Synthesis and optical properties of C3-ethynylated chlorin and π-extended chlorophyll dyads

Article abstract of DOI:10.1016/j.tet.2011.06.020

A C3-ethynylated chlorophyll derivative was prepared from methyl pyropheophorbide-d possessing a 3-formyl group by treatment of Bestmann-Ohira reagent. The mono-substituted acetylene was subjected to coupling reactions at the terminal acetylenic carbon at

Full text of DOI:10.1016/j.tet.2011.06.020

Tetrahedron 67 (2011) 6065e6072
Contents lists available at ScienceDirect
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journal homepage: www.elsevier.com/locate/tet
Synthesis and optical properties of C3-ethynylated chlorin and
p-extended
chlorophyll dyads
a
,
b
a
a
a,
*
Shin-ichi Sasaki , Keisuke Mizutani , Michio Kunieda , Hitoshi Tamiaki
a
Department of Bioscience and Biotechnology, Faculty of Science and Engineering, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan
Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 9 May 2011
Received in revised form 7 June 2011
Accepted 8 June 2011
Available online 16 June 2011
A C3-ethynylated chlorophyll derivative was prepared from methyl pyropheophorbide-d possessing a 3-
formyl group by treatment of BestmanneOhira reagent. The mono-substituted acetylene was subjected
to coupling reactions at the terminal acetylenic carbon atom to form a series of
derivatives. Replacement of the terminal hydrogen to phenyl, phenylethynyl and C3-chlorin-ethynyl
caused red-shifts of their Q (0,0) maxima from 675 to 679, 686, and 696 nm, respectively. Optical
p-extended chlorophyll
y
2
properties of C3 -substituted 3-ethynyl-chlorophyll derivatives including chlorophyll dyads were in-
Keywords:
Chlorophyll
BestmanneOhira reagent
Visible absorption spectra
Tetrapyrrole
vestigated in comparison with those of their related compounds. Partial quenching of the fluorescence
emission (
dyads (
¼0.29), suggesting a through-space interaction between the two chlorin macrocycles in
a molecule.
F
flu¼0.14) was observed for ortho-substituted dyad, compared to meta- (
F
¼0.27) and para-
F
Ó 2011 Elsevier Ltd. All rights reserved.
1. Introduction
(
Bacterio)chlorophylls [¼(B)Chls] play the leading role in light
absorption and energy/electron-transfer in natural photosynthesis.
They have several kinds of C3-substituents on their cyclic tetra-
pyrrole macrocycles consisting of porphyrin, chlorin and bacterio-
chlorin
the porphyrin unit. Chls-a/b have the same C3-vinyl group on the
chlorin -system, while Chl-d has a formyl group at the 3-position,
which causes a red-shift of the longest absorbing (Q ) maxima from
62 (Chl-a) to 688 nm (Chl-d) in diethylether. BChl-g also has a C3-
p-systems (see Fig.1). All Chls-c possess a C3-vinyl group on
p
y
1
6
vinyl group on the bacteriochlorin skeleton, and electron-
withdrawing ability of the C3-acetyl group in BChls-a/b contrib-
utes to bathochromic shifts of the electronic absorption bands.
Fig. 1. Structures of naturally occurring (B)Chls possessing different
porphyrin, chlorin, and bacteriochlorin (left to right).
p-skeletons:
(bacterio)chlorin skeleton are important for practical uses. For ex-
Combination of the C3-functional group with the
p-conjugated
ample, 3-trifluoroacetyl-(bacterio)chlorins were applied to an an-
skeleton of (B)Chl pigments makes different ranges of light ab-
sorption possible as their monomeric states. On the contrary, BChls-
c/d/e have a C3-1-hydroxyethyl group on the chlorin unit to form
3
alytical ethanol sensor as well as visual sensing reagents for
4
alcohol/amine detection and 3-(2-carboxyvinyl)-derivatives have
5
2
successfully been applied to dye-sensitized solar cells.
self-aggregates and absorb a wide range of light in a chlorosome.
