Synthesis and characterization of partially β-fluorinated 5,10,15,20-tetraphenylporphyrins and some derivatives

Article abstract of DOI:10.1016/S0040-4020(02)00677-4

The synthesis of partially β-fluorinated meso-tetraphenylporphyrins using Lindsey conditions, has been examined, starting either from 3,4-difluoro-1H-pyrrole or from 3-fluoro-1H-pyrrole. In the case of the first synthon, condensation with pyrrole and benzaldehyde afforded a mixture of porphyrins of general formula β-F_nTPP (n=0,2,4,6,8) displaying linearly correlated spectroscopic and electrochemical properties. With the second synthon, condensation with benzaldehyde produced an unresolvable mixture of β-tetrafluoroporphyrins presenting spectroscopic and electrochemical properties in coherence with those observed in the first case. Preliminarily, the synthesis and isolation of the hitherto unknown 3-fluoro-1H-pyrrole has been approached via several methods.

Full text of DOI:10.1016/S0040-4020(02)00677-4

Tetrahedron 58 (2002) 6713–6722
Synthesis and characterization of partially b-fluorinated
5
,10,15,20-tetraphenylporphyrins and some derivatives
a,*
b
Jacques Leroy, Emmanuel Porhiel and Arnaud Bondon
b
a
Ecole Normale Sup e´ rieure, D e´ partement de Chimie, UMR CNRS 8640, 24 rue Lhomond, 75231 Paris Cedex 05, France
Laboratoire de Chimie Organom e´ tallique et Biologique, UMR CNRS 6509, Universit e´ de Rennes 1, 35042 Rennes Cedex, France
b
Received 17 April 2002; revised 29 May 2002; accepted 17 June 2002
Abstract—The synthesis of partially b-fluorinated meso-tetraphenylporphyrins using Lindsey conditions, has been examined, starting either
from 3,4-difluoro-1H-pyrrole or from 3-fluoro-1H-pyrrole. In the case of the first synthon, condensation with pyrrole and benzaldehyde
afforded a mixture of porphyrins of general formula b-F
n
TPP (n¼0,2,4,6,8) displaying linearly correlated spectroscopic and electrochemical
properties. With the second synthon, condensation with benzaldehyde produced an unresolvable mixture of b-tetrafluoroporphyrins
presenting spectroscopic and electrochemical properties in coherence with those observed in the first case. Preliminarily, the synthesis and
isolation of the hitherto unknown 3-fluoro-1H-pyrrole has been approached via several methods. q 2002 Elsevier Science Ltd. All rights
reserved.
1
. Introduction
b-substituents would display inter alia, very high oxidation
potentials as a consequence of the lack of destabilization of
3
b
The synthesis of b-halogenated metalloporphyrins and their
use as oxidation catalysts of organic substrates has attracted
considerable attention during the last 10 years. Never-
theless, these studies were mainly restricted to the halogens
bromine and chlorine, due to relatively easy access to such
complexes by direct halogenation of the parent porphyrin.
Whereas iodine has received little attention as a
b-substituent, the indirect introduction of fluorine at the
pyrrolic b-positions has only recently been rendered
possible by the development of routes to 3,4-difluoro-1H-
the HOMOs due to ring distortion. Nevertheless, the
predicted higher resistance to oxidation was partially
challenged by catalysis studies on some metalated
4
b-octafluoroporphyrins.
Assuming that the physicochemical properties of
b-octafluoro-meso-tetraarylporphyrins are mainly governed
by the strong s-electron-withdrawing effects of the
peripheral fluorine atoms, it was advisable to check this
feature on partially fluorinated analogs. Since the Lindsey
procedure proved to be valuable for the synthesis of
b-octafluoroporphyrins bearing meso-tetraaryl sub-
1
pyrrole (1). Thus, the synthesis and characterization of the
first b-octafluoro-meso-tetraarylporphyrins, members of a
new class of highly electron-deficient ligands, has been
2
stituents, we applied it to the preparation of partially
2
a
2b
reported in 1997 by us and others. These porphyrins and
their metal complexes have been found to display original
features e.g. blue-shifted electronic absorption spectra as
well as positively shifted redox potentials, compared to the
benchmark 5,10,15,20-tetraphenylporphyrin (TPPH2).
Another remarkable feature for these ligands was their
nearly planar structure, in opposition to the distorted one of
other encumbered electron-deficient porphyrins. Many
studies on variously substituted porphyrins have been
devoted to a better understanding of the relationship existing
between the physicochemical properties of the ligand and
fluorinated analogs, starting either from a mixture of 3,4-
difluoropyrrole and pyrrole or from the hitherto unknown
3-fluoro-1H-pyrrole (2). In this paper, we will report first
our attempts to prepare 2 in pure form via several routes. In
a second part, the synthesis and characterization of
porphyrins of the type b-F TPP (n¼2,4,6) will be presented.
n
2. Results and discussion
3
a
2.1. Routes to 3-fluoro-1H-pyrrole
the s, p and steric effects prevailing in the macrocycle. As
confirmed afterwards for fluorine, it was anticipated that
planar porphyrins bearing electron-withdrawing
5
6
On the contrary to 3-chloro- or 3-bromo-1H-pyrrole,
3-fluoro-1H-pyrrole (2) was unreported in literature. Never-
theless, functionalized N-unsubstituted 3-fluoropyrrole
moieties have already been obtained through various
synthetic procedures. The first examples of such com-
pounds, 3, have been obtained by Buhr via thermally or
Keywords: fluorinated pyrroles; protecting groups; fluorinated porphyrins;
electronic spectra.
*
Corresponding author. Tel.: þ33-1-44-32-34-09; fax: þ33-1-44-32-24-
02; e-mail: jacques.leroy@ens.fr
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00677-4

6714
J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
photochemically induced ring contraction of 2-azido-3,3-
difluorocyclobutenes in the presence of nucleophilic arenes
e.g. benzene. Pyrrole 4 was prepared via a multistep
prepared by Barnes and co-workers from the 3-bromo
1
4
analog 6 (Scheme 1). Curiously, it appeared from a
literature survey that 7 was never deprotected to give
access to the 3-fluoro-1H-pyrrole (2) we required for the
synthesis of b-tetrafluoro-5,10,15,20-tetraphenylporphyrin
(b-F TPPH ) (23) (vide infra). For this peculiar use, the
7
sequence involving at the fluorination step a modified
Schiemann reaction i.e. the photolysis of a diazonium
tetrafluoroborate salt. This compound was used for the
preparation in low yield of 2,7,12,17-tetrafluoro-3,8,13,18-
4
2
isolation of 2 was unnecessary as we briefly reported in a
15
8
a
tetramethylporphyrin. More recently, the same group
prepared ring-monofluorinated analogs of meso-porphyrin
IX and related compounds from the 4-fluoropyrroles 5
obtained by thermal decarboxylation of the corresponding
recent paper. This compound was conveniently prepared
as a 102 M solution in dichloromethane by deprotection of
7 with 1 M n-tetrabutylammonium fluoride in tetrahydro-
furan, followed by an aqueous washing and subsequent
drying. The deprotection reaction was fast and quantitative
2
2
via the photochemical decomposition of diazonium tetra-
-carboxylic acids. As previously, fluorine was introduced
1
19
as checked by H and F NMR (Scheme 1). Nevertheless,
for the sake of full characterization, we found it useful to
isolate the pyrrole 2 in pure form. With this aim in view,
three routes have been investigated.
8
b,c
fluoroborate salts.
