatization
of the resulting â-hydroxyesters. Side-chain alkyl 2-hydroxy-2-(phenanthr-1-yl)propionates 14 were
obtained by bromine/lithium permutation of dihydrophenanthryl bromides 12a-c with butyllithium
followed by quenching of the lithiated intermediates with methyl pyruvate or ethyl 3,3,3-
trifluoropyruvate and subsequent DDQ-promoted aromatization. The alkyl 2-hydroxy-2-(phenanthr-
1-yl)propionates 25 were prepared by reacting 8-bromo-1,3-difluorophenanthrene 24 with butyl-
lithium for 10 seconds at -110 °C and subsequent addition of the suitable pyruvate to the lithiated
intermediates. Alkyl 2-hydroxy-2-(phenanthr-2-yl)propionates 26 and 29 were suitably obtained
by site-selective metalation of 1,3-difluorophenanthrene 28 and the bromophenanthrene 24,
respectively, with LDA followed by quenching of the metalated intermediates with the suitable
alkyl pyruvate. Fluorination of the above R-hydroxypropionates with DAST, followed by the alkaline
hydrolysis, allowed the expected 2-(phenanthryl)propionic acids 1-5 to be obtained in satisfactory
overall yields.
Introduction
cially those belonging to the “Profen” family, have
received particular attention. For example, 2-(fluoroaryl)-
propionic acids such as flurbiprofen and flunoxaprofen
belong to the most successful NSAIDs. Of course, the use
of fluorinated aromatics in the synthesis of different
biologically active compounds has stimulated the re-
search toward new fluorination techniques and new
regioselectively fluorinated aromatics to be used as
valuable building blocks. In this respect, the organo-
metallic approach developed by M. Schlosser3 looks quite
Owing to its surprising peculiarities,1 fluorine, a
fascinating element, is a cornerstone in the synthesis of
modern drugs. Fluorinated drugs include a vast range
of pharmaceutical applications from anesthetics to che-
motherapeutic drugs, from corticoids to neuroleptics, and
more recently, even cardiovascular drugs.2 Fluorinated
nonsteroidal antiinflammatory drugs (NSAIDs), espe-
(1) Schlosser, M. The Chemical and Physiological Size of Fluorine.
In Enantiocontrolled Synthesis of Fluoro-Organic Compounds: Ster-
eochemical Challenges and Biomedical Targets; Soloshonok, V. A., Ed.;
Wiley: Chichester, 1999. Schlosser, M. Angew. Chem. 1998, 110, 1538-
1556; Angew. Chem., Int. Ed. 1998, 37, 1496-1513. Schlosser, M.;
Michel, D. Tetrahedron 1996, 52, 99-108. Schlosser, M. Tetrahedron
1978, 34, 3-17. Welch, T.; Eswarakrishnan, S. Fluorine in Bioorganic
Chemistry; Wiley: New York, 1991. Biomedical Aspects of Fluorine
Chemistry; Filler, R., Kobayashi, Y., Eds.; Kodansha, Ltd.: Tokyo and
Elsevier Biomedical: Amsterdam, 1982.
(2) Organofluorine Compounds in Medicinal Chemistry and Bio-
medical Applications; Filler, R., Kobayashi, Y., Yagupolskii, L. M., Eds.;
Elsevier: Amsterdam, 1993.
(3) Schlosser, M.; Rausis, T. Eur. J. Org. Chem. 2004, 1018-1024.
Schlosser, M.; Mangano, G.; Leroux, F. Eur. J. Org. Chem. 2004, 1014-
1017. Marull, M.; Schlosser, M. Eur. J. Org. Chem. 2003, 1576-1588.
Schlosser, M.; Gorecka, J.; Castagnetti, E. Eur. J. Org. Chem. 2003,
452-462. Heiss, C.; Schlosser, M. Eur. J. Org. Chem. 2003, 447-451.
10.1021/jo048294k CCC: $30.25 © 2005 American Chemical Society
Published on Web 12/30/2004
J. Org. Chem. 2005, 70, 611-623
611

Ricci and Ruzziconi
CHART 1
promising. Given that C-F bonds are stronger than C-H
bonds, replacing the R-hydrogen of a 2-arylpropionic acid
with the quasi-isosteric fluorine1 conveys a higher con-
figurational stability to the chiral carbon,4 thus allowing
the drug pharmacodynamics, as well as the stereochem-
ical matching with the receptor, to be investigated.
Up to now, only a limited number of methods have
been disclosed for the synthesis of side-chain fluorinated
2-arylpropionic acids. One of them, developed by G. Haufe
et al.,5 was a novel access to ibuprofen and naproxen. It
consists of oxidizing 2-aryl-2-fluoropropanols obtained
either by bromofluorination of 2-arylpropenes followed
by hydroxylation or, more conveniently, by BF3-catalyzed
hydrolytic ring opening of 2-arylpropene oxides. In the
same time period, M. Schlosser et al.6 prepared the
R-fluorinated analogue of ibuprofen by treating ethyl
2-hydroxy-2-(4-isobutylphenyl)propionate with dieth-
ylaminosulfur trifluoride (DAST) followed by the hy-
drolysis of the resulting ester or nitrile. More recently,
S. Rozen reported a quite general entry to R-fluoroalca-
noic acids, including 2-aryl-2-fluoropropionic acids, based
on the acyl hypofluorite-promoted electrophilic fluorina-
tion of ketene-acetals.7
To date, only a few R-fluorinated profens are known,
and 2-arylperfluoropropionic acids are even less common.
To our knowledge, these kinds of compounds have been
isolated in only three instances and each time by mere
accident.8
The increasing attention to the pharmacological prop-
erties of fluorinated profens and the lack of a method to
prepare them spurred us to search for a general approach
to new fluorinated 2-arylpropionic acids, particularly
2-(phenanthryl)propionic acids. Apart from the intrinsic
importance of the selective functionalization of polycyclic
arenes, our interest in this class of aromatics arose from
the observation that phenanthrene nucleus is at the base
of several enzyme inhibitors and other pharmacologically
important drugs.9 In this connection, it was reported that
2-(phenanthr-1-yl)propionic acid (1a) exhibits a biological
activity as NSAID comparable to that of common regis-
tered profens such as fenbufen.10 In this article, we
suggest a general approach to nucleus and/or side-chain
regioselectively fluorinated 2-(phenanthryl)propionic ac-
ids on the basis of an original combination of radical and
organometallic chemistry.
3,4-dihydrophenanthren-1(2H)-one (6a) and its 6-fluoro-
(6b) and 6,8-difluoro- (6c) analogues as the starting
materials (Chart 1).
Ketones 6a-c were prepared by an oxidative annula-
tion method developed in our laboratory.11 This method
is based on the ceric ammonium nitrate (CAN)-mediated
addition of the easily accessible 3-(fluoroaryl)-1-trimeth-
ylsilyloxycyclohexenes (7)12 to ethyl vinyl ether, which
affords a mixture of cyclic (8) and acyclic (9) acetals
(Scheme 1).
Cyclization of the latter in concentrated sulfuric acid
and in the presence of a stoichiometric amount of 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ) provides the
targeted phenanthrenones 6a-c in satisfactory (41-53%)
yield.13
The Reformatsky reaction of phenanthrenones 6b,c
with ethyl R-bromopropionate,10 followed by the dehy-
dratation of the resulting â-hydroxyester in refluxing
formic acid (Scheme 2), proved to be the most convenient
route leading to ethyl 2-(3,4-dihydrophenanthren-1-yl)-
propionates 10a-c. DDQ-promoted aromatization of the
latter in benzene at 55 °C, followed by the hydrolysis of
the resulting 2-phenanthrylpropionates 11a-c in metha-
nolic KOH, afforded the corresponding 2-(phenanthren-
1-yl)propionic acids 1a-c in approximately 70% overall
yields.
Results and Discussion
Nucleus and side-chain regioselectively polyfluorinated
2-phenanthrylpropionic acids 1-5 were prepared using
(4) Hamman, S. J. Fluorine Chem. 1993, 60, 225-232.
(5) Goj, O.; Kotila, S.; Haufe, G. Tetrahedron 1996, 52, 12761-
12774. Goj, O.; Haufe, G. Liebigs Ann. 1996, 1289-1294.
(6) Schlosser, M.; Michel, D.; Guo, Z.-W.; Sih, C. J. Tetrahedron
1996, 52, 8257-8262.
(7) Rozen, S.; Hagooly, A.; Harduf, R. J. Org. Chem. 2001, 66, 7464-
7468.
(8) Barna, P. M. Chem. Ind. (London) 1966, 2054.
(9) Toegersen, H. S.; Peschke, B.; Hansen, T. K.; Andersen, K. E.
PCT Int. Appl. WO 96 05195, 1996; Chem. Abstr. 1996, 125, 58521m.
Adams, J. L.; Garigipati, R. S. U.S. Patent 5,140,047, 1992; Chem.
Abstr. 1993, 118, 80647j. Berlin, K. D.; Durham, N. N.; Desjardins, C.
U.S. Patent 3,987,055, 1976; Chem. Abstr. 1977, 86, 106893j. Brown,
G. R.; Bamford, A. M.; Bowyer, J.; James, D. S.; Rankine, N.; Tang,
E.; Torr, V.; Culbert, E. J. Bioorg. Med. Chem. Lett. 2000, 10, 575-
579.
(11) Gourve`s, J.-P.; Ruzziconi, R.; Vilarroig, L. J. Org. Chem. 2001,
66, 617-619. Lupattelli, P.; Ruzziconi, R.; Scafato, P.; Alunni, S.; Belli
Paolobelli, A. J. Org. Chem. 1998, 63, 4506-4509.
(12) Reetz, M. T.; Kindler, A. J. Organomet. Chem. 1995, 502, C5-
C7.
(13) To avoid using the expensive DDQ, in one experiment cycliza-
tion of 8 and 9 was carried out in 85% aq phosphoric acid at 60 °C by
employing Fe2(SO4)3 as the oxidant. However, although the reaction
mixture worked up better, much lower yields (∼15%) of pure ketone
6a-c were obtained.
(10) Eir´ın, A.; Ferna´ndez, F.; Go´mez, G.; Lo´pez, C.; Santos, A. Arch.
Pharm. (Weinheim, Ger.) 1987, 320, 1110-1118.
612 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
SCHEME 1a
SCHEME 3a
a (a) CH2dCHOEt, CAN, MeOH, rt; (b) 80% aq H2SO4, DDQ, 0
°C.
SCHEME 2a
a (a) NH2NH2‚H2O, C6H6/EtOH, 80 °C; (b) CuBr2-tBuOLi, THF,
20 °C; (c) 1. BuLi, THF, 2. RCOCO2R′, THF, -75 °C; 3. aq NH4Cl;
(d) DDQ; toluene, 90 °C.
catalyzed Friedel-Crafts alkylation of substituted ben-
zenes with methyl trifluoropyruvate. A copper(II)-
catalyzed enantioselective method for the formation of
optically active alkyl 2-aryl-2-hydroxy-3,3,3-trifluoropro-
pionates making use of chiral bisoxazoline ligands was
published by Jørgensen.18 However, in both cases, ac-
ceptable yields were only achieved when the reaction was
assisted by powerful electron-releasing groups present
in the aromatic substrate. In contrast, our method does
not suffer from such restrictions.
The reaction of 1-bromo-6,8-difluoro-3,4-dihydrophenan-
threne (12c) with butyllithium turned out to be a more
complex process than expected. Of course, the acidity of
the C7-H bond flanked by two fluorine atoms should
increase the deprotonation rate to such an extent that it
could effectively compete with the bromine/metal ex-
change. As a matter of the fact, the reaction of bromodi-
hydrophenanthrene 12c with butyllithium in THF at
a (a) 1. CH3CHBrCO2Et, Zn/Hg, C6H5-DEE, refl; 2. HCO2H, refl;
(b) DDQ, C6H6, 55 °C; (c) KOH, MeOH, rt.
The key products for the synthesis of side-chain
fluorinated 2-(phenanthryl)propionic acids 2a-c and
3a-c were 1-bromo-3,4-dihydrophenanthrene (12a) and
its 6-fluoro- (12b) and 6,8-difluoro- (12c) analogues. They
were prepared from ketones 6a-c by lithium tert-
butoxide/CuBr2-promoted bromination of the correspond-
ing hydrazones in anhydrous THF.14
Butyllithium-promoted bromine/lithium permutation
in 12a,b in THF at -75 °C, followed by the addition of
either methyl pyruvate or ethyl 3,3,3-trifluoropyruvate,
gave the corresponding 2-(3,4-dihydrophenanthren-1-yl)-
2-hydroxypropionates 13a-b or the 3,3,3-trifluoropropi-
onate analogues 13c-d thereof (Scheme 3). Once again,
DDQ-promoted aromatization enabled the conversion of
hydroxyesters 13a-d into the corresponding 2-(phenan-
thren-1-yl)-2-hydroxypropionates 14a-d in 60-70% over-
all yield.15
(15) Similar results were obtained by changing the metalation/
alkylation/aromatization sequences. Namely, aromatization of 10a,b
with DDQ followed butyllithium-promoted halogen-lithium exchange
and successive alkylation of the resulting 1-lithiophenanthrene inter-
mediate with alkyl pyruvates. However, because of the low stability
of the vinylic bromide in the presence of DDQ, lower yields of the
corresponding aromatic 1-bromophenanthrenes were obtained, and
they were contaminated by substantial amounts of unidentified
dibromoderivatives.
(16) Ding, R.; Zhang, H. B.; Chen, Y. J.; Liu, L.; Wang, D.; Li, C. J.
Synlett 2004, 555-557.
(17) Prakash, G. K. S.; Yan, P.; To¨ro¨k, B.; Olah, G. A. Synlett. 2003,
527-531.
In an extension of previous work by Olah,17 C. J. Li 16
recently elaborated the synthesis of several methyl
2-aryl-2-hydroxy-3,3,3-trifluoropropionates by Lewis acid-
(18) Zhuang, W.; Gathergood, N.; Hazell, R. G.; Jørgensen, K. A. J.
Org. Chem. 2001, 66, 1009-1013. See also Corma, A.; Garc´ıa, H.;
Moussaif, A.; Sabater, M. J.; Zniber, R.; Redouane, A. Chem. Commun.
2002, 1058-1059.
(14) Takeda, T.; Sasaki, R.; Yamauchi, S.; Fujiwara, T. Tetrahedron
1997, 53, 557-566.
J. Org. Chem, Vol. 70, No. 2, 2005 613

Ricci and Ruzziconi
SCHEME 4
-100 °C for 90 min, before quenching with methyl
pyruvate, afforded a mixture of five products that were
easily separated by chromatography on silica gel and
identified as methyl 2-(6,8-difluoro-3,4-dihydrophenan-
thren-1-yl)-2-hydroxypropionate (15a, 7%), methyl 2-(8-
bromo-1,3-difluoro-5,6-dihydrophenanthren-2-yl)-2-hy-
droxypropionate (16a, 16%), methyl 2-(1,3-difluoro-5,6-
dihydrophenanthren-2-yl)-2-hydroxypropionate (17a, 54%),
the 2,8-dialkylated derivative (18a, <1%), and 6,8-
difluoro-3,4-dihydrophenanthrene (19, 14%) (Scheme 4).
In fact, the product composition varied substantially
as a function of the reaction time. The yield of trapping
product 15a diminished from 38% to 22% and to 7% after
5, 20, 35, and 90 min, respectively, whereas that of 17a
increased in the same intervals from 17% to 32%, 34%,
and 50%, respectively. The relative amounts of 16a, 18a,
and 19 remained practically unchanged.
