A convenient preparation of thioether functionalized porphyrins

Article abstract of DOI:10.1016/j.tet.2006.09.091

This paper describes a convenient and high yielding three-step approach for the synthesis of trans-tetraphenylporphyrins possessing two thioethers in the ortho positions, which will facilitate the synthesis of more elaborate and complex porphyrin architec

Full text of DOI:10.1016/j.tet.2006.09.091

Tetrahedron 62 (2006) 11908–11915
A convenient preparation of thioether functionalized porphyrins
*
Michael M. Pollard and John C. Vederas
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2
Received 21 August 2006; revised 20 September 2006; accepted 22 September 2006
Available online 27 October 2006
Abstract—This paper describes a convenient and high yielding three-step approach for the synthesis of trans-tetraphenylporphyrins possess-
ing two thioethers in the ortho positions, which will facilitate the synthesis of more elaborate and complex porphyrin architectures. Their
synthesis is realized by a double nucleophilic aromatic substitution of 2 equiv of a thiolate on 2,6-dichlorobenzaldehyde to generate a bis-
thioether substituted benzaldehyde. This aldehyde is then condensed with 2 equiv of pyrrole to give a dipyrromethane, which in the final
step reacts with an aromatic aldehyde to give a series of thioether-substituted trans-tetraphenylporphyrins.
Ó 2006 Elsevier Ltd. All rights reserved.
A
1. Introduction
R
R
R
R
NH
N
Porphyrins are a core structural motif that is central to the re-
search of a wide variety of fields including material science,1
supramolecular chemistry,2 catalysis,3 biomimetic chemis-
try,3d,4 and small molecule sensing.5 Among porphyrins,
trans-substituted meso-tetraphenylporphyrins (TPPs) are es-
pecially attractive because they reduce the symmetry of the
molecule and provide an opportunity for selective function-
alization. The resulting linear substitution pattern can be
conveniently harnessed for the construction of large, derivat-
ized porphyrinic scaffolds and complex architectures.
N
HN
A
A
R
R
ABAB Trans substituted porphyrin
+
O
NH HN
dipyrromethane
H
N
+
R
R
O
Figure 1. Retrosynthesis for C2-symmetric ABAB trans-porphyrins.
Functionalization at the ortho positions (R groups, Fig. 1) of
the meso-aryl group of TPPs is crucial to the successful de-
velopment of many of these systems.3,5 This substitution
pattern is advantageous because it places the functionality
over the porphyrin core, thus enabling the chemists to alter
the photophysical or catalytic property of the system by
proximity and steric effects.
via 2,6-bis-(methoxymethyl)benzaldehyde (five steps to
the aldehyde and nine steps to the functionalized porphyrin).
Higuchi et al.7 described the preparation of 2,6-diamido-
phenyl meso substituted porphyrins, requiring 10 chemical
transformations. Starting with 2,6-dimethoxybenzaldehyde,
Lindsey et al.8 reported the preparation of TPPs possessing
alkoxy ethers at both ortho positions of the meso-phenyl
groups. Foxon et al.9 prepared similarly substituted porphy-
rins substituted by chiral ethers starting from resorcinol
(three steps). Additionally, Rose et al.10 reported a carefully
optimized synthesis of the air sensitive meso-tetrakis(2,6-
diamino-4-tert-butylphenyl)porphyrin (five steps), which
required 3 weeks for a good yield in its final step.
The low yields universal to the preparation of porphyrins
make elaborate multistep synthesis of their precursors unat-
tractive. Nevertheless, the utility of porphyrins decorated
with the desired 2,6-disubstituted phenyl groups on the
meso positions is highlighted by the numerous, often lengthy,
and expensive approaches taken by various researchers to
prepare these molecules. Recent examples include the
work of Jux6 who described a useful approach to trans-
TPPs bearing meso-2,6-bis(bromomethyl)phenyl groups
Here, we report a conceptually simple, convenient, and effi-
cient method for the preparation of 2,6-dithioether
substituted benzaldehydes. These aldehydes are readily con-
verted to dipyrromethanes upon treatment with a Lewis acid,
which are then applied in a scrambling free synthesis of C2-
symmetric trans-TPPs. We envision that this approach will
Keywords: trans-Porphyrins; Thioethers; Synthesis; Dipyrromethanes; 2,6-
Disubstituted aldehydes.
* Corresponding author. Tel.: +1 780 492 5475; fax: +1 780 492 2134;
e-mail: john.vederas@ualberta.ca
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.091

M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
11909
facilitate the synthesis of complex porphyrin architectures,
which are useful for broad range of applications in the field
of porphyrin chemistry including catalysis, biomimetic
chemistry, and material science.
dichlorobenzaldehyde with 2.2 equiv of thiols 1c–1e and
1g and K2CO3 in DMF furnished the corresponding di-
thioether products 2c–2e and 2g in good to excellent yields,
typically without the need for chromatography.
Notably, tert-butyl mercaptan (1f) was unreactive when the
above conditions were employed (Table 1, i and ii), probably
due to the lower acidity of this thiol. This transformation
proceeded efficiently when the deprotonation of the thiol
was performed with NaH in DMF prior to the addition of
the aldehyde, affording the product in 88% yield.
2. Results and discussion
2.1. 2,6-Disubstituted benzaldehydes
We anticipated that starting from the inexpensive 2,6-di-
chlorobenzaldehyde, a variety of thiols could be introduced
at the ortho positions via thioethers using nucleophilic aro-
matic substitution. This was inspired by one example in
the literature where Gairns et al.11 prepared 2,6-bis(phenyl-
sulfanyl)benzaldehyde 2a from 2,6-dichlorobenzaldehyde
and potassium thiophenolate in HMPA over 2 days. We
sought to employ mild conditions while avoiding the use
of the known carcinogen HMPA.
The use of only 1 equiv of thiol 1h in the procedure leads to
the selective formation of the monosubstituted product 2h
in 82% isolated yield after recrystallization of the crude
reaction product (Fig. 2). 1H NMR analysis of the crude re-
action mixture showed 90% conversion to the desired 2h as
well as 6% of the disubstituted product 2e and 4% starting
aldehyde.12
We found that when heated to 60 ꢀC for 30 min, 2,6-dichlor-
obenzaldehyde reacted smoothly with potassium thiopheno-
late to give the double substitution product in 93% yield
without chromatography (Table 1).
