Synthesis, Chiroptical Properties, and Solid-State Structure Determination of Two New Chiral Dipyrrin Difluoroboryl Chelates

Article abstract of DOI:10.1021/ja030542r

Two new types of optically active BODIPY fluorophores bearing chiral phenyl substituents either at the meso-position or at both external α-positions have been synthesized. Their chiroptical properties are strongly dependent both on the position of the chi

Full text of DOI:10.1021/ja030542r

Published on Web 01/27/2004
Synthesis, Chiroptical Properties, and Solid-State Structure
Determination of Two New Chiral Dipyrrin Difluoroboryl
Chelates
Albert Gossauer,*,† Freddy Nydegger,† Tibor Kiss,† Robert Sleziak,† and
Helen Stoeckli-Evans‡
Contribution from the Chemiedepartement der UniVersita¨t, Ch. du Muse´e 9,
CH-1700 Fribourg, Switzerland, and Institut de Chimie de l’UniVersite´,
AVenue de BelleVeaux 51, CH-2007 Neuchaˆtel, Switzerland
Received September 19, 2003; E-mail: albert.gossauer@unifr.ch
Abstract: Two new types of optically active BODIPY fluorophores bearing chiral phenyl substituents either
at the meso-position or at both external R-positions have been synthesized. Their chiroptical properties
are strongly dependent both on the position of the chiral group and on the protonation of the chromophore.
The solid-state structures of one of the difluoroboryl chelates bearing the chiral phenyl substituent at the
meso-position (9a) as well as of the corresponding ligand (8a) and its perchlorate have been determined
by X-ray diffraction analysis. These are, to the best of our knowledge, the first crystal structures of a dipyrrin
free base and of a dipyrrin salt which have been obtained by X-ray diffraction analysis. Hence, for the first
time, the helical structure of a protonated dipyrrin chromophore has been proved experimentally.
Because of their photochemical stability and exceptional
spectral properties, particularly their high absorption coefficients
(ꢀmax ≈ 7 × 104 to 105 L mol-1 cm-1 at λmax g 500 up to 630
nm1) and high quantum yields of emission (Φ > 0.5),2-12
dipyrrin difluoroboryl chelates (4,4-difluoro-4-bora-3a,4a-diaza-
s-indacenes), which are marketed under the trade name BO-
DIPY,13 have multiple applications in chemistry and biology.
Thus, they have been used as fluorescent probes for proton1,14-18
and metal ions detection,19,20 as well as for DNA sequencing21-23
and for the study of dynamics, structure, and function of
biologicalsystemssuchasmonosaccharides,24 lipidmembranes,5,25-27
and proteins.5,27,28 Moreover, BODIPY chromophores are used
in chromatography,29 as dopants in liquid crystals,30 as laser
dyes,31-37 and as constitutive elements in optoelectronic
devices.7,14,38-49 Recently, the chiroptical properties of chiral
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† Chemiedepartement der Universita¨t.
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‡ Institut de Chimie de l’Universite´.
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10.1021/ja030542r CCC: $27.50 © 2004 American Chemical Society

Two New Dipyrrin Difluoroboryl Chelates
A R T I C L E S
more than 40 years ago.54 In agreement with this hypothesis
are the high rotational strength (∆ꢀmax ≈ 100) of the (achiral)
protobiliverdin IXγ chromophore, which occurs in the cabbage
butterfly (Pieris brassicae L.) bound to an apoprotein,55 as well
as the high optical activity ([R]20 ) -2370°) of the planar
D
chiral metacycloprodigiosin (a metabolite of Streptomyces
longisporus ruber), in alkaline solution.56
In view of a better understanding of the chiroptical properties
of “chirally perturbed” dipyrrin chromophores, a systematic
study of a series of structurally more simple derivatives than
the urobilins would be suitable. Thus, the present work deals
with such a study of dipyrrin difluoroboryl chelates, in which
the symmetry-breaking moiety is a phenyl ring bearing a chiral
substituent at the ortho position. As a chiral substituent on the
phenyl ring, which is attached either at the meso-C-atom
(compounds 9a and 9b) or at both R-positions of the dipyrrin
chromophore (compound 15), the (trifluoromethyl)methoxy-
methyl group was chosen because of its firmly established
dissymmetrizing effect.57
Figure 1. Both light absorption and fluorescence emission of urobilinoid
BF3 complexes are strongly circular polarized.
BODIPY fluorophores46 and their use in enantiomeric discrimi-
nation50 have been reported.
Within the scope of our work on the optical activity of
urobilins (a class of bile pigments, which possess the dipyrrin
chromophore), some chiral difluoroboron complexes were
synthesized which display an extremely high circular polariza-
tion of both light absorption and photoluminescence (Figure 1).51
The latter property could be of particular interest for the analysis
of enantiomeric mixtures as it enables the characterization of a
particular chromophore not only by the wavelength of emitted
light but also by the sign of its Cotton effect. Moreover, chiral
fluorophores emitting circular polarized light have practical use
within different sensor systems52 and in light-emitting diodes
(LED)53 as well.
In fact, the high optical dissymmetry of the dipyrrin chro-
mophore which has been observed in urobilin difluoroboryl
complexes is surprising because the chromophore in such metal
chelates is planar, as it was proved in our own work by X-ray
diffraction analysis. A possible explanation for this phenomenon
could be that the origin of the circular polarization of these
compounds is a “chiral perturbation” of the inherently achiral
boron complexing dipyrrin chromophore rather than an inherent
dissymmetric chromophore, as suggested by Moscowitz et al.
Experimental Results
BODIPY Fluorophores with a Chiral Substituent at the
meso-Position. The synthesis of the dipyrrin difluoroboryl
chelates 9a and 9b was carried out following the conventional
route by condensation of ethyl58,59 or benzyl60 3,4-dimethylpyr-
role-2-carboxylate with 2-(2,2,2-trifluoro-1-methoxyethyl) benz-
aldehyde (6) to yield dipyrrylmethanes 7a and 7b, respectively
(cf. ref 61), which were subsequently oxidized with 3,5-dichloro-
2,6-dicyano-p-benzoquinone (DDQ) to the corresponding dipyr-
rin derivatives 8a and 8b, respectively, a procedure which has
been reported to be particularly suitable for the synthesis of
5-aryldipyrrins.62 Subsequent chelation of 8a/b with boron
trifluoride etherate63 afforded the desired fluorophores 9a/b (cf.
Scheme 1).
Optically active 6 was synthesized in six conventional steps
starting with the known65 ethylene acetal of o-bromobenzalde-
hyde. Resolution of racemic 2-[2-(2,2,2-trifluoro-1-hydroxy-
ethyl)phenyl]dioxolane (3) was carried out by fractional crys-
tallization of the corresponding ester of (-)-ω-camphanic acid
according to the procedure reported by Jurczak et al. for the
resolution of 2,2,2-trifluoro-1-phenylethanol.66 The thus obtained
pure diastereomer (+)-4 (ee: >98% as determined by 1H NMR
spectroscopy) yielded, on recrystallization from diethyl ether,
crystals in a suitable quality for X-ray diffraction analysis, which
enabled one to establish the relative configuration of all
asymmetric C-atoms present in the molecule (cf. Figure 2).
Because the absolute configuration of (-)-ω-camphanic acid
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9
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A R T I C L E S
Gossauer et al.