From a mechanistic point of view, it is quite likely that
the initial attack of butyllithium at 12c turns into both
halogen/metal exchange at C-1 and deprotonation at C-7
to give the 1-lithio derivative 20, and the C-7-lithiated
bromophenanthrene 21, respectively, with bromine/
lithium permutation being 3 times faster. Then, slow
transmetalation occurs, converting the more basic species
20 into the less basic species 22 and 23. After quenching
with methyl pyruvate, the R-hydroxyesters 15a, 16a, 17a,
and 18a were obtained from 20, 21, 22, and 23, respec-
tively (Scheme 4). In the same way, the replacement of
methyl pyruvate by ethyl trifluoropyruvate led to a
mixture of the corresponding ethyl 2-(phenanthryl)-3,3,3-
trifluoropropionates 15b, 16b, 17b, and 18b of practically
identical composition.
8-bromo-1,3-difluorophenanthrene (24), obtained in 65%
yield by DDQ-promoted aromatization of 12c.19 This was
done because we believed that two interdependent favor-
able conditions would have been accomplished: a faster
bromine/lithium exchange that could compete effica-
ciously with the deprotonation at C-7 and a slower
equilibration as a consequence of a lower basicity of the
aryllithium with respect to a vinyllithium species.
Similar to dihydrophenanthrene 12c, the reaction of
24 with butyllithium at -100 °C for 90 min, followed by
the addition of methyl pyruvate, afforded a mixture of
four products that were identified as methyl 2-(6,8-
difluorophenanthren-1-yl)-2-hydroxypropionate (25a, 46%),
2-(1,3-difluorophenanthren-2-yl)-2-hydroxypropionate (26a,
31%), the 1,7-dialkylated 6,8-difluorophenanthrene (27a,
<1%), and 1,3-difluorophenanthrene (28, 7%) (Scheme
5). Traces of methyl 2-(8-bromo-1,3-difluorophenanthryl)-
2-hydroxypropionate (29) were also detected.
As above, a quantitative GLC analysis of the mixture
was carried out at various reaction times. The pattern
looked quite different from that observed in the reaction
of the corresponding dihydroderivative 12c. Here, a
nearly quantitative bromine/lithium permutation was
observed, and the equilibration toward the most ther-
modynamically stable intermediate 1,3-difluoro-2-lithio-
phenenthrene was significantly slower. Like dihydro-
phenanthrene 19 in the reaction of 12c, 1,3-difluoro-
phenanthrene 28 most probably works as the catalyst of
the whole process, as the amount remains low and
practically unchanged. At lower temperatures, equilibra-
tion could be controlled to the point that the expected
(19) A one-step procedure to prepare 21 by reacting the ketone 3c
with PBr3 at 90 °C was unsuccessful. The product was obtained in
very low yield and was contaminated by unidentified dibromo deriva-
tives.
To find a more selective process leading to regio-
isomerically pure hydroxyester 25, the dihydrobromo-
phenanthrene 12c was replaced by the corresponding
614 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
SCHEME 5
SCHEME 6a
1-alkylated difluorophenanthrenes 25a and 25b were
obtained as the only products in 61 and 65% of yield,
respectively, when 24 was made to react with butyl-
lithium at -110° for only 10 seconds before the mixture
was quenched with methyl pyruvate or ethyl trifluoro-
pyruvate. The product, contaminated by only a small
amount (6%) of the starting bromoarene, was easily
purified by chromatography on silica gel. This proved to
be the only way to prepare 25a,b cleanly.20
The regioselective lithiation of fluoroaromatics by
lithium dialkylamide bases, without problems of compet-
ing halogen/metal exchange, was thoroughly examined
by M. Schlosser.21 It can also be successfully exploited
in our case. As evidence, both regioisomerically pure
bromoarylpropionate 29a and the corresponding trifluoro
analogue 29b were easily obtained in 83 and 88% yield,
respectively, by metalation of 24 with lithium diisoprop-
ylamide (LDA) in THF at -50 °C and subsequent
quenching of the reaction mixture with methyl pyruvate
or ethyl trifluoropyruvate. Of course, both propionate 26a
and its trifluoro analogue 26b can be prepared in fairly
good yield (67 and 73%, respectively) by metalation of
1,3-difluorophenanthrene (28) with either butyllithium
or LDA in THF at -50 °C and subsequent quenching
with the suitable pyruvate (Scheme 6).
(20) Indeed, a three-step alternative approach to 12h could be
envisaged consisting of protecting C-7 by the SiMe3 group by reacting
21 with LDA and by quenching the reaction mixture with trimethyl-
chlorosilane, butyllithium-promoted bromine/metal exchange and suc-
cessive alkylation with methyl pyruvate, and last, removal of TMS
group.21 Unfortunately, this strategy did not fit our case. Deprotection
of the silylated intermediate by tetrabutylammonium fluoride in THF
resulted in an extended degradation of the hydroxy ester.
a (a) 1. BuLi, THF, -110 °C, 10 s; 2. RCOCOOR′; 3. H3O+; (b)
1. LDA, THF, -50 °C, RCOCOOR′; 3. H3O+; (c) 1. BuLi, 1.5 equiv,
THF, -50 °C, H2O; (d) LDA (or BuLi), THF, -50 °C, RCOCOOR′;
3. H3O+; (e) 1. BuLi, 2.5 equiv, THF, -75 °C, 2. RCOCOOR′ 2
equiv; 3. H3O+.
(21) Mongin, F.; Schlosser, M. Tetrahedron Lett. 1996, 37, 6551-
6554. Schlosser, M.; Heiss, C. Eur. J. Org. Chem. 2003, 4618-4624.
J. Org. Chem, Vol. 70, No. 2, 2005 615

Ricci and Ruzziconi
SCHEME 7a
Of course, the synthesis of the above fluorinated
products is only one applicative example of our strategy.
In general, this method provides a valuable access to
regioselectively functionalized and fluorinated polycyclic
aromatic compounds.
Experimental Section
If not specified otherwise, 1H NMR and 1H-decoupled 13C
NMR spectra were recorded at 400 and 100 MHz, respectively,
in CDCl3 solution using tetramethylsilane as an internal
standard. 19F NMR spectra were recorded at 376 MHz in
CDCl3 solution using CFCl3 as a reference standard. IR spectra
were registered in CHCl3 solution in the 4000-625 cm-1 range.
Gas-chromatographic analyses were performed using 30 m ×
0.32 mm capillary columns loaded with two different station-
ary phases: DB-5 MS (5% phenyl-methylpolysiloxane) and DB-
35 MS (5% phenylmethylpolysiloxane) at 70-310 °C. Mass
spectra were obtained at 70 eV. Melting points were corrected
after calibration performed with authentic standards.
Reagents and Solvents. 3,4-dihydrophenanthren-(2H)-1-
one (6a), 6-fluoro-3,4-dihydrophen-anthren-(2H)-1-one (6b),
and 6,8-difluoro-3,4-dihydrophenanthren-(2H)-1-one (6c) were
available from a previous study.11 All organic and inorganic
reagents of the highest purity were used as purchased.
Tetrahydrofuran and diethyl ether were distilled from potas-
sium hydroxide in the presence of cuprous chloride and
redistilled from sodium wire in the presence of benzophenone.
a (a) DAST, CH2Cl2, 0 °C; (b) 1. KOH, MeOH, 25 °C; 2. H3O+.
Standard Procedure for the Synthesis of Nucleus-
Fluorinated Ethyl 2-(Phenanthren-1-yl)propionates
(11b,c). The fluorinated phenanthrenones 6b,c (10.0 mmol)
and a solution of ethyl 2-bromopropionate (3.9 g, 21 mmol) in
benzene (25 mL) were added to a freshly prepared zinc
amalgam (5.0 g) in a 1:1 (v/v) benzene/DEE mixture (50 mL).
After addition of iodine (0.050 g, 0.2 mmol), the mixture was
refluxed for 90 min. During this time, further zinc amalgam
(0.5 g) and an iodine crystal were added every 20 min. The
reaction mixture was treated with 5% aq HCl (50 mL), the
organic phase was separated, washed with 5% aq NH3 (50 mL)
and then with water (50 mL) and dried with Na2SO4. After
solvent evaporation, formic acid (30 mL) was added, and the
mixture was ref1uxed for 30 min. Water (30 mL) was added,
and the mixture was extracted with hexanes (2 × 30 mL). The
organic phase was washed with saturated aq Na2CO3 (30 mL)
and dried with Na2SO4. After solvent evaporation, the crude
product was dissolved in benzene (10 mL) together with 2,3-
dichloro-5,6-dihydrobenzoquinone (DDQ) (2.19 g, 9.7 mmol),
and the mixture was made to react for 40 min at 55 °C. Most
of the solvent was evaporated, and the remaining brown slurry
was passed through a silica gel column (100 mL) by eluting
with 9:1 (v/v) hexane/ethyl acetate mixture. They were identi-
fied as ethyl 2-(6-fluorophenanthren-1-yl)propionate (11b)
(65% from 6b) and ethyl 2-(6,8-difluorophenanthren-1-yl)-
propionate (11c) (78% from 6c) on the basis of their analyti-
cal and spectroscopic properties.
11b: (75% from 6b); viscous oil; 1H NMR (200 MHz) δ 8.58-
8.48 (six peaks, X portion of an ABX system, 1 H), 8.32 (dd, J
) 11.4 and 2.5 Hz, 1 H), 8.01 (d, J ) 9.3 Hz, 1 H), 7.89 (dd, J
) 8.8 and 6.0 Hz, 1 H), 7.79 (d, J ) 9.3 Hz, 1 H), 7.71-7.54 (7
peaks, AB portion of an ABX system, 2 H), 7.37 (td, J ) 8.4
and 2.5 Hz, 1 H), 4.57 (q, J ) 7.1 Hz, 1 H), 4.17 (q, J ) 7.1 Hz,
2 H), 1.70 (d, J ) 7.1 Hz, 3 H), 1.19 (t, J ) 7.1 Hz, 3 H); 13C
NMR (50 MHz) δ 169.7, 156.5 (d, J ) 243 Hz), 132.6, 127.0 (d,
J ) 8.4 Hz), 125.3 (d, J ) 8.8 Hz), 124.9 (d, J ) 11.9 Hz),
124.8, 121.5, 121.2, 120.7, 117.0, 115.8, 110.6 (d, J ) 23.8 Hz),
102.9 (d, J ) 22.3 Hz), 55.8, 36.6, 13.2, 8.9; 19F NMR δ -113.60
(ddd, J ) 11.3, 8.0, and 6.0 Hz); IR (CCl4) νmax 3062 (w), 2983-
2868, 1736 (s), 1631 (m), 1602 (m), 1461 (s), 1205 (s), 1192 (s)
cm-1; MS m/z (%) 299 (M+, 31), 223 (100), 202 (11), 183 (3).
Elem anal. calcd for C19H17FO2: C, 77.01; H, 5.78. Found: C,
76.77; H, 5.83.
Side-chain fluorination of all the above alkyl 2-phenan-
thryl-2-hydroxypropionates 14, 25, 26, and 29 did not
present any surprises. Their reaction with DAST pro-
ceeded smoothly in CH2Cl2 at 0 °C, as described in the
literature, to give the corresponding alkyl 2-fluoro-2-
phenanthrylpropionates 30 and 31 in excellent yields
(65-93%) (Scheme 7). Finally, the alkaline hydrolysis of
the alkyl R-fluoropropionates 30 and 31 under mild
conditions allowed the targeted fluoropropionic acids 2-5
to be obtained in satisfactory overall yields (76-94%).
With reference to the biological activity of fluorinated
analogues of known profens, it has been reported that
replacement of an R-hydrogen of the arylpropionic acid
by fluorine usually brings about a substantial decrease
in antiinflammatory activity; therefore, a drop in biologi-
cal activity of our side-chain fluorinated 2-phenanthryl-
propionic acids is quite probable. On the contrary,
numerous examples of increased activity of fluoroaryl-
containing drugs compared with the hydrogenated par-
ent, cause us to expect an analogous positive effect from
2-(fluorophenanthryl)propionic acids.22-24 Biological tests
are under way.
(22) The structure was tentatively assigned, with high confidence
level, on the basis of the GLC retention time and mass-spectrum
analogy of the corresponding hydrogeno-derivative 27a.
(23) According to the well-established structure of cyclooxygenase
(COX),24 the sickle-shaped phenanthryl moiety could allow the above
nucleus-fluorinated phenanthrylpropionic acids to be docked, to some
extent, into the COX-2 active pocket with the carboxylic group anchored
to Arg 120 and the fluorinated ring placed within the van der Waals
contact of Thyr 385. This could bring about a selective inhibition of
COX-2 that would avoid ulcerogenic side effects associated with most
of the currently NSAIDs.
(24) Picot, D.; Loll, P. J.; Garavito, M. Nature 1994, 367, 243. See
also Soliva, R.; Almansa, C.; Kalko, S. G.; Luque, F. J.; Orozco, M. J.
Med. Chem. 2003, 46, 1372-1382. Palomer, A.; Cabre´, F.; Pascual, J.;
Campos, J.; Trujillo, M. A.; Entrena, A.; Gallo, M. A.; Garc´ıa, L.;
Mauleo´n, D.; Espinosa, A. J. Med. Chem. 2002, 45, 1402-1411.
Makara, G. M. J. Med. Chem. 2001, 44, 3563-3571. Palomer, A.; Pe´rez,
J. J.; Navea, S.; Lorenz, O.; Pascual, J.; Garc´ıa, L.; Mauleo´n, D. J.
Med. Chem. 2000, 43, 2280-2284.
616 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
11c: (78% from 6c); mp 102-103 °C (from ethanol); 1H NMR
(200 MHz) δ 8.53-8.45 (six peaks, X portion of an ABX system,
1 H), 8.12 (br d, J ) 11.4 Hz, 1 H), 8.05 (A portion of an AB
system, J ) 9.6 Hz, 1 H), 8.04 (B portion of an AB system, J
) 9.6 Hz, 1 H), 7.72-7.63 (7 peaks, AB portion of an ABX
system, 2 H), 7.12 (ddd, J ) 9.9, 8.6, and 2.3 Hz, 1 H), 4.56 (q,
J ) 7.1 Hz, 1 H), 4.17 (q, J ) 7.1 Hz, 2 H), 1.70 (d, J ) 7.1 Hz,
3 H), 1.19 (t, J ) 7.1 Hz, 3 H); 13C NMR (CDCl3, 50 MHz) δ
174.6, 160.8 (dd, J ) 244.6 and 13.0 Hz), 159.5 (dd, J ) 251.5
and 13.2 Hz), 138.0, 132.9, 130.3, 129.6, 126.8, 126.4, 122.4,
121.5, 18.6 (d, J ) 5.5 Hz), 117.9 (d, J ) 15.5 Hz), 104.0 (dd,
J ) 22.2 and 4.0 Hz), 101.7 (dd, J ) 27.6 and 24.4 Hz), 61.0,
41.7, 18.3, 14.1; 19F NMR δ -111.09 (dt, J ) 10.7 and 8.0 Hz),
-118.48 (t, J ) 8.6 Hz); IR (CCl4) νmax 3078 (w), 2965-2869,
1735 (s), 1637 (s), 1257 (m), 1189 (s), 1113 (s) cm-1; MS m/z
(%) 314 (M+, 44), 241 (100), 220 (15), 201 (8). Elem anal. calcd
for C19H16F2O2: C, 72.60; H, 5.13. Found: C, 72.42; H, 5.17.
Synthesis of 1-Bromo-3,4-dihydrophenanthrenes (12a-
c). Hydrazine monohydrate (4.1 g, 82 mmol) was added to a
solution of the suitable phenanthrenone (20 mmol) in a 1:1
benzene/dry ethanol mixture (60 mL), and the solvent was
slowly distilled until the disappearance of the ketone moni-
tored by TLC (after about 40 mL of distilled benzene/ethanol/
water mixture). The solvent was further evaporated at reduced
pressure (15 mmHg), and the remaining solid was dried at 50
°C/1 mmHg until constant weight. Butyllithium (37.5 mL, 1.6
M in hexanes, 60 mmol) was added dropwise to a solution of
tert-butyl alcohol (5.0 g, 60 mmol) in anhyd THF (80 mL) at 0
°C under nitrogen atmosphere. After 5 min, CuBr2 (26.8 g, 0.12
mol) was added, and the resulting brown mixture was further
stirred for 20 min before a THF (40 mL) solution of the above
hydrazone was added dropwise. After 3 h of stirring at 20 °C,
water (150 mL) was added, the fine precipitate was filtered
on Celite, and the solid was washed with THF (3 × 50 mL).