35 °C, K2CO3
HO
HO
Cl
Cl
S
Cl
SH
O
O
2h
1h
This method also succeeded with aliphatic thiols (Table 1,
entries 1b–1g). At 60 ꢀC, over 3 h, 2,6-dichlorobenzalde-
hyde reacts with 2.2 equiv of KSMe to give dithioether 2b
in excellent yield. The application of similar conditions to
other substrates shows how this nucleophilic aromatic sub-
stitution is general for many aliphatic thiols. Treatment of
Figure 2. Selective monosubstitution of the dichlorobenzaldehyde.
2.2. Dipyrromethanes
With the series of 2,6-disubstituted aldehydes available, we
attempted to prepare the corresponding dipyrromethanes us-
ing the conditions developed by Lindsey et al.13 Treatment
of aldehyde 2a with TFA in excess pyrrole gives dipyrro-
methane 3a in 53% yield (Table 2). Application of this
procedure to aldehydes 2b–2f followed by flash chromato-
graphy gave the desired dipyrromethanes 3b–3f, respec-
tively, in moderate yields ranging from 31–51% with no
observed scrambling. These results are typical for dipyrro-
methanes, which cannot be distilled or selectively precipi-
tated.13,14 The successful application of the method to
aldehyde 2h bearing an unprotected alcohol highlights the
convenience of this method for the rapid access of porphyrin
precursors under mild conditions without the need for
elaborate protecting group strategy.
Table 1. Synthesis of 2,6-dithioether aldehydes
DMF, 60 °C
Thiol
+
RS
SR
Cl
Cl
conditions i, ii or iii
O
O
1a-g
2a-g
Thiol
Conditions
Product
Yield (%)
R
1a
1b
ii
i
2a
2b
93
93
S
Me
S
2.3. Porphyrins
S
1c
i
2c
89
Initially, we explored the use of dipyrromethane 2a in the
synthesis of ABAB C2-symmetric trans-TPPs. Since stan-
dard conditions15 for the synthesis of trans-TPPs typically
give significant amounts of scrambling of the meso substitu-
ents, we employed conditions developed by Lindsey et al.
to minimize this for the preparation of porphyrins from 5-
(2,6-dichlorophenyl)dipyrromethane and 5-mesityldipyrro-
methanes.13
MeO
1d
1e
i
i
2d
2e
71
83
S
HO
S
1f
iii
i
2f
88
89
S
O
1g
2g
Treating 1 equiv of 3a and 1 equiv of p-tolualdehyde with
1.78 equiv of TFA in DCM,13 followed by oxidation with
DDQ furnished the ABAB trans-porphyrin 4a in 25% yield
(Table 3, entry 1). Although the yields initially may seem
modest, they are quite reasonable for this type of porphyrin
formation.1a
N
S
O
Conditions: (i) 2.0 or 2.2 equiv of both thiol and K2CO3; (ii) commercially
available potassium thiomethoxide was used, and the reaction was done in
a glove box; (iii) thiol 1f was premixed with NaH in DMF before the slow
addition of the aldehyde.

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M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
Table 2. Preparation of difunctionalized dipyrromethanes
In conclusion, we have developed a quick, convenient, and
inexpensive way to prepare trans-TPPs bearing thioethers
in the 2 and 6 positions of the meso-phenyl groups. Con-
sidering the mild conditions used, this method should be
compatible with a wide range of functionality, making it an
attractive approach for the preparation of elaborate porphy-
rin architectures. Moreover, since these systems also bear
multiple thioether functions, it offers the possibility of using
these thioether porphyrins for applications requiring their
self-assembly on gold surfaces.
Pyrrole
TFA
R1
R2
R1
R2
15 min
O
NH HN
3a-g
2a-g
R1
R2
Aldehyde
Product Yield (%)
2a
R1¼R2¼
R1¼R2¼
3a
3b
53
31
S
3. Experimental
Me
2b
S
3.1. General remarks
S
2c
2d
2f
R1¼R2¼
R1¼R2¼
R1¼R2¼
R1¼Cl
3c
3d
3f
48
51
46
40
All reagents and solvents used were of ACS grade and were
used without further purification unless otherwise men-
tioned. All processes involving air or moisture sensitive
reactants and/or requiring anhydrous conditions were per-
formed under a positive pressure of pre-purified argon using
flame-dried glassware. Unless otherwise specified, solutions
of Na2CO3 and NaOH refer to saturated aqueous solutions.
MeO
S
S
R2 = HO
2h
3h
S
Compound visualization during TLC analysis was achieved
by UV fluorescence, and simply heating on a hot plate for
30 s (this is particularly effective for dipyrromethanes,
which develop a green color, which is different from the
reaction byproducts).
This procedure was successfully applied to the synthesis of
a series of porphyrins. Employing Lindsey’s conditions,13
porphyrins 4b–4i were prepared in moderate to good yields
(19–51%). The use of dipyrromethane 3h in the synthesis
gave porphyrin 4h as a mixture of rotamers, which were sep-
arated by careful flash chromatography to give 17% of the
a,a-isomer and 16% of the a,b-isomer.
Infrared spectra (IR) were recorded on a Nicolet Magna 750
FT-IR spectrometer as either a cast or microscope (mscope).
Table 3. Synthesis of C2-symmetric trans-porphyrins
R3
R1
R2
R1
R2
R3
NH
N
R1
R2
1) TFA, CH2Cl2, rt
2) DDQ, rt
N
HN
+
NH HN
3a-g
O
R3
4a-g
R1
R2
R3
Dipyrromethane
Product
Yield (%)
25
3a
R1¼R2¼
R1¼R2¼
4a
TMS
Me
S
Me
3b
S
4b
19
S
S
Me
Me
3c
R1¼R2¼
R1¼R2¼
4c
51
21
MeO
3d
4d
S
O
R1 = HO
3h
R1¼Cl
4h
4i
33a (a,a¼17%, a,b¼16%)
3
S
I
3c
R1¼R2¼
21
MeO
a
Due to the hindered rotation around the porphyrin-meso-aryl bond, the a,a- and the a,b-isomer could be separated.

M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
11911
Cast refers to the evaporation of a solution on a NaCl plate.