Scheme 1 a
a (a) C4H9Li in THF, then F3C-CO2C2H5 (cf. ref 64); (b) NaBH4 in H3COH; (c) (-)-camphanic acid chloride in pyridine, then fractional crystallization;
(d) NaOH in methanol; (e) AgO2/ICH3; (f) HCl in THF; (g) BF3‚O(C2H5)2 in CH2Cl2; (h) DDQ in CH2Cl2; (i) BF3‚O(C2H5)2/diisopropylamine in CH2Cl2.
BODIPY Fluorophores with Chiral Substituents at the
r-Positions. Although a straightforward synthesis of 1,5,9-
triaryldipyrrins as ligands for BODIPY dyes has been reported
recently,6 a synthesis using aldehyde 6, as a starting material,
seemed to be more appropriate for our purpose because its
absolute configuration had been unequivocally established as
described above. Thus, optically active 6 was reacted with the
Grignard derivative of 2-(2-bromoethyl)-1,3-dioxolane according
to the procedure given in ref 69 to yield carbinol 10, as a mixture
of epimers, which, on oxidation, was transformed into a single
enantiomer of ketone 11. Deprotection of the aldehyde group
of 11 and subsequent reaction with ammonium acetate according
to the conditions of Paal-Knorr’s synthesis of pyrroles (cf. ref
70) yielded the R-arylpyrrole 12, which on reaction with
bezaldehyde was transformed into dipyrrylmethane 13. As
before, the latter was subsequently oxidized with DDQ to the
corresponding dipyrrin derivative 14, which was reacted with
boron trifluoride etherate to yield the desired BF2 complex 15
(cf. Scheme 2).
Figure 2. Molecular structure of (+)-2-[2-(2,2,2-trifluoro-1-hydroxyethyl)-
phenyl] dioxolane camphanoate ((+)-4) as obtained from X-ray diffraction
analysis.
has been unequivocally determined to be 1S,4R,67 the (S)-
configuration must be assigned to the chiral phenyl substituent
in the dextrorotatory ester 4. Alkaline hydrolysis of the latter
yielded optically active dioxolane (S)-3, which was transformed
into the corresponding methyl ether 5 to avoid intramolecular
nucleophilic addition of the hydroxy group to the aldehyde group
after deprotection of the latter. On tratement with acid, 5 was
transformed into the desired o-[(2,2,2-trifluoro-1-methoxy)ethyl]
benzaldehyde (6). Like the corresponding methyl ether of (S)-
2,2,2-trifluoro-1-phenylethanol,68 the (S)-enantiomer of 6 is
Discussion
The magnitude of the Cotton effect in the optically active
dipyrrin difluoroboryl chelates 9a and 9b described in the
present work is considerably lower than that in the case of the
urobilin derivatives previously decribed51 (cf. Figures 3 and 4).
(68) Peters, H. M.; Feigl, D. M.; Mosher, H. S. J. Org. Chem. 1968, 33, 4245-
4250.
dextrorotatory ([R]20 ) +128.8°).
D
(69) Khanna, I. K.; Weier, R. M.; Yu, Y.; Collins, P. W.; Miyashiro, J. M.;
Koboldt, C. M.; Veenhuizen, A. W.; Currie, J. M.; Seibert, K.; Isakson, P.
C. J. Med. Chem. 1997, 40, 1619-1633.
(67) Metzenthin, T.; Schreiber, A.; McMullan, R. K.; Koetzle, T. F.; Mosher,
H. S.; Bau, R. J. Org. Chem. 1997, 62, 5017-5022.
(70) Lucchesini, F. Tetrahedron 1992, 48, 9951-9966.
9
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Two New Dipyrrin Difluoroboryl Chelates
A R T I C L E S
Scheme 2 a
a (a) 1,3-Dioxolan-1-yl-(CH2)2BrMg in THF; (b) PCC in CH2Cl2; (c) AcONH4 in AcOH; (d) C6H5CHO in CH2Cl2; (e) DDQ in CH2Cl2; (f) BF3‚O(C2H5)2/
Et3N in CH2Cl2.
Figure 5. Molecular structure of 9a as obtained from X-ray diffraction
analysis.
Figure 3. CD spectra of 8a (s), its conjugated acid (‚ ‚ ‚), and the
corresponding difluoroboryl chelate 9a (- - -), all in CH2Cl2.
Figure 6. CD spectra of 14 (s), its conjugated acid (‚ ‚ ‚), and the
corresponding difluoroboryl chelate 15 (- - -), all in CH2Cl2.
the meso (C5)-position seems to be less important than that of
the asymmetric centers C4 and C16 in urobilin derivatives. On
Figure 4. CD spectra of 8b (s), its conjugated acid (‚ ‚ ‚), and the
the other hand, difluoroboryl complex 15 (Figure 6), in which
the perturbing chiral centers are located - like in the urobilins
- at the ends of the chromophore, displays a Cotton effect of
a magnitude comparable to that of the difluoroboryl chelate of
mesourobilin IIIR-8,12-despropionic acid, although its specific
corresponding difluoroboryl chelate 9b (- - -), all in CH2Cl2.
As expected, the X-ray diffraction analysis of the boron
chelate 9b confirms that the corresponding dipyrrin chromophore
is planar (cf. Figure 5). Therefore, the “chiral perturbation”
introduced by the asymmetric substituent on the phenyl ring at
rotation ([R]20 ) +720° vs -2940°) is less spectacular.
D
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J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004 1775

A R T I C L E S
Gossauer et al.
the meso-position of the dipyrrin molecule. This is in agreement
with Moscowitz’s interpretation of the optical activity of
urobilinoids. It is noteworthy, however, that in the case of
compound 14 both the free base and its conjugated acid display
CD curves of the same sign, whereas the corresponding
difluoroboryl chelate shows an opposite Cotton effect.
Unfortunately, in the urobilin series neither the structure of
the free bases nor that of their corresponding conjugated acids
has been proven, until now, by X-ray diffraction analysis, so
that a comparison with the results obtained in the present work
relies on the assumption that the structures of their chromophores
in basic and acidic medium, respectively, resemble those of more
simple substituted dipyrrins. As a matter of fact, the structures
depicted in Figures 7-9 are, to the best of our knowledge, the
first crystal structures of dipyrrin free bases (9a/b) and of a
dipyrrin salt (Figure 9), which have been obtained by X-ray
diffraction analysis.
Figure 7. Molecular structure of 8a as obtained from X-ray diffraction
analysis.
From the present work, it must be concluded that both a
“chiral perturbation” of an inherently planar dipyrrin chro-
mophore and a twisting deformation of the latter may give rise
to high optical activity of the corresponding derivatives.
However, to understand the relationship between the structural
and optical dissymmetry of this class of compounds, a larger
number of compounds of unequivocally determined structure
is necessary. Therefore, the syntheses of further dipyrrin
difluoroboryl chelates analogous to 9a/b and 14 bearing more
efficient chiral substituents on the phenyl rings are currently in
progress.
Figure 8. Molecular structure of 8b as obtained from X-ray diffraction
analysis.