The organic phase was separated, and the aqueous phase was
extracted with diethyl ether (3 × 100 mL). The collected
organic phases were dried with Na2SO4, and the solvent was
evaporated at reduced pressure. The remaining crude was
passed through a SiO2 column (80 g) by eluting with petroleum
ether to get the pure bromodihydrophenanthrene.
120.9, 120.6, 119.2 (d, J ) 4.7 Hz), 103.4 (dd, J ) 21.7 and 4.4
Hz), 101.3 (dd, J ) 29.4 and 23.9 Hz), 24.9, 21.4; 19F NMR δ
-111.3 (dt, J ) 11.0 and 8.5 Hz, 1 F), -118.0 (t, J ) 8.5 Hz,
1 F); IR (CHCl3) νmax 3091, 2947-2835, 1643, 1222, 1116, 1067
cm-1; MS m/z (%) 296 (M+ + 1, 45), 294 (M+ - 1, 45), 215
(100), 195 (24), 107 (18). Elem anal. calcd for C14H9BrF2: C,
56.98; H, 3.07. Found: C, 57.08; H, 3.13.
General Procedure for the Preparation of Alkyl 2-Hy-
droxy-2-(phenanthren-1-yl)propionates (14a-d). Butyl-
lithium (1.60 M in hexane, 1.25 mL, 2.0 mmol) was added to
a solution of bromo derivative 12a (or 12b) (2.0 mmo1) in THF
(10 mL) at -75 °C under nitrogen atmosphere. After 30 min,
methyl pyruvate or ethyl 3,3,3-trifluoropyruvate (2.2 mmol)
was added, the co1d bath was removed, and the temperature
was allowed to rise at 25 °C. Saturated aq NH4Cl (30 mL) was
added, the mixture was extracted with diethyl ether (3 × 25
mL), and the collected organic phase was dried with Na2SO4.
After solvent was evaporated, the crude product was dissolved
in toluene (50 mL) together with DDQ (3.0 mmol), and the
mixture was allowed to react 2 h at 80 °C. The solvent was
evaporated at reduced pressure, and the crude solid was
passed through a short column of silica gel (eluent, 7:3
petroleum ether/diethyl ether) to collect pure R-hydroxyester.
Methyl
2-hydroxy-2-(phenanthr-1-yl)propionate
(14a): (60%); mp 154-155 °C; 1H NMR δ 8.75 (d, J ) 8.4 Hz,
1 H), 8.69 (dd, J ) 8.1 and 0.5 Hz, 1 H), 8.12 (d, J ) 9.3 Hz,
1 H), 7.87 (dd, J ) 7.7 and 1.4 Hz, 1 H), 7.78 (dd, J ) 7.5 and
1.0 Hz, 1 H), 7.75 (d, J ) 9.4 Hz, 1 H), 7.66-7.57 (m, 3 H),
3.67 (s, 3 H), 3.65 (br s, 1 H), 2.05 (s, 3 H); 13C NMR δ 178.0,
137.3, 131.3, 131.3, 130,6, 130.0, 128.3, 127.4, 126.7, 126.6,
125.5, 124.7, 123.7, 123.0, 122.9, 76.2, 53.2, 27.6; IR (CHCl3)
νmax 3535, 3020, 2953, 2855, 1729, 1602, 1263, 1222, 1131 cm-1
;
MS m/z (%) 280 (M+, 37), 221 (92), 205 (12), 176 (25), 43 (100).
Elem anal. calcd for C18H16O3: C, 77.12; H, 5.75. Found: C,
76.89; H, 5.81.
Methyl 2-hydroxy-2-(6-fluorophenanthren-1-yl)propi-
onate (14b): (70%); mp 131-132 °C; 1H NMR δ 8.63 (d, J )
8.4 Hz, 1 H), 8.33 (dd, J ) 11.3 and 2.3 Hz, 1 H), 8.12 (d, J )
9.3 Hz, 1 H), 7.88 (dd, J ) 8.7 and 6.0 Hz, 1 H), 7.83 (d, J )
7.4 Hz, 1 H), 7.76 (d, J ) 9.3 Hz, 1 H), 7.67 (t, J ) 7.8 Hz, 1
H), 7.38 (td, J ) 8.5 and 2.3 Hz, 1 H), 3.71 (s, 3 H), 3.67 (s, 1
H), 2.08 (s, 3 H); 13C NMR δ 177.9, 161.6 (d, J ) 243.8 Hz),
137.4, 132.1 (d, J ) 8.3 Hz), 130.7 (d, J ) 4.2 Hz), 130.5 (d, J
) 8.8 Hz), 130.2, 128.0, 127.2, 125.6, 125.3, 123.8, 122.3, 115.9
(d, J ) 23.9 Hz), 108.0 (d, J ) 22.3 Hz), 76.2, 53.3, 27.6; 19F
NMR -113.6 (ddd, J ) 11.4, 7.7, and 6.4 Hz); IR (CHCl3) νmax
3537, 3023, 2956, 2848, 1730, 1605, 1458, 1260, 1133, 838
cm-1; MS m/z (%) 298 (M+, 34), 239 (100), 223 (14), 195 (18),
175 (10), 43 (87). Elem anal. calcd for C18H15FO3: C, 72.47; H,
5.07. Found: C, 72.60; H, 5.11.
1-Bromo-3,4-dihydrophenanthrene (12a): (77%); mp
59-61 °C; 1H NMR (200 MHz) δ 8.06-7.99 (m, 1 H), 7.82 (dd,
J ) 7.6 and 2.0 Hz, 1 H), 7.82 (d, J ) 8.7 Hz, 1 H), 7.74 (d, J
) 8.7 Hz, 1 H), 7.57-7.42 (m, 2 H), 6.55 (t, J ) 4.9 Hz, 1 H),
3.26 (t, J ) 8.2 Hz, 2 H), 2.48 (td, J ) 8.9 and 4.9 Hz, 2 H);
13C NMR δ 133.4, 132.2, 132.1, 130.7, 130.0, 128.6, 126.5,
126.3, 125.8, 124.7, 123.6, 121.8, 25.1, 22.7; IR (CHCl3) νmax
3063, 3019, 2945, 2887, 2835, 1612, 1036 cm-1; MS m/z (%)
260 (M+ + 1, 31), 258 (M+ - 1, 32), 179 (100), 151 (10), 152
(12), 76 (12). Elem anal. calcd for C14H11Br: C, 64.89; H, 4.28.
Found: C, 64.98; H, 4.19.
Ethyl 2-hydroxy-2-(phenanthren-1-yl)-3,3,3-trifluoro-
1
1-Bromo-6-fluoro-3,4-dihydrophenanthrene (12b): (68%);
propionate (14c): (63%); mp 114-115 °C; H NMR δ 8.79
1
mp 80-81°C; H NMR δ 7.83 (dd, J ) 8.9 and 6.0 Hz, 1H),
(d, J ) 8.5 Hz, 1 H), 8.67 (d, J ) 8.2 Hz, 1 H), 8.06 (d, J ) 9.4
Hz, 1 H), 7.89-7.85 (m, 2 H), 7.75 (d, J ) 9.4 Hz, 1 H), 7.67-
7.58 (m, 3 H), 4.53 (br s, 1 H), 4.37-4.15 (sym m, ABX3 system,
2 H), 1.08 (t, J ) 7.1 Hz, 3 H); 13C NMR (50 MHz) δ 170.6,
131.6, 131.2, 130.4, 130.1, 129.3, 128.4, 127.9, 127.0, 126.9,
126.4 (q, J ) 2.9 Hz), 125.3, 124.7, 123.7 (q, J ) 286.5 Hz),
122.9, 122.3, 80.2 (q, J ) 28.6 Hz), 64.3, 13.6; 19F NMR δ -73.0
(s); MS (70 eV) m/z (%) 348 (M+, 45), 275 (80), 205 (37), 178
(100), 88 (13). Elem anal. calcd For C19H15F3O3: C, 65.52; H,
4.34. Found: C, 65.31; H,4.27.
7.80-7.74 (four peaks, AB system, JAB ) 8.7 Hz, 2H), 7.65 (dd,
J ) 11.5 and 2.2 Hz, 1H), 7.27 (td, J ) 8.7 and 2.4 Hz, 1H),
6.60 (t, J ) 4.9 Hz, 1H), 3.20 (t, J ) 8.4 Hz, 2H), 2.52 (td, J )
8.7 and 4.9 Hz, 2H); 13C NMR δ 161.1 (d, J ) 244.2 Hz), 131.6
(d, J ) 8.6 Hz), 131.4 (d, J ) 5.9 Hz), 130.9 (d, J ) 9.1 Hz),
130.8, 130.6, 130.4 126.4, 124.0 (d, J ) 1.8 Hz), 121.5, 116.1
(d, J ) 25.4 Hz), 107.2 (d, J ) 21.6 Hz), 25.0, 22.7; 19F NMR
δ -113.6 (ddd, J ) 11.6, 7.6, and 6.3 Hz); IR (CHCl3) νmax 3062,
2946-2835, 1617, 1516, 1200, 1172, 840 cm-1; MS m/z (%) 278
(M+ + 1, 37), 276 (M+ - 1, 40), 197 (100), 177 (20), 98 (17).
Elem anal. calcd for C14H10BrF: C, 60.68; H, 3.64. Found: C,
60.81; H, 3.56.
Ethyl 2-hydroxy-2-(6-fluorophenanthren-1-yl)-3,3,3-
trifluoropropionate (14d): (65%); mp 132-134 °C; 1H NMR
δ 8.63 (d, J ) 8.4 Hz, 1 H), 8.27 (dd, J ) 11.3 and 2.3 Hz, 1
H), 8.04 (d, J ) 9.4 Hz, 1 H), 7.93 (br d, J ) 7.6 Hz, 1 H), 7.84
(dd, J ) 8.7 and 6.0 Hz, 1 H), 7.72 (d, J ) 9.4 Hz, 1 H), 7.64
(t, J ) 8.1 Hz, 1 H), 7.36 (td, J ) 8.5 and 2.4 Hz, 1 H), 4.58 (s,
1H), 4.36 (dq, J ) 10.7 and 7.1 Hz, 1 H), 4.22 (dq, J ) 10.7
and 7.1 Hz, 1 H), 1.11 (t, J ) 7.1 Hz, 3 H); 13C NMR δ 170.4,
161.7 (d, J ) 244.3 Hz), 131.9 (d, J ) 8.4 Hz), 130.9 (d, J )
4.2 Hz), 130.5 (d, J ) 8.8 Hz), 130.4, 129.4, 127.9, 127.2, 127.0
1-Bromo-6,8-difluoro-3,4-dihydrophenanthrene (12c):
(72%); mp 91-93 °C; 1H NMR δ 7.94 (d, J ) 8.8 Hz, 1H), 7.78
(d, J ) 8.8 Hz, 1H), 7.41 (dt, J ) 11.0 and 1.1 Hz, 1H), 6.95
(ddd, J ) 10.1, 8.7, and 2.3 Hz, 1H), 6.59 (t, J ) 4.9, 1H), 3.12
(t, J ) 8.4 Hz, 2H), 2.51-2.45 (m, 2H); 13C NMR (50 MHz) δ
160.2 (dd, J ) 244.5 and 12.8 Hz), 159.6 (dd, J ) 253.4 and
13.4 Hz), 132.0 (d, J ) 5.1 Hz), 131.9, 131.3, 124.4, 121.2,
J. Org. Chem, Vol. 70, No. 2, 2005 617

Ricci and Ruzziconi
(d, J ) 2.8 Hz), 125.4, 124.8, 123.6 (q, J ) 286.5 Hz), 121.6,
116.1 (d, J ) 23.8 Hz), 108.0 (d, J ) 22.5 Hz), 80.1 (q, J )
28.6 Hz), 64.3, 13.6; 19F NMR δ -73.1 (s, 3 F), -113.6 (ddd, J
) 12.1, 8.2, and 6.8 Hz, 3 F); IR (CHCl3) νmax 3574, 3501, 3032,
2988, 2940, 1739, 1602, 1464, 1251, 1171, 994, 838 cm-1; MS
m/z (%) 366 (M+, 50), 293 (77), 223 (30), 196 (100). Elem anal.
calcd for C19H14F4O3: C, 62.30; H, 3.85. Found: C, 62.21; H,
3.78.
Products from the Reaction of 1-Bromo-6,8-difluoro-
2,3-dihydrophenanthrene with Butyllithium and Suc-
cessive Alkylation with Either Methyl Pyruvate or Ethyl
Trifluoropyruvate. Butyllithium (1.60 M in hexane, 1.3 mL,
2.0 mmol) was added to a solution of 12c (2.0 mmo1) in THF
(10 mL) at -98 °C under nitrogen atmosphere. After 90 min,
methyl pyruvate (1.5 equiv) was added, and the temperature
was allowed to rise at 25 °C. Water (20 mL) was added, the
mixture was extracted with diethyl ether (3 × 10 mL), and
the collected organic phases were dried with Na2SO4. After
the solvent was evaporated, chromatography of the crude
product on silica gel (eluent, 7:3 petroleum ether/diethyl ether)
allowed five products to be separated that were identified as
follows on the basis of the following spectroscopic and analyti-
cal characteristics.
Methyl 2-(6,8-difluoro-3,4-dihydrophenanthren-1-yl)-
2-hydroxypropionate (15a): (7%); mp 116-118 °C; 1H NMR
δ 7.87-7.66 (AB system, J ) 9.0 Hz, 2 H), 7.45 (d, J ) 11.3
Hz, 1 H), 6.91 (ddd, J ) 10.4, 8.8, and 2.2 Hz, 1 H), 6.45 (t, J
) 4.8 Hz, 1 H), 3.69 (s, 3 H), 3.51(s, 1 H), 3.04 (t, J ) 8.2 Hz,
2 H), 2.44 (dd, J ) 8.2 and 4.9 Hz, 2 H), 1.76 (s, 3 H); 13C
NMR δ 177.6, 160.0 (dd, J ) 244.0 and 12.9 Hz), 159.6 (dd, J
) 253.0 and 13.5 Hz), 137.2, 132.7 (dd, J ) 9.7 and 6.0 Hz),
131.9 (dd, J ) 5.8 and 2.6 Hz), 128.6, 122.4, 119.9 (d, J ) 16.1
Hz), 118.5 (d, J ) 4.7 Hz), 103.5 (dd, J ) 21.4 and 4.1 Hz),
100.6 (dd, J ) 29.3 and 24.0 Hz), 75.8, 53.2, 26.7, 23.2, 22.7;
19F NMR δ -118.8 (t, J ) 8.7 Hz, 1 F), -112.3 (q, J ) 9.2 Hz,
1 F); IR (CHCl3) νmax 3693, 3027, 2954-2837, 1729, 1640, 1404,
1241, 1116, 991, 848 cm-1; MS m/z (%) 318 (M+, 53), 301 (7),
259 (100), 241 (12), 215 (30), 201 (20); Elem anal. calcd for
C18H16F2O3: C, 67.92; H, 5.07. Found: C, 67.73; H, 5.14.