In view of the construction of artificial models of natural pho-
tosynthetic antennae, many porphyrin derivatives have been syn-
Thus, naturally occurring (B)Chls realize light absorption at vari-
ous wavelengths by tuning C3-substituents on their tetrapyrrole
units. Synthetic modification of the C3-substituents has led to the
development of new dye components with various functionalities,
of which absorption bands at the long-wavelength region of
thesized to form large oligomers covalently linked by
p-
6
conjugation units. Since acetylene coupling is one of the most
widely used techniques to form such porphyrin assembly, a chlo-
rophyll-derived ethynyl-chlorin appears to be a more direct and
suitable component for developing model compounds related to
7
natural photosynthesis. Although several covalently-linked
*
Corresponding author. Fax: þ81 77 561 2659; e-mail address: tamiaki@se.
8
ritsumei.ac.jp (H. Tamiaki).
chlorin dimers have been reported, there are only limited
0
040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.06.020

6066
S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
examples of chlorophyll dyads fixed with rigid spacers.7,9 Moreover,
alteration of the acetylene unit at the 3-position would lead to
development of new types of chlorophyll derivatives, since trans-
formation of the C3-substituent along the y-axis causes drastic
dehydrogenated) state of 1, as in 4, had not been prepared before
11
our preliminary report. Treatment of 3 with commercially avail-
14
2
able BestmanneOhira reagent [(MeO) P(O)C(COMe)N
2
]
in the
presence of Cs CO in THF and MeOH afforded a 3-ethynyl-chlorin 4
2
3
1
b,10
spectral changes, especially at the Q
y
peak position (vide supra).
in 37% yield. To prepare other types of chlorins possessing a C3-
triple bond substituent, the 3-formyl group of 3 was changed to
We have preliminarily reported a synthetic route of C3-
11
15
ethynylated chlorin and some of its derivatives. Here we syn-
thesized a series of rigid chlorin dimers using acetylene coupling,
and optical properties of C3-ethynyl and its related chlorins as well
as chlorin-dyads were elucidated by UVevis, circular dichroism,
and fluorescence emission spectroscopies.
a dibromoethylene unit and the following dehydrobromination
16
by tetrabutylammonium fluoride (TBAF) in DMF
gave 3-
bromoethynyl-chlorin 6 (14% for the two-steps isolated yield) to-
gether with 4 (7%) as a side product. On the other hand, conden-
17
sation of 3 with hydroxylamine gave oxime 7, which was
dehydrated to give 3-cyano-chlorin 8. Two different reaction con-
ditions for the dehydration of 7 were examined, and treatment with
2
. Results and discussion
1
8
EtOPOCl
2
/DBU in CH
2
Cl
2
(67%) was found to give a better yield
19
Synthetic routes of 3-ethynyl-chlorophyll derivative and its re-
than that with trichlorotriazine in DMF (44%). Zinc- and copper-
lated compounds are shown in Scheme 1. The starting material is
metallations of 4 at the central position were done as previously
reported.
The reactivity of the terminal acetylene of 4 is expected to allow
versatile reactions, such as Sonogashira-coupling with aromatic
halides and Glaser-coupling with other ethynylated compounds.
2
0
methyl pyropheophorbide-a (1) prepared by modifying Chl-
12
a according to reported procedures. Although the reduction (hy-
13
drogenation) of C3-vinyl to ethyl group (1/2) and the oxidation
12
1 2
to formyl group (1/3) were reported, the oxidized (3 ,3 -
Br
Br
Br
N
N
N
N
NH
N
N
NH
N
N
g
Mg
4
+
HN
HN
O
O
O
COOMe
COO-phytyl
COOMe
COOMe
5
6
Chl-a
a
f
H
OHC
N
N
N
NH
N
N
NH
N
N
e
d
M
N
HN
HN
O
O
O
COOMe
(M = H
COOMe
COOMe
b
b
1
2
)
Zn-1 (M = Zn)
Cu-1 (M = Cu)
3
4 (M = H
2
)
Zn-4 (M = Zn)
Cu-4 (M = Cu)
c
h
HO
N
N
N
N
N
N
NH
N
N
NH
N
N
i or j
M
HN
HN
O
O
O
COOMe
(M = H2)
COOMe
COOMe
b
2
Zn-2 (M = Zn)
Cu-2 (M = Cu)
7
8
Scheme 1. Reagents and conditions: (a) concd H
2
SO
4
, MeOH; collidine, reflux; (b) M(OAc)
, CH Cl ; (g) TBAF, DMF; (h) HONH
2
$xH
2
O, MeOH/CH
2
Cl
2
; (c) 10% Pd/C, H
2
, acetone; (d) NaIO
4
, OsO
4
, THF-aq AcOH; (e)
, DBU,
(
MeO) P(O)C(COMe)N , Cs CO , THF/MeOH; (f) CBr
2
ꢀ
2
2
3
4
, PPh
3
2
2
2
$HCl, K
2
CO
3
, MeOH/CH
2
Cl ; (i) 2,4,6-trichloro-1,3,5-triazine, DMF; (j) EtOPOCl
2
2
2 2
MS 4 A, CH Cl .