Experimental Section
Materials. Solvents for chemical reactions and chromatography were
generally dried and distilled prior to use. All air- and water-sensitive
reactions were carried out under Ar. Reactions were monitored by thin-
layer chromatography (TLC) on Merck silica gel 60 F254 (0.2 mm)
precoated aluminum foils. Column chromatography (CC) and flash
chromatography (FC) were done on silica gel 60 (0.063-0.200 mm,
700-230 mesh) and silica gel 60 (0.040-0.063 mm, 230-400 mesh),
respectively, from E. Merck AG. Dimethylformamide (DMF), trifluo-
roacetic acid (TFA), tetrahydrofuran (THF), 2,3-dichloro-5,6-dicyano-
p-benzoquinone (DDQ), and other reagents were purchased from Fluka
Chemie AG (CH-9471 Buchs, Switzerland).
Instruments. Melting points (mp) were determined with a hot stage
apparatus (Thermovar, C. Reichert AG, Vienna) equipped with a digital
thermometer. UV/vis spectra were recorded in CH2Cl2 on a Hewlett-
Packard 8452A diode-array or a Perkin-Elmer Lambda 40 spectrometer;
λmax (log ꢀ) in nm. Specific optical rotations ([R]20D) were measured
on a Perkin-Elmer 241-MC polarimeter, and CD spectra were measured
in a CD spectropolarimeter Jasco J-715. Wavelengths (λ) and band
amplitudes (∆ꢀmax) are quoted in nm and L mol-1 cm-1, respectively.
Quantum yields of fluorescence (Φ) were measured, relative to
rhodamine 6G (Φ ) 0.88 in ethanol), as standard, on a Perkin-Elmer
MPF-4 fluorescence spectrophotometer. NMR (in CDCl3): Bruker
Figure 9. Molecular structure of 8a perchlorate as obtained from X-ray
diffraction analysis.
Also, the corresponding ligands (8a/b and 14) display weak
Cotton effects (cf. Figures 3, 4, and 6, respectively). According
to the X-ray diffraction analysis of 8a and 8b (cf. Figures 7
and 8, respectively), their molecules are essentially planar in
the solid state. In acidic solution, however, the protonated
dipyrrin chromophores of 8a and 8b show strong Cotton effects,
which are of sign opposite to those of the corresponding free
bases and difluoroboryl chelates (cf. Figures 3 and 4). The
1
Avance DRX 500 (1H, 500.13 MHz; 13C, 125.76 MHz); H and 13C
chemical shifts (δ) are given in ppm relative to Me4Si as internal
standard, J values in Hz. Assignments are based on homonuclear
COSY-45, 1H{1H} NOE difference correlations, and/or chemical shifts.
13C signal multiplicities were determined by attached proton test (APT)
experiments. Mass spectra: EI-MS (electron ionization, 70 eV) and
ESI-MS (electrospray ionization, positive mode) were measured on HP
5988 A and Bruker 4.7T BioAPEX II instruments, respectively.
Combustion analyses were carried out by Ilse Beetz, Microanalytical
Laboratory, Kronach (Germany).
highest specific rotation ([R]20 ) -4892°) was found for
D
compound 8a; it corresponds to the values measured in the
urobilin series for N-protonated species. As revealed by X-ray
diffraction analysis, the conjugated acid of 8a is, at least in the
solid state, markedly twisted clockwise (cf. Figure 9), so that
evidently the high rotational strength of the inherent dissym-
metric chromophore, which is actually opposite to that of (P)-
helicene, is superimposed to that of the chiral substituent on
9
1776 J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004

Two New Dipyrrin Difluoroboryl Chelates
A R T I C L E S
X-ray diffraction analyses were carried out, except for compound
(+)-4, at 153(2) K on a Stoe Image Plate Diffraction System71 equipped
with a two-circle goniometer using Mo KR (λ ) 0.71073 Å) graphite-
monochromated radiation. Intensity data for (+)-4 were collected at
room temperature (293 K) on a Stoe AED2 four-circle diffractometer
using Cu KR graphite-monochromated radiation (λ ) 1.54186 Å). The
structures were solved by direct methods using the program SHELXS-
97.72 H-atoms were included in calculated positions and treated as riding
atoms using SHELXL default parameters. H-atoms bound to N were
located from difference Fourier maps and refined isotropically. F 2
refinements and all further calculations were carried out using SHELXL-
97.73 The non-H atoms were refined anisotropically, using weighted
full-matrix least-squares on F 2.
Crystal Data for (+)-4. C21H23F3O6, M ) 428.39, colorless plates
(0.53 × 0.38 × 0.13 mm). Crystal cell parameters were determined
from (ω values of 26 reflections and their equivalents in the range
10.60° <Θ < 23.15°: orthorhombic, P 21 21 21, a ) 6.3446(5) Å, b
) 11.1480(8) Å, c ) 28.869(2) Å, V ) 2041.9(3) Å3, Z ) 4; density
(calc.) ) 1.394 g cm-3; of 4035 measured reflections, 2852 were
independent and 2714 were observed with I > 2σ (I). R1 ) 0.0378,
wR2 ) 0.1001 for 364 parameters.
Crystal Data for 8a. C28H31F3N2O5, M ) 532.55, red rods (0.30 ×
0.20 × 0.20 mm). Crystal cell parameters were determined from (ω
values of 8000 reflections and their equivalents in the range 2.04° <
Θ < 25.96°: monoclinic, C2, a ) 24.694(2) Å, b ) 12.3509(7) Å, c
) 18.4241(14) Å, â ) 111.657(9)°, V ) 5222.6(7) Å3, Z ) 8; density
(calc.) ) 1.355 g cm-3; of 20 771 measured reflections, 9161 were
independent and 6915 were observed with I > 2σ (I). R1 ) 0.0345,
wR2 ) 0.0709 for 693 parameters. In the crystal, there are two
independent molecules per asymmetric unit which stack head-to-tail
and are almost parallel to each other with a separation of ca. 3.46(1)
Å.
Crystal Data for 8a Perchlorate. C28H32F3N2O5, ClO4, M ) 633.01,
red rods (0.50 × 0.07 × 0.07 mm). Crystal cell parameters were
determined from (ω values of 6667 reflections and their equivalents
in the range 1.59° < Θ < 24.95°: monoclinic, P 21, a ) 9.7201(14)
Å, b ) 11.7883(12) Å, c ) 12.7055(19) Å, R ) γ ) 90°, â ) 91.197-
(12)°, V ) 1455.5(3) Å3, Z ) 2; density (calc.) ) 1.444 g cm-3; of
10 183 measured reflections, 4619 were independent and 3155 were
observed with I > 2σ (I). R1 ) 0.0485, wR2 ) 0.0855 for 397
parameters.
being stirred for 15 min at about -70 °C, the mixture was transferred
to an addition funnel and added dropwise to a cooled (-78 °C) solution
of ethyl trifluoracetate (3.13 g, 22 mmol) in 50 mL of dry THF. The
mixture was then allowed to warm to room temperature, diluted with
water, and extracted with CH2Cl2. The organic layer was dried (Na2-
SO4), and the solvent was removed in a rotary evaporator to yield 4.05
g (82%) of crude product which was purified by CC (hexane/AcOEt
1
5:1): 3.76 g (76%) of colorless liquid 2. H NMR: 7.66, 7.59, 7.51,
7.48 (4 m, 4H), 6.22 (s, CH), 3.99 (m, CH2), 3.88 (m, CH2). 13C
NMR: 185.3 (q, JC,F ) 36, CdO), 138.6 (arom. C-(2)), 130.9 (arom.