Methyl 2-(8-bromo-1,3-difluoro-5,6-dihydrophenan-
thren-2-yl)-2-hydroxypropionate (16a): (16%); mp 121-122
°C; 1H NMR δ 7.96-7.78 (AB system, JAB ) 8.9 Hz, 2 H), 7.43
(d, J ) 14.0 Hz, 1 H), 6.59 (t, J ) 4.9 Hz, 1 H), 4.00 (s, 1 H),
3.83 (s, 3 H), 3.10 (t, J ) 8.18, 2 H), 2.47 (td, J ) 8.5, 4.9 Hz,
2 H), 2.04 (dd, 4.2 and 1.5 Hz, 3 H); 13C NMR δ 175.9, 159.0
(dd, J ) 246.6 and 9.2 Hz), 157.2 (dd, J ) 255.9 and 9.2 Hz),
132.3, 131.6, 130.9 (dd, J ) 5.9 and 3.0 Hz), 130.8 (dd, J )
11.4 and 6.5 Hz), 124.8, 121.2 (d, J ) 18.5 Hz), 121.0, 119.7
(d, J ) 8.1 Hz), 115.1 (dd, J ) 18.5 and 13.6 Hz), 104.4 (dd, J
) 24.5 and 3.7 Hz), 73.4, 53.5, 26.4 (dd, J ) 8.1 and 3.3 Hz),
24.9, 22.7; 19F NMR δ -118.2 (t, J ) 8.7 Hz, 1 F), -113.1 (dd,
J ) 13.5 and 4.0 Hz, 1 F); IR (CHCl3) νmax 3525, 3023, 2955-
2836, 1742, 1644, 1498, 1259, 1230, 1138 cm-1; MS m/z (%)
398 (M+ + 1, 10), 396 (M+ - 1, 10), 339 (93), 337 (100), 257
(9), 207 (14). Elem anal. calcd for C18H15BrF2O3: C, 54.43; H,
3.81. Found: C, 54.32; H, 3.73.
(100), 43 (21). Elem anal. calcd for C18H16F2O3: C, 67.92; H,
5.07. Found: C, 68.09; H, 4.98.
Methyl 2-[1,3-difluoro-5,6-dihydro-8-(1-hydroxy-1-meth-
oxycarbonylethyl)phenanthren-2-yl]-2-hydroxypropi-
onate (18a): (<1%); mp 143-145 °C; 1H NMR δ 7.86-7.67
(AB system, JAB ) 8.9 Hz, 2 H), 7.45 (d, J ) 14.3 Hz, 1 H),
6.44 (t, J ) 7.7 Hz, 1 H), 4.01 (s, 1 H), 3.80 (s, 3 H), 3.66 (s, 3
H), 3.52 (s, 1 H), 3.00 (t, J ) 7.7 Hz, 2 H), 2.42 (m, 2 H), 2.01
(d, J ) 2.5 Hz, 3 H), 1.74 (s, 3 H); 13C NMR δ 177.5, 176.0,
158.6 (dd, J ) 245.5 and 9.3 Hz), 157.1 (dd, J ) 255.6 and 9.6
Hz), 137.05, 132.8, 132.7, 131.3 (dd, J ) 11.8 and 6.0 Hz),
128.7, 122.8, 120.3 (d, J ) 18.0 Hz), 119.0 (d, J ) 8.4 Hz),
114.4 (dd, J ) 19.0 and 13.6 Hz), 104.4 (d, J ) 23.7 Hz), 75.7,
73.4, 53.4, 26.6, 26.3 (dd, J ) 7.2 and 2.4 Hz), 22.9, 22.6; 19F
NMR δ -118.8 (d, J ) 13.0 Hz, 1 F), -114.2 (s, 1 F); IR (CHCl3)
νmax 3529, 3023, 2955-2839, 1737, 1643, 1261, 1136 cm-1; MS
m/z (%) 420 (M+, 10), 361 (100), 207 (23). Elem anal. calcd for
C22H22F2O6: C, 62.85; H, 5.27. Found: C, 62.98; H, 5.31.
6,8-Difluoro-3,4-dihydrophenanthrene (19): (14%); mp
49-50 °C; 1H NMR δ 7.89 (d, J ) 8.5 Hz, 1 H), 7.41 (br d, J )
11.1 Hz, 1 H), 7.20 (d, J ) 8.5 Hz, 1 H), 6.91 (ddd, J ) 10.3,
8.7, and 2.3 Hz, 1 H), 6.56 (dt, J ) 9.5 and 1.8 Hz, 1 H), 6.18
(dt, J ) 9.5 and 4.4 Hz, 1 H), 3.09 (t, J ) 8.8 Hz, 2 H), 2.48
(tdd, J ) 8.9, 4.4, and 1.8 Hz, 2 H); 13C NMR δ 160.0 (dd, J )
244 and 12.9 Hz), 159.6 (dd, J ) 253 and 13.6 Hz), 133.0, 132.8
(dd, J ) 9.9 and 5.9 Hz), 129.6, 129.4 (dd, J ) 6.2 and 3.1 Hz),
127.9, 124.8, 120.3 (d, J ) 15.6 Hz), 118.9 (d, J ) 5.7 Hz),
103.0 (dd, J ) 21.3 and 4.3 Hz), 100.3 (dd, J ) 29.3 and 24.1
Hz), 22.9, 22.7; 19F NMR δ -112.25 (dt, J ) 11.0 and 8.3 Hz,
1 F), -118.59 (dd, J ) 10.0 and 8.0 Hz, 1 F); IR (CHCl3) νmax
3083, 3042, 2935-2834, 1645, 1634, 1517, 1401, 1245, 1115
cm-1; MS m/z (%) 216 (M+, 100), 201 (52), 188 (15), 107 (8).
Elem anal. calcd for C14H10F2: C, 77,77; H, 4.66. Found: C,
77.57; H, 4.59.
In a second experiment, using a precooled syringe, samples
of the reaction mixture (200 µL) were taken at different
reaction times (5, 20, 35, and 90 min) and poured into a
solution of methyl pyruvate (1.5 equiv) in THF (5 mL). Water
(20 mL) was added, the mixture was extracted with diethyl
ether (3 × 10 mL), and the collected organic phases were
analyzed by GLC after calibration with known amounts of pure
products.
In the same way, the corresponding hydroxytrifluoro-
pyruvates were obtained by just replacing methyl pyruvate
by ethyl 3,3,3-trifluoropyruvate as alkylating reagent. They
were characterized as follows.
Ethyl 2-(6,8-difluoro-3,4-dihydrophenanthren-1-yl)-2-
hydroxy-3,3,3-trifluoropropionate (15b): (6%); mp 77-79
°C; 1H NMR δ 7.87-7.61 (AB system, JAB ) 9.0 Hz, 2 H), 7.46
(d, J ) 11.3 Hz, 1 H), 6.94 (ddd, J ) 10.3, 8.3, 2.0 Hz, 1 H),
6.73 (br s, 1 H), 4.30 (s, 1 H), 4.20 (sym m, 2 H), 3.14 (dt, J )
15.8 and 6.8 Hz, 1 H), 2.95 (ddd, J ) 15.8, 12.6, and 6.8 Hz, 1
H), 2.54-2.38 (m, 2 H), 1.01 (t, J ) 7.1 Hz, 3 H); 13C NMR δ
169.8, 160.1 (dd, J ) 244.0 and 12.7 Hz), 159.5 (dd, J ) 253.3
and 13.5 Hz), 132.4, 131.3, 129.9, 127.5, 124.7, 123.2 (q, J )
286.4 Hz), 121.8, 120.1 (d, J ) 16.0 Hz), 118.7, 103.5 (dd, J )
21.6 and 4.3 Hz), 101.0 (dd, J ) 29.3 and 23.9 Hz), 79.4 (q, J
) 28.6 Hz), 64.1, 22.8 (2 C), 13.5; 19F NMR δ -118.5 (t, J )
8.7 Hz, 1 F), 111.8 (q, J ) 8.7 Hz, 1 F), -73.2 (s, 3 F); IR
(CHCl3) νmax 3692, 3496, 3090, 3027, 2985-2834, 1741, 1641,
1599, 1249, 1177, 1116, 897, 849 cm-1; MS m/z (%) 386 (M+,
100), 313 (47), 243 (37), 215 (67). Elem anal. calcd for
C19H15F5O3: C, 59.07; H, 3.91. Found: C, 58.96; H, 4.03.
Ethyl 2-(8-bromo-1,3-difluoro-5,6-dihydrophenanthren-
2-yl)-2-hydroxy-3,3,3-trifluoropropionate (16b): (15%);
viscous oil; 1H NMR δ 7.98-7.80 (AB system, JAB ) 8.9 Hz, 2
H), 7.48 (d, J ) 14.5 Hz, 1 H), 6.61 (t, J ) 4.8 Hz, 1 H), 4.64
(br s, 1 H), 4.49-4.31 (m, 2 H), 3.10 (t, J ) 8.6 Hz, 2 H), 2.48
(td, J ) 8.6 and 4.8 Hz, 2 H), 1.30 (t, J ) 7.2 Hz, 3 H); 13C
NMR δ 168.0, 157.9 (dd, J ) 247.5 and 8.0 Hz), 157.1 (dd, J )
259.0 and 8.0 Hz), 133.0, 132.2, 131.6 (dd, J ) 11.2 and 6.8
Hz), 130.9 (dd, J ) 6.0 and 2.8 Hz), 125.2, 123.9, 122.8 (q, J )
Methyl 2-(1,3-difluoro-5,6-dihydrophenanthren-2-yl)-
2-hydroxypropionate (17a): (54%); mp 101-103 °C; 1H
NMR δ 7.87 (d, J ) 8.6 Hz, 1 H), 7.41 (d, J ) 14.2 Hz, 1 H),
7.20 (d, J ) 8.6 Hz, 1 H), 6.54 (dt, J ) 9.5 and 1.7 Hz, 1 H),
6.17 (dt, J ) 9.5 and 4.3 Hz, 1 H), 3.99 (s, 1 H), 3.82 (s, 3 H),
3.05 (t, J ) 8.8 Hz, 2 H), 2.45 (tdd, J ) 8.8, 4.4, and 1.8 Hz, 2
H), 2.03 (dd, J ) 4.1 and 1.6 Hz, 3 H); 13C NMR δ 176.0, 158.8
(dd, J ) 245.7 and 9.4 Hz), 157.3 (dd, J ) 255.0 and 9.3 Hz),
133.3, 131.5 (dd, J ) 11.0 and 6.8 Hz), 129.9, 129.0 (dd, J )
5.6 and 2.8 Hz), 127.8, 125.3, 120.7 (d, J ) 18 Hz), 119.4 (d, J
) 8.2 Hz), 114.2 (dd, J ) 18.4 and 13.9 Hz), 103.9 (dd, J )
24.2 and 3.7 Hz), 73.4, 53.4, 26.4 (dd, J ) 4.6 and 2.9 Hz),
22.8, 22.5; 19F NMR δ -114.1 (d, J ) 13.9 Hz, 1 F), -118.7 (s,
1 F); IR (CHCl3) νmax 3524, 3024, 2953-2834, 1742, 1642, 1256,
1232, 1138, 1017, 848 cm-1; MS m/z (%) 318 (M+, 12), 259
618 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
284.0 Hz), 120.8 (t, J ) 9.8 Hz), 120.0 (d, J ) 7.1 Hz), 108.7
(dd, J ) 18.6 and 14.9 Hz), 104.7 (dd, J ) 24.6 and 4.2 Hz),
76.2 (q, J ) 32.5 Hz), 63.7, 24.8, 22.6, 13.7; 19F NMR δ -114.5
(q, J ) 24.2 Hz, 1 F), -112.5 (quint, J ) 11.8 Hz, 1 F), -75.6
(dd, J ) 24.2 and 10.8 Hz, 3 F); IR (CHCl3) νmax 3588, 3481,
(12), 193 (11), 43 (66). Elem anal. calcd for C18H14F2O3: C,
68.35; H, 4.46. Found: C, 68.52; H, 4.39.
Methyl 2-(8-bromo-1,3-difluorophenanthren-2-yl)-2-
1
hydroxypropionate (29a): (1%); mp 160-162 °C; H NMR
δ 8.26 (d, J ) 8.4 Hz, 1 H), 8.04 (d, J ) 9.5 Hz, 1 H), 7.90 (d,
J ) 13.9 Hz, 1 H), 7.87 (d, J ) 9.5 Hz, 1 H), 7.84 (d, J ) 8.1
Hz, 1 H), 7.39 (t, J ) 8.0 Hz, 1 H), 4.13 (s, 1 H), 3.85 (s, 3 H),
2.07 (dd, J ) 3.6 and 2.1 Hz, 3 H); 13C NMR δ 175.8, 154.9
(dd, J ) 247.4 and 9.3 Hz), 157.2 (dd, J ) 254.6 and 9.1 Hz),
131.9, 130.9 (d, J ) 11.2 and 6.5 Hz), 130.9, 129.9 (dd, J ) 4.4
and 2.8 Hz), 127.3, 125.3 (t, J ) 2.4 Hz), 123.7, 122.5, 119.7
(dd, J ) 9.1 and 1.9 Hz), 118.7 (dd, J ) 17.6 and 1.8 Hz), 116.3
(dd, J ) 17.6 and 14.2 Hz), 104.7 (dd, J ) 25.4 and 4.0 Hz),
73.3, 53.6, 26.4 (dd, J ) 7.1 and 4.0 Hz); 19F NMR δ -111.5
(dd, J ) 13.4 and 3.2 Hz, 1 F), -117.8 (s, 1 F); IR (CHCl3) νmax
3524, 3023, 2956-2848, 1743, 1641, 1255, 1137 cm-1; MS m/z
(%) 396 (M+ + 1, 8),394 (M+ - 1, 10), 337 (100), 335 (100), 257
(13), 212 (22), 43 (46). Elem anal. calcd for C18H13BrF2O3: C,
54.71; H, 3.32. Found: C, 54.55; H, 3.42.
3024, 2987-2837, 1755, 1644, 1296, 1174, 1120, 1024 cm-1
;
MS m/z (%) 466 (M+ + 1, 53), 464 (M+ - 1, 53), 393 (93), 391
(93), 323 (100), 321 (99), 293 (10), 241 (19), 214 (84). Elem anal.
calcd for C19H14BrF5O3: C, 49.05; H, 3.03. Found: C, 49.11;
H, 3.12.
Ethyl 2-(1,3-difluoro-5,6-dihydrophenanthren-2-yl)-2-
hydroxy-3,3,3-trifluoropropionate (17b): (48%); viscous oil;
1H NMR δ 7.91 (d, J ) 8.6 Hz, 1 H), 7.47 (d, J ) 14.3 Hz, 1
H), 7.24 (d, J ) 8.6 Hz, 1 H), 6.55 (dt, J ) 9.6 and 1.8 Hz, 1
H), 6.21 (dt, J ) 9.5 and 4.4 Hz, 1 H), 4.59 (t, J ) 2.0 Hz, 1
H), 4.48-4.35 (sym m, 2 H), 3.07 (t, J ) 8.8 Hz, 2 H), 2.48
(tdd, J ) 8.9, 4.4, and 1.8 Hz, 2 H), 1.31 (t, J ) 7.1 Hz, 3 H);
13C NMR δ 168.0, 157.7 (dd, J ) 246.6 and 8.2 Hz), 157.2 (dd,
J ) 258.0 and 8.2 Hz), 134.2, 132.3, (dd, J ) 10.9 and 7.0 Hz),
130.5, 129.1 (dd, J ) 5.4 and 3.0 Hz), 127.6, 122.9 (q, J ) 284.0
Hz), 120.3 (d, J ) 17.7 Hz), 119.6 (t, J ) 8.3 Hz), 107.6 (dd, J
) 18.2 and 15.2 Hz), 104.2 (dd, J ) 24.1 and 3.6 Hz), 74.6 (q,
J ) 32.5 Hz), 64.1, 22.8, 22.4 13.6; 19F NMR δ -115.2 (q, J )
23.0 Hz, 1 F), -113.6 (q, J ) 11.2 Hz, 1 F), -75.7 (dd, J )
23.0 and 11.2 Hz, 3 F); IR νmax 3593, 3481, 3032, 2942-2835,
1755, 1643, 1295, 1229, 1171 cm-1; MS m/z (%) 386 (M+, 56),
313 (96), 243 (100), 214 (21). Elem anal. calcd for C19H15F5O3:
C, 59.07; H, 3.91. Found: C, 59.18; H, 4.02.