Mass spectra (MS) were recorded on a Kratos AEIMS-50
high-resolution mass spectrometer (HRMS), using electron
impact ionization (EI), Applied Biosystems (sinapinic acid
as the matrix), and Micromass ZabSpec Hybrid Sector-
TOF using positive mode electrospray (ES). Microanalyses
were obtained on Perkin–Elmer 240 or Carlo Erba 1180
elemental analyzer. Nuclear magnetic resonance (NMR)
spectra were obtained on Inova Varian 400 and 500 MHz in-
struments. 1H NMR chemical shifts are reported in parts per
million (ppm) downfield relative to tetramethylsilane (TMS)
using the residual solvent resonance as the reference: CDCl3,
d 7.24; CD3OD, d 3.30. The coupling constants reported are
within an error range of 0.2–0.4 Hz. 13C NMR shifts are
reported relative to: CDCl3, d 77.0; CD3OD, d 49.0. Porphy-
rin a-carbon signals are typically not reported because of
signal broadening due to NH tautomerization.16 Signals
are reported within 0.1 ppm except where close peaks neces-
sitate an additional significant figure.
(MeOH) gave 2b as a white solid (1.85 g, 93%): mp 95–
97 ꢀC; IR (CHCl3, cast) 2981, 2921, 2861, 2767, 1670,
1550, 1437, 1416, 1200, 949, 756 cmꢂ1; 1H NMR (CDCl3,
500 MHz) d 2.42 (s, 6H), 7.05 (d, 2H, J¼8.0 Hz), 7.36 (t,
1H, J¼8.0 Hz), 10.64 (s, 1H); 13C NMR (CDCl3,
125 MHz) d 16.2, 121.9, 129.4, 132.9, 145.7, 189.9; HRMS
(EI) calcd for C9H10OS2: 198.0173, found: 198.0175 [M+]
(100.0%). Anal. Calcd for C9H10OS2: C, 54.51; H, 5.08.
Found: C, 54.25; H, 5.06.
3.1.4. 2,6-Bis(4-methoxybenzylsulfanyl)benzaldehyde
(2c). 4-Methoxybenzylmercaptan (900 mL, 6.00 mmol)
was added to an argon flushed (20 min) stirred mixture of
2,6-dichlorobenzaldehyde (525 mg, 3.00 mmol), K2CO3
(996 mg, 7.00 mmol), and DMF (3 mL). The mixture was
stirred for 5 min, and then heated to 60 ꢀC for 2 h until a light
yellow solid precipitated. Water (15 mL) and EtOAc
(25 mL) were then added to the reaction mixture, which
was then filtered, the solid was washed with cold EtOAc
(3ꢁ5 mL), and dried in vacuo to give analytically pure 2c
(290 mg). The filtered organic layer was separated, washed
with water (5ꢁ15 mL), dried (Na2SO4), and concentrated
in vacuo. Purification of this crude residue by recrystalliza-
tion from Hex/EtOAc (4/1) gave a further 810 mg (total
1.11 g, 90%): mp 142–143 ꢀC; IR (CH2Cl2, cast) 2953,
2930, 2833, 2755, 1664, 1609, 1557, 1304, 1257, 1177,
3.1.1. 5-(3,5-Dioxo-4-aza-tricyclo[5.2.12,6]dec-8-en-4-
yl)ethanethiol (1g). Norborn-5-ene-2,3-endo-dicarboxylic
anhydride17 (1.64 g, 10.0 mmol), triethylamine (2.02 g,
20.0 mmol), and 2-thioethanolamine hydrochloride (1.13 g,
10.0 mmol) were dissolved in DMF (10 mL) and placed
in a sealed tube. The solution was purged with argon
(20 min), the reaction vessel was sealed, and then heated at
140 ꢀC for 14 h. The tube was then cooled, the reaction mix-
ture was diluted with water (50 mL), extracted with EtOAc
(50 mL), and the organic layer was washed with water
(3ꢁ50 mL), dried (Na2SO4), and concentrated in vacuo. Pu-
rification by flash chromatography eluting with Hex/EtOAc
(4/1) afforded a white solid (290 mg, 11%): mp 111–
114 ꢀC; IR (CHCl3, cast) 3062, 2989, 2944, 2871, 2559,
1
1031, 772 cmꢂ1; H NMR (CDCl3, 500 MHz) d 3.82 (s,
6H), 4.11 (s, 4H), 6.86 (AA0BB0, 4H), 7.26 (m, 6H), 7.26
(t, 1H, J¼8.0 Hz), 10.67 (s, 1H); 13C NMR (CDCl3,
125 MHz) d 38.3, 55.3, 114.1, 126.0, 127.8, 130.1, 131.9,
132.7, 143.6, 159.6, 191.3; HRMS (EI) calcd for
C23H22O3S2: 410.1010, found: 410.1010 [M+] (14.6%).
Anal. Calcd for C23H22O3S2: C, 67.29; H, 5.40; S, 15.62.
Found: C, 66.96; H, 5.58; S, 15.40.
1766, 1701, 1395, 1336, 1159, 724 cmꢂ1
;
1H NMR
(CDCl3, 500 MHz) d 1.33 (t, 1H), 1.50 (dt, 1H, J¼9.0,
1.5 Hz), 1.69 (dt, 2H, J¼8.5, 1.5 Hz), 2.53 (m, 2H), 3.22
(dd, 2H, J¼1.5, 3.0 Hz), 3.35 (m, 2H), 3.47 (m, 2H), 6.07
(t, 2H, J¼2.0 Hz); 13C NMR (CDCl3, 125 MHz) d 22.0,
41.3, 45.0, 45.8, 52.3, 134.4, 177.2; HRMS (EI) calcd for
C13H15O2NS: 265.0772, found: 265.0774 [M+] (21.3%).
3.1.5. 2,6-Bis(allylsulfanyl)benzaldehyde (2d). Allyl mer-
captan (5.0 mL, 70% purity; stench!) was added to an argon
flushed stirred suspension of 2,6-dichlorobenzaldehyde
(1.75 g, 10.0 mmol) and K2CO3 (4.14 g, 30.0 mmol) in
DMF (10 mL). The mixture was heated to 65 ꢀC for 10 h,
cooled, diluted with EtOAc (20 mL), and water (10 mL),
and then separated. The organic layer was washed with
Na2CO3 (2ꢁ20 mL), water (4ꢁ20 mL), dried (Na2SO4),
and concentrated in vacuo. Purification of the crude residue
by flash chromatography (Hex/EtOAc, 7/1) gave 2d as an oil
(1.77 g, 71%); IR (neat film) 3081, 2978, 2858, 1670, 1636,
1561, 1552, 1435, 1406, 1202, 988, 922, 772 cmꢂ1; 1H NMR
(CDCl3, 400 MHz) d 3.56 (dt, 4H, J¼1.2, 6.8 Hz), 5.13 (dq,
2H, J¼1.1, 10.0 Hz), 5.21 (dq, 2H, J¼1.4, 17.2 Hz), 5.86
(ddt, 2H, J¼17.0, 10.2, 6.8 Hz), 7.23 (AB2, 2H), 7.36
(AB2, 1H), 10.73 (s, 1H); 13C NMR (CDCl3, 125 MHz)
d 36.9, 118.8, 125.9, 132.0, 132.4, 132.5, 143.1, 191.4;
HRMS (EI) calcd for C13H14OS2: 250.0486, found:
250.0479 [M+] (14.5%).