Firstly, several attempts were made to isolate 2 from the
reaction mixture obtained after desilylation. Since 2 could
be reasonably anticipated to be more volatile than 3,4-
1
difluoropyrrole, the use of a solvent like tetrahydrofuran
was discarded, dichloromethane appearing to be the most
appropriate. Deprotection of 7 with tetra-n-butylammonium
fluoride trihydrate exclusively in this solvent led, after an
aqueous work up and rotary evaporation of the solvent at
2108C, to a mixture of 2 and triisopropylsilanol. The
reaction being conducted on small quantities of 7, a classical
fractional distillation was not possible. Bulb-to-bulb
distillation under the water-pump vacuum led to low
amounts of 2 contaminated either by remaining traces of
solvent (no heating applied) or triisopropylsilanol (heating
at ca. 408C). Therefore, a part of the crude mixture was
submitted to a preparative GLC (SE30 column) at low oven
temperature (ca. 708C) affording on cooling (dry ice–
acetone), the pyrrole 2 as a colorless liquid turning to
green–black on standing at room temperature (rt). Never-
theless, the quantity of 2 collected was too low to determine
its boiling point experimentally. Calculations predicted, for
this compound, a boiling point of 136.43^13.008C at
760 mm Hg and 144.82^20.008C for 3,4-difluoropyrrole
3
-Alkyl or -aryl substituted-4-fluoropyrrole-2-carboxylates
or -2-tosyl have been obtained in low yields, along with
other products, by Michael type addition of isocyano-
methylide anions to a-fluoroalkenyl sulfones and sulfox-
ides. A high yielding route to 3-fluoro-2,5-disubstituted
pyrroles, starting from a,a-difluoro-g-iodo-g-(electron-
withdrawing group) substituted ketones has been reported.
Ethyl 3-fluoropyrrole-2-carboxylate has been obtained as
the major product (no yield reported) in the reduction of a
9
1
0
1
1
cyclic difluoro hemiaminal and more recently, the already
a
8
16
known ethyl 4-fluoro-3,5-dimethylpyrrole-2-carboxylate
has been prepared in 40% yield by rhodium-catalyzed
cyclocondensation of ethyl isocyanoacetate with 3-fluoro-
(experimental 160–1628C ) vs 129.76^9.008C for pyrrole
1
7
1
(experimental 1318C). The H NMR spectrum of 2 was
deceptive since the signals of the H-2 and H-5 protons
overlapped, giving a multiplet, even at high sweep
frequency (600 MHz) Their respective chemical shifts
1
2
2
,4-pentanedione.
1
1
1
13
Except ethyl 3-fluoropyrrole-2-carboxylate, a possible
precursor of 2 via a saponification–decarboxylation
sequence, all the b-fluoropyrroles reported above were too
heavily functionalized to be used in the Lindsey-type
porphyrin synthesis we envisioned. We finally focused our
attention on 3-fluoro-1-(triisopropylsilyl)pyrrole (7), first
could be obtained from a H– C heterocorrelated spec-
trum, the proton signal at 6.49 ppm being connected with
the C-5 resonance at 115.4 ppm and that located at 6.50 ppm
with the C-2 resonance at 101 ppm. The H-4 signal
appeared roughly as a quartet, including the couplings
1
3
1
9
with the H-2 and H-5 protons and with fluorine. F NMR
Scheme 1. Reagents and conditions: (i) 1 M n-Bu
rt; (iii) flash-thermolysis, 1808C.
4
NF/THF, THF or MeCN (R¼Br) or 1 M n-Bu
4
2
NF/MeCN, MeCN (R¼Br, F), rt; (ii) Boc O, DMAP, MeCN,

J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
6715
spectroscopy was not very informative either, giving rise to
a poorly resolved complex multiplet as the signal. Finally,
no obvious proton–proton or proton–fluorine coupling
constant could be extracted from the observed patterns. The
by treatment of N-Boc prolinate 12 with trifluoroacetic acid
then displacement of the resulting trifluoroacetate with
2
4
sodium carbonate. Unexpectedly, the reaction of 13 with
manganese dioxide led to the loss of fluorine and methyl
pyrrole-2-carboxylate 14 was obtained instead of the
expected methyl 4-fluoropyrrole-2-carboxylate (17)
(Scheme 2).
1
3
C NMR spectrum was more explicit, the four carbon
resonances being assigned unambiguously, displaying
coupling constants in the range of those observed e.g.
18
with fluoropyridines.
Owing to this result, it was anticipated that the same
process, when applied to the 4,4-difluoroproline methyl
ester 16, would lead to the desired 4-fluoropyrrole 17. The
starting material 16 was also prepared from the trans-4-
hydroxy-L-proline 11, via the N-Boc-protected 4,4-difluoro-
A second procedure for the isolation of 2 starting from 7 was
investigated (Scheme 1). Since the major problem was the
predictable volatility of the desired pyrrole, we thought to
convert it in situ into the heavier N-Boc protected
2
3
3
-fluoropyrrole 10. Two advantages were expected from
proline methyl ester (15). N-Boc deprotection of 15 with
trifluoroacetic acid afforded, after basic treatment, the free
base 16 which was aromatized in good yield by treatment
with activated manganese dioxide into methyl 4-fluoro-1H-
this transformation. First, an easiest isolation and second,
the possibility of a thermal, solvent-free deprotection of 10
leading to 2, along with carbon dioxide and isobutylene.
Such a procedure was successfully used for the synthesis of
2
5
pyrrole-2-carboxylate (17). Saponification of this ester
gave the corresponding acid 18 which was submitted to a
flash thermolysis at 3008C in a sealed vacuum flask. Clean
decarboxylation of the infusible acid was partially thwarted
by extensive decomposition. Nevertheless, low amounts of
3-fluoropyrrole (2) could be extracted from the resulting
mixture by vacuum transfer into a cooled receiver.
Attempted decarboxylation at lower temperature (1808C)
in the presence of copper powder was unsuccessful
(Scheme 3).
3
cursor. We tried the tert-butoxycarbonylation reaction
,4-bis(trifluoromethyl)-1H-pyrrole from its N-Boc pre-
1
9
20
6
on the more readily accessible 3-bromopyrrole 8 either on
2
1
the isolated compound or directly in situ after desilylation.
The N-Boc protected 3-bromopyrrole 9 was obtained from
the N-TIPS analog 6 in 52% yield after purification. Despite
various reaction conditions, when the same sequence was
applied to 7, without intermediate isolation of 2, only small
amounts of N-Boc protected 3-fluoropyrrole 10 could be
obtained with difficulty. Nevertheless and as expected, a
sample of (impure) 10 was deprotected into 2 upon heating
at 1808C in a sealed glass-tube, although accompanied by a
substantial amount of metallic-like, blue–black deposit.
From the two last methods examined above to prepare 2, it
could be concluded that this compound is unstable, as
8
b,c
suggested for pyrroles 5.
The harsh reaction conditions
used for decarboxylation are probably responsible for this
apparent instability. Nonetheless, 3-chloropyrrole has been
Further experiments in this way required disposal of
substantial amounts of 7. In practice, the access to this
starting material did not prove to be fully satisfactory in our
hands, the yield (36%) being limited by the concomitant
formation of the reduction product, N-(triisopropylsilyl)-
pyrrole, and a problematic scaling up.
5
reported to be unstable and we verified that 3-bromopyrrole
6
(8) (mixed with triisopropylsilanol) decomposed quickly
on standing at rt. On the other hand, (impure) samples of 2
obtained by desilylation of 7 seemed not to decompose at rt.