Methyl 2-(1,3-difluorophenanthren-2-yl)-2-hydroxypro-
pionate (26a): (31%); mp 122-124 °C; 1H NMR δ 8.48-8.45
(m, 1 H), 8.08 (d, J ) 13.3 Hz, 1 H), 7.93 (d, J ) 9.1 Hz, 1 H),
7.91-7.87 (m, 1 H), 7.76 (d, J ) 9.1 Hz, 1 H), 7.69-7.63 (m, 2
H), 4.03 (s, 1 H), 3.84 (s, 3 H), 2.07 (dd, J ) 3.6 and 2.2 Hz, 3
H); 13C NMR δ 176.0, 159.2 (dd, J ) 246.6 and 9.2 Hz), 157.3
(dd, J ) 253.6 and 9.0 Hz), 132.5, 131.5 (dd, J ) 11.0 and 6.7
Hz), 128.8, 128.5, 127.9, 127.1, 127.0, 123.0, 118.8 (d, J ) 17.3
Hz), 118.3 (d, J ) 8.9 Hz), 115.7 (dd, J ) 17.1 and 14.6 Hz),
104.6 (dd, J ) 24.9 and 3.3 Hz), 73.4, 53.5, 26.4 (d, J ) 4.0
Hz); 19F NMR δ -112.6 (br d, J ) 13.8 Hz), -118.3 (br s); IR
(CHCl3) νmax 3524, 3023, 2956, 2850, 1742, 1640, 1260, 1140,
814 cm-1; MS m/z (%) 316 (M+, 14), 257 (100), 241 (7), 209
(11). Elem anal. calcd for C18H14F2O3: C, 68.35; H, 4.46.
Found: C, 68.62; H, 4.54.
8-Bromo-1,3-difluorophenanthrene (24). To a solution
of 12c (2.9 g, 10 mmol) in toluene (60 mL) was added DDQ
(3.6 g, 16 mmol), and the mixture was stirred for 5 h at 90 °C.
The solvent was evaporated at reduced pressure (15 mmHg),
and the remaining crude was passed through a short SiO2
column by eluting with petroleum ether to collect pure 24 as
1
white flat crystals (1.9 g, 65%): mp 141-143 °C; H NMR δ
Methyl 2-[6,8-Difluoro-7-(1-hydroxy-1-methoxycarbonyl-
8.34 (d, J ) 8.3 Hz, 1 H), 8.09 (d, J ) 9.3 Hz, 1 H), 7.93 (d, J
) 9.0 Hz, 2 H), 7.87 (d, J ) 7.6 Hz, 1 H), 7.42 (t, J ) 7.9 Hz,
1 H), 7.08 (td, J ) 9.5 and 1.7 Hz, 1 H); 13C NMR δ 161.0 (dd,
J ) 245.7 and 12.9 Hz), 159.6 (dd, J ) 252.4 and 13.2 Hz),
132.1 (dd, J ) 9.7 and 5.7 Hz), 131.8, 131.1, 130.6 (dd, J ) 4.4
and 3.0 Hz), 127.3, 125.0, 123.9, 122.7, 119.7 (dd, J ) 6.4 and
1.3 Hz), 118.4 (dd, J ) 15.6 and 1.9 Hz), 104.0 (dd, J ) 22.4
and 4.2 Hz), 102.3 (dd, J ) 27.7 and 24.2 Hz); 19F NMR δ
-110.3 (q, J ) 8.7 Hz, 1 F), -117.7 (t, J ) 8.7 Hz, 1 F); IR
νmax 3082, 1637, 1521, 1437, 1126, 998, 850 cm-1; MS m/z (%)
294 (M+ + 1, 100), 292 (M+ - 1, 93), 213 (35), 212 (47), 193
(39), 106 (17). Elem anal. calcd for C14H7BrF2: C, 57.37; H,
2.41. Found: C, 57.29; H, 2.48.
ethyl)phenanthren-1-yl]-2-hydroxypropionate(27a):(<1%);
1
mp 181 °C dec; H NMR (acetone-d6) δ 8.76 (d, J ) 8.4 Hz, 1
H), 8.37 (d, J ) 14.1 Hz, 1 H), 8.30 (d, J ) 9.6 Hz, 1 H), 7.96
(d, J ) 7.5 Hz, 1 H), 7.93 (d, J ) 9.6 Hz, 1 H), 7.72 (t, J ) 8.3
Hz, 1 H), 3.76 (s, 3 H), 3.59 (s, 3 H), 3.2 (very br, 2 H), 1.99 (s,
3 H), 1.97 (dd, J ) 2.8 and 1.9 Hz, 3 H); 13C NMR (acetone-d6)
δ 176.1, 174.6 (d, J ) 3.1 Hz), 159.3 (dd, J ) 250 and 9.5 Hz),
156.8 (dd, J ) 257 and 9.5 Hz), 139.8, 131.6 (dd, J ) 11.2 and
6.5 Hz), 130.4, 129.4 (dd, J ) 6.2 and 3.1 Hz), 126.5, 125.7,
124.3 (t, J ) 2.5 Hz), 123.6, 117.9 (d, J ) 17.8 Hz), 117.6 (d,
J ) 8.0 Hz), 112.6, 105.0 (dd, J ) 25.6 and 3.5 Hz), 75.7, 73.3,
52.2, 51.9, 26.9, 26.1 (dd, J ) 6.1 and 3.6 Hz); 19F NMR
(acetone-d6) δ -112.8 (m), -120.15 (br d, J ) 16.6 Hz); IR
(CHCl3) νmax 3690, 3525, 3040, 2956, 2852, 1740, 1602, 1262,
1134 cm-1; MS m/z (%) 418 (M+, 9), 359 (100), 299 (7), 239
(11), 43 (17). Elem anal. calcd for C22H20F2O6: C, 63.16; H,
4.82. Found: C, 63.38; H, 4.95.
Products from the Reaction of 8-Bromo-1,3-difluo-
rophenanthrene with Butyllithium and Subsequent
Alkylation with Methyl Pyruvate and Ethyl Trifluoro-
pyruvate. The procedure was identical to that used in the
reaction of butyllithium with 12c. After 90 min, usual workup
and chromatography of the crude product on silica gel (eluent
7:3 petroleum ether/diethyl ether mixture) allowed five prod-
ucts to be separated that were identified by their analytical
and spectroscopic characteristics as follows.
1
1,3-Difluorophenanthrene (28): (6%); mp 90-92 °C; H
NMR δ 8.51-8.46 (m, 1 H), 8.07 (br d, J ) 10.7 Hz, 1 H), 7.95
(d, J ) 9.1 Hz, 1 H), 7.92-7.87 (m, 1 H), 7.73 (d, J ) 9.1 Hz,
1 H), 7.69-7.62 (m, 2 H), 7.09 (ddd, J ) 10.1, 8.7, and 2.3 Hz,
1 H); 13C NMR δ 160.8 (dd, J ) 245 and 12.9 Hz), 159.6 (dd,
J ) 251 and 13.0 Hz), 132.6 (dd, J ) 9.7 and 5.8 Hz), 132.5,
129.0 (dd, J ) 4.8 and 2.9 Hz), 128.8, 127.7, 127.0, 126.5, 123.0,
118.4 (dd, J ) 5.5 and 2.3 Hz), 118.2 (dd, J ) 6.5 and 1.6 Hz),
103.7 (dd, J ) 22.3 and 4.2 Hz), 101.7 (dd, J ) 28.0 and 24.3
Hz); 19F NMR δ -111.51 (q, J ) 9.0 Hz, 1 F), -118.24 (t, J )
9.0 Hz, 1 F); IR (CHCl3) νmax 3059, 1638, 1604, 1529, 1118,
996, 852, 820 cm-1; MS m/z (%) 214 (M+, 100), 193 (7), 107
(8), 94 (7). Elem anal. calcd for C14H8F2: C, 78,50; H, 3.76.
Found: C, 78.48; H, 3.69.
Methyl 2-(6,8-difluorophenanthren-1-yl)-2-hydroxypro-
1
pionate (25a): (46%); mp 149-151 °C; H NMR δ 8.56 (d, J
) 8.5 Hz, 1 H), 8.13 (d, J ) 9.6 Hz, 1 H), 8.10 (br d, J ) 11.1
Hz, 1 H), 7.96 (d, J ) 9.6 Hz, 1 H), 7.83 (dd, J ) 7.5 and 0.9
Hz, 1 H), 7.66 (dd, J ) 8.3 and 7.6 Hz, 1 H), 7.09 (ddd, J ) 9.9
Hz, 8.7 and 2.3 Hz, 1 H), 3.69 (s, 3 H), 3.66 (s, 1 H), 2.05 (s, 3
H); 13C NMR δ 117.8, 160.7 (dd, J ) 224.6 and 12.9 Hz), 159.5
(dd, J ) 251.8 and 13.3 Hz), 137.6, 132.8 (dd, J ) 9.7 and 5.8
Hz), 130.6, 130.0 (t, J ) 3.4 Hz), 126.0, 125.9, 124.1, 122.8,
118.7 (d, J ) 5.4 Hz), 117.8 (d, J ) 15.7 Hz), 104.0 (dd, J )
22.3 and 4.0 Hz), 101.9 (dd, J ) 27.7 and 24.3 Hz), 76.1, 53.4,
27.6; 19F NMR δ -111.1 (dd, J ) 10.9 and 8.0 Hz), -118.5 (t,
J ) 8.6 Hz); IR (CHCl3) νmax 3538, 3025, 2956, 2849, 1730,
1261, 1128, 810 cm-1; MS m/z (%) 316 (M+, 37), 257 (100), 241
GLC analysis of the reaction products at variable reaction
times was performed in the same way as described above for
the reaction of the bromodihydrophenanthrene 12c.
In the same way, the following 2-hydroxy-2-(phenanthryl)-
3,3,3-trifluoropropionates were obtained by just replacing
J. Org. Chem, Vol. 70, No. 2, 2005 619

Ricci and Ruzziconi
methyl pyruvate by ethyl 3,3,3-trifluoropyruvate as alkylating
reagent. They were identified as follows.
of the mixture with methyl pyruvate only 10 s after the
addition of butyllithium. Usual workup and chromatography
of the crude product on silica gel (eluent, petroleum ether, and
then 1:3 petroleum ether/diethyl ether mixture) allowed pure
product (58%) to be separated from the unreacted bromo
derivative (∼5%). In the same way, the corresponding ethyl
3,3,3-trifluorpropionate derivative 25b was prepared in 61%
of yield by using ethyl 3,3,3-trifluoropyruvate as the alkylating
reagent.
The following procedure was used to prepare hydroxyester
29a as the sole reaction product in 88% yield. Butyllithium
(1.59 M in hexane, 1.25 mL 2.0 mmol) was added to a solution
of diisopropylamine (300 µL, 220 mg, 2.1 mmol) in anhyd THF
(10 mL) at -30 °C under nitrogen. After cooling to -50 °C,
solid 8-bromo-1,3-difluorophenanthrene (24) was added under
stirring, and the mixture was allowed to react for 1 h before
methyl pyruvate (200 mg, 2.0 mmol) was added. The temper-
ature was increased to 25 °C, saturated aq NH4Cl (30 mL) was
added, the phases were separated, and the aqueous phase was
again extracted with diethyl ether (3 × 25 mL). The collected
organic phases were dried with Na2SO4, and the solvent was
evaporated at reduced pressure. The remaining crude product
was passed through a short SiO2 column by eluting with a 7:3
v/v petroleum ether/diethyl ether mixture to get the pure
product. In the same way, the corresponding trifluoropionate
25b was obtained in 83% yield just by replacing methyl
pyruvate with ethyl trifluoropyruvate as the alkylating re-
agent.
Ethyl 2-(6,8-difluorophenanthren-1-yl)-2-hydroxy-3,3,3-
trifluoropropionate (25b): (39%); mp 124-126 °C; 1H NMR
δ 8.55 (d, J ) 8.5 Hz, 1 H), 8.09 (d, J ) 9.6 Hz, 1 H), 8.03 (d,
J ) 10.8 Hz, 1 H), 7.94 (d, J ) 9.5 Hz, 2 H), 7.63 (t, J ) 8.0
Hz, 1 H), 7.08 (ddd, J ) 9.8, 8.7, and 2.2 Hz, 1 H), 4.63 (s, 1
H), 4.41-4.19 (sym m, 2 H), 1.12 (t, J ) 7.1 Hz, 3 H); 13C NMR
δ 170.3, 160.9 (dd, J ) 245.3 and 12.9 Hz), 159.4 (dd, J ) 252.2
and 13.3 Hz), 132.6 (dd, J ) 9.8 and 5.6 Hz), 130.7, 130.2 (dd,
J ) 4.4 and 3.0 Hz), 129.7, 127.5 (q, J ) 3.1 Hz), 125.8, 125.0,
123.6 (q, J ) 286.4 Hz), 122.0, 119.2 (d, J ) 5.0 Hz), 117.7
(dd, J ) 15.6 and 1.6 Hz), 104.0 (dd, J ) 22.5 and 4.2 Hz),
102.1 (dd, J ) 27.7 and 24.0 Hz), 80.1 (q, J ) 28.7 Hz), 64.4,
13.4; 19F NMR δ -73.1 (s, 3 F), -110.5 (q, J ) 8.5 Hz, 1 F),
-118.3 (t, J ) 8.5 Hz, 1 F); IR (CHCl3) νmax 3500, 3227, 3025,
2986-2872, 1740, 1639, 1258, 1207, 1177, 1118, 1006, 809
cm-1; MS m/z (%) 384 (M+, 41), 311 (67), 241 (31), 214 (100),
193 (11), 106 (4). Elem anal. calcd for C19H13F5O3: C, 59.38;
H, 3.41. Found: C, 59.21; H, 3.48.
Ethyl 2-(1,3-difluorophenanthren-2-yl)-2-hydroxy-3,3,3-
trifluoropropionate (26b): (32%, from the reaction of 24
with butyllithium at -98 °C in THF followed by quenching
the reaction mixture with ethyl trifluoropyruvate 90 min after;
63%, as the only reaction product from the reaction of 21 with
LDA or butyllithium at -50 °C followed by quenching with
1
methyl pyruvate 1 h after): mp 99-101 °C; H NMR δ 8.38
(m, 1 H), 8.04 (d, J ) 13.8 Hz, 1 H), 7.88-7.84 (m, 2 H), 7.71-
7.62 (m, 3 H), 4.69 (t, J ) 1.9 Hz, 1 H), 4.52-4.38 (sym m, 2
H), 1.32 (t, J ) 7.1 Hz, 3 H); 13C NMR δ 168.1, 158.3 (dd, J )
247.8 and 8.1 Hz), 157.1 (dd, J ) 256.2 and 7.8 Hz), 132.7,
132.6 (dd, J ) 11.2 and 7.0 Hz), 128.8, 128.4, 128.2 (dd, J )
3.9 and 2.9 Hz), 127.5, 127.3, 123.0, 122.9 (q, J ) 284.2 Hz),
118.4, 118.1 (d, J ) 7.9 Hz), 109.2 (dd, J ) 17.0 and 15.3 Hz),
104.8 (dd, J ) 25.0 and 3.9 Hz), 76.3 (q, J ) 32.5 Hz), 64.5,
14.1; 19F NMR δ -75.5 (dd, J ) 21.9 and 13.0 Hz, 3 F), -111.9
(quint, J ) 13.0 Hz, 1 F), -115.2 (q, J ) 21.9 Hz, 1 F); IR
(CHCl3) νmax 3479, 3231, 3023, 2988-2870, 1755, 1641, 1290,
1245, 1174, 1121, 1023, 815 cm-1; MS m/z (%) 384 (M+, 37),
311 (62), 292 (4), 241 (100), 213 (22), 193 (11), 106 (6). Elem
anal. calcd for C19H13F5O3: C, 59.38; H, 3.41. Found: C, 59.48;
H, 3.32.