3.1.2. 2,6-Bis(phenylsulfanyl)benzaldehyde (2a). Thio-
phenol (2.05 mL, 22.0 mmol) was added to a nitrogen
flushed (20 min) stirred mixture of 2,6-dichlorobenzalde-
hyde (1.75 g, 10.0 mmol), K2CO3 (3.04 g, 2.20 mmol), and
DMF (5.0 mL). The mixture was stirred for 5 min, and
then heated to 60 ꢀC until the reaction was complete as
judged by TLC (Hex/EtOAc 6/1) (ca. 30 min). The mixture
was diluted with water (15 mL), the product was filtered,
rinsed with water (6ꢁ10 mL), and dried in vacuo at 55 ꢀC
for 3 h to give the aldehyde 2a (3.11 g, 93%). All spectro-
scopic data were consistent with the reported data.11
3.1.3. 2,6-Bis(methylsulfanyl)benzaldehyde (2b). Under
inert atmosphere (glove box), NaSMe (1.46 g, 21.0 mmol)
was added portionwise to a stirred solution of 2,6-dichloro-
benzaldehyde (1.75 g, 10.0 mmol) in DMF (10 mL) (cau-
tion, exothermic!). The mixture was stirred for 20 min,
then heated to 60 ꢀC, and stirred for 1 h. The mixture was
cooled to rt, diluted with EtOAc (25 mL), and washed
with water (3ꢁ15 mL), dried (Na2SO4), and concentrated
invacuo. Purification of the crude residue by recrystallization
3.1.6. 2,6-Bis(2-hydroxyethylsulfanyl)benzaldehyde (2e).
2-Mercaptoethanol (1.72 g, 1.50 mL, 22.0 mmol) was added
to a stirred degassed suspension of K2CO3 (3.00 g,
22.0 mmol) and 2,6-dichlorobenzaldehyde (1.75 g,
10.0 mmol) in DMF (5 mL). This mixture was heated to
65 ꢀC for 8 h, cooled to rt, filtered, and recrystallized from
CHCl3/Hex to give 2.14 g (83%) of a light yellow solid:
mp 130–131 ꢀC; IR (mscope) 3231 (br), 2928, 2872, 1670,

11912
M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
1
1200 cmꢂ1; H NMR (CDCl3, 500 MHz) d 3.14 (t, 4H,
J¼6.3 Hz), 3.83 (t, 4H, J¼6.0 Hz), 7.31–7.32 (A2B, 1H),
7.38–7.41 (A2B, 2H), 10.76 (s, 1H); 13C NMR (CD3OD,
125 MHz) d 36.9, 61.1, 126.5, 133.4, 134.1, 144.5, 192.5;
HRMS (EI) M+ C11H914O3S2 calcd: 258.0385, found:
258.0384.
(CH2Cl2, cast) 3253 (br), 2924, 2880, 2767, 1667,
1415 cmꢂ1; 1H NMR (CDCl3, 500 MHz) d 2.13 (br s, 1H),
3.15 (t, 2H, J¼6.0 Hz), 3.88 (t, 2H, J¼6.0 Hz), 7.21 (dd,
1H, J¼8.0, 1.0 Hz), 7.31 (d, 1H, J¼8.5 Hz), 7.37 (t, 1H,
J¼8.0 Hz), 10.58 (d, 1H, J¼0.5 Hz); 13C NMR (CDCl3,
125 MHz), d 35.1, 60.2, 124.7, 126.5, 129.5, 133.5, 139.9,
143.9, 190.5; HRMS (EI) M+ C9H9O2S37Cl calcd:
217.9982, found: 217.9971.
3.1.7. 2,6-Bis(tert-butylsulfanyl)benzaldehyde (2f). tert-
Butyl mercaptan (2.45 mL, 22.0 mmol) was added dropwise
to a stirred degassed suspension of NaH (50% in mineral
oil, 0.96 g, 20.0 mmol) in DMF (5 mL). After the hydro-
gen evolution ceased, 2,6-dichlorobenzaldehyde (1.75 g,
10.0 mmol) was added portionwise (caution, exothermic!).
This mixture was stirred for 2 h at 60 ꢀC, cooled to rt, diluted
with water (ca. 80 mL), and extracted with EtOAc
(3ꢁ40 mL). The combined organic extracts were washed
with water (4ꢁ20 ml), and concentrated in vacuo to give
an amber oil. This material was heated to 100 ꢀC in vacuo
for 20 min, and then cooled to give a yellow solid. This
was recrystallized from MeOH to give the title compound
as a yellow crystalline solid (2.03 g, 72%). The mother li-
quor from the recrystallization was concentrated in vacuo,
and the solid was again recrystallized to give an additional
452 mg (total yield, 88%): mp 58.0–59.5 ꢀC; 1H NMR
(CDCl3, 500 MHz) d 1.12 (s, 18H), 7.31–7.32 (A2B, 1H),
7.38–7.41 (A2B, 2H), 10.76 (s, 1H); 13C NMR (CD3OD,
125 MHz) d 11.4, 41.1, 126.5, 133.4, 134.2, 146.5, 192.2;
HRMS (EI) M+ C15H22OS2 calcd: 282.1112, found:
282.1115.
3.1.10. 5-(2,6-Bis(phenylsulfanyl)phenyl)dipyrrometh-
ane (3a). TFA (30 mL, 0.40 mmol) was added to a degassed
stirred solution of aldehyde 2a (1.29 g, 4.00 mmol) in
pyrrole (10.7 g). The solution was stirred for 15 min, and
then the reaction was quenched by the addition of 0.1 M
NaOH (4 mL). EtOAc (20 mL) was added and the layers
were separated. The organic layer was washed with water
(3ꢁ10 mL), dried (Na2SO4), and concentrated in vacuo.