S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
6067
Scheme 2 overviews synthetic routes of
p
-extended chlorins de-
11: 58%) than those of the above direct coupling of 4. When free-
base 4 was treated with Cu(OAc) in pyridine, a doubly copper-
metallated complex of 11 was obtained in 63% yield.
Fig. 2a shows the absorption spectra of three kinds of chlorins,
2, 1, and 4, possessing ethyl, vinyl, and ethynyl groups, respectively,
rived from C3-ethynylated (Zn-)4. Copper-free Sonogashira-cou-
pling21 of free-base 4 using Pd-catalyst with excess iodobenzene or
phenylacetylene gave the expected products in moderate yields (9:
2
7
0%, 10: 67%). Without additional reactants, homocoupling of the
terminal acetylene of 4 occurred under the same conditions to form
chlorin dyad 11 in 88% yield. On the other hand, coupling reactions
of 4 with 0.52 molar ratio of ortho-, meta-, and para-diiodobenzene
gave the corresponding chlorin-dyads (12: 32%, 13: 57%, 14: 58%).
The lower yield of ortho-dyad 12 compared to those of 13 and 14 is
ascribed to the steric hindrance of the two chlorin macrocycles
fixed on the ortho-positions of the benzene ring spacer with rigid
acetylene unit. Actually, an intramolecular interaction between the
chromophores of 12 was observed by spectroscopies (vide infra).
Coupling reactions of zinc complex Zn-4 in the presence of copper-
catalyst22 followed by demetallation with HCl also gave chlorins
at the 3-position in CH
2 2 x
Cl . The Soret (300e450 nm), Q (450e
600 nm) and Q bands (550e700 nm) were shifted to a longer
y
wavelength in this order, which were consistent with an increase in
the bond order of the substituents reflecting the group electro-
negativity (ethyl 2.48; vinyl 2.79; ethynyl 3.07). The same ten-
dency was also observed for both zinc chlorins Zn-2, Zn-1, Zn-4
(Fig. 2b) and copper chlorins Cu-2, Cu-1, Cu-4 (Table 1). Metal in-
sertion of 3-ethynyl-chlorin 4 caused a red-shift of the Soret band
2
3
and a blue-shift of the Q
y
peak (Fig. 2), which is similar to the
metallation effects on 3-ethyl- and 3-vinyl-chlorins as previously
24
reported.
Fluorescence emission peaks excited at the Soret
9
e11, but their isolated overall yields were lower (9: 38%, 10: 50%,
maxima were shifted to a longer wavelength in the same order of 3-
Scheme 2. Reagents and conditions: (a) Pd
2 3 3 3 2 2 2 2 3 2 2 2 2 3 2 2
(dba) , P(o-tolyl) , Et N, toluene; (b) Zn(OAc) $2H O, MeOH/CH Cl ; Pd(PPh ) Cl , Cu(OAc) $H O, Et N; aq HCl; (c) Zn(OAc) $2H O,
MeOH/CH Cl ; Cu(OAc) $H O, pyridine; aq HCl.
2
2
2
2

6068
S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
ethyl, 3-vinyl and 3-ethynyl group as those of absorption bands.
The Stokes shifts of 3-ethynyl-chlorins (4, Zn-4) were comparable
to those of 3-ethyl-chlorins (2, Zn-2), and were smaller than those
of 3-vinyl-chlorins (1, Zn-1). Zinc insertion caused decrease of the
fluorescence quantum yield, and copper-metallation completely
quenched the emission.