1,3-Difluorophenanthrene (28) was obtained in 73% of
yield from the reaction of the bromide 24 with butyllithium
(1.5 equiv) at -75 °C in THF followed by quenching of the
reaction mixture with H2O).
Hydroxyester 26a was obtained as the sole reaction product
as follows. Butyllithium (1.61 M in hexanes, 0.6 mL, 1.0 mmol)
was added to a solution of 1,3-difluorophenanthrene (28), (0.21
g, 1.0 mmol) in anhyd THF (5 mL) at -50 °C. After 10 min,
methyl pyruvate was added, the cold bath was removed, and
the temperature was increased to 25 °C. After usual work up,
chromatography of the crude product on silica gel (eluent, 7:3
petroleum ether/diethyl ether) allowed the pure 26a (57%) to
be obtained. In the same way, using ethyl trifluoropyruvate
as the alkylating reagent, the corresponding trifluoropropi-
onate 26b was obtained in 63% yield.
General Procedure for the Side-Chain Fluorination
of the 2-Hydroxy-2-(phenanthryl)propionic esters 14, 25,
26, and 29. Diethylaminosulfur trifluoride (DAST) (0.17 mL,
0.21 g, 1.28 mmol) was added to a solution of the hydroxyester
(1.0 mmol) in dry dichloromethane (2 mL) at 0°C under
nitrogen atmosphere. The mixture was made to react for 30
min before water (10 mL) was carefully added. The organic
phase was separated, washed with water (20 mL), and dried
with sodium su1fate. After solvent evaporation, chromatog-
raphy of the crude product on silica gel (100 mL, eluent 4:1
(v/v) petroleum ether/diethyl ether) allowed the alkyl 2-fluoro-
2-phenanthrenylpropionates 30 and 31 to be obtained with the
following spectroscopic and analytical characteristics.
Ethyl 2-(8-bromo-1,3-difluorophenanthren-2-yl)-2-hy-
droxy-3,3,3-trifluoropropanoate (29b): (∼1%); mp 98-100
1
°C; H NMR δ 8.41 (d, J ) 8.3 Hz, 1 H), 8.20 (d, J ) 9.4 Hz,
1 H), 8.08 (d, J ) 13.7 Hz, 1 H), 8.00 (d, J ) 9.4 Hz, 1 H), 7.96
(d, J ) 7.4 Hz, 1 H), 7.52 (t, J ) 8.0 Hz, 1 H), 4.66 (br s, 1 H),
4.54-4.40 (sym m, 2 H), 1.34 (t, J ) 7.1 Hz, 3 H); 13C NMR δ
168.0, 158.6 (dd, J ) 249 and 8.0 Hz), 157.1 (dd, J ) 257 and
7.8 Hz), 132.5, 132.3 (dd, J ) 11.2 and 6.7 Hz), 131.4, 129.8
(dd, J ) 4.0 and 2.9 Hz), 127.7, 126.1, 122.8 (q, J ) 284 Hz),
122.7, 119.8 (d, J ) 7.8 Hz), 118.7 (d, J ) 17.6 Hz), 110.1 (dd,
J ) 17.2 and 15.2 Hz), 105.2 (dd, J ) 25.3 and 3.9 Hz), 76.3
(q, J ) 32.6 Hz), 64.6, 13.7; 19F NMR δ -75.47 (dd, J ) 22.6
and 12.9, 3 F), -110.61 (quint J ) 12.9 Hz, 1 F), -114.50 (q,
J ) 22.6 Hz, 1 F); IR (CHCl3) νmax 3479, 3215, 3038-3022,
2987-2874, 1755, 1642, 1304, 1243, 1174, 1126, 1021 cm-1
;
Methyl
2-fluoro-2-(phenanthren-1-yl)propionate
MS m/z (%) 464 (M+ + 1, 26), 462 (M+ - 1, 25), 391 (46), 389
(46), 321 (90), 319 (89), 212 (100), 106 (16). Elem anal. calcd
for C19H12BrF5O3: C, 49.27; H, 2,61. Found: C, 49.11; H, 2.52.
(30a): (93%); mp 121-122 °C; 1H NMR δ 8.78 (d, J ) 7.5 Hz,
1 H), 8.68 (dd, J ) 7.1 and 1.8 Hz, 1 H), 8.12 (ddd, J ) 9.4,
2.2, and 0.6 Hz, 1 H), 7.88 (dd, J ) 7.7 and 1.6 Hz, 1 H), 7.79
(d, J ) 9.3 Hz, 1 H), 7.78 (dt, J ) 7.5 and 1.4 Hz, 1 H), 7.68-
7.58 (m, 3 H), 3.70 (s, 3 H), 2.20 (d, J ) 22.6 Hz, 3 H); 13C
NMR δ 172.5 (d, J ) 26.4 Hz), 134.7 (d, J ) 20.0 Hz), 131.4,
131.2, 130.3, 129.5, 128.4, 127.9, 126.9, 126.8, 125.5, 124.7 (d,
J ) 7.6 Hz), 124.4, 122.9, 122.7, (d, J ) 6.6 Hz), 95.0 (d, J )
182.0 Hz), 53.0, 24.4 (d, J ) 24.8); 19F NMR δ -139.5 (q, J )
22.5 Hz); MS (70 eV) m/z (%) 282 (M+, 45), 223 (100), 202 (40),
101 (10). Elem anal. calcd C18H15FO2: C, 76.58; H, 5.36.
Found: C, 76.39; H, 5.43.
1,3-Difluorophenanthrene (28) (6%) and traces of ethyl
2-[6,8-difluoro-7-(1-hydroxy-1-ethoxycarbonylethyl)phenanthr-
1-yl]-2-hydroxypropionate (27b) were also detected. The latter
was identified on the basis of the analogy of its mass spectrum
with that of 27a.
The relative amounts of the above product at different
reaction times were determined by GLC after calibration with
known amounts of pure products.
Regioselective Alkylation of 8-Bromo-1,3-difluoro-
phenanthrene and 1,3-Difluorophenanthrene. Pure hy-
droxyester 25a was prepared by performing the reaction of
24 with butyllithium in THF at -108 °C followed by quenching
Methyl 2-fluoro-2-(6-fluorophenanthren-1-yl)propi-
onate (30b): (87%); mp 157-159 °C; 1H NMR δ 8.62 (d, J )
8.3 Hz, 1 H), 8.28 (d, J ) 112 Hz, 1 H), 8.10 (d, J ) 9.2 Hz, 1
620 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
H), 7.85 (dd, J ) 8.7 and 6.3 Hz, 1 H), 7.80 (d, J ) 7.4 Hz, 1
H), 7.76 (d, J ) 9.2 Hz, 1 H), 7.65 (t, J ) 8.0 Hz, 1 H), 7.35
(td, J ) 8.5 and 1.9 Hz, 1 H), 3.72 (s, 3 H), 2.21 (d, J ) 22.6
Hz, 3 H); 13C NMR δ 172.4 (d, J ) 26.4 Hz), 161.6 (d, J )
244.5 Hz), 134.8 (d, J ) 20.1 Hz), 131.8 (d, J ) 8.4 Hz), 130.5
(d, J ) 8.9 Hz), 129.8, 128.1, 127.2, 125.6, 125.3 (d, J ) 7.5
Hz), 124.6, 122.0 (d, J ) 4.8 Hz), 116.0 (d, J ) 23.9 Hz), 108.0
(d, J ) 22.4 Hz), 95.8, 94.0, 53.0, 24.4 (d, J ) 24.8 Hz); 19F
NMR δ -113.2 (dt, J ) 11.7 and 6.6 Hz), -139.6 (q, J ) 22.6
Hz); IR (CHCl3) νmax 3026, 2956, 2852, 1749, 1608, 1263, 1127,
840 cm-1; MS m/z (%) 300 (M+, 39), 241 (100), 220 (36). Elem
anal. calcd for C18H14F2O2: C, 71.99; H, 4.70. Found: C, 71.88;
H, 4.61.
Ethyl 2-(phenanthren-1-yl)-2,3,3,3-tetrafluoropropi-
onate (30c): (92%); mp 81-83 °C; 1H NMR δ 8.85 (d, J ) 8.4
Hz, 1 H), 8.67 (d, J ) 8.2 Hz, 1 H), 8.11 (d, J ) 9.4 Hz, 1 H),
7.92-7.87 (m, 2 H), 7.81 (d, J ) 9.4 Hz, 1 H), 7.70-7.60 (m, 3
H), 4.40-4.23 (sym m, ABX3 system, 2 H), 1.19 (t, J ) 7.1 Hz,
3 H); 13C NMR δ 164.8 (d, J ) 25.0 Hz), 131.4, 131.2, 130.2,
129.6, 128.5, 128.4, 127.2, 127.1, 126.6 (d, J ) 19.4 Hz), 126.2
(d, J ) 6.5 Hz), 125.7, 125.4, 122.8, 122.1, (qd, J ) 285.1 and
29.3 Hz), 121.9 (d, J ) 7.7 Hz), 94,4 (dq, J ) 190.0 and 31.1
Hz), 63.6, 13.7; 19F NMR δ -157.8 (q, J ) 9.0 Hz), -73.8 (d, J
) 9.0 Hz); MS (70 eV) m/z (%) 350 (M+, 56), 277 (100), 257
(18), 227 (34), 207 (20). Elem anal. calcd for C19H14F4O2: C,
65.14; H, 4.03. Found: C, 65.35; H, 4.11.
121.8 (qd, J ) 285 and 29.2 Hz), 121.7 (d, J ) 8.0 Hz), 119.9
(d, J ) 5.9 Hz), 117. 9 (d, J ) 15.2 Hz), 104.0 (dd, J ) 22.6
and 4.1 Hz), 102.4 (dd, J ) 27.6 and 24.1 Hz), 94.2 (dq, J )
199 and 31.3 Hz), 63.7, 13.7; 19F NMR δ -73.88 (d, J ) 8.7
Hz, 3 F), -110.00 (q, J ) 9.0 Hz, 1 F), -117.94 t, J ) 9.0 Hz,
1 F), -158.09 (q, J ) 8.7 Hz, 1 F); IR (CHCl3) νmax 3089, 3036,
2987-2841, 1758, 1640, 1298, 1186, 1119, 1084, 852, 815 cm-1
;
MS m/z (%) 386 (M+, 45), 313 (100), 293 (18), 263 (44), 243
(23), 131 (11). Elem anal. calcd for C19H12F6O2: C, 59.08; H,
3.13. Found: C, 58.89; H, 2.99.
Methyl 2-(1,3-difluorophenanthren-2-yl)-2-fluoropro-
1
pionate (31a): (90%); mp 127-129 °C; H NMR δ 8.39-8.36
(m, 1 H), 8.01 (d, J ) 13.4 Hz, 1 H), 7.86 (d, J ) 9.0 Hz, 1 H),
7.86-7.83 (m, 1 H), 7.70 (d, J ) 9.0 Hz, 1 H), 7.64-7.61 (m, 2
H), 3.88 (s, 3 H), 2.21 (ddd, J ) 22.7, 3.0, and 2.0 Hz, 3 H); 13
C
NMR δ 170.9 (d, J ) 26.0 Hz), 158.6 (ddd, J ) 248.5, 8.4, and
2.5 Hz), 157.3 (ddd, J ) 256.0, 8.3, and 3.9 Hz), 132.6, 132.4
(dd, J ) 10.6 and 6.9 Hz), 128.8, 128.3 (t, J ) 3.4 Hz), 128.2,
127.2, 123.0, 118.5 (d, J ) 16.7 Hz), 118.1 (d, J ) 8.6 Hz),
112.2 (q, J ) 13.8 Hz), 104.6 (dd, J ) 24.3 and 3.5 Hz), 91.7
(d, J ) 184.7 Hz), 53.2, 24.2 (ddd, J ) 24.6, 5.9, and 4.0 Hz);
19F NMR δ -112.5 (t, J ) 14.0 Hz, 1 F), -117.3 (d, J ) 14.9
Hz, 1 F), -137.6 to -137.9 (sym m, 1 F); IR (CHCl3) νmax 3024,
2957-2850, 1760, 1642, 1301, 1131, 1035, 814 cm-1; MS m/z
(%) 318 (M+, 25), 298 (11), 259 (100), 238 (32), 207 (11). Elem
anal. calcd for C18H13F3O2: C, 67.92; H, 4.12. Found: C, 67.79;
H, 3.98.
Ethyl 2-(6-fluorophenanthren-1-yl)-2,3,3,3-tetrafluo-
ropropionate (30d): (83%); mp 77-79 °C; 1H NMR δ 8.67
(d, J ) 8.4 Hz, 1 H), 8.25 (d, J ) 11.2 Hz, 1 H), 8.07 (d, J )
9.3 Hz, 1 H), 7.94 (d, J ) 7.6 Hz, 1 H), 7.84 (dd, J ) 8.5 and
6.2 Hz, 1 H), 7.77 (d, J ) 9.3 Hz, 1 H), 7.67 (t, J ) 8.0 Hz, 1
H), 7.36 (td, J ) 8.4 and 1.3 Hz, 1 H), 4.39 (dq, J ) 10.7 and
7.1 Hz, 1 H), 4.31 (dq, J ) 10.7 and 7.1 Hz, 1 H), 1.22 (t, J )
7.1 Hz, 3 H); 13C NMR δ 164.7 (d, J ) 25 Hz), 161.8 (d, J )
244.9 Hz), 131.7 (d, J ) 8.4 Hz), 130.8 (d, J ) 4.0 Hz), 130.6
(d, J ) 8.9 Hz), 129.9, 128.0, 127.9, 126.8 (d, J ) 6.5 Hz), 126.7,
125.8, 125.4, 121.8 (qd, J ) 285.0 and 29.3 Hz), 121.2 (d, J )
7.6 Hz), 116.4 (d, J ) 23.9), 108.0 (d, J ) 22.5), 94.3 (dq, J )
199.4 and 31.4 Hz), 63.6, 13.7; 19F NMR δ -73.8 (d, J ) 8.5
Hz, 3 F), -112.6 (m, 1 F), -158.0 (q, J ) 8.5, 1 F); IR (CHCl3)
νmax 3032, 2988-2863, 1759, 1608, 1514, 1296, 1254, 1183,
1030, 840 cm-1; MS m/z (%) 368 (M+, 63), 295 (100), 275 (17),
245 (32), 225 (15). Elem anal. calcd for C19H13F5O2: C, 61.96;
H, 3.56. Found: C, 62.00; H, 3.49.