Purification by flash chromatography (Hex/EtOAc¼8/1)
gave an amber solid (928 mg, 53%); IR (CH2Cl2, cast)
1
3390, 3056, 1674, 1552, 1476, 1438, 749 cmꢂ1; H NMR
(CDCl3, 300 MHz) d 6.13 (m, 2H), 6.21 (q, 2H,
J¼3.0 Hz), 6.70 (dd, 2H, J¼2.7, 1.5 Hz), 6.78 (s, 1H),
7.18 (t, 1H, J¼7.8 Hz), 7.16 (d, 2H, J¼7.8 Hz), 7.20–7.35
(m, 10H), 8.63 (br s, 2H); 13C NMR (CDCl3, 100 MHz)
d 40.9, 107.8, 108.6, 116.9, 127.2, 127.9, 129.3, 130.9,
131.3 (br), 132.9, 136.5, 137.7 (br), 143.5; HRMS (EI) calcd
for C27H22S2N2: 438.1224, found: 438.1225 [M+], (100%).
3.1.11. 5-(2,6-Dithiomethoxyphenyl)dipyrromethane
(3b). TFA (129 mL, 1.66 mmol) was added to a degassed
stirred solution of aldehyde 2b (990 mg, 5.0 mmol) in pyr-
role (20 mL). After the solution was stirred for 25 min, the
reaction was quenched by the addition of 0.1 M NaOH
(20 mL). The mixture was diluted with EtOAc (30 mL)
and separated. The organic layer was washed with water
(2ꢁ20 mL), dried (Na2SO4), concentrated in vacuo, and
purified by flash chromatography (Hex/EtOAc¼5/1) to
give a colorless foam (509 mg, 31%): mp 102–104 ꢀC; IR
3.1.8. 2,6-Bis(2-(3,5-dioxo-4-aza-tricyclo[5.2.12,6]dec-8-
en-4-yl)ethanethio)benzaldehyde (2g). A solution of thiol
1g (223 mg, 0.842 mmol) and 2,6-dichlorobenzaldehyde
(85 mg, 0.49 mmol) in dry DMF (2 mL) was degassed with
a stream of argon for 30 min. K2CO3 (138 mg, 1.00 mmol)
was added under an argon blanket and the mixture was main-
tained at this temperature for a further 5 min under argon.
The mixture was heated to 60 ꢀC and stirred for 4 h. The mix-
ture was cooled, diluted with H2O (10 mL), and extracted
with EtOAc (3ꢁ15 mL). The combined organic layers
were washed with water (3ꢁ20 mL), dried (Na2SO4), and
concentrated in vacuo. Purification of the crude residue by
flash chromatography eluting with Hex/EtOAc (2/1 to 1/2)
afforded the aldehyde 2g as a yellow solid (239 mg, 89%):
Rf ¼0.2 (Hex/EtOAc, 4/3), mp 117–119 ꢀC; IR (CHCl3,
cast) 2989, 2860, 1764, 1698, 1670, 1562, 1396, 1335,
1203, 1126, 750 cmꢂ1; 1H NMR (CDCl3, 500 MHz) d 1.50
(d, 2H, J¼8.5 Hz), 1.69 (dt, 2H, J¼8.5, 1.5 Hz), 2.93 (m,
4H), 3.21 (dd, 4H, J¼1.5, 3.0 Hz), 3.34 (m, 4H), 3.54 (m,
4H), 6.07 (t, 2H, J¼1.8 Hz), 7.36 (AB2, 2H), 7.45 (AB2,
1H), 10.61 (s, 1H); 13C NMR (CDCl3, 125 MHz) d 29.9,
40.0, 44.9, 45.8, 52.2, 124.9, 131.7, 133.2, 134.5, 142.2,
177.2, 190.6; HRMS (EI) calcd for C29H28O5S2N2:
548.14398, found: 548.14340 [M+] (1.20%).
(CHCl3, cast) 3373, 2917, 1557, 1433, 1027, 715 cmꢂ1
;
1H NMR (CDCl3, 500 MHz) d 2.42 (s, 6H), 6.08 (m, 2H),
6.19 (m, 2H), 6.52 (s, 1H), 6.72 (m, 2H), 7.13 (d, 2H,
J¼8.0 Hz), 7.21 (t, 1H, J¼7.6 Hz), 8.67 (s, 2H); 13C NMR
(CDCl3, 125 MHz) d 17.7, 39.9, 107.7, 108.3, 116.6,
124.8, 127.6, 130.6, 138.4, 139.1; HRMS (EI) calcd for
C17H18S2N2: 314.0912, found: 314.0907 [M+] (100.0%).
Anal. Calcd for C17H18S2N2C: 64.97; H, 5.73; N, 8.92.
Found: C, 65.12; H, 5.44; N, 8.89.
3.1.12. 5-(2,6-Bis(4-methoxybenzylsulfanyl)phenyl)di-
pyrromethane (3c). TFA (710 mg mL, 6.23 mmol) was
added to a degassed stirred solution of aldehyde 2c
(1.44 g, 3.50 mmol) in pyrrole (35 mL) and CH2Cl2 (ca.
5 mL added to dissolve the aldehyde). After the solution
was stirred for 15 min, the reaction was quenched by the ad-
dition of 0.1 M NaOH (20 mL). EtOAc (50 mL) was added,
the layers were separated, and the organic layer was washed
with water (2ꢁ40 mL), dried (Na2SO4), concentrated in va-
cuo, and purified by flash chromatography (Hex/EtOAc, 4/1)
to give a light yellow foam (880 mg, 48%): Rf¼0.2 (Hex/
EtOAc¼4/1), mp 65–70 ꢀC (dec); IR (CH2Cl2, cast) 3387,
3.1.9. 2-Chloro-6-(2-hydroxyethylsulfanyl)benzaldehyde
(2h). 2-Mercaptoethanol (780 mg, 700 mL, 10.0 mmol)
was added to a stirred degassed suspension of K2CO3
(1.40 g, 10.0 mmol) and 2,6-dichlorobenzaldehyde (1.75 g,
10.0 mmol) in DMF (5 mL) at 0 ꢀC. This mixture was heated
to 40 ꢀC for 3 h, cooled to rt, diluted with water (ca. 70 mL),
and filtered. This material was recrystallized from EtOAc/
Hex to give a light yellow solid: mp 114–115 ꢀC; IR
2932, 2834, 1609, 1554, 1511, 1249 cmꢂ1 1H NMR
;
(CDCl3, 500 MHz) d 3.70 (s, 6H), 4.02 (s, 4H), 6.02 (m,
2H), 6.13 (q, 2H, J¼3.0 Hz), 6.58 (dt, 2H, J¼1.5, 2.7 Hz),

M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
11913
6.72 (s, 1H), 6.82 (AA0BB0, 4H), 7.08–7.18 (m, 6H), 7.89 (br
s, 2H); 13C NMR (CDCl3, 125 MHz) d 40.1 (br), 40.7, 55.6,
107.8, 108.6, 114.3, 116.9, 127.6, 129.6, 130.3, 131.0, 131.4,
137.6, 143.7, 159.2; HRMS (EI) calcd for C31H30O2N2S2:
526.1749, found: 526.1753 [M+] (61.3%).