2.2. Synthesis from 3,4-difluoro-1H-pyrrole and
characterization of porphyrins b-F TPP (n52,4,6)
So we were conducted to examine the preparation of the
hitherto unknown 4-fluoro-pyrrole-2-carboxylic acid (18), a
compound susceptible of being thermally decarboxylated
into 2. Since substituted pyrroles could be prepared by
dehydrogenation of pyrrolidines with activated manganese
n
By condensation of a mixture of 3,4-difluoro-1H-pyrrole
1
(1) and pyrrole with benzaldehyde in dichloromethane
2
3
under Lindsey conditions (each pyrrole at ca. 5.10 M,
22
2
2
23
dioxide in refluxing tetrahydrofuran, the aromatization of
a 3-fluoroprolinate derivative by this method appeared to be
feasible. With this aim in view, we prepared the N-Boc
protected cis-fluoroproline methyl ester 12 from the trans-4-
benzaldehyde 10 M and BF ·Et O 10 M) followed by
3 2
1
3
DDQ oxidation, a mixture of porphyrins was obtained.
Under our unoptimized conditions (pyrrole ratios, concen-
trations, etc.), variously fluorinated porphyrins were
2
3
hydroxy-L-proline (11). Since the treatment of 12 with
manganese dioxide left the starting material unchanged, we
looked for the N-deprotected cis-4-fluoroproline methyl
ester (13). This seemingly unreported compound was
obtained with some difficulty (due inter alia to its volatility)
obtained, along with TPPH as major product. A rough
2
separation was first realized by column chromatography
associated to an UV–visible monitoring, affording, by order
of elution, the porphyrins b-F TPPH (19), b-F TPPH
2
8
2
6
(20), b-F TPPH (opp and adj isomers) (21) and
2
4
Scheme 2. Reagents and conditions: (i) TFA, CH
2
Cl
2
, then NaHCO
3
/H O, rt; (ii) MnO
2
2
, THF, 808C.

6716
J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
2 2 3 2 2 2
Scheme 3. Reagents and conditions: (i) TFA, CH Cl , then NaHCO /H O, rt; (ii) MnO , THF, 808C; (iii) 4 M KOH/H O, MeOH, rt; (iv) flash-thermolysis.
b-F TPPH (22) in low yields and impure form. A further,
2
counterpart (2) (expressed in electronvolts) (Fig. 2), where n
is the number of fluorine atoms.
2
more efficient separation was also effected by column
chromatography, but after metalation of the free bases
samples with zinc acetate. The four new partially fluorinated
Zn complexes 20(Zn)–22(Zn) thus obtained (Fig. 1) have
been characterized by UV–visible spectroscopy (Table 1),
NMR and high-resolution mass spectrometry (see
Section 4). As anticipated, the UV–visible absorption
l ðSoretÞ ðnmÞ ¼ 417:5 2 1:50n
E ðSoretÞ ðeVÞ ¼ 2:97 þ 0:01097n
ð1Þ
ð2Þ
The already known Zn(II) complex of b-octafluoro-meso-
2
tetraphenylporphyrin also fits these equations.
spectra of the new porphyrins b-F TPPZn (n¼2,4,6) are
n
hypsochromically shifted relative to the b-unsubstituted
TPPZn. Remarkably, the recorded shifts are directly
proportional to the number of fluorine atoms at the
periphery, both for the Soret (B) and the two Q bands. For
example, the Soret band wavelength follows the linear
relationship (1) (expressed in nanometers), or its energy
2.3. Synthesis from 3-fluoro-1H-pyrrole and
characterization of porphyrins b-F TPP
4
As we shortly reported in a paper on the electrochemical
1
5
oxidation of preformed porphyrinogens, 3-fluoro-1H-
pyrrole (2) and benzaldehyde condense under Lindsey
8
Figure 1. b-Fluoroporphyrins obtained from a mixture of 3,4-difluoropyrrole, pyrrole and benzaldehyde (b-F TPPZn and TPPZn are not represented).

J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
Table 1. Spectroscopic data for the free bases and their metal complexes
Compound max (nm)
6717
a
NH shift (ppm)
l
Ref.
b
b
Soret band
Q bands
c
c
TPPH
2
418
410
425
515, 549, 590, 645
505, 538, 583, 637
522, 561, 670
22.78
23.45
23.00
This work
This work
This work
b-F
b-Br
b-F
TPPZn
4
TPPH
2
(23)
0
4
b -F
4
TPPH (24)
2
8
TPPH
2
403
418
414
411
411
412
408
406
422
499, 533, 581, 639
547, 584
543, 581
540, 576
539, 578
540, 578
537, 576
534, 572
551
24.16
2
This work
This work
This work
This work
This work
This work
2
b-F
b-F
2
TPPZn (22(Zn))
TPPZn (23(Zn))
4
opp-b-F
adj-b-F
4
TPPZn (21(Zn))
TPPZn (21(Zn))
4
b-F
b-F
6
TPPZn (20(Zn))
TPPZn
8
0
This work
b-Br
b-F
4
b -F
TPPCu (23(Cu))
4
TPPZn (24(Zn))
4
407
419
531
546
This work
This work
0
b-Br
4
b -F
4
TPPCu (24(Cu))
a
In CDCl
3
.
b
c
In CH
2
Cl
2
.
Values in accord with the literature data (Ref. 2b).
isomeric tetrafluoroporphyrins was foreseeable, following
the four possible arrangements depicted in Fig. 4. The
isomers could not be separated by thin-layer or column
chromatography and purification of the crude product was
conveniently achieved by column chromatography of the
dicationic porphyrins (silica gel, dichloromethane saturated
with perchloric acid as eluent), affording, after neutraliz-
ation, a mixture of the isomeric free porphyrins 23. The
1
9
presence of isomers was confirmed by the F NMR
spectrum of the porphyrin b-F TPPZn (23(Zn)) obtained
4
after metalation with zinc acetate but it was not possible to
determine their nature and distribution. Six unresolved
singlets of variable intensities were observed. Examination
of the four possible isomeric structures a–d (Fig. 3)
indicated that configurations a and d would exhibit only
one kind of fluorine atom vs, respectively, four and two for
1
9
configurations b and c, leading to a maximum of eight
F
1
9
NMR signals. A F spectrum of 23 gave no information on
the isomer distribution since only a very broad singlet was
observed, due to the NH proton exchange. The aromatic part
B
Figure 2. Plot of the energy of the Soret band, E of the porphyrins b-
F
n
TPPZn vs the number of fluorine atoms, n (black triangle: 23(Zn)).
1
of the H NMR spectrum of 23 was no more informative on
conditions to give porphyrins b-F TPPH (23) (Fig. 3) in
4
the various isomers present. Furthermore, the NH resonance
signal appeared as a singlet. As observed for the
symmetrical analogs opp-21 and adj-21, the UV–visible
absorption spectra of the porphyrins b-F TPPH (23) and
2
good yields, either after oxidation with DDQ (38%) or
electrochemical oxidation (35%). Owing to the unsym-
metrical structure of 2, the obtainment of a mixture of
4
2
Figure 3. b-Tetrafluoroporphyrins obtained from 3-fluoropyrrole and benzaldehyde (only one of the possible regioisomers is represented).