Optical properties of the selected chlorophyll derivatives are
summarized in Table 1 to compare the substituent effects at the 3-
2
position, CH¼X and C^Y. Replacement of the C3 -carbon atom
with oxygen or nitrogen atom (1/3 or 7) caused a red-shift of the
peak of both absorption and fluorescence emission spectra, ap-
parently due to the nature of their electronegativities. On the other
2
hand, substitution of the two hydrogen atoms on the C3 -carbon of
1
with bromine atoms (1/5) had little effect on the peak positions
of the spectra, while decreasing the fluorescence emission quan-
tum yield (21/8%) mainly due to a heavy atom effect. Similar ef-
fects of heteroatom or halogen were also observed for three kinds
of chlorins possessing a triple bond at the C3-position. Change of
2
the CH to nitrogen atom in the 3 -position of the C3-triple bond
(4/8) caused red-shifts of the peak maxima of the spectra, be-
cause a cyano moiety strongly withdraws conjugated -electron.
p
Although the spectra of 4 and 6 appear to be almost the same, re-
placement of the hydrogen with bromine atom on the C3 -carbon
slightly decreased the fluorescence quantum yield (26/17%) as
Fig. 2. Electronic absorption spectra of (a) 3-ethyl-chlorin 2 (solid thin line), 3-vinyl-
chlorin 1 (dotted line), and 3-ethynyl-chlorin 4 (solid thick line) and (b) zinc 3-ethyl-
chlorin Zn-2 (solid thin line), zinc 3-vinyl-chlorin Zn-1 (dotted line), and zinc 3-
2
ethynyl-chlorin Zn-4 (solid thick line) in CH
2
Cl
2
. All spectra were normalized at
expected (vide supra). Full widths at half maxima (FWHM) of the Q
0,0) absorption and the main fluorescence emission bands appear
y
their Soret peaks.
(
to reflect the nature of the bond character: chlorins 4, 6 and 8
Table 1
2 2
Optical properties of chlorophyll derivatives in CH Cl
Z
Y
H
X
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
M
M
M
M
M
O
O
O
O
O
COOMe
M-1, 3, 5, 7
COOMe
COOMe
M-4, 6, 8~10
COOMe
COOMe
M-2
11~14
a
ꢀ1
ꢀ1
Compound
l
abs/nm
Int (Q
y
(0,0)/Int (Soret)
l
em/nm (FWHM /cm
)
F
flu
Stokes shift/cm
110
a
ꢀ1
)
Soret
Q
x
Q
y
(FWHM /cm
(0,0)
(0,1)
(0,0)
(0,1)
1
(X¼CH
2
, M¼H
2
)
414
425
425
410
422
422
428
415
427
428
413
415
420
415
419
423
419
411
420
419
508
518
507
504
510
503
522
511
519
510
507
511
514
514
513
517
519
514
515
516
539
557
552
534
554
547
554
540
560
555
537
541
543
544
542
546
552
545
545
545
610
606
605
600
598
597
633
616
613
611
611
618
619
667 (450)
655 (460)
653 (600)
656 (390)
644 (390)
642 (520)
694 (430)
675 (360)
662 (410)
660 (530)
668 (410)
677 (370)
679 (410)
685 (320)
679 (380)
686 (380)
696 (440)
683 (690)
681 (420)
685 (450)
0.43
0.74
0.72
0.40
0.72
0.66
0.81
0.61
0.75
0.74
0.48
0.58
0.59
0.84
0.56
0.64
0.95
0.54
0.59
0.68
672 (470)
0.21
Zn-1 (X¼CH
Cu-1 (X¼CH
2
, M¼Zn)
, M¼Cu)
660 (480)
0.16
120
b
b
b
2
2
(M¼H
2
)
658 (390)
0.20
50
Zn-2 (M¼Zn)
Cu-2 (M¼Cu)
647 (430)
0.12
70
b
b
b
3
4
(X¼O, M¼H
2
)
698 (470)
677 (380)
0.21
0.22
80
40
(Y¼CH, M¼H
2
)
Zn-4 (Y¼CH, M¼Zn)
665 (430)
0.15
70
b
b
b
Cu-4 (Y¼CH, M¼Cu)
5
6
7
8
9
1
1
1
1
1
(X¼CBr
2
, M¼H
2
)
671 (460)
678 (360)
682 (420)
686 (320)
681 (400)
688 (400)
700 (410)
687 (570)
686 (420)
689 (430)
0.08
0.17
0.22
0.23
0.26
0.27
0.34
0.14
0.27
0.29
70
20
70
20
40
40
80
90
110
80
(Y¼CBr, M¼H
2
)
(X¼NOH, M¼H
(Y¼N, M¼H
2
)
2
)
626/647
620
(Y¼CC
6
H
5
, M¼H
2
)
0 (Y¼CC^CC
1 (Z¼none)
6
H
5
, M¼H
2
)
626
628
628
621
2 (Z¼o-C
6
H
4
)
3 (Z¼m-C
4 (Z¼p-C
6
H
4
)
6
H
4
)
624
a
Full width at half maximum.