40.3, 59.8, 107.4, 108.6, 117.0, 128.1, 130.2, 135.7, 137.7;
HRMS (EI) calcd for C17H17ON2S35Cl: 332.0750, found:
332.0750 [M+] (100%).
3.1.16. 5,15-Bis(2,6-diphenylsulfanylphenyl)-10,20-bis(p-
tolyl)porphyrin (4a). TFA (144 mL, 1.78 mmol) was added
to a degassed solution of 3a (438 mg, 1.00 mmol) and p-
tolualdehyde (120 mg, 1.00 mmol) in CH2Cl2 (100 mL).
After the solution was stirred for 30 min, DDQ (340 mg,
1.50 mmol) was added. After an additional 1 h, the reaction
mixture was filtered through a Florisil column (2 cmꢁ
10 cm), and eluted with CH2Cl2. The purple fractions were
combined, and concentrated in vacuo to give a purple solid.
This solid was purified further by flash chromatography
(Hex/EtOAc) to give the title compound (154 mg, 25%);
IR (CH2Cl2, cast) 3316, 3072, 2956, 2156, 1549, 1248,
3.1.13. 5-(2,6-Bis(allylsulfanyl)phenyl)dipyrromethane
(3d). TFA (30 mL, 0.40 mmol) was added to a degassed
stirred solution of aldehyde 2d (1.00 g, 4.00 mmol) in pyr-
role (10.7 g). After the solution was stirred for 15 min, the
reaction was quenched by the addition of 0.1 M NaOH
(4 mL). The mixture was diluted with EtOAc (20 mL) and
separated. The organic layer was washed with water
(3ꢁ10 mL), dried (Na2SO4), and concentrated in vacuo. Pu-
rification by flash chromatography (Hex/EtOAc¼8/1) gave
an amber solid (760 mg, 51%); IR (CH2Cl2, cast) 3380,
3080, 2976, 1665, 1634, 1555, 1427, 1027, 922, 749 cmꢂ1
;
797 cmꢂ1; H NMR (CDCl3, 500 MHz) d –2.38 (s, 2H),
1
1H NMR (CDCl3, 400 MHz) d 3.49, (d, 4H, J¼7.2 Hz),
5.10 (m, 4H), 5.82 (m, 2H), 6.07 (m, 2H), 6.20 (m, 2H),
6.72 (m, 2H), 6.78 (s, 1H), 7.18 (t, 1H, J¼8.0 Hz), 7.33 (d,
2H, J¼8.0 Hz), 8.65 (br s, 2H); 13C NMR (CDCl3,
100 MHz) d 38.4, 40.4, 107.5, 108.5, 116.5, 118.1, 127.2,
130.1, 131.1, 133.3, 137.0, 143.1; HRMS (EI) calcd for
C21H22S2N4: 366.1224, found: 366.1221 [M+] (100%).
0.40 (s, 18H), 7.1–7.2 (s, 20H), 7.23 (d, 4H, J¼8.0 Hz),
7.45 (t, 2H, J¼8.0 Hz), 7.88 (AA0MM0, 4H), 8.22 (AA0MM0,
4H), 8.77 (s, 8H); 13C NMR (CDCl3, 100 MHz) d 0.09, 95.4,
105.2, 115.8, 119.0, 122.4, 126.2, 127.9, 129.1, 129.4, 130.0
(br), 130.3, 131.4 (br), 133.5, 134.2, 134.5, 139.5, 142.4,
143.1; MS (ES) 1239.4 [MH+]; UV 432, 524, 559, 598,
660 nm.
3.1.14. 5-(2,6-Bis(tert-butylsulfanyl)phenyl)dipyrrome-
thane (3f). TFA (23 mL, 0.30 mmol) was added to a degassed
stirred solution of aldehyde 2f (846 mg, 3.0 mmol) in pyr-
role (15 mL) and CH2Cl2 (ca. 5 mL added to dissolve the
aldehyde). After the solution was stirred for 15 min, the
reaction was quenched by the addition of 0.1 M NaOH
(30 mL). The mixture was diluted with EtOAc (100 mL)
and separated. The organic layer was washed with water
(2ꢁ40 mL), dried (Na2SO4), concentrated in vacuo, and
purified by flash chromatography (Hex/EtOAc) to give 3f
3.1.17. 5,15-Bis(2,6-thiomethoxyphenyl)-10,20-bis(p-
tolyl)porphyrin (4b). TFA (69 mL, 0.89 mmol) was added
to a solution of dipyrromethane 3b (157 mg, 0.500 mmol)
and p-tolualdehyde (60 mg, 0.50 mmol) in freshly distilled
CH2Cl2 (50 mL). After the solution was stirred for 30 min,
DDQ (170 mg, 0.75 mmol) was added and the mixture
was stirred for further 45 min. The crude mixture was fil-
tered through a Florisil column (2.5ꢁ15 cm) and eluting
with CH2Cl2. Concentration in vacuo gave a purple solid
(40 mg, 19%); IR (CH2Cl2, cast) 3319, 2916, 1555, 1428,
1
1
as a light yellow foam (549 mg, 46%); H NMR (CDCl3,
965, 786 cmꢂ1; H NMR (CDCl3, 500 MHz) d ꢂ2.43 (s,
500 MHz) d 1.18 (s, 18H), 5.94–5.96 (m, 2H), 6.12 (q, 2H,
J¼3.0 Hz), 6.65 (dd, 2H, J¼1.5, 3.0 Hz), 7.09 (s, 1H),
7.15 (t, 1H, J¼8.0 Hz), 7.61 (d, 2H, J¼8.0 Hz), 8.52 (br s,
2H, NH); 13C NMR (CDCl3, 125 MHz) d 31.5, 41.4, 48.0,
107.2, 108.2, 115.7, 125.9, 131.8, 137.3 (br, 2 overlapping
C, supported with the HMBC spectrum), 149.6 (1C not ob-
served); HRMS (EI) calcd for C23H30N2S2: 398.1850,
found: 398.1841 [M+], (51%).