6718
J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
performed with bromine in a chloroform/dichloromethane
mixture in analogy to the octabromination of the complex
2
6
0
mixture of isomers) in 70% yield. The latter was
TPPCu, leading to the complex b-Br b -F TPPCu
4
4
(
demetalated in dichloromethane with sulfuric acid, afford-
0
ing the free base b-Br b -F TPPH in 65% yield after
4
4
2
purification (mixture of isomers). Further metalation with
zinc acetate afforded quantitatively the zinc complex
0
isomers (Scheme 4).
b-Br b -F TPPZn, always as an inseparable mixture of
4
4
The effects of b-bromination of meso-tetraarylporphyrins
on their physicochemical properties have been widely
studied. They are an admixture of steric and electronic
effects in which the bulkiness of bromine appears to play a
prevailing role by distorting the macrocycle, at least beyond
2
7
a minimum number of bromine atoms. The new mixed
haloporphyrins have been characterized by UV–visible
spectroscopy (Table 1), the spectra displaying no shoulders
or excessive band widths, indicating close spectroscopic
properties for these isomers despite somewhat hetero-
geneous structures. As anticipated, the introduction of four
bromine atoms in the free base or metalated fluoro-
Figure 4. Possible arrangements of the isomeric b-tetrafluoroporphyrins 23
and derivatives.
b-F TPPZn (23(Zn)) are hypsochromically shifted relative
4
porphyrins b-F TPP induces a red shift of their whole
4
to the b-unsubstituted TPPH and TPPZn (Table 1), the
2
spectra. For the Soret band, this shift varies from 11 (Zn
complex) to 15 nm (free base).
shifts (Soret and Q bands) being also the half of those
2
observed for the b-octafluoro analogs b-F TPP, always in
8
comparison to the same TPP reference compounds.
Consequently, the wavelengths found for 23(Zn) fit the
least-squares lines established for the porphyrins b-Fn-
TPPZn i.e. TPPZn and 19(Zn)–22(Zn) (Fig. 2). It should be
emphasized that the absorption spectrum of 23(Zn) did not
display shoulders or particularly broad bands and was quasi
superimposable to that of its regioisomers opp-21 and adj-
3
. Conclusion
In conclusion, we have shown that 3-fluoro-1H-pyrrole
prepared in situ from 3-fluoro-1-(triisopropylsilyl)pyrrole
may be validly used for the preparation of b-tetrafluoro-
5
,10,15,20-tetraphenylporphyrins. Although obtained as an
2
1. The redox potentials of the free base porphyrin 23 and its
Zn(II) complex 23(Zn) have been measured by cyclic
voltammetry in CH Cl (see Section 4). Remarkably,
unresolved mixture, these porphyrins display homogeneous
spectroscopic and electrochemical properties, linearly
correlated to those observed with the other terms of the
2
2
b-tetrafluorination of TPPH resulted in positive shifts of
2
series b-F TPP (n¼0,2,4,6,8) prepared from 3,4-difluoro-
n
the oxidation and reduction potentials that are the average of
the corresponding values for TTP and b-F TPP (H and Zn):
1
H-pyrrole. This remarkable coherence is clearly a direct
8
2
consequence of the strong electron-withdrawing character
of fluorine which overwhelms other structural effects e.g.
macrocycle distortion.
1
=2
1=2
1=2
E
ðb-F TPPÞ ¼ ½E ðTPPÞ þ E ðb-F TPPÞꢀ=2
1
4
8
As mentioned above, the H NMR spectrum of the mixture
of isomeric free base porphyrins 23 only displays a singlet
for the NH resonances located at d 23.45 ppm. Again, this
value is the average of the NH chemical shifts for TPPH2
and b-F TPPH i.e. 22.78 and 24.16 ppm, respectively.
4. Experimental
4.1. General
8
2
0
2
.4. Preparation of the b-Br b -F TPPZn complex
4
Methylene chloride was distilled from CaH prior to use.
2
4
Benzaldehyde was distilled under argon immediately prior
to use. The remaining reagents were used as received from
commercial sources. Manganese(IV) oxide, precipitated
active, was purchased from Merck. After work up, solvent
removal was effected by rotary evaporation under the water-
pump vacuum unless otherwise specified. Column chroma-
tography was performed on silica gel 60 (230–400 mesh)
with the indicated solvents. Thin layer chromatography
Once the mixture of b-tetrafluoroporphyrins 23 had been
prepared, it was appealing to introduce bromine atoms on
the free b-positions to have access to mixed b-halo-
porphyrins. After several attempts, we found convenient
to use the copper complex b-F TPPCu (23(Cu)) as a
4
substrate for the introduction of bromine, mainly for an easy
demetalation. The bromination of the complex 23(Cu) was
Scheme 4.

J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
6719
(
TLC) was carried out on precoated silica gel 60F254 plates
acetonitrile (3 mL). DMAP (19.2 mg, 0.157 mmol) and
di-tert-butyl dicarbonate (0.35 g, 1.60 mmol) were added.
Evolution of gas started and after 20 min, TLC (cyclo-
and compounds were visualized by UV fluorescence or the
specified staining reagents. Preparative GLC was performed
using a Varian Aerograph Model 920 apparatus equipped
with a SE-30 column. UV–visible spectra were obtained
using an Uvikon 941 spectrometer. NMR spectra were
hexane, UV) revealed the presence of 9 (R ¼0.33;
f
R (6)¼0.66; R (8)¼0.12). Stirring was continued for 1 h
f
f
and to the mixture was added ether (15 mL) then 1 M
aqueous KHSO (6.5 mL). The organic layer was washed
obtained in CDCl at rt, either at the University de Rennes 1
3
4
(
at the Ecole Normale Sup e´ rieure (Bruker AC 250 or DRX
Bruker DPX 200, AC 300P or DMX 500 spectrometers) or
with 1 M aqueous KHSO (5£3 mL), water (5 mL), 1 M
4
aqueous NaHCO (3 mL) and then brine (3£5 mL). After
3
1
4
reported in ppm using the residual chloroform as a chemical
00 spectrometers). H NMR chemical shifts (d ) are
drying (MgSO ) and filtration, removal of the solvent at rt
4
afforded an oil which was purified by flash column
chromatography (eluent: cyclohexane/ethyl acetate 95:5)
1
9
shift reference (7.24 ppm). F NMR chemical shifts are
1
3
given relative to CFCl as reference. C NMR chemical
3
to give the pyrrole 9 (170 mg, 52% vs 6. TLC: R ¼0.55) as a
f
1
3
1
shifts are reported using CDCl as a reference (77.0 ppm).
3
fluid, colorless oil: H NMR (250.13 MHz, CDCl ) d 1.56
3
Splitting patterns are abbreviated as follows: s, singlet, d,
doublet, t, triplet, q, quartet, quint, quintuplet and m,
multiplet. Cyclic voltammograms were obtained using a
PAR M 263 apparatus. EI and CI mass spectra were
recorded on a Jeol JMS-700 spectrometer.
(s, 9H, Me), 6.19 (dd, 1H, J¼3.3, 1.6 Hz, H-4), 7.14 (dd, 1H,
J¼3.3, 2.5 Hz, H-5 or H-2), 7.21 (approx dd [unsym. t], 1H,
1
3
J¼2.2, 1.7 Hz, H-2 or H-5); C NMR (62.89 MHz, CDCl )
3
d 27.88 (Me), 84.38 (C HMe ), 100.50 (CBr), 114.59 (C-4),
3
119.40, 120.43 (C-2, C-5), 147.73 (CO); MS (CI, NH ): m/z
3
7
9
þ
81
þ
2
46 [M BrþH] , 248 [M BrþH] .
4
4
.2. N-protected fluoropyrroles routes
1
3
-Bromo-1H-pyrrole (8). H NMR (250.13 MHz, CDCl ) d
3
.2.1. 3-Fluoro-1H-pyrrole (2) from 7. To a stirred
1
6.21 (m, 1H, H-4), 6.69 (q, 1H, J¼2.86 Hz, H-2 or H-5),
4
solution of 7 (174 mg, 0.72 mmol) in CH Cl (1 mL)
2
6.75 (approx q, H-5 or H-2).
2
was added a solution of tetra-n-butylammonium fluoride
trihydrate (238 mg, 0.75 mmol) in CH Cl (1 mL) at rt.