C-(1)), 131.6, 128.5, 127.0, 126.9 (4 arom. CH), 115.6 (q, JC,F ) 291,
CF3), 100.8 (CH), 64.3 (2 CH2). EI-MS: 247 (54, M + 1), 246 (5,
M+), 203 (100), 186 (59), 182 (41), 177 (12), 155 (37), 151 (14), 149
(8), 133 (85), 105 (44), 77 (48). ESI-MS (exact mass): 247.0572 ([M
+ H]+, calc. for C11H10F3O3+: 247.0576).
1-[2-(1,3-Dioxolan-2-yl)phenyl]-2,2,2-trifluoro-1-ethanol (3). A
solution of 2 (3.5 g, 14.2 mmol) in dry MeOH (50 mL) was cooled to
10 °C, and NaBH4 (0.53 g, 14 mmol) was added portionwise over 10
min. The mixture was stirred for 1 h at room temperature, poured into
water (500 mL), and extracted with Et2O. The combined organic layer
was washed (brine), dried over MgSO4, and evaporated: 3.44 g (97%)
of colorless highly viscous oil rac-3. 1H NMR: 7.67-7.60 (m, 2 arom.
H), 7.47-7.39 (m, 2 arom. H), 6.02 (s, CH), 5.57 (dq, J ) 4.8, 6.9,
CH), 4.19-4.01 (m, 4H, CH2CH2), 3.32 (d, J ) 4.8, OH). 13C NMR:
135.8 (arom. C-(2)), 133.2 (arom. C-(1)), 129.6, 129.3, 128.1, 126.8
(4 arom. CH), 124.5 (q, JC,F ) 282, CF3), 101.8 (CH), 68.8 (q, JC,F )
32, CHCF3), 65.2, 65.1 (2 CH2). EI-MS: 248 (2, M+), 247 (12, M -
1), 230 (42), 203 (4), 167 (6), 155 (8), 149 (26), 133 (11), 105 (16),
73 (100). ESI-MS (exact mass): 271.0554 ([M + Na]+, calc. for
C11H11F3O3Na+: 271.0553).
(1S)-1-[2-(1,3-Dioxolan-2-yl)phenyl]-2,2,2-trifluoroethyl 4,7,7-tri-
methyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate (4). To a
solution of rac-3 (3.4 g, 13.7 mmol) in dry pyridine (30 mL) was added
(-)-camphanic acid chloride (3.4 g, 15.7 mmol) at 5 °C. The mixture
was stirred overnight at room temperature, then diluted with water (100
mL), and finally extracted with CH2Cl2. The combined extract was
washed with water, dried over MgSO4, and evaporated. The residue of
crude ester (5.7 g, 97%) was dissolved in ether (100 mL), and the
solution was cooled overnight at -15 °C. The resulting crystalline
fraction was recrystallized twice from an n-hexane/ether mixture: 2.2
g of pure (S)-4. Crystals suitable for X-ray analysis were grown from
a solution of Et2O by slow evaporation. Mp 136-137 °C. [R]20
)
Crystal Data for 8b. C38H35F3N2O5, M ) 656.68, red blocks (0.35
× 0.25 × 0.15 mm). Crystal cell parameters were determined from
(ω values of 3227 reflections and their equivalents in the range 2.17°
< Θ < 25.98°: triclinic, P1, a ) 11.2174(13) Å, b ) 12.3780(14) Å,
c ) 12.8428(14) Å, R ) 74.290(13)°, â ) 72.683(13)°, γ ) 84.530-
(14)°, V ) 1638.6(3) Å3, Z ) 2; density (calc.) ) 1.331 g cm-3; of
13 057 measured reflections, 10 792 were independent and 2775 were
observed with I > 2σ (I). R1 ) 0.0459, wR2 ) 0.0767 for 865
parameters.
D
1
1
+8.5° (c ) 3.45, CH2Cl2). ee: >98% (determined by H NMR). H
NMR: 7.63 (m, 2 arom. H), 7.46 (m, 1 arom. H), 7.43 (m, 1 arom. H),
7.03 (q, J ) 6.6, CH), 6.09 (s, CH), 4.23-4.03 (m, 4H, CH2CH2),
2.43 (m, 1H), 2.05 (m, 1H), 1.95 (m, 1H), 1.70 (m, 1H), 1.12 (s, CH3),
1.09 (s, CH3), 0.91 (s, CH3). 13C NMR: 178.0 (CdO), 165.8 (CdO),
137.4 (arom. C-(2)), 129.5 (arom. C-(1)), 130.5, 129.8, 128.9, 127.7
(4 arom. CH), 123.6 (q, JC,F ) 282, CF3), 102.2 (CH), 91.01 (C(1′)),
68.5 (q, JC,F ) 34, CHCF3), 65.6, 65.5 (2 CH2), 55.2, 55.0 (C(4′), C(7′)),
31.0, 29.3 (C(5′), C(6′)), 17.0, 16.8 (2 H3C-C(7′), 10.0 (H3C-C(4′)).
ESI-MS (exact mass): 451.1339 ([M + Na]+, calc. for C21H23F3O6-
Na+: 451.1339).
Crystal Data for 9b. C38H34BF5N2O5, M ) 704.48, red blocks (0.30
× 0.25 × 0.25 mm). Crystal cell parameters were determined from
(ω values of 8000 reflections and their equivalents in the range 1.91°
< Θ < 25.93°: triclinic, P-1 (No. 2), a ) 12.5290(8) Å, b ) 14.5853-
(10) Å, c ) 20.0347(14) Å, R ) 77.050(8)°, â ) 81.031(8)°, γ )
(1S)-1-[2-(1,3-Dioxolan-2-yl)phenyl]-2,2,2-trifluoro-1-ethanol ((S)-
3). To a solution of 4 (2.1 g, 4.9 mmol) in MeOH (5 mL) was added
10% aqueous NaOH solution (25 mL). The mixture was refluxed for
2 h, then diluted with water (100 mL), and extracted with Et2O. The
combined extract was washed (brine), dried over MgSO4, and evapo-
73.014(8)°, V ) 3396.3(4) Å3, Z ) 4; density (calc.) ) 1.378 g cm-3
;
of 26 913 measured reflections, 12 336 were independent and 4725
were observed with I > 2σ (I). R1 ) 0.0794, wR2 ) 0.1865 for 945
parameters.
1-[2-(1,3-Dioxolan-2-yl)phenyl]-2,2,2-trifluoro-1-ethanone (2). A
solution of 165 (4.6 g, 20 mmol) in dry THF (100 mL) was cooled to
-78 °C under Ar, and 14 mL of 1.6 M n-buthyllithium in hexane was
added dropwise. A white precipitate separated during the addition. After
rated: 1.16 g (95%) of colorless highly viscous oil (S)-3. [R]20
+33.1° (c ) 3.75, CH2Cl2). ee: >98% (determined by H NMR in
R(-)-1-(9-anthryl)-2,2,2-trifluoroethanol as chiral additive).
)
D
1
2-{2-[(1S)-2,2,2-Trifluoro-1-methoxyethyl]phenyl}-1,3-dioxo-
lane (5). To a solution of (S)-3 (1.1 g, 4.4 mmol) in CH3I (8 mL) was
added silver oxide (2.1 g). The mixture was refluxed for 3 h, then diluted
with Et2O (50 mL), and filtered. The solid was extracted with three
20-mL portions of Et2O. The combined organic solutions were
(71) IPDS Software 2000, Stoe & Cie. GmbH, Darmstadt, Germany.