2H), 2.20 (s, 12H), 2.66 (s, 6H), 7.40 (AA0BB0, 4H), 7.47
(d, 4H, J¼8.0 Hz), 7.75 (t, 2H, J¼8.3 Hz), 8.06 (AA0BB0,
4H), 8.56 (d, 4H, J¼4.5 Hz), 8.82 (d, 4H, J¼4.5 Hz); 13C
NMR (CDCl3, 125 MHz) d 16.2, 21.6, 114.7, 119.7, 120.5,
127.3, 129.5, 129.8 (br), 131.8 (br), 134.5, 137.2, 137.4,
139.0, 143.4; HRMS (ES) calcd for C50H43N4S4:
827.2371, found: 827.2371 [MH+].
3.1.18. 5,15-Bis(2,6-bis(4-methoxybenzylsulfanyl)-
phenyl)-10,20-bis(p-tolyl)porphyrin (4c). TFA (137 mL,
1.78 mmol) was added to a solution of dipyrromethane
3c (526 mg, 1.00 mmol) and p-tolualdehyde (120 mg,
1.00 mmol) in freshly distilled CH2Cl2 (100 mL). After the
solution was stirred for 30 min, DDQ (340 mg, 1.5 mmol)
was added and the mixture was stirred for further 45 min.
The crude mixture was filtered through an alumina column
(2.5ꢁ15 cm) and eluted with CH2Cl2. Concentration of the
purple eluent gave a purple solid (322 mg, 51%); IR
(CH2Cl2, cast) 3350, 3317, 2924, 2933, 1609, 1582, 1511,
3.1.15. 5-(2-Chloro-6-(2-hydroxyethylsulfanyl)phenyl)-
dipyrromethane (3h). TFA (710 mg mL, 6.23 mmol) was
added to a degassed stirred solution of aldehyde 2h
(756 mg, 3.50 mmol) in pyrrole (35 mL) and CH2Cl2 (ca.
5 mL added to dissolve the aldehyde prior to the addition
of pyrrole). After the solution was stirred for 15 min, the re-
action was quenched by the addition of 0.1 M NaOH
(20 mL). The mixture was diluted with EtOAc (50 mL)
and separated. The organic was washed with water (2ꢁ
40 mL), dried (Na2SO4), concentrated in vacuo, and purified
by flash chromatography (Hex/EtOAc, 4/1 to 2/1) to give a
light yellow foam (480 mg, 1.45 mmol, 40%); IR (CHCl3,
1
1249, 798 cmꢂ1; H NMR (CDCl3, 400 MHz) d ꢂ2.36 (s,
2H), 2.75 (s, 6H), 3.64 (s, 12H), 3.82 (s, 8H), 6.57 (AA0BB0,
8H), 6.86 (AA0BB0, 8H), 7.61 (m, 6H), 7.52 (AA0BB0, 4H),
8.05 (AA0BB0, 4H), 8.56 (d, 4H, J¼4.5 Hz), 8.82 (d, 4H,
J¼4.5 Hz); 13C NMR (CDCl3, 125 MHz) d 21.7, 37.9,
55.2, 113.6, 115.5, 124.6, 128.6, 129.0, 129.6, 131.3 (br),
134.6, 137.1, 139.2, 140.6, 141.5, 158.4; MS (ES) 1251.4
[MH+]; labs 430, 523, 555, 602, 660 nm.
cast) 3358, 1667, 1556, 720 cmꢂ1 1H NMR (CDCl3,
;
500 MHz) d 1.83 (br s, 1H), 3.00 (t, 2H, J¼5.5 Hz), 3.61
(t, 2H, J¼5.5 Hz), 6.01–6.05 (m, 2H), 6.17 (q, 2H,
J¼3.0 Hz), 6.50–6.67 (br s, 1H), 6.68–6.70 (m, 2H), 7.12
(t, 1H, J¼8.0 Hz), 7.26 (d, 1H, J¼8.0 Hz), 7.33 (br s, 1H),
8.60–8.80 (br s, 2H); 13C NMR (CDCl3, 125 MHz) d 38.4,

11914
M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
3.1.19. 5,15-Bis(2,6-diallylsulfanylphenyl)-10,20-bis(p-
tolyl)porphyrin (4d). TFA (144 mL, 1.78 mmol) was added
to a degassed solution of 3d (467 mg, 1.00 mmol) and 4-
(trimethylsilylethynyl)benzaldehyde (202 mg, 1.00 mmol)
in CH2Cl2 (100 mL). After the solution was stirred for
30 min, DDQ (340 mg, 1.50 mmol) was added. After an
additional 1 h, the reaction mixture was filtered through
a Florisil column (2 cmꢁ10 cm) and eluted with CH2Cl2.