4.2.3. 3-Fluoro-1-(tert-butoxycarbonyl)pyrrole (10). To a
2
2
1
4
After disappearance of the starting material (ca. 10 min by
TLC, petroleum ether as eluent, R (7)¼0.48, revelation:
stirred solution of 7 (300 mg, 0.61 mmol) in acetonitrile
(5 mL) was added at rt a 1 M solution of tetra-n-
butylammonium fluoride trihydrate in acetonitrile
(1.5 mL). After 30 min, DMAP (20 mg, 0.164 mmol) and
di-tert-butyl dicarbonate were added. Evolution of gas
commenced within 1–2 min. Stirring was continued for 4 h
f
iodine vapor), CH Cl (5 mL) was added to the mixture
2
2
which was washed with water (2£3 mL) then brine (3 mL).
The organic layer was dried (MgSO ) and filtered.
4
Evaporation of the solvent at 2108C afforded a fluid oil
(
250 mg) composed from ca. 44% of 2 and 56% of
after which ether (20 mL) then 1 M aqueous KHSO (6 mL)
4
triisopropylsilanol. Distillation bulb-to-bulb at rt under the
water-pump pressure (ca. 20 mm Hg) afforded in the
condenser at 2708C a small amount of liquid composed
of 2 and residual CH Cl as the major component. By
were added. After partitioning, the organic layer was
washed with 1 M aqueous KHSO4 (3£5 mL), water
(5 mL), 1 M aqueous NaHCO3 (5 mL) and brine
(3£5 mL). After drying (MgSO ), removal of the solvent
2
2
4
heating the mixture at ca. 408C, a liquid containing 2 and
1
at rt afforded an oil (210 mg), mixture of 10 (18%), 2 (55%)
19
triisopropylsilanol in the ratio 27:1 (evaluation by H NMR)
was obtained.
and triisopropylsilyl fluoride (27%) (estimation by
NMR). Flash column chromatography (eluent: cyclo-
F
hexane/ethyl acetate 95:5; TLC: R (7),0.40, revelation:
f
1
3
5
6
-Fluoro-1H-pyrrole (2). H NMR (250.13 MHz, CDCl ) d
3
phosphomolybdique reagent then heat) afforded the pyrrole
1
.97 (apparent q, 1H, J¼2.5 Hz, H-4), ,6.50 (m [7 lines:
10 as an impure oil (21 mg, 18%): H NMR (250.13 MHz,
CDCl ) d 1.56 (s, 9H, Me), 6.03 (approx dd, 1H, J¼3.4,
19
.531, 6.521, 6.514, 6.504, 6.493, 6.483, 6.471 ppm], 2H,
3
1
9
H-2, H-5), 7.70 (v br t, J,54 Hz, NH); F NMR
235.36 MHz, CDCl ) d 2168.47 (m);
1.8 Hz, H-4), 6.92 (approx q, 1H, J¼2.2 Hz, H-2 or H-5),
1
3
(
(
(
(
C NMR
7.02 (approx q, 1H, J¼3.6 Hz, H-5 or H-2). F NMR
3
62.89 MHz, CDCl ) d 97.19 (d, J¼17.3 Hz, C-4), 100.99
(235.36 MHz, CDCl ) d-160.97 (t, J¼4.0 Hz); MS (GC/EI):
3
3
þ
6) (d, J¼29.6 Hz, C-2), 115.35 (d, J¼6.7 Hz, C-5), 152.51
d, J¼236.9 Hz, CF); HRMS(EI) m/z 85.0306 (M calcd for
m/z 185 (M ).
1
3
C H FN: 85.0327) ( C NMR and high-resolution mass
4
4.3. Fluoroprolines routes
4
spectra have been obtained on a sample of 2 prepared by
thermal decarboxylation of 18).
4.3.1. Methyl (2S,4S)-4-fluoro-2-prolinate (13). To a
stirred solution of methyl (2S,4S)-N-tert-butoxycarbonyl-
4-fluoro-2-prolinate (12) (200 mg, 0.81 mmol) in CH Cl
2 2
(10 mL) was added trifluoroacetic acid (TFA) (0.9 mL) at rt.
After ca. 2 h, TLC analysis showed complete consumption
of the starting material (eluent: cyclohexane/ethyl acetate
75:25, revelation: TFA vapor, ninhydrin/EtOH spray
2
3
4
.2.2. 3-Bromo-1-(tert-butoxycarbonyl)pyrrole (9). To a
6
stirred solution of 6 (400 mg, 1.32 mmol) in THF (4 mL)
under argon was added tetra-n-butylammonium fluoride
(1.4 mL, 1 M in THF) at rt. After 10 min, ether (15 mL) was
added and the organic layer washed with water (10 mL),
brine (10 mL) and dried over MgSO . Removal of the
4
2
then heat, R (12)¼0.28, R (13, CF CO ),0). Evaporation
f
f
3
2
solvent at rt afforded a colorless viscous oil [the same
compound was obtained when operating in CH CN using a
of the solvent and excess TFA under reduced pressure
(water-pump then oil-pump) at rt afforded the trifluoro-
acetate salt of 13 as a colorless oil (280 mg): MS (CI, NH )
3
ca. 1 M solution of tetra-n-butylammonium fluoride tri-
hydrate in CH CN] which was immediately dissolved in dry
3
þ
148 (MH ).
3

6720
J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
To a stirred solution of the above trifluoroacetate (97.4 mg,
.37 mmol) in CH Cl (2 mL) was added water (0.2 mL)
4.3.4. Methyl 4-fluoro-pyrrole-2-carboxylate (17). To a
stirred solution of 16 (169 mg, 1.02 mmol) in THF (15 mL)
was added activated manganese dioxide (746 mg,
8.58 mmol). The suspension was refluxed for 3 h then
filtered after cooling through a pad of Celite which was
rinsed with THF. Evaporation of the solvent under reduced
pressure gave an off-white crystalline solid (134.4 mg).
Flash column chromatography (CH Cl as eluent; TLC:
0
2
2
then powdered anhydrous sodium carbonate (70 mg,
.66 mmol) at rt. After 15 min of stirring, an additional
0
sodium carbonate (300 mg) was added. After ca. 1 h of
drying, the liquid was collected with a Pasteur pipette and
evaporated at 2108C affording 13 as a colorless, fluid oil
1
(
(
37.7 mg, 69%) (caution: volatile product!): H NMR
250.13 MHz, CDCl ) d 2.21 (m, 1H, H-3), 2.34 (m, 1H,
2
2
R (17)¼0.38, UV revelation) afforded the pyrrole 17 as a
3
f
0
H-3 ), 2.41 (br s, 1H, NH), 2.87 (ddd, 1H, J¼37.6, 13.4,
white microcrystalline solid (106.5 mg, 73%): mp 94.2–
95.48C; H NMR (CDCl , 250.13 MHz) d 3.83 (s, 3H, Me),
0
1
3
3
.3 Hz, H-5), 3.37 (dd, 1H, J¼22.0, 13.4 Hz, H-5 ), 3.73 (s,
H, Me), 3.79 (dd, 1H, J¼7.9, 5.8 Hz, H-2), 5.12 (dq, 1H,
3
6.58 (apparent t [poorly resolved], 1H, J,2.0 Hz, H-3), 6.71
(apparent td, 1H, J¼3.4, 1.8 Hz, H-5), 8.98 (br s, 1H, NH);
F NMR (235.36 MHz, CDC ) d 2163.01 (m); C NMR
3
1
9
J¼53.8, 2.8 Hz, H-4); F NMR (235.36 MHz, CDCl ) d
3
1
3
19
13
2
174.39 (m); C NMR (62.89 MHz, CDCl ) d 37.72 (d,
3
J¼21.6 Hz, C-3), 52.33 (s, CH ), 53.91 (d, J¼22.8 Hz, C-5),
(62.89 MHz, CDCl ) d 51.69 (s, CH ), 101.95 (d,
3 3
3
58.78 (s, C-2), 93.67 (d, J¼175.0 Hz, CF), 174.51 (s, CO);
HRMS (CI, CH ): m/z 148.0780 (MH calcd for
J¼15.8 Hz, C-3 or C-5), 107.36 (d, J¼28.4 Hz, C-5 or
C-3), 118.80 (d, J¼6.3 Hz, C-2), 151.85 (d, J¼241.70 Hz,
C-4), 161.35 (d, J¼3.1 Hz, CO). Anal. calcd for C H FNO :
þ
4
C H FNO : 148.0774).