(72) Sheldrick, G. M. Acta Crystallogr. 1990, A46, 467-473.
(73) Sheldrick, G. M. SHELXL-97; Universita¨t Go¨ttingen, Germany.
9
J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004 1777

A R T I C L E S
Gossauer et al.
evaporated, and the yellow residue was distilled in a Kugelrohr
Diethyl (S)-5-{2-[2,2,2-Trifluoro-1-methoxyethyl)phenyl]-2,3,7,8-
tetramethyl-10H-dipyrrin-1,9-dicarboxylate (8a). To a solution of
7a (900 mg, 1.68 mmol) in benzene (10 mL) was added DDQ (386
mg, 1.7 mmol) in CH2Cl2 (20 mL). The mixture was stirred for 3 h at
room temperature. The reaction mixture was evaporated to dryness,
and the residue was purified by FC (n-hexane/AcOEt, 4:1) to yield
655 mg (73%) of 8a, as a dark-red solid, which was recrystallized from
n-hexane. Mp 139.5-141.5 °C. Crystals suitable for X-ray analysis
were grown from a solution of n-hexane by slow evaporation of the
solvent. UV/vis (CH2Cl2): 470 (4.35). UV/vis (CH2Cl2 + HCl): 399
(4.08), 534 (4.80). CD (3.92 × 10-5 M, CH2Cl2): 489 (+3.4). CD
apparatus (120 °C, 0.05 mbar): 1.05 g (90%) of colorless liquid. (S)-
1
5. [R]20 ) +84.6° (c ) 4.61, CH2Cl2). H NMR: 7.67-7.59 (m, 2
D
arom. H), 7.48-7.38 (m, 2 arom. H), 6.00 (s, CH); 5.26 (q, J ) 6.6,
CH), 4.20-4.00 (m, 4H, CH2CH2), 3.38 (s, OCH3). 13C NMR: 137.5
(arom. C-(2)), 131.8 (arom. C-(1)), 129.8, 129.7, 128.7, 126.8 (4 arom.
CH), 124.4 (q, JC,F ) 282, CF3), 101.9 (CH), 76.6 (q, JC,F ) 31,
CHCF3), 65.6, 65.4 (2 CH2), 58.1 (CH3). EI-MS: 262 (4, M+), 261
(15, M - 1), 247 (7), 230 (100), 217 (13), 203 (23), 193 (8), 187 (23),
167 (12), 155 (19), 149 (28), 133 (40), 121 (23), 119 (19), 109 (26),
105 (16), 91 (26), 73 (66), 45 (69). ESI-MS (exact mass): 285.0708
([M + Na]+, calc. for C12H13F3O3Na+: 285.0709).
(1.96 × 10-5 M, CH2Cl2 + HCl): 534 (-21). [R]20 ) +471° (c )
D
1.79 × 10-2, CH2Cl2). [R]20D ) - 4892° (c ) 1.79 × 10-3, CH2Cl2 +
2-[(1S)-2,2,2-Trifluoro-1-methoxyethyl]benzaldehyde (6). To a
solution of (S)-5 (1.0 g, 3.8 mmol) in THF/H2O (2:1) (25 mL) were
added five drops of concentrated HCl (35%). The mixture was stirred
overnight at room temperature, then diluted with water (300 mL), and
finally extracted with Et2O. The combined extract was washed with
10% NaHCO3 solution and brine, dried (MgSO4), and evaporated: 0.80
1
HCl). H NMR: 13.29 (br. s, NH), 7.75 (br. d, J ) 8.0, 1 arom. H),
7.57 (td, J ) 7.6, 1.5, 1 arom. H), 7.50 (td, J ) 7.6, 1.4, 1 arom. H),
7.31 (ddd, J ) 7.8, 1.4, 0.5, 1 arom. H), 4.52 (q, J ) 6.6, CH), 4.42
(q, J ) 7.1, 2 CH2), 3.24 (s, OCH3), 2.15 (d, J ) 0.5, CH3), 2.12 (d,
J ) 0.5, CH3), 1.46, 1.45 (2t, J ) 7.1, 2 CH3), 1.20, 1.21 (2s, 2 CH3).
13C NMR: 163.04, 162.69 (2 CO), 146.30, 141.86, 141.75, 140.94,
139.55, 138.56, 137.31, 136.86, 133.234, 13214, 131.10, (11 quarternary
g (96%) of colorless liquid. (S)-6. [R]20 ) +128.8° (c ) 6.46, CH2-
D
1
Cl2). H NMR: 10.1 (s, CHO), 7.87, 7.81, 7.68, 7.63 (4 m, 4 arom.
C), 130.34, 130.10, 129.94, 129.47 (4 arom. CH), 125.06 (q, JC,F
)
H), 6.00 (q, J ) 6.4, CH), 3.46 (s, OCH3). 13C NMR: 193.4 (CHO),
135.0 (arom. C-(2)), 134.6 (arom. C-(1)), 134.9, 134.2, 130.0, 129.5
(4 arom. CH), 124.1 (q, JC,F ) 282, CF3), 76.0 (q, JC,F ) 31, CHCF3),
59.0 (OCH3). EI-MS: 218 (4, M+), 203 (55), 198 (100), 186 (73), 183
(53), 158 (58), 155 (76), 149 (25), 138 (22), 133 (96), 127 (73), 119
(57), 109 (62), 105 (54), 91 (71), 89 (40), 77 (63), 69 (26), 63 (42), 51
(60). ESI-MS (exact mass): 241.0446 ([M + Na]+, calc. for C10H9F3O2-
Na+: 241.0447).
285, CF3), 78.15 (q, JC,F ) 31, CHCF3), 61.39, 61.31 (2 CH2), 60.70
(OCH3), 14.87, 14.86, 12.30, 11.44, 10.86, 10.72 (6 CH3). ESI-MS
(exact mass): 533.2261 ([M + H]+, calc. for C28H32F3N2O5+: 533.2258).
A sample (25 mg) of 8a, dissolved in CH2Cl2 (50 mL), was transformed
into the corresponding perchlorate by shaking the solution with 15%
aqueous HClO4. The organic layer was dried over Na2SO4, and the
residue obtained after evaporation of the solvent was dissolved in 1
mL of CH2Cl2, pentane was added (5 mL), and the solution was cooled
overnight at 0-5 °C. Crystals suitable for X-ray analysis were obtained
by recrystallization from CH2Cl2/n-pentane. Mp 207-210 °C (dec).
Anal. Calcd for C28H32ClF3N2O9 (633.01): C, 53.12; H, 5.10; N, 4.43.
Found: C, 53.30; H, 5.03; N, 4.42.
Diethyl (S)-5-{2-[2,2,2-Trifluoro-1-methoxyethyl)phenyl]-5,11-
dihydro-2,3,7,8-tetramethyl-10H-dipyrrin-1,9-dicarboxylate (7a).