Methyl 2-(8-bromo-1,3-difluorophenanthren-2-yl)-2-
fluoropropionate (31b): (70%); mp 121-123 °C; 1H NMR δ
8.39 (d, J ) 8.4 Hz, 1 H), 8.17 (d, J ) 9.4 Hz, 1 H), 8.05 (d, J
) 13.3 Hz, 1 H), 7.98 (d, J ) 9.4 Hz, 1 H), 7.94 (d, J ) 7.6 Hz,
1 H), 7.49 (t, J ) 7.9 Hz, 1 H), 3.91 (s, 3 H), 2.23 (ddd, J )
22.7, 3.0, and 1.9 Hz, 3 H); 13C NMR δ 170.7 (d, J ) 26.0 Hz),
158.9 (ddd, J ) 252, 8.3, and 2.6 Hz), 157.3 (ddd, J ) 257, 8.5,
and 4.0 Hz), 132.3, 132.0 (ddd, J ) 11.0, 6.5, and 1.5 Hz), 131.3,
130 (t, J ) 3.5 Hz), 127.6, 127.1, 125.7, 123.9, 122.7, 119.8 (d,
J ) 8.2 Hz), 118.7 (d, J ) 17.4 Hz), 113.1 (ddd, J ) 22.5, 17.8,
and 14.0 Hz), 105.0 (dd, J ) 24.7 and 3.7 Hz), 53.3, 24.2 (ddd,
J ) 24.6, 6.1, and 3.8 Hz); 19F NMR δ -111.34 (t, J ) 15.1
Hz, 1 F), -116.86 (d, J ) 15.4 Hz, 1 F), -138.28 (qt, J ) 22.7
and 15.4 Hz, 1 F); IR (CHCl3) νmax 3038, 2956-2851, 1762,
1643, 1300, 1147, 1131, 916 cm-1; MS m/z (%) 398 (M+ + 1,
23), 396 (M+ - 1, 24), 378 (11), 376 (9), 339 (99), 337 (100),
320 (36), 318 (38), 258 (57), 238 (70), 218 (31), 109 (24). Elem
anal. calcd for C18H12BrF3O2: C, 54.43; H, 3,05. Found: C,
54.29; H, 2.96.
Methyl 2-(6,8-difluorophenanthren-1-yl)-2-fluoropro-
1
pionate (30e): (85%); mp 138-140 °C; H NMR δ 8.59 (d, J
) 8.2 Hz, 1 H), 8.17 (dd, J ) 9.6 and 1.7 Hz, 1 H), 8.10 (d, J
) 11.0 Hz, 1 H), 8.02 (d, J ) 9.6 Hz, 1 H), 7.85 (d, J ) 7.5 Hz,
1 H), 7.69 (t, J ) 7.9 Hz, 1 H), 7.11 (ddd, J ) 9.9, 8.6, and 2.2
Hz, 1 H), 3.75 (s, 3 H), 2.23 (d, J ) 22.6 Hz, 3 H); 13C NMR δ
172.2 (d, J ) 26.4 Hz), 160.8 (dd, J ) 245 and 12.9 Hz), 159.5
(dd, J ) 252 and 13.2 Hz), 135.1 (d, J ) 20.1 Hz), 132.6 (dd,
J ) 9.8 and 5.7 Hz), 130.2, 129.9 (t, J ) 3.2 Hz), 126.1, 125.9
(d, J ) 7.5 Hz), 124.8, 122.5 (d, J ) 7.0 Hz), 119.3 (d, J ) 6.1
Hz), 117.9 (d, J ) 15.6 Hz), 104.0 (dd, J ) 22.3 and 4.2 Hz),
102.1 (dd, J ) 27.8 and 24.2 Hz), 94.9 (d, J ) 183 Hz), 53.1,
24.4 (d, J ) 24.8 Hz); 19F NMR δ -110.71 (dt, J ) 10.7 and
8.2 Hz, 1 F), -118.19 (t, J ) 8.5 Hz, 1 F), -139.6 (q, J ) 22.6
Hz, 1 F); IR (CHCl3) νmax 3085, 3034, 2958, 2848, 1749, 1640,
1274, 1258, 1210, 1126, 998, 852 cm-1; MS m/z (%) 318 (M+,
33), 259 (100), 239 (53), 219 (8), 119 (12). Elem anal. calcd for
C18H13F3O2: C, 67.92; H, 4.12. Found: C, 67.79; H, 3.98.
Ethyl 2-(6,8-difluorophenanthren-1-yl)-2,3,3,3-tetra-
fluoropropionate (30f): (82%); mp 100-102 °C dec; 1H NMR
δ 8.65 (d, J ) 8.4 Hz, 1 H), 8.11 (d, J ) 9.5 Hz, 1 H), 8.07 (d,
J ) 10.8 Hz, 1 H), 8.03 (d, J ) 9.5 Hz, 1 H), 7.96 (dd, J ) 7.7
and 1.1 Hz, 1 H), 7.70 (t, J ) 8.0 Hz, 1 H), 7.12 (ddd, J ) 9.8,
8.6, and 2.3 Hz, 1 H), 4.43-4.28 (sym m, 2 H), 1.23 (t, J ) 7.1
Hz, 3 H); 13C NMR δ 164.6 (d, J ) 24.9 Hz), 161.0 (dd, J )
246 and 12.9 Hz), 159.5 (dd, J ) 253 and 13.2 Hz), 132.5 (dd,
J ) 9.9 and 5.6 Hz), 130.3, 130.2 (ddd, J ) 4.6, 2.9, and 1.1
Hz), 127.4 (d, J ) 6.7 Hz), 127.1 (d, J ) 19.5 Hz), 126.1, 125.9,
Ethyl 2-(1,3-difluorophenanthren-2-yl)-2,3,3,3-tetra-
fluoropropionate (31c): (75%); mp 76-78 °C; 1H NMR δ 8.44
(m, 1 H), 8.10 (d, J ) 13.3 Hz, 1 H), 7.92-7.88 (m, 2 H), 7.74
(d, J ) 9.1 Hz, 1 H), 7.70-7.66 (m, 2 H), 4.47 (sym m, 2 H),
1.37 (t, J ) 7.1 Hz, 3 H); 13C NMR δ 162.8 (d, J ) 22.6 Hz),
157.8 (ddd, J ) 250, 7.1, and 3.3 Hz), 157.6 (ddd, J ) 259, 7.1,
and 3.7 Hz), 133.6 (dd, J ) 10.5 and 6.7 Hz), 132.9, 132.9,
128.9, 128.7, 128.2 (dd, J ) 4.4 and 3.0 Hz), 127.7 (t, J ) 2.5
Hz), 127.5, 123.1, 121.3 (qd, J ) 283 and 29.1 Hz), 118.5 (dd,
J ) 16.2 and 2.0 Hz), 117.9 (8.7 and 1.6 Hz), 105.0 (dd, J )
23.9 and 4.2 Hz), 90.5 (dq, J ) 201 and 34.1 Hz), 63.7, 13.7;
19F NMR δ -77.53 (q, J ) 10.2 Hz, 3 F), -111.97 (sept J )
11.3 Hz, 1 F), -114.67 (sext, J ) 13.0 Hz, 1 F), -168.40 (m, 1
F); IR (CHCl3) νmax 3038, 3026, 2929, 2857, 1769, 1641, 1310,
1270, 1199, 1035, 820 cm-1; MS m/z (%) 386 (M+, 41), 313
(100), 293 (17), 263 (42), 243 (22), 131 (14). Elem anal. calcd
for C19H12F6O2: C, 59.08; H, 3,13. Found: C, 59.21; H, 3.20.
Ethyl 2-(8-bromo-1,3-difluorophenanthren-2-yl)-2,3,3,3-
tetrafluoropropionate (31d): (65%); mp 98-100 °C; 1H
NMR δ 8.34 (d, J ) 8.3 Hz, 1 H), 8.13 (d, J ) 9.6 Hz, 1 H),
8.04 (d, J ) 13.2 Hz, 1 H), 7.93 (d, J ) 7.3 Hz, 1 H), 7.92 (d,
J ) 9.6 Hz, 1 H), 7.47 t, J ) 8.1 Hz, 1 H), 4.54-4.42 (sym m,
2 H), 1.38 (t, J ) 7.1 Hz, 3 H); 13C NMR δ 162.7 (d, J ) 22.6
Hz), 158.1 (ddd, J ) 251, 7.1, and 3.3 Hz), 157.6 (ddd, J )
260, 7.1, and 3.6 Hz), 133.1 (dd, J ) 10.7 and 6.6 Hz), 132.7,
131.4, 129.7 (dd, J ) 4.1 and 2.7 Hz), 127.7, 126.2 (t, J ) 2.3
J. Org. Chem, Vol. 70, No. 2, 2005 621

Ricci and Ruzziconi
Hz), 123.9, 122.7, 121.3 (qd, J ) 284 and 29.0 Hz), 119.4 (dd,
J ) 8.5 and 1.3 Hz), 118.5 (dd, J ) 16.5 and 2.0 Hz), 106.0
(ddd, J ) 21.8, 17.2, and 13.7 Hz), 105.3 (dd, J ) 24.3 and 4.2
Hz), 90.4 (dq, J ) 201 and 34.2 Hz), 63.8, 13.7; 19F NMR δ
-77.48 (q, J ) 10.2 Hz, 3 F), -110.79 (quint, J ) 11.2 Hz, 1
F), -114.04 (sext, J ) 11.1 Hz, 1 F), -168.58 (m, 1 F); IR
Hz), 136.2 (d, J ) 20 Hz), 132.8 (d, J ) 8.5 Hz), 131.7 (d, J )
8.9 Hz), 131.4 (d, J ) 4.2 Hz), 130.9, 129.1, 127.7, 126.9, 126.8,
125.7, 123.5 (dd, J ) 7.6 and 2.4 Hz), 116.8 (d, J ) 24 Hz),
108.9 (d, J ) 23 Hz), 95.4 (d, J ) 181 Hz), 24.6 (d, J ) 25 Hz);
19F NMR (acetone-d6) δ -139.3 (q, J ) 22.5 Hz, 1 F), -114.5
(ddd, J ) 12.8, 7.3, 5.5 Hz, 1 F); IR (KBr) νmax 3200-1944 (br),
1712, 1509, 1300, 1100, 948, 837 cm-1; Elem anal. calcd for
C17H12F2O2: C, 71,32; H, 4,23. Found: C, 71.24; H, 4.15.
(CHCl3) νmax 3058, 2954-2858, 1769, 1644, 1303, 1270 cm-1
;
MS m/z (%) 466 (M+ + 1, 63), 464 (M+ - 1, 70), 393 (100), 391
(94), 374 (12), 372 (12), 343 (78), 341 (86), 313 (23), 261 (50),
243 (59), 207 (58), 106 (14). Elem anal. calcd for C19H11-
BrF6O2: C, 49.06; H, 2.38. Found: C, 48.89; H, 2.25.
2-(6,8-Difluorophenanthr-1-yl)-2-fluoropropionic acid
1
(2c): (76%); mp 181 °C dec; H NMR (acetone-d6) δ 8.84 (d, J
) 8.5 Hz, 1 H), 8.38 (dd, J ) 11.2 and 0.9 Hz, 1 H), 8.34 (dd,
J ) 9.8 and 2.2 Hz, 1 H), 8.01-7.98 (m, 2 H), 7.60 (td, J ) 8.5
and 1.1 Hz, 1 H), 7.34 (ddd, J ) 10.3, 8.9, and 2.3 Hz, 1 H),
2.22 (d, J ) 22.6 Hz, 3 H); 13C NMR (acetone-d6) δ 172.2 (d, J
) 26.3 Hz), 160.9 (dd, J ) 244 and 13.2 Hz), 159.4 (dd, J )
250 and 13.5 Hz), 135.6 (d, J ) 20.1 Hz), 132.8 (dd, J ) 10.1
and 5.6 Hz), 130.3, 129.9 (t, J ) 3.1 Hz), 126.6 (d, J ) 6.3 Hz),
126.5, 125.1, 123.3 (d, J ) 7.7 Hz), 118.2 (d, J ) 6.3 Hz), 117.7
(dd, J ) 17.5 and 2.0 Hz), 104.5 (dd, J ) 22.7 and 4.3 Hz),
101.9 (dd, J ) 28.4 and 24.4 Hz), 94.5 (d, J ) 181 Hz), 23.7 (d,
J ) 24.6 Hz); 19F NMR (acetone-d6) δ -111.89 (q, J ) 9.1 Hz,
1 F), -119.83 (t, J ) 8.5 Hz, 1 F), -139.22 (q, J ) 22.4 Hz, 1
F); IR (KBr) νmax 3436, 3300-2000 (br), 3083, 2922, 1733, 1638,
1302, 1114, 996, 811 cm-1. Elem anal. calcd for C17H11F3O2:
C, 67.11; H, 3.64. Found: C, 66.98; H, 3.49.
General Procedure for the Preparation of 2-(Phenan-
thryl)-2-fluoropropionic acids 2-5. Each alkyl 2-fluoro-2-
(phenanthryl)propionate 30-31 (1.0 mmol) was made to react
for 2 h in 5% methanolic KOH (25 mL) at 20 °C. The solvent
was evaporated, the resu1ting so1id was dissolved in water
(30 mL), and the mixture was extracted with diethyl ether (2
× 20 mL). The clear solution was acidified with 5% aq HCl
until pH 1, the resu1ting white suspension was extracted with
ethyl acetate (3 × 20 mL), and the collected organic phases
were dried with Na2SO4. After solvent evaporation, the
remaining white solid was crystallized from ethanol to obtain
the pure acid. The acids 2-5 were identified on the basis of
their spectroscopic and analytical characteristics.
2-(6-Fluorophenanthren-1-yl)propionic acid (1b): (88%);
mp 213-215 °C; 1H NMR (DMSO-d6) δ 12.45 (s, 1 H), 8.73 (d,
J ) 8.1 Hz, 1 H), 8.61 (dd, J ) 11.7 and 1.6 Hz, 1 H), 8.04 (m,
2 H), 7.89 (d, J ) 9.3, 1 H), 7.66-7.48 (m, 3 H), 4.54 (q, J )
6.9 Hz, 1 H), 1.52 (d, J ) 6.9 Hz, 3 H); 13C NMR (DMSO-d6) δ
176.1, 161.6 (d, J ) 242 Hz), 138.8, 132.2 (d, J ) 8.6 Hz), 131.3
(d, J ) 8.9 Hz), 130.1 (d, J ) 3.9 Hz), 130.0, 128.4, 126.9, 126.9,
126.4, 122.9, 121.8, 116.2 (d, J ) 23.8 Hz), 108.7 (d, J ) 22.3
Hz), 41.6, 18.7; 19F NMR (DMSO-d6) δ -113.1 (ddd, J ) 11.7,
8.3, and 6.3 Hz); IR (KBr) νmax 3447-2370 (br), 3076, 2986-
2931, 1691, 1603, 1461, 1206, 838 cm-1; MS (70 eV) m/z (%)
268 (M+, 47), 223 (100), 209 (16), 196 (20). Elem anal. calcd
for C17H13FO2: C, 76.11; H, 4.88. Found: C, 76.05; H, 4.79.
2-(Phenanthr-1-yl)-2,3,3,3-tetrafluoropropionic acid
1
(3a): (93%); mp 50-52 °C; H NMR δ 8.80 (d, J ) 8.4 Hz, 1
H), 8.62 (d, J ) 8.1 Hz, 1 H), 8.11 (d, J ) 9.3 Hz, 1 H), 7.89 (d,
J ) 7.5 Hz, 1 H), 7.80 (d, J ) 7.7 Hz, 1 H), 7.73 (d, J ) 9.4 Hz,
1 H), 7.65-7.54 (m, 3 H), 7.26 (br s, 1 H); 13C NMR δ 168.1 (d,
J ) 25.6 Hz), 131.5, 131.2, 130.1, 129.7, 128.7, 128.4, 127.3,
127.2, 126.2 (d, J ) 9.6 Hz), 126.0 (d, J ) 22.2 Hz), 125.9,
125.3, 122.8, 121.7 (qd, J ) 285.1 and 29.1 Hz), 121.8 (d, J )
8.8 Hz), 94.4 (dq, J ) 199.6 and 31.0 Hz); 19F NMR δ -157.9
(q, J ) 7.9 Hz, 1 F), -73.6 (d, J ) 7.9 Hz, 3 F). Elem anal.
calcd For C17H10F4O2: C, 63.36; H, 3.13. Found: C, 63.45; H,
3.02.