6
11
2
6
6
2
C, 50.35; H, 4.22; N, 9.78. Found: C, 49.98; H, 4.21; N,
9.52.
4
.3.2. Methyl pyrrole-2-carboxylate (14). To a stirred
solution of 13 (33.8 mg, 0.23 mmol) in THF (1.5 mL) was
added manganese oxide (160 mg, 1.84 mmol). The suspen-
sion was refluxed for 3 h and diluted after cooling with THF
4.3.5. 4-Fluoro-pyrrole-2-carboxylic acid (18). To a
stirred solution of 17 (300 mg, 2.1 mmol) in methanol
(17 mL) was added 4 M aqueous KOH (35 mL) at rt.
Stirring was continued overnight then methanol was
evaporated at rt. The residual liquid was acidified (aqueous
HCl) and extracted with ether (4£30 mL). The organic
phase was washed with water (2£30 mL) then brine
(30 mL). After drying (Na SO ) and filtration, removal of
(5 mL), then filtered through a pad of Celite which was
rinsed with THF. Evaporation of the solvent under reduced
pressure afforded the pyrrole 14 as an off-white crystalline
1
solid (19.5 mg, 68% crude): H NMR (250.13 MHz, CDCl )
3
d 3.83 (s, 3H, Me), 6.25 (apparent q, 1H, J¼3.5 Hz, H-5),
6.90 (m, 1H, H-3 or H-4), 6.94 (m, 1H, H-4 or H-3), 9.14 (br
s, 1H, NH); MS (EI): m/z 125 (M ).
2
4
þ
the solvent under reduced pressure afforded the acid 18 as
1
an amorphous off-white solid (251 mg, 93%): H NMR
(250.13 MHz, acetone-d ) d 6.57 (m [poorly resolved],
4.3.3. Methyl (2S)-4,4-difluoro-2-prolinate (16). To a
stirred solution of methyl (2S )-N-tert-butoxycarbonyl-4,4-
6
1H, H-3), 6.91 (apparent td, 1H, J¼3.4, 1.8 Hz, H-5),
2
3
19
difluoro-2-prolinate (15) (500 mg, 1.88 mmol) in CH Cl
2
10.73 (br s, 1H, CO H); F NMR (235.36 MHz, acetone-
2
2
1
3
(
30 mL) was added TFA (2 mL) at rt. The mixture was
stirred overnight (TLC analysis: cyclohexane/ethyl acetate
5:25, revelation: TFA vapor, ninhydrin/EtOH spray then
d6) d 2164.50 (m); C NMR (62.89 MHz, acetone-d ) d
6
101.83 (d, J¼15.8 Hz, C-3 or C-5), 108.32 (d,
J¼28.1 Hz, C-5 or C-3), 120.21 (d, J¼6.2 Hz, C-2),
152.59 (d, J¼238.1 Hz, C-4), 161.67 (d, J¼3.0 Hz,
CO H). Anal. calcd for C H FNO : C, 46.52; H, 3.12;
7
2
heat, R (15)¼0.48, R (16, CF CO ),0) and the solvent and
f
f
3
2
excess TFA evaporated under reduced pressure at rt to give
the trifluoroacetate salt of 16 as an oil. Saturated aqueous
NaHCO3 (3 mL) was added under stirring (caution:
effervescence!) then ether (15 mL). After 15 min of stirring,
the aqueous phase was extracted with ether (2£10 mL). The
combined organic phases were dried (Na SO ). After
2
5
4
2
N, 10.85. Found: C, 46.61; H, 3.12; N, 10.58. MS (EI):
þ
m/z 129 (M ).
4.4. Porphyrin synthesis
2
4
filtration, removal of the solvent under reduced pressure at
rt (caution: volatile product!) afforded 16 as a slightly
4.4.1. From 3,4-difluoro-1H-pyrrole (porphyrins
b-F TPP, 19–22). To a stirred solution of 3,4-difluoro-
1H-pyrrole (1) (37.1 mg, 0.36 mmol), pyrrole (24.1 mg,
0.36 mmol) and benzaldehyde (76.4 mg, 0.72 mmol) in
n
2
0
1
yellow to brown, fluid oil (270 mg, 87%): [a] ¼216.98
D
(
distillation at 408C under 0.05 mm Hg afforded as small
c¼1.11, CHCl ). Attempted purification by bulb-to-bulb
3
CH Cl (72 mL) under argon at rt, BF .Et O (60 mL) was
2
2
2
3
2
0
amount of more pure 16 as a colorless liquid: [a] ¼217.18
added via a syringe. After 1 h, DDQ (120 mg, 0.53 mmol)
was added and stirring was maintained for an additional
hour. After evaporation of the solvent, a rough separation of
the porphyrins was performed under their dicationic form by
column chromatography, eluting with CH Cl saturated
D
1
(
(
1
c¼1.04, CHCl ); H NMR (400.13 MHz, CDCl ) d 2.37
3
3
apparent qd, 1H, J¼14.3, 6.4 Hz, H-3), 2.54 (apparent qd,
0
H, J¼14.3, 8.8 Hz, H-3 ), 2.65 (br s, 1H, NH), 3.15
(
apparent q, 1H, J¼12.8 Hz, H-5), 3.31 (apparent q, 1H,
2
2
0
9
J¼12.5 Hz, H-5 ), 3.74 (s, 3H, Me), 3.96 (dd, 1H, J¼8.8,
with perchloric acid. The organic layer was washed with
water until neutral and dried over MgSO . After removal of
1
6
.4 Hz, H-2); F NMR (376.49 MHz, CDCl ) d 299.74
3
4
(
center of an AB type pattern): d (F ) 299.37 (dquint, 1F,
A
the solvent, the residue was treated with zinc(II) acetate
28
according to the procedure of Bhyrappa and Krishnan.
2
J¼233.4 Hz, F ),
d
(F ) 2100.11 (dquint, 1F,
B
A
2
13
J¼233.4 Hz, F ); C NMR (62.89 MHz, CDCl ) d 38.82
Column chromatography on silica gel with CH Cl as eluent
2
B
3
2
(
t, J¼26.0 Hz, C-3), 52.42 (s, CH ), 53.69 (t, J¼29.0 Hz,
and UV–visible monitoring, afforded by order of elution,
small amounts (yields not determined) of the porphyrins
b-F TPPZn, b-F TPPZn, opp-b-F TPPZn and adj-b-
3
C-5), 57.88 (t, J¼4.5 Hz, C-2), 130.04 (t, J¼250.0 Hz,
CF ), 173.08 (s, CO); HRMS (CI, CH ): m/z 166.0679
2
4
8
6
4
þ
(
MH calcd for C H F NO : 166.0681).
10
F TPPZn, b-F TPPZn.
4 2
6
2
2

J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
6721
1
b-F TPPZn (20(Zn)). H NMR (200.13 MHz, CDCl ) d
6
plete, the solvents were evaporated in vacuo and the
porphyrins 23(Zn) or 23(Cu) were purified by column
chromatography on silica gel using CH Cl as eluent.