The purple fractions were combined, and concentrated
in vacuo to give a purple solid. This solid was purified further
by flash chromatography (Hex/EtOAc, 6/1) to give the title
compound (98 mg, 21%): Rf ¼0.5 (Hex/EtOAc, 3/1); IR
(CH2Cl2, cast) 3318, 3021, 2918, 1636, 1553, 1347,
J¼7.4 Hz), 1.98 (quin, 4H, J¼7.0 Hz), 2.72 (t, 4H,
J¼6.0 Hz), 3.39 (t, 4H, J¼5.8 Hz), 4.24 (t, 4H, J¼6.4 Hz),
7.25 (d, 4H, J¼7.8 Hz), 7.58 (dd, 2H, J¼1.6, 7.8 Hz), 7.66
(t, 2H, J¼8.0 Hz), 7.69 (dd, 2H, J¼1.6, 8.0 Hz), 8.09 (dd,
2H, J¼2.8, 0.4 Hz), 8.15 (dd, 2H, J¼2.8, 0.4 Hz), 8.63 (d,
4H, J¼4.8 Hz), 8.89 (d, 4H, J¼4.8 Hz); 13C NMR (CDCl3,
125 MHz) d 14.0, 19.4, 31.5, 36.7, 59.7, 68.0, 112.8,
114.6, 120.1, 125.3, 126.5, 129 (br), 130.0, 132 (br),
133.8, 135.59, 135.63, 138.0, 140.4, 142.0, 144–148 (br),
159.0; HRMS (ES) calcd for C56H53N4O4S2Cl2: 979.2885,
found: 979.2884. Data for a,b-isomer: IR (CH2Cl2, cast)
3600–3200, 3317, 2956, 2925, 1505, 1472, 1429, 1245,
1
1174 cmꢂ1; H NMR (CDCl3, 500 MHz) d ꢂ2.42 (s, 2H),
1
982 cmꢂ1; H NMR (CDCl3, 500 MHz) d ꢂ2.40 (s, 2H,
1.27 (t, 6H, J¼7.4 Hz), 1.39 (br s, 2H), 1.68 (Hex, 4H,
J¼7.4 Hz), 1.98 (quin, 4H, J¼7.0 Hz), 2.70 (t, 4H,
J¼5.8 Hz), 3.37 (t, 4H, J¼5.8 Hz), 4.24 (t, 4H, J¼6.6 Hz),
7.25 (AA0BB0, 4H), 7.53 (d, 2H, J¼7.8 Hz), 7.61 (t, 2H,
J¼7.9 Hz), 7.67 (d, 2H, J¼8.0 Hz), 8.14 (AA0BB0, 2H),
8.65 (d, 4H, J¼4.8 Hz), 8.92 (d, 4H, J¼4.8 Hz); 13C NMR
(CDCl3, 100 MHz) d 14.0, 19.4, 31.5, 38.7, 59.7, 68.0,
112.8, 114.6, 120.1, 125.3, 126.5, 129.2 (br), 130.0, 132.0
(br), 133.8, 135.6, 140.0, 142.0, 159.0; HRMS (ES) calcd
for C56H53N4O4S2Cl2: 979.2885, found: 979.2886.
NH), 2.67 (s, 6H), 3.49 (dt, 8H, J¼5.5, 1.3 Hz), 4.92 (dq,
4H, J¼10.0, 1.3 Hz), 5.02 (dq, 4H, J¼17.0, 1.5 Hz), 5.51
(ddt, 4H, J¼17.5, 10.0, 6.8 Hz), 7.51 (AA0BB0, 8H), 7.67
(t, 2H, J¼7.5 Hz), 8.10 (AA0BB0, 4H), 8.59 (d, 4H,
J¼5.0 Hz), 8.78 (d, 4H, J¼4.8 Hz); 13C NMR (CDCl3,
125 MHz) d 21.6, 36.5, 115.4, 117.8, 124.2, 127.4, 128.9,
129.8 (br), 131.5 (br), 133.2, 134.6, 137.2, 139.2, 140.6,
141.3; HRMS (ES) calcd for C58H51S4N4: 931.2997, found:
931.3004 [MH+].
3.1.20. 5,15-Bis(2,6-diphenylsulfanylphenyl)-10,20-bis(p-
tolyl)porphyrin (4i). TFA (144 mL, 1.78 mmol) was added
to a degassed solution of 3c (366 mg, 1.00 mmol) and p-tol-
ualdehyde (120 mg, 1.00 mmol) in CH2Cl2 (100 mL). After
the solution was stirred for 30 min, DDQ (340 mg,
1.50 mmol) was added. After an additional 1 h, the reaction
mixture was filtered through a Florisil column (2 cmꢁ
10 cm) and eluted with CH2Cl2. The purple fractions were
combined, and concentrated in vacuo to give a purple solid.
This solid was purified further by flash chromatography
(Hex/EtOAc, 6/1) to give the title compound as a purple
solid (155 mg, 21%): Rf ¼0.5 (Hex/EtOAc, 3/1); IR
(CH2Cl2, cast) 3316, 2930, 1682, 1609, 1511, 1301, 1249,
Acknowledgements
We gratefully acknowledge the financial support from the
Natural Sciences and Engineering Research Council of Can-
ada (NSERC) and the Canada Research Chair in Bioorganic
and Medicinal Chemistry.
References and notes
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1
800 cmꢂ1; H NMR (CDCl3, 500 MHz) d ꢂ2.52 (s, 2H,
NH), 3.60 (s, 12H), 3.78 (s, 8H), 6.50 (AA0MM0, 8H), 6.78
(AA0MM0, 8H), 7.47 (d, J¼7.5 Hz, 4H), 7.59 (t, J¼7.5 Hz,
2H), 7.97 (AA0MM0, 4H), 8.07 (AA0MM0, 4H), 8.49 (d,
J¼5.5 Hz, 4H), 8.67 (d, J¼5.5 Hz, 4H); 13C NMR (CDCl3,
125 MHz) d 37.8, 55.1, 93.9, 113.5, 116.0, 118.1, 124.5,
128.5, 129.1, 129.6, 130 (br), 131 (br), 135.8, 136.3,
140.2, 141.5, 141.7, 158.5, (two carbon signals not ob-
served); MS (ES) 1475.1 [MH+].
3.1.21. 5,15-Bis(2-chloro-6-(2-hydroxyethylsulfanyl)-
phenyl-10,20-bis(4-butoxyphenyl)porphyrin (4h). TFA
(144 mL, 1.78 mmol) was added to a solution of 3h
(332 mg, 1.00 mmol) and 4-butoxybenzaldehyde18
(192 mg, 1.00 mmol) in CH2Cl2 (100 mL). After the solu-
tion was stirred 30 min, DDQ (340 mg, 1.50 mmol) was
added and the mixture was stirred for further 45 min. The
crude mixture was filtered through a Florisil column
(2.5ꢁ15 cm) and eluted with CH2Cl2/2% MeOH in
CH2Cl2 until no further porphyrin was eluted. The eluent
was concentrated in vacuo and purified by flash chromato-
graphy to give the a,a-isomer (82 mg, 17%) and the a,b-iso-
mer (77 mg, 16%). Data for the a,a-isomer: IR (CH2Cl2,
cast) 3600–3150, 3316, 2955, 2924, 2854, 1505, 1466,
4. Balaban, T. S. Acc. Chem. Res. 2005, 38, 612–623.
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1
1245 cmꢂ1; H NMR (CDCl3, 500 MHz) d ꢂ2.46 (s, 2H),
1.11 (t, 6H, J¼7.4 Hz), 1.60 (br s, 2H), 1.67 (Hex, 4H,

M. M. Pollard, J. C. Vederas / Tetrahedron 62 (2006) 11908–11915
11915
11. Gairns, R. S.; Grant, R. D.; Moody, C. J.; Rees, C. W.; Tsoi,
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