b
Non-fluorescence.

S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
6069
possessing a linear triple bond substituent (3-C^Y) showed
a sharper peak compared to the corresponding chlorins 1, 5, and 7
those of the other chlorins (10: 27%, 13: 27%, 14: 29%), it is rea-
sonable to assume that the two chlorin macrocycles fixed at the
ortho-position interacted with each other in the ground state to
cause partial fluorescence quenching and also gave the lower
(
3-CH¼X), respectively. More conformationally flexible C3-
substituents with a double bond can take various rotamers in-
cluding two energetically stable conformers coplanar with a chlorin
1
synthetic yield due to the steric hindrance. Although the H NMR
p
-system, and their rotational deviations from the chlorin
p
-plane
spectrum of 12 indicated the free-rotation of the two chlorin
macrocycles along the 3-ethynyl bridge at room temperature, ap-
parent up-field shifts of several proton signals were observed. As
summarized in Table 2, chemical shifts of the C7/C8-substituents of
12 appeared more than 1 ppm upper-field compared to those of the
other chlorin-dyads. A molecular modelling study suggests that
chlorin 12 tends to form an intramolecular partially stacked con-
formation, in which the B-ring is located in the shielding region of
enhance the energy levels of their Q bands, while there is no
y
possible conformational pattern of the linear triple bond
substituents.25
Fig. 3a gives absorption spectra of three types of chlorins 9e11
derived from 3-ethynyl-chlorin 4. Replacement of the terminal
2
6
hydrogen to phenyl group (4/9) and further
phenylethynyl to phenylbutadiynyl unit (4/10) caused slight red-
shifts of their absorption maxima (Table 1). The Q peak maximum
of chlorin dimer 11 appeared at a longer-wavelength region
696 nm) with a high intensity [Int(Q
p-extension by the
y
the neighbouring chlorin p-system in a molecule (Fig. S1).
Table 2
(
y
)/Int(Soret)¼0.95] than those
Selected 1H NMR chemical shifts (
d/ppm) of chlorin-dyads 11e14 in CDCl
3
of 10 possessing a phenylacetylene unit (686 nm and 0.64), sug-
gesting that the two chlorin macrocycles interacted in a molecule
through the linear butadiyne spacer along the y-axis. As can be seen
in Figs. 3b and 3c, chlorin-dyads 13 and 14 showed similar ab-
sorption and CD spectra, which also resemble those of 10. On the
contrary, ortho-substituted 12 had a little broader spectrum than
Proton
5-H
o-Dyad 12
m-Dyad 13
p-Dyad 14
Dimer 11
9.25
1.91
1.80
0.67
9.70
3.37
3.73
1.72
9.65
3.35
3.73
1.74
9.50
3.27
3.58
1.66
7
8
8
-CH
3
-CH
2
1
-CH
3
ꢀ
1
did 10, 13, and 14 (FWHM; 10: 380, 12: 690, 13: 420, 14: 450 cm ).
Because the fluorescence quantum yield of 12 (14%) is lower than
3. Conclusions
We have shown a facile synthetic route of transforming the C3-
formyl to the ethynyl group on a chlorin macrocycle, and the
strategy of -extension directly connected to the 3-position of the
chlorin ring is demonstrated. Coupling reactions were performed to
synthesize a series of -conjugated chlorin-dyads, among which
dyad 11 connecting two chlorin rings via butadiyne spacer showed
peak maximum at the longest wavelength region. On the other
p
p
Q
y
hand, relative broadening of visible bands and partial quenching of
the fluorescence were observed for ortho-substituted dyad 12,
suggesting a through-space interaction between the two chlorin
macrocycles in a molecule.