3
7.76 (m, 12H, m-H and p-H), 8.07 (m, 8H, o-H), 8.83 (s, 2H,
1
b-H); F NMR (188.31 MHz, CDCl ) d 2143.02 (d, 2F,
9
3
2
2
J¼4.8 Hz, F or F ), 2143.07 (s, 2F, F ), 2143.42 (d, 2F,
b
c
a
1
J¼4.8 Hz, F or F ); UV–visible (CH Cl ) l
(nm) (rel.
int.) 408 (100), 537 (4.9), 576 (1.1); HRMS (FAB): m/z
Zn(II) porphyrins 23(Zn). H NMR (200.13 MHz, CDCl ) d
3
c
b
2
2
max
7.62–7.82 (m, 12H, m-H and p-H), 7.97–8.14 (m, 8H, o-H),
19
þ
64
4
7
84.1061 (M calcd for C H F N Zn: 784.1040).
6
8.16–8.32 (m, 4H, b-H); F NMR (188.31 MHz, CDCl ) d
3
4
4
22
2
2124.52 (s), 2124.62 (s), 2124.82 (s, major peak); UV–
124.16 (s), 2124.34 (s), 2124.41 (s, minor peak),
1
opp-b-F TPPZn (opp-21(Zn)). H NMR (200.13 MHz,
4
2
5
CDCl ) d 7.77 (m, 12H, m-H and p-H), 8.11 (m, 8H,
3
o-H), 8.83 (s, 4H, b-H); F NMR (188.31 MHz, CDCl ) d
3
visible (CH Cl ) l
max
(nm) (1£10 ) 411 (4.011), 540
2
2
1
9
1/2
(0.172), 576 (0.036); CV (CH Cl /TBAPF ) E (V)¼1.20,
2
2
6
2
143.98 (s); UV–visible (CH Cl ) l (nm) (rel. int.) 411
max
0.96, 21.26, 21.63.
Cu(II) porphyrins 23(Cu). UV–visible (CH Cl ) l (nm)
max
2
2
(
(
100), 539 (6.3), 578 (3.0); HRMS (FAB): m/z 748.1249
þ
64
4
M calcd for C H F N Zn: 748.1229).
4
4
24
4
2
2
(rel. int.) 407 (100), 531 (4.7).
1
adj-b-F TPPZn (adj-21(Zn)). H NMR (200.13 MHz,
4
CDCl ) d 7.80 (m, 12H, m-H and p-H), 8.16 (m, 8H,
3
4.4.4. [2,7,12,17-Tetrabromo-3,8,13,18-tetrafluoro-
5,10,15,20-tetraphenylporphinato]copper (24(Cu)), free
base (24) and Zn(II) complex (24(Zn)). To a stirred
solution of porphyrins 23(Cu) in 25 mL of CHCl /CCl
4
o-H), 8.83 (d, 2H, J¼4.8 Hz, H or H ), 8.93 (d, 2H,
a
b
1
9
J¼4.8 Hz, H or H ); F NMR (188.31 MHz, CDCl ) d
b
a
3
2
143.69 (d, 2F, J¼5.0 Hz, F or F ), 2143.96 (d, 2F,
(nm) (rel.
b a 2 2 max
a
b
3
J¼5.0 Hz, F or F ); UV–visible (CH Cl ) l
(1:1), was added slowly bromine (160 mL) in the same
solvent (7 mL), at rt. After 4 h of stirring, a solution of
pyridine (400 mL) in CHCl /CCl (1:1) was added dropwise
int.) 412 (100), 540 (6.6), 578 (3.1).
3
4
1
b-F TPPZn (22(Zn)). H NMR (200.13 MHz, CDCl ) d
2
(caution: exothermic reaction!). The mixture was stirred
overnight and quenched with a 20% aqueous Na S O
2 5
3
7
.76 (m, 12H, m-H and p-H), 8.14 and 8.21 (m, 8H, o-H),
.84 (d, 2H, J¼4.8 Hz, H or H ), 8.94 (d, 2H, J¼4.8 Hz, H
2
8
or H ), 8.95 (s, 2H, H ); F NMR (188.31 MHz, CDCl ) d
solution (30 mL). After decantation, the organic phase
was dried over MgSO . After filtration and evaporation
b
1
c
c
9
b
a
3
4
2
144.52 (s); UV–visible (CH Cl ) l (nm) (rel. int.) 414
max
of the solvents, the copper complex 24(Cu) was purified
by column chromatography on silica gel using CHCl as
eluent.
2
2
(
(
100), 543 (6.5), 581 (3.1); HRMS (FAB): m/z 712.1431
þ
3
64
M calcd for C H F N Zn: 712.1417).
44 26 2 4
4
.4.2. From 3-fluoro-1H-pyrrole (porphyrins b-F TPP,
4
Cu(II) porphyrins 24(Cu). UV–visible (CH Cl ) l
2
(nm)
2
max
2
pyrrole (7) (120 mg, 0.5 mmol) in CH Cl (1.2 mL) under
3). To a stirred solution of 3-fluoro-1-(triisopropylsilyl)-
1
(rel. int.) 419 (100), 546 (7.0).
4
2
2
argon was added a 1 M solution of tetra-n-butylammonium
fluoride in THF (0.5 mL, 0.5 mmol) at rt. After 5 min,
CH Cl (50 mL) was added. The solution was washed with
Demetalation procedure and Zn insertion. The brominated
copper complex 24(Cu) was dissolved in chloroform
(20 mL) and concentrated sulfuric acid (4 mL) was added
cautiously to the stirred solution. When demetalation was
complete (UV–visible monitoring), the mixture was
neutralized by addition of 4N aqueous NaOH. After
separating layers, the organic phase was dried (MgSO4),
filtered and evaporated. The free base 24 was purified by
column chromatography (CH Cl as eluent). Zinc insertion
2
2
water (3£10 mL) and dried (MgSO ). After filtration, to this
4
solution under argon was added benzaldehyde (53 mg,
0
.5 mmol). The mixture was stirred at rt while BF ·Et O
3 2
(
21 mL, 0.16 mmol) was added via a syringe. After 1 h,
DDQ (85 mg, 0.37 mmol) was added and the reaction
stirred for an additional hour. After evaporation of the
solvent, the porphyrins were purified under their dicationic
form by column chromatography on silica gel, eluting with
CH Cl saturated with perchloric acid. The organic layer
2
2
was carried out with Zn(OAc) ·4H O in a CH Cl /CH OH
3
2
2
2
2
mixture as for 23.
2
2
was washed with water until neutral and dried over MgSO4.
After removal of the solvent in vacuo, the mixture of
porphyrins 23 was obtained as a purple solid (32 mg, 38%):
2,7,12,17-Tetrabromo-3,8,13,18-tetrafluoro-5,10,15,20-
1
tetraphenylporphyrin (24). H NMR (200.13 MHz, CDCl )
3
d-3.00 (br s, 2H, NH), 7.75 (m, 12H, m-H and p-H), 8.07 (m,
19
1
H NMR (200.13 MHz, CDCl ) d 23.45 (br s, 2H, NH),
3
8H, o-H); F NMR (188.13 MHz, CDCl ) d 2118.10 (br s,
3
7
.64–7.80 (m, 12H, m-H, p-H), 8.00–8.10 (m, 8H, o-H),
1
4F), 2121.74 (br s, 4F); UV–visible (CH Cl ) l
2
(nm)
max
2
9
25
8
.10–8.22 (m, 4H, b-H); F NMR (188.31 MHz, CDCl ) d
3
(1£10 ) 425 (1.661), 522 (0.126), 561 (0.081), 670
2
5
1/2
2
4
124.96 (br s); UV–visible (CH Cl ) l
(nm) (1£10
)
10 (2.478), 505 (0.188), 538 (0.065), 583 (0.064), 637
(0.057); CV (CH Cl /TBAPF ): E
2
20.78, 20.89.