2-(6,8-Difluorophenanthr-1-yl)propionic acid (1c): (93%);
mp 205-207 °C; 1H NMR (DMSO-d6) δ 8.82 (d, J ) 8.2 Hz, 1
H), 8.60 (br d, J ) 11.4 Hz, 1 H), 8.22-8.02 (AB system, JAB
) 9.5 Hz, 2 H), 7.76 (t, J ) 7.8 Hz, 1 H), 7.70 (d, J ) 7.3 Hz,
1 H), 7.63 (ddd, J ) 11.0, 9.2, and 223 Hz, 1 H), 4.61 (q, J )
7.1 Hz, 1 H), 3.37 (br s, 1 H), 1.58 (d, J ) 7.1 Hz, 3 H); 13C
NMR (DMSO-d6) δ 175.6, 160.4 (dd, J ) 242.7 and 13.3), 158.8
(dd, J ) 249.7 and 13.6 Hz), 138.7, 132.6 (dd, J ) 9.9 and 5.4
Hz), 129.9, 129.2, 127.1, 126.7, 122.9, 122.4, 117.8, 117.3 (d, J
) 15.3 Hz), 104.9 (d, J ) 22.2 Hz), 102.1 (t, J ) 26.4 Hz), 41.1,
18.2; 19F NMR (DMSO-d6) δ -110.6 (ddd, J ) 11.3, 8.9, and
7.5 Hz), -118.6 (dd, J ) 10.1 and 7.5 Hz); IR (CHCl3) νmax
3430, 3025, 1638, 1596 cm-1; MS m/z (%) 240 (M+ - HCOOH,
100), 239 (96), 219 (12), 119 (13). Elem anal. calcd for
C17H12F2O2: C, 71.32; H, 4.23. Found: C, 71.38; H, 4.25.
2-Fluoro-2-(phenanthr-1-yl)propionic acid (2a): (87%);
mp 155-157 °C; 1H NMR (DMSO-d6) δ 9.00 (d, J ) 8.2 Hz, 1
H), 8.91 (d, J ) 8.1 Hz, 1 H), 8.21 (dd, J ) 9.4 and 2.5 Hz, 1
H), 8.03 (dd, J ) 7.7 and 1.4 Hz, 1 H), 7.96 (d, J ) 9.4 Hz, 1
H), 7.92 (d, J ) 7.7 Hz, 1 H), 7-80-7.70 (m, 3 H), 2.18 (d, J
) 22.8 Hz, 3 H), 3,5 (br s, 1 H); 13C NMR (DMSO-d6, 50 MHz)
δ 173.1 (d, J ) 25.9 Hz), 135.0 (d, J ) 20.0 Hz), 130.8, 130.6,
129.9, 129.2, 128.3, 127.4, 127.2, 127.2, 126.0, 125.6 (d, J )
5.6 Hz), 124.6, 123.3, 122.8 (d, J ) 6.7 Hz), 94.5, (d, J ) 180.2
Hz), 24.0 (d, J ) 24.1 Hz); 19F NMR (DMSO-d6, 376 MHz) δ
-139.11 (q, J ) 22.5 Hz). Elem anal. calcd for C17H13FO2: C,
76.11; H, 4.88. Found: C, 75.99; H, 4.93.
2-(6-Fluorophenanthr-1-yl)-2,3,3,3-tetrafluoropropi-
onic acid (3b): (81%); mp 179 °C dec; 1H NMR (acetone-d6) δ
9.03 (d, J ) 8.0 Hz, 1 H), 8.7 (very br s, 1 H), 8.57 (dd, J )
11.5 and 2.4 Hz, 1 H), (8.19 (dd, J ) 9.5 and 1.5 Hz, 1 H), 8.06
(dd, J ) 8.9 and 6.0 Hz, 1 H), 8.04 (dd, J ) 7.7 and 1.2 Hz, 1
H), 7.97 (d, J ) 9.4 Hz, 1 H), 7.84 (td, J ) 8.0 and 1.0 Hz, 1
H), 7.51 (td, J ) 8.5 and 2.5 Hz, 1 H); 13C NMR (acetone-d6) δ
164.9 (d, J ) 24.8 Hz), 161.9 (d, J ) 243 Hz), 131.8 (d, J ) 8.7
Hz), 131.0 (d, J ) 9.0 Hz), 130.9 (d, J ) 3.7 Hz), 129.8, 128.2,
127.9, 126.9 (dd, J ) 8.5 and 2.3 Hz), 126.6, 126.5, 125.8, 122.2
(qd, J ) 284 and 29.4 Hz), 121.2 (d, J ) 7.6 Hz), 116.4 (d, J )
24.1 Hz), 108.2 (d, J ) 22.9 Hz), 94.3 (dq, J ) 197 and 30.8
Hz); 19F NMR (acetone-d6) δ -74.56 (d, J ) 8.8 Hz, 3 F),
-113.78 (q, J ) 8.3 Hz, 1 F), -158.25 (q, J ) 8.8 Hz, 1 F); IR
(KBr) νmax 3250-2000 (br), 3034, 2897, 1736, 1633, 1436, 1267,
1175, 998, 906, 833 cm-1. Elem anal. calcd for C17H9F5O2: C,
60.01; H, 2.67. Found: C, 60.15; H, 2.56.
2-(6,8-Difluorophenanthr-1-yl)-2,3,3,3-tetrafluoropro-
1
pionic acid (3c): (88%); mp 204 °C dec; H NMR (acetone-
d6) δ 9.02 (d, J ) 8.3 Hz, 1 H), 8.45 (dd, J ) 11.3 and 1.1 Hz,
1 H), 8.27 (d, J ) 9.8 Hz, 1 H), 8.09-8.07 (m, 2 H), 7.87 (td, J
) 8.0 and 1.0 Hz, 1 H), 7.41 (ddd, J ) 10.2, 8.9, and 2.3 Hz, 1
H); 13C NMR (acetone-d6) δ 164.8 (d, J ) 24.8 Hz), 161.2 (dd,
J ) 244 and 13.2 Hz), 159.4 (dd, J ) 251 and 13.6 Hz), 132.7
(dd, J ) 10.1 and 5.4 Hz), 130.3 (t, J ) 3.4 Hz), 130.1, 127.6
(dd, J ) 8.5 and 2.3 Hz), 127.1(d, J ) 19.4 Hz), 126.8, 126.4,
122.1 (qd, J ) 284 and 29.3 Hz), 122.0 (d, J ) 8.3 Hz), 119.4
(d, J ) 6.3 Hz), 117.7 (d, J ) 15.6 Hz), 104.6 (dd, J ) 23.0 and
4.3 Hz), 102.5 (dd, J ) 28.4 and 24.3 Hz), 94.2 (dq, J ) 197
and 30.8 Hz); 19F NMR (acetone-d6) δ -74.62 (d, J ) 9.2 Hz,
3 F), -111.12 (q, J ) 9.2 Hz, 1 F), 119.56 (t, J ) 9.2 Hz, 1 F),
-158.29 (br, 1 F); IR (KBr) νmax 3588, 3300-2000 (br),
1750, 1640, 1294, 1270, 1185, 1119, 1000, 852 cm-1. Elem anal.
calcd for C17H8F6O2: C, 57.00; H, 2.25. Found: C, 57.19; H,
2.26.
2-Fluoro-2-(6-fluorophenanthr-1-yl)propionic acid (2b):
1
(93%); mp 180-182 °C; H NMR (acetone-d6) δ 8.87 (d, J )
8.5 Hz, 1 H), 8.53 (dd, J ) 11.6 and 2.4 Hz, 1 H), 8.27 (dd, J
) 9.4 and 2.4 Hz, 1 H), 8.03 (dd, J ) 8.8 and 8.6 Hz, 1 H),
7.95 (ddd, J ) 7.5, 1.7, and 1.1 Hz, 1 H), 7.88 (d, J ) 9.4 Hz,
1 H), 7.73 (ddd, J ) 8.5, 7.5, and 1.2 Hz, 1 H), 7.46 (td, J )
8.6 and 2.5 Hz, 1 H), 2.21 (d, J ) 22.6 Hz, 3 H); 13C NMR
(acetone-d6, 50 MHz) δ 173.2 (d, J ) 26 Hz), 162.6 (d, J ) 242
622 J. Org. Chem., Vol. 70, No. 2, 2005

Fluorinated 2-(Phenanthryl)propionic Acids
2-(1,3-Difluorophenanthr-2-yl)-2-fluoropropionic acid
(4a): (87%); mp 219 °C dec; 1H NMR (acetone-d6) δ 8.69-8.67
(m, 1 H), 8.58 (d, J ) 13.4 Hz, 1 H), 7.98-7.96 (m, 1 H), 7.92-
7.84 (four peaks, AB system, JAB ) 9.0 Hz, 2 H), 7.72-7.69
(m, 2 H), 2.20 (ddd, J ) 22.8, 3.2, and 2.1 Hz, 3 H); 13C NMR
(acetone-d6) δ 170.5 (d, J ) 26.1 Hz), 158.8 (dd, J ) 247 and
7.2 Hz), 157.1 (ddd, J ) 255, 8.1, and 3.2 Hz), 132.7, 132.7,
132.4 (dd, J ) 11.1 and 7.2 Hz), 128.8, 128.4, 127.6, 127.5,
123.5, 118.4 (d, J ) 16.7 Hz), 117.7 (d, J ) 8.6 Hz), 112.9 (ddd,
J ) 22.5, 17.9, and 15.0 Hz), 104.9 (dd, J ) 24.5 and 2.6 Hz),
91.5 (d, J ) 183 Hz), 23.7 (dt, J ) 24.4 and 4.0 Hz); 19F NMR
(acetone-d6) δ -112.77 (t, J ) 13.7 Hz, 1 F), -118.40 (d, J )
14.8 Hz, 1 F), -137.70 (m, 1 F); IR (KBr) νmax 3300-2000 (br),
3005, 2922, 1740, 1642, 1397, 1217, 1145, 1028, 919, 818, 754
cm-1. Elem anal. calcd for C17H11F3O2: C, 67.11; H, 3.64.
Found: C, 67.31; H, 3.59.
J ) 20.7 Hz), 128.3 (dd, J ) 7.2 and 4.3 Hz), 128.2, 127.7,
123.7, 121.8 (qd, J ) 283 and 29 Hz), 118.3, (dd, J ) 16.2 and
1.8 Hz), 117.4 (dd, J ) 8.6 and 1.5 Hz), 105.5 (dd, J ) 21.0
and 4.0 Hz), 90.6 (dq, J ) 198 and 33 Hz); 19F NMR (acetone-
d6) δ -78.34 (q, J ) 9.8 Hz, 3 F), -112.57 (br s, 1 F), -115.84
(m, 1 F), -169.19 (br s, 1 F); IR (CHCl3) νmax 3300-1944 (br),
3036, 2930-2855, 1756, 1640, 1302, 1200 cm-1. Elem anal.
calcd for C17H8F6O2: C, 57.00; H, 2.25. Found: C, 56.84; H,
2.17.
2-(8-Bromo-1,3-difluorophenanthr-2-yl)-2,3,3,3-tetra-
1
fluoropropionic acid (5b): (88%); mp 207 °C dec; H NMR
(acetone-d6) δ 8.56 (d, J ) 8.6 Hz, 1 H), 8.35 (d, J ) 13.7 Hz,
1 H), 8.00 (d, J ) 9.5 Hz, 1 H), 7.93 (dd, J ) 7.6 and 0.9 Hz,
1 H), 7.89 (d, J ) 9.5 Hz, 1 H), 7.51 (dd, J ) 8.2 and 7.8 Hz,
1 H); 13C NMR (acetone-d6) δ 162.7 (d, J ) 22.0 Hz), 158.0
(ddd, J ) 250, 7.0, and 3.3 Hz), 157.2 (ddd, J ) 259, 7.3, and
3.9 Hz), 133.1 (dd, J ) 11.1 and 6.6 Hz), 132.8, 130.9, 129.6
(dd, J ) 4.3 and 2.7 Hz), 128.1, 125.9 (t, J ) 2.4 Hz), 123.5,
123.0, 121.6 (qt, J ) 283 and 29.2 Hz), 119.0 (dd, J ) 8.7 and
1.6 Hz), 118.1 (dd, J ) 16.3 and 1.9 Hz), 105.9 (dd, J ) 24.6
and 4.1 Hz), 105.8 (m), 90.4 (dq, J ) 199 and 37.5 Hz); 19F
NMR (acetone-d6) δ -78.33 (q, J ) 10.0 Hz, 3 F), -111.7 (sept,
J ) 11.3 Hz, 1 F), -115.36 (sext, J ) 12.1 Hz, 1 F), 169.59 (m,
1 F); IR (KBr) νmax 3447, 3300-2000 (br), 3068, 1759, 1643,
1214, 1191, 1128, 997, 758 cm-1. Elem anal. calcd for C17H7-
BrF6O2: C, 46.71; H, 1.61. Found: C, 46.57; H, 1.56.
2-(8-Bromo-1,3-difluorophenanthr-2-yl)-2-fluoropropi-
onic acid (4b): (94%); mp 164 °C dec; 1H NMR (acetone-d6) δ
8.58 (d, J ) 8.6 Hz, 1 H), 8.26 (d, J ) 13.5 Hz, 1 H), 8.01 (d,
J ) 9.4 Hz, 1 H), 7.93 (dd, J ) 7.6 and 0.9 Hz, 1 H), 7.90 (d,
J ) 9.4 Hz, 1 H), 7.52 (dd, J ) 8.3 and 7.7 Hz, 1 H), 2.20 (ddd,
J ) 22.9, 3.6, and 2.0 Hz, 3 H); 13C NMR (acetone-d6) δ 170.5
(d, J ) 26.0 Hz), 159.1 (ddd, J ) 248, 8.6, and 2.6 Hz), 157.1
(ddd, J ) 256, 8.8, and 4.0 Hz), 132.4, 131.8 (ddd, J ) 11.2,
6.3, and 1.3 Hz), 130.7, 129.9 (t, J ) 3.0 Hz), 127.9, 125.3 (t,
J ) 2.3 Hz), 123.4, 123.0, 119.5 (dd, J ) 9.2 and 1.5 Hz), 118.3
(d, J ) 17.3 Hz), 113.5 (ddd, J ) 22.7, 18.4, and 14.0 Hz), 105.3
(dd, J ) 25.0 and 3.7 Hz), 91.4 (d, J ) 184 Hz), 23.7 (ddd, J )
24.5, 6.7, and 3.7 Hz); 19F NMR (acetone-d6) δ -111.54 (t, J )
14.6 Hz, 1 F), -117.97 (d, J ) 15.7 Hz, 1 F), 137.97 (m, 1 F);
IR (KBr) νmax 3421, 3300-2000 (br), 3068, 2924, 2842, 1749,
1643, 1235, 1143, 1029, 802, 757 cm-1; Elem anal. calcd for
C17H10BrF3O2: C, 53.29; H, 2.63. Found: C, 53.11; H, 2.55.
2-(1,3-Difluorophenanthr-2-yl)-2,3,3,3-tetrafluoropro-
Acknowledgment. This work is dedicated to
Professor Manfred Schlosser as a token of profound
esteem and gratitude. Thanks are due to Ministero
dell’Istruzione dell’Universita` e della Ricerca (MIUR)
and to University of Perugia for financial support (PRIN
2004).
1
pionic acid (5a): (86%); mp 178 °C dec; H NMR (acetone-
d6) δ 8.73 (m, 1 H), 8.47 (d, J ) 13.7 Hz, 1 H), 8.04-7.99 (m,
1 H), 7.98-7.89 (m, 2 H), 7.77-7.72 (m, 2 H); 13C NMR
(acetone-d6, 50 MHz) δ 163.3 (d, J ) 22.0 Hz), 157.9 (ddd, J )
249, 7.4, and 3.2 Hz), 157.3 (ddd, J ) 258, 7.3, and 3.8 Hz),
133.6 (dd, J ) 10.6 and 6.7 Hz), 132.9, 128.9, 128.9, 128.7 (d,
Supporting Information Available: 1H, 13C, and 19F
NMR spectra of all the reported new products. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO048294K
J. Org. Chem, Vol. 70, No. 2, 2005 623