Freshly distilled BF3‚OEt2 (100 µL, 0.8 mmol) was added under Ar to
a mixture of 420 mg (1.92 mmol) of (S)-6 and 700 mg (4.18 mmol) of
ethyl 3,4-dimethylpyrrol-2-carboxylate58 in dry CH2Cl2 (5 mL). The
solution was stirred for 12 h at room temperature, diluted with CH2Cl2
(200 mL), washed with aqueous 10% NaHCO3 solution and water, dried
Dibenzyl (S)-5-{2-[2,2,2-trifluoro-1-methoxyethyl)phenyl]-2,3,7,8-
tetramethyl-10H-dipyrrin-1,9-dicarboxylate (8b) was synthesized by
the same procedure as described for 8a starting with 350 mg (0.53
mmol) of 7b. After purification by FC (CH2Cl2), 235 mg (67%) of 8b
was obtained, as a dark-red solid, which was recrystallized from CHCl3/
n-hexane. Mp 140-141 °C. UV/vis (CH2Cl2): 472 (4.32). UV/vis (CH2-
Cl2 + HCl): 402 (4.09), 536 (4.81). CD (5.74 × 10-5 M, CH2Cl2):
(MgSO4), and evaporated. The residue was purified by FC (CH2Cl2):
1
925 mg (90%) of (S)-7a. [R]20 ) -170.0° (c ) 1.00, CH2Cl2). H
D
NMR: 8.18 (s, NH), 8.01 (s, NH), 7.61 (d, J ) 7.6, 1H, arom. H),
7.38 (td, J ) 7.5, 1.4, 1 arom. H), 7.34 (td, J ) 7.5, 1.4, 1H, arom. H),
6.84 (dd, J ) 7.8, 1.4, 1H, arom. H), 5.69 (s, CH), 4.58 (q, J ) 6.4,
CH), 4.33-4.16 (m, 2 × CH2), 2.84 (s, OCH3), 2.27, 2.26, 1.86, 1.72
(4s, 4 × CH3), 1.34, 1.30 (2t, J ) 7.1, 2 × CH3). 13C NMR: 162.35,
162.00 (2 CO), 139.21, 131.65, 130.95, 130.38, 128.29, 128.20, 119.15,
118.92, 118.70, 118.48 (10 arom. C), 130.67, 129.29, 128.82, 128.69
(4 arom. CH), 124.44 (q, JC,F ) 282, CF3), 76.82 (q, JC,F ) 31, CHCF3),
60.54, 60.43 (2 × CH2), 58.00 (OCH3), 37.86 (CH), 15.01, 14.91, 11.19,
11.07, 9.03, 8.87 (6 × CH3). ESI-MS (exact mass): 535.2417 ([M +
H]+, calc. for C28H34F3N2O5+: 535.2414).
488 (+4.6). CD (1.28 × 10-5 M, CH2Cl2 + HCl): 535 (-22). [R]20
D
) +520° (c ) 4.22 × 10-3, CH2Cl2). [R]20 ) -4330° (c ) 5.75 ×
D
1
10-3, CH2Cl2 + HCl). H NMR: 13.37 (s, NH), 7.75 (br. d, J ) 7.9,
1 arom. H), 7.57 (td, J ) 7.5, 1.4, 1 arom. H), 7.50 (td, J ) 7.5, 1.3,
1 arom. H), 7.46 (m, 4 arom. H), 7.38-7.28 (m, 7 arom. H), 5.33,
5.27 (2d, J ) 12.6, CH2), 5.32, 5.26 (2d, J ) 12.6, CH2), 4.51 (q, J )
6.5, CH), 3.24 (s, OCH3), 2.14, 2.12, 1.20, 1.19 (4s, 4 CH3). 13C NMR:
162.34, 161.96 (2 × CO), 145.74, 141.69, 141.37, 140.15, 139.10,
138.28, 136.78, 136.36, 136.13, 136.11, 132.77, 131.88, 130.83 (13
quarternary C), 129.90, 129.65, 129.50, 129.01 (4 arom. CH), 128.53
(2 arom. CH), 128.52 (2 arom. CH), 128.08 (2 arom. CH), 128.05 (2
arom. CH), 128.00 (2 arom. CH), 124.58 (q, JC,F ) 285, CF3), 77.69
(q, JC,F ) 31, CHCF3), 66.31, 66.24 (2 CH2), 60.25 (OCH3), 11.83,
10.97, 10.46, 10.32 (4 CH3). ESI-MS (exact mass): 657.2573 ([M +
H]+, calc. for C38H36F3N2O5+: 657.2570).
Dibenzyl (S)-5-{2-[2,2,2-trifluoro-1-methoxyethyl)phenyl]-5,11-
dihydro-2,3,7,8-tetramethyl-10H-dipyrrin-1,9-dicarboxylate (7b) was
synthesized by the same procedure as described for 7a starting with
240 mg (1.1 mmol) of (S)-6 and 520 mg (2.26 mmol) of benzyl 3,4-
dimethylpyrrol-2-carboxylate.59 After the mixture was stirred for 7 h
at room temperature, the yield of pure 7b amounted to 435 mg (60%).
1
[R]20 ) -150.9° (c ) 3.20, CH2Cl2). H NMR: 8.17 (s, NH), 7.99
D
Diethyl (S)-8-[2-(2,2,2-Trifluoro-1-methoxyethyl)phenyl]-1,2,6,7-
tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-3,5-dicar-
boxylate (9a). A solution of 8a (53.3 mg, 0.10 mmol) in dry CH2Cl2
(5 mL) was cooled under Ar to 0 °C before 0.2 mL of N,N-
diisopropylethylamine was added. After 2 min of stirring, freshly
distilled BF3‚OEt2 (1 mL) was added dropwise, during 2 min. After 20
min, the same portions of N,N-diisopropylethylamine and BF3‚OEt2
were added likewise, and, thereafter, the pink-red strongly fluorescent
mixture was stirred for 30 min at 0 °C before it was diluted with CH2-
Cl2 (80 mL), washed with H2O (2 × 50 mL), dried (MgSO4), and
evaporated. The residue was purified by two successive FC (AcOEt/
(s, NH), 7.60 (d, J ) 7.7, 1 arom. H), 7.44-7.27 (m, 12 arom. H),
6.83 (d, J ) 7.8, 1 arom. H), 5.68 (s, CH), 5.28, 5.27 (2d, J ) 12.6,
CH2), 5.28, 5.19 (2d, J ) 12.6, CH2), 4.56 (q, J ) 6.4, CH), 2.81 (s,
OCH3), 2.27, 2.26, 1.84, 1.70 (4s, 4 CH3). 13C NMR: 161.5, 161.2 (2
× CO), 138.5, 136.5, 136.2, 131.1, 130.8, 118.2, 118.3, 118.2, 117.9
(9 arom. C), 130.2, 128.9, 128.6, 128.5, 128.4, 128.2, 128.1, 128.0,
127.9, 127.8 (10 arom. CH), 123.9 (q, JC,F ) 282, CF3), 76.4 (q, JC,F
) 31, CHCF3), 65.8, 65.7 (2 CH2), 57.5 (OCH3), 37.5 (CH), 10.8, 10.7,
8.6, 8.4 (4 CH3). ESI-MS (exact mass): 659.2724 ([M + H]+, calc.
for C38H38F3N2O5+: 659.2727).
9
1778 J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004

Two New Dipyrrin Difluoroboryl Chelates
A R T I C L E S
hexane 1:1), to yield 44 mg (77%) of the BF2 chelate of 9a, as a dark-
red solid, which was recrystallized from n-hexane. Mp 143-145 °C.