(V)¼1.57, 1.09,
2
2
max
2
6
1
/2
(
0.054); CV (CH Cl /TBAPF ) E
2
(V)¼1.17, 21.08,
2
6
2
1.35.
[2,7,12,17-Tetrabromo-3,8,13,18-tetrafluoro-5,10,15,20-
1
tetraphenylporphinato]zinc
(200.13 MHz, CDCl ) d 7.59 (m, 12H, m-H and p-H),
(24(Zn)).
H
NMR
4
.4.3. [2,7,12,17-Tetrafluoro-5,10,15,20-tetraphenyl-
3
9
1
porphinato]zinc (23(Zn)) or copper (23(Cu)). To a stirred
solution of porphyrins 23 (13.7 mg, 0.02 mmol) in 15 mL of
CH Cl /CH OH (2:1) was added a 5-fold excess of
Zn(OAc) ·4H O or Cu(OAc) . The reaction was monitored
2
by UV–visible spectroscopy. When metalation was com-
7.90 (m, 8H, o-H); F NMR (282.40 MHz, CDCl /CD OD
3 3
(4:1)) d 2118.21 (s, major peak); 2118.34, 2118.36,
2118.41, 2120.90 and 2120.94 (s, minor peaks); UV–
2
2
3
2
5
visible (CH Cl ) l
(nm) (1£10 ) 422 (2.082), 551
(0.121); CV (CH Cl /TBAPF ): E
2 6
2
2
2
2
max
1
/2
(V)¼1.16, 1.03,
2

6722
J. Leroy et al. / Tetrahedron 58 (2002) 6713–6722
þ
2
1.25, 21.53. HRMS (FAB, m-NBA)): m/z 1061.7665 (M
12. Takaya, H.; Kojima, S.; Murahashi, S.-I. Org. Lett. 2001, 3,
421–424.
7
9
66
calcd for C H Br4F4 Zn: 1061.7630).
4 20
4
1
1
1
3. Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827–836.
4. Barnes, K. D.; Hu, Y.; Hunt, D. A. Synth. Commun. 1994, 24,
Acknowledgments
1
749–1755.
5. Bondon, A.; Porhiel, E.; Pebay, C.; Thouin, L.; Leroy, J.;
Moinet, C. Electrochim. Acta 2001, 46, 1899–1903.
6. This work. Determined by Siwoloboff’s method.
We deeply thank Dr D. Buisson, Universit e´ R. Descartes,
Paris, for his helpful assistance in the preparative GLC
experiments and the Brittany Region for the financial
support as a grant to E. Porhiel.
1
1
7. These values were obtained using the ACD/I-Lab Web service
(ACD/Boiling Point and Vapor Pressure 5.0).
8. Breitmaier, E.; Voelter, W. Carbon-13 NMR Spectroscopy.
1
VCH: New York, 1987.
19. Leroy, J.; Cantacuz e` ne, D.; Wakselman, C. Synthesis 1982,
13–315.
References
3
1
2
3
. (a) Leroy, J.; Wakselman, C. Tetrahedron Lett. 1994, 35,
605–8608. (b) Woller, E. K.; Smirnov, V. V.; DiMagno, S. G.
J. Org. Chem. 1998, 63, 5706–5707.
20. Grehn, L.; Ragnarsson, U. Angew. Chem. Int. Ed. Engl. 1984,
23, 296.
8
21. The unstable 3-bromo-1H-pyrrole (8) was obtained following
the procedure described in Ref. 6 as a mixture with
. (a) Leroy, J.; Bondon, A.; Toupet, L.; Rolando, C. Chem. Eur.
J. 1997, 3, 1890–1893. (b) Woller, E. K.; DiMagno, S. G.
J. Org. Chem. 1997, 62, 1588–1593.
1
triisopropylsilanol. Curiously, its H NMR spectrum did not
fit exactly with that described in this work, perhaps due to a
different sweep frequency, the differences concerning essen-
tially the multiplicity of the signals. The N-Boc derivative 9
. (a) Parusel, A. B. J.; Wondmagegn, T.; Ghosh, A. J. Am.
Chem. Soc. 2000, 122, 6371–6374. Wertsching, A. K.; Koch,
A. S.; DiMagno, S. G. J. Am. Chem. Soc. 2001, 123,
1
13
displayed close but distinct H and C NMR spectra from that
of the 2-bromo isomer [Groenendaal, L.; Loo, M. E. Van.;
Vekemans, J. A. J. M.; Meijer, E. W. Synth. Commun. 1995,
25, 1589–1600]. Trace amounts of this latter were identified in
3
932–3939, and references cited therein. (b) Takeuchi, T.;
Gray, H. B.; Goddard, III, W. A. J. Am. Chem. Soc. 1994, 116,
730–9732.
. (a) Porhiel, E.; Bondon, A.; Leroy, J. Tetrahedron Lett. 1998,
9, 4829–4830. (b) Porhiel, E.; Bondon, A.; Leroy, J. Eur.
9
1
3
4
the C NMR spectrum of 9.
3
22. Bigg, D. C. H.; Bonnaud, B. Synthesis 1994, 465–467.
23. Demange, L.; M e´ nez, A.; Dugave, C. Tetrahedron Lett. 1998,
39, 1169–1172, and personal communication.
J. Inorg. Chem. 2000, 1097–1105.
5
6
. De Rosa, M. J. Org. Chem. 1982, 47, 1008–1010.
. Bray, B. L.; Mathies, P. H.; Naef, R.; Solas, D. R.; Tidwell,
T. T.; Artis, D. R.; Muchowski, J. M. J. Org Chem. 1990, 55,
24. Direct fluorination with DAST of the chlorhydrate of 11, as
described for the cis isomer [Tran, T. T.; Patino, N.; Condom,
R.; Frogier, T.; Guedj, R. J. Fluorine Chem. 1997, 82,
125–130]. Failed.
6317–6328.
7
8
. Buhr, G. Chem. Ber. 1973, 106, 3544–3558.
. (a) Onda, H.; Toi, H.; Aoyama, Y.; Ogoshi, H. Tetrahedron
Lett. 1985, 26, 4221–4224. (b) Suzuki, A.; Toi, H.; Aoyama,
Y.; Ogoshi, H. Heterocycles 1992, 33, 87–90. (c) Suzuki, A.;
Tomizawa, T.; Hayashi, T.; Mizutani, T.; Ogoshi, H. Bull.
Chem. Soc. Jpn 1996, 69, 2923–2933.
25. (a) The preparation of methyl 4-chloro-, 4-bromo- and 4-iodo-
1H-pyrrole-2-carboxylates has been reported: B e´ langer, P.
Tetrahedron Lett. 1979, 2505–2508. (b) See also: Bergauer,
M.; Gmeiner, P. Synthesis 2002, 274–278.
26. Spyroulias, G. A.; Coutsolelos, A. G. Polyhedron 1995, 14,
2483–2490.
9
. Uno, H.; Sakamoto, K.; Tominaga, T.; Ono, N. Bull. Chem.
Soc. Jpn 1994, 67, 1441–1448.
27. Kadish, K. M.; D’Souza, F.; Villard, A.; Autret, M.; Van
Caemelbecke, E.; Bianco, P.; Antonini, A.; Tagliatesta, P.
Inorg. Chem. 1994, 33, 5169–5170.
1
0. Qiu, Z.-M.; Burton, D. J. Tetrahedron Lett. 1994, 35,
319–4322.
1. Shi, G.-q.; Cai, W.-l. J. Org. Chem. 1995, 60, 6289–6295.
4
1
28. Bhyrappa, P.; Krishnan, V. Inorg. Chem. 1991, 30, 239–245.