UV/vis (CH2Cl2): 425 (3.99), 538 (4.62). Emission spectrum (CH2-
solvent was removed under reduced pressure. The residue was purified
by CC on silica gel using ethyl acetate:hexane (1:3) as eluant, to yield
646.2 mg (89%) of 11 as a colorless oil. Rf ) 0.37 (silica gel, ethyl
acetate:n-hexane 1:2); [R]20D ) 85.4° (c ) 11 mg/cm3 in CH2Cl2). 1H
NMR: δ 2.13 (m, 2H, CH2), 2.95 (ddd, J ) 17.8, 8.2, 6.3 Hz, 1H),
3.17 (ddd, J ) 17.8, 8.2, 6.6 Hz, 1H), 3.46 (s, 3H, CH3), 3.92 (m, 4H,
2 × CH2O), 4.99 (t, J ) 4.2 Hz, 1H), 5.72 (q, J ) 6.6 Hz, 1H), 7.47
(dt, J ) 7.7, 1.3 Hz, 1H), 7.57 (dt, J ) 7.5, 1.4 Hz, 1H), 7.74 (dd, J
) 7.8, 1.4 Hz, 1H), 7.79 (d, J ) 7.9 Hz, 1H). 13C NMR (125.77 MHz,
Cl2): λmax (exc.) 366; λmax (em) 567. Φ ) 0.93. CD (4.1 × 10-5 M,
1
CH2Cl2): 546 (+2.0). [R]20 ) +350° (c ) 1.1 × 10-5, CH2Cl2). H
D
NMR: 7.81 (br. d, J ) 7.9, 1 arom. H), 7.63 (td, J ) 7.6, 1.4, 1 arom.
H), 7.56 (td, J ) 7.5, 1.3, 1 arom. H), 7.244 (ddd, J ) 7.7, 1.5, 0.5, 1
arom. H), 4.53 (q, J ) 6.5, CH), 4.53-4.41 (m, 2 CH2), 3.34 (s, OCH3),
2.006 (d, J ) 0.4, CH3), 1.986 (d, J ) 0.4, CH3), 1.452, 1.448 (2t, J
) 7.1, 2 CH3), 1.30, 1.29 (2s, 2 CH3). 13C NMR: 162.59 (2 CO), 147.12,
145.62, 145.57, 143.53, 141.90, 134.84, 133.84, 132.95, 132.65, 130.32,
130.12 (11 quarternary C), 130.98, 130.79, 129.79, 128.70 (4 arom.
CH), 124.90 (q, JC,F ) 285, CF3), 78.37 (q, JC,F ) 31, CHCF3), 62.65,
62.55 (2 CH2), 61.01 (CH3), 14.48 (2 CH3), 12.63, 12.05, 10.04, 9.95
(4 CH3). ESI-MS (exact mass): 603.2066 ([M + Na]+, calc. for
C28H3011BF5N2O5Na+: 603.2060).
3
CDCl3): δ 27.8, 35.3, 58.6, 65.0, 75.4 (q, JC-F ) 30.7 Hz), 103.2,
124.0 (q, 1JC-F ) 282.6 Hz), 128.4, 128.8, 129.0, 131.7, 132.3, 139.0,
203.4. ESI-MS (exact mass): 341.0974 (M + Na+), calcd for
C15H17F3O4Na: 341.0971. Anal. Calcd for C15H17F3O4: C, 56.60; H,
5.38. Found: C, 56,65; H, 5.36.
(S)-2-[2-(2,2,2-Trifluoro-1-methoxyethyl)phenyl]-1H-pyrrole (12).
A mixture of 11 (231.7 mg, 0.73 mmol) and ammonium acetate (1.18
g, 15.29 mmol) in 30 mL of acetic acid was refluxed under Ar
atmosphere until no more ketone was detectable by TLC (12-16 h).
Thereafter, the mixture was cooled to room temperature, poured into
ice-water (200 mL), neutralized with solid NaHCO3, and extracted with
CH2Cl2 (3 × 50 mL). The combined organic layers were washed with
water (50 mL), dried (MgSO4), and after removal of the solvent the
residue was purified by CC on silica gel using diethyl ether:hexane
(1:10) as eluant to yield 129.2 mg (70%) of 12 as a yellowish oil which
was crystallized from pentane at ca. -100 °C to give 111.4 mg (60%)
of slightly yellow needles. Mp 51.2-52.3 °C. Rf ) 0.35 (diethyl ether:
hexane (1:3) on silica gel). [R]20D ) 138.6° (c ) 6.53 mg/cm3 in CH2-
Dibenzyl (S)-8-[2-(2,2,2-trifluoro-1-methoxyethyl)phenyl]-1,2,6,7-
tetramethyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-3,5-dicar-
boxylate (9b) was synthesized by the same procedure as described for
9a starting with 90 mg (0.137 mmol) of 8b. After purification by two
successive FC (AcOEt/hexane 4:5), 58.9 mg (61%) of 9b was obtained
as a dark-red solid, which was recrystallized from CHCl3/n-hexane.
Mp 127-128.5 °C. UV/vis (CH2Cl2): 424 (3.96), 540 (4.58). Emission
spectrum (CH2Cl2): λmax (exc.) 366; λmax (em) 571. Φ ) 0.86. CD
(6.00 × 10-5 M, CH2Cl2): 543 (+2.05). [R]20 ) +327° (c ) 1.2 ×
D
10-2 M, CH2Cl2). 1H NMR: 7.80 (br. d, J ) 7.9, 1 arom. H), 7.62 (td,
J ) 7.6, 1.4, 1 arom. H), 7.56 (td, J ) 7.5, 1.3, 1 arom. H), 7.51 (m,
4 arom. H), 7.38-7.28 (m, 6 arom. H), 7.23 (ddd, J ) 7.7, 1.5, 0.5, 1
arom. H), 5.451, 5.418 (2d, J ) 12.35, CH2), 5.447, 5.436 (2d, J )
12.26, CH2), 4.50 (q, J ) 6.4, CH), 3.32 (s, OCH3), 1.96 (d, J ) 0.5,
CH3), 1.94 (d, J ) 0.5, CH3), 1.29, 1.28 (2s, 2 CH3). 13C NMR: 161.89
(2 × CO), 146.28, 145.31, 144.70, 143.15, 141.50, 135.20, 135.09,
134.22, 133.49, 132.62, 132.13, 130.05, 129.82 (13 quat. C), 130.51,
130.30, 129.32 (3 arom. CH), 128.70 (4 arom. CH), 128.50 (2 arom.
CH), 128.49 (2 arom. CH), 128.35, 128.32, 128.13 (3 arom. CH),
124.38 (q, JC,F ) 285, CF3), 77.86 (q, JC,F ) 31, CHCF3), 67.97, 67.86
(2 CH2), 60.53 (OCH3), 12.12, 11.53, 9.64, 9.54 (4 CH3). ESI-MS (exact
mass): 727.2371 ([M + Na]+, calc. for C38H3411BF5N2O5Na+: 727.2373).
1
Cl2). H NMR: δ 3.25 (s, 3H, CH3), 4.97 (q, J ) 6.6 Hz, 1H), 6.27
(m, 1H), 6.33 (m, 1H), 6.92 (m, 1H), 7.42 (m, H-arom, 3H), 7.68 (m,
3
H-arom, 1H), 8.33 (br. s, NH, 1H). 13C NMR: δ 57.5, 77.4 (q, JC-F
1
) 27.4 Hz), 109.5, 109.7, 119.0, 124.3 (q, JC-F ) 282.2 Hz), 128.0,
128.3, 129.2, 129.3, 129.8, 130.8, 135.2. ESI-MS (exact mass):
256.0947 (M + H+), calcd for C13H13F3NO: 256.0943. Anal. Calcd
for C13H12F3NO: C, 61.17; H, 4.74; N, 5.49. Found: C, 61.23; H, 4.70;
N, 5.48.
(S,S)-1,9-Bis-[2-(2,2,2-trifluoro-1-methoxyethyl)phenyl]-5-phenyl-
10H-dipyrrin (14). Benzaldehyde (47 mg, 0.45 mmol) and 12 (84 mg,
0.33 mmol) were dissolved in 30 mL of CH2Cl2, and the solution was
degassed by bubbling Ar for 30 min. Two drops of TFA were added,
and the solution was stirred for 16 h at room temperature under Ar
atmosphere. Thereafter, DDQ (30 mg, 0.13 mmol) was added, and
stirring was continued for 2 h at room temperature. The reaction mixture
was diluted with 100 mL of CH2Cl2, washed with saturated aqueous
NaHCO3 solution and water, and dried over MgSO4. The residue
obtained after evaporation of the solvent under reduced pressure was
purified by CC on silica gel using ethyl acetate/n-hexane (1:10),
containing 0.5% triethylamine, as eluant to yield 68 mg (70%) of 14
as orange crystals. Mp 143-144 °C. Rf ) 0.47 (ethyl acetate/n-hexane
(1:3) on silica gel). UV/vis (c ) 1.15 × 10-5 M in CH2Cl2): 476 (4.56).
UV/vis (c ) 2.01 × 10-5 M in CH2Cl2 saturated with HCl): 393 (4.10),
562 (5.00). CD (3.69 × 10-5 M, CH2Cl2): 482 (-5.3). CD (1.48 ×
(S)-3-(1,3-Dioxolan-2-yl)-1-[2-(2,2,2-trifluoro-1-methoxyethyl)-
phenyl]propan-1-one (11). A solution of 605.8 mg (3.35 mmol) of
2-(2-bromoethyl)-1,3-dioxolane (Fluka Chemie GmbH) in dry THF (15
mL) was added dropwise during 2 h to 78.5 mg of Mg turnings under
Ar atmosphere at 28 °C. Thereafter, stirring was continued for 1 h at
the same temperature and the thus obtained Grignard reagent solution
was added dropwise during 20 min under stirring to an ice-cooled
solution of aldehyde 6 (603.4 mg, 2.77 mmol) in 8 mL of THF.
Thereon, stirring was continued for 2 h at 0 °C and then for 1 h at
room temperature. Finally, a saturated aqueous solution of ammonium
chloride (15 mL) was added, the organic layer was separated, and the
aqueous layer was extracted with ethyl ether (3 × 50 mL). The
combined organic layers were washed with 100 mL of brine, dried
over MgSO4, and the solvent was evaporated under reduced pressure.
By CC of the residue on silica gel using ethyl acetate:hexane (1:3) as
eluant, 29.3 mg of unreacted aldehyde 6 was retrieved, and a colorless
oil (732.6 mg, 87%) was obtained, consisting of a mixture of two
epimeric alkohols, which were transformed, without further purification,
into ketone 11.
10-5 M, CH2Cl2 + HCl): 566 (-9.0). [R]20 ) -391° (c ) 2.2 ×
D
1
10-2, CH2Cl2). H NMR: 12.58 (br. s, NH), 7.72-7.67 (m, 2 arom.
H), 7.63-7.58 (m, 2 arom. H), 7.56-7.41 (m, 9 arom. H), 6.72 (d, J
) 4.3, 2 CH), 6.55 (d, J ) 4.1, 2 CH), 5.42 (q, J ) 6.4, 2 CH), 3.12
(s, 2 OCH3). 13C NMR: 154.67, 142.68, 142.25, 137.95, 136.20, 131.95
(C), 131.79, 130.92, 130.70, 130.14, 129.97, 129.91, 129.26, 128.62,
120.39 (CH), 124.93 (q, JC,F ) 282, CF3), 77.47 (q, JC,F ) 31, CHCF3),
58.29 (OCH3). ESI-MS (exact mass): 597.1945 ([M + H]+, calc. for
C33H27F6N2O2+: 597.1971).
Thus, the mixture was dissolved in 15 mL of dry CH2Cl2 and the
solution was added dropwise to a suspension of pyridinium chloro-
chromate (986 mg, 4.57 mmol), sodium acetate (376 mg, 4.58 mmol),
and pyridine (362 mg, 4.58 mmol) in 15 mL of dry CH2Cl2 under Ar
atmosphere. The mixture was stirred for 90 min at room temperature
before a saturated aqueous solution of NaHCO3 was added until no
more CO2 was evolved. The heterogeneous mixture was filtered, and
the solid residue was washed on the filter with CH2Cl2 (40 mL). The
organic phase was separated from the filtrate, dried (MgSO4), and the
(S,S)-3,5-Bis-[2-(2,2,2-trifluoro-1-methoxyethyl)phenyl]-5-phenyl-
8-phenyl-4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (15). To a solu-
tion of 13 (30 mg, 5 × 10-5 mol) in 10 mL of 1,2-dichloroethane were
subsequently added triethylamine (0.2 mL, 1.44 mmol) and boron tri-
fluoride etherate (0.2 mL, 1.58 mmol); the resulting mixture was stirred
for 10 min at 25 °C, and then heated under reflux for 30 min. The
9
J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004 1779

A R T I C L E S
Gossauer et al.
fluorescent reaction mixture was filtered through basic alumina, and
the residue obtained after evaporation of the solvent was purified by
CC on silica gel using ethyl acetate/n-hexane (1:6) as eluant. Pure 15
(31 mg, 95%) was obtained by crystallization from ethyl acetate/n-
hexane (1:5) as orange crystals. Mp: 292-294 °C. Rf ) 0.43 (ethyl
acetate/n-hexane (1:3) on silica gel); [R]20D ) +720° (c ) 2.8 × 10-2
in CH2Cl2). UV/vis (CH2Cl2): 353 (4.29), 520 (4.87). CD (2.89 × 10-5
M in CH2Cl2): 518 (+12.4). Emission spectrum (CH2Cl2): λmax (exc.)
520; λmax (em.) 555. Φ ) 0.39. 1H NMR: 7.73-7.67 (m, 2 arom. H),
7.66-7.54 (m, 5 arom. H), 7.49-7.27 (m, 6 arom. H), 6.96 (br. d, J )
4.0, 2H), 6.44 (br. s, 2H), 4.64 (br. s, 2H), 3.32 (br. s, 2 OCH3). 13C
NMR: 156.84, 147.05, 135.99, 134.42, 134.21, 132.49 (C), 131.11,
131.08, 129.99, 128.85, 127.98 (CH), 124.50 (q, JC,F ) 282, CF3), 78.12
(q, JC,F ) 30, CHCF3), 58.38 (OCH3). ESI-MS (exact mass): 667.1775
([M + Na]+, calc. for C33H2511BF8N2O2Na+: 667.1774).
Acknowledgment. Financial support of this work by the
Swiss National Foundation (Project No. 2000-065091) is
gratefully acknowledged.
Supporting Information Available: Experimental spectra
(PDF) and crystallographic details (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
Full tables of atomic parameters and bond lengths and angles
from the X-ray diffraction analyses may be obtained from the
Cambridge Crystallographic Data Centre, U.K.
JA030542R
9
1780 J. AM. CHEM. SOC. VOL. 126, NO. 6, 2004