4
4
. Experimental section
.1. General
Electronic absorption and fluorescence emission spectra were
measured on a Hitachi U-3500 and F-4500 spectrometer, re-
spectively. Fluorescence quantum yields were measured at room
temperature using a Hamamatsu Photonics absolute PL quantum
yield measurement system C9920-02. All melting points were
measured with a Yanagimoto micro melting apparatus and were
1
13
uncorrected. H and C NMR spectra were recorded on a JEOL JNM-
ECA-600HR spectrometer in CDCl . Chemical shifts are reported
relative to the residual solvent peak:
3
1
d
¼7.26 ppm (CHCl
3
) for
H
1
3
13
NMR and
d
¼77.0 ppm ( CDCl
3
) for C NMR. Proton peaks were
1
1
assigned by He H COSY and NOESY or ROESY spectra, and carbon
signals except for quaternary peaks were assigned by DEPT and
13
1
2 2
Ce H COSY spectra. FTIR spectra in CH Cl were measured with
a Shimadzu IRAffinity-1 spectrophotometer. Atmospheric pressure
chemical ionization (APCI) quadrupole mass spectra (MS) and laser
desorption ionization time of flight (TOF) MS were measured by
Shimadzu LCMS-2010 EV and AXIMA-CFRþ apparatus, re-
spectively; methanol solutions were injected for APCI-MS and no
matrix was used for TOF-MS. Fast atom bombardment-mass spec-
troscopy (FAB-MS) data were measured by a JEOL GCmate II spec-
Fig. 3. (a) Electronic absorption spectra of 3-phenylethynyl-chlorin 9 (solid thin line),
3
-phenylbutadiynyl-chlorin 10 (dotted line), and chlorin dimer 11 (solid thick line) in
CH Cl and (b) electronic absorption and (c) circular dichroism of ortho-dyad 12 (solid
thin line), meta-dyad 13 (dotted line), and para-dyad 14 (solid thick line) in CH Cl
Inset of (b) indicates fluorescence emission spectra (excited at their Soret bands) of
2e14 in CH Cl . Absorption spectra were normalized at their Soret peaks.
2 2
trophotometer; FAB-MS samples were dissolved in CH Cl , m-
2
2
nitrobenzyl alcohol and glycerol were used as the matrix, and
PEG600 was added as an internal reference. Flash column chro-
matography (FCC) was performed with silica gel (Merck, Kieselgel
2
2
.
1
2
2

6070
S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
6
10
0). HPLC was done with a packed column (Nacalai, Cosmosil 5SL-II,
reaction mixture was poured into aqueous saturated NaHCO
extracted with CH Cl . The extract was washed with H O, dried
over anhydrous Na SO , filtered and concentrated in vacuo. The
crude product was purified by FCC (Et O/CH Cl
¼7:93) followed by
recrystallization from CH Cl and hexane to give a 1:2 mixture of 4
(7.4 mg, 42%) The mixture was separated by HPLC
3
, and
f
ꢁ250 mm).
2
2
2
Methyl pyropheophorbide-a (1),12 zinc methyl pyropheo-
2
4
phorbide-a (Zn-1),27 copper methyl pyropheophorbide-a (Cu-1),
methyl mesopyropheophorbide-a (2), zinc methyl mesopyro-
28
2
2
2
13
2
2
20b
pheophorbide-a (Zn-2),
copper methyl mesopyropheophorbide-
and
(CH
6
a (Cu-2),1 methyl pyropheophorbide-d (3), methyl 3-devinyl-3-
3a
12
ClCH
Cl/CH
OH¼99.5:0.5, 4 ml/min) at retention time (t
)¼
2
2
3
R
11
ꢂ
ethynyl-pyropheophorbide-a (4) and methyl pyropheophorbide-
15 min for 6 and t
(CH Cl
511 (0.12), 415 (1.00), 321 nm (0.22); IR (CH
CeH), 2193 (C^C), 1734 (ester-C]O), 1696 (keto-C]O), 1618,
R
¼16 min for 4. 6: black solid; mp >300 C; VIS
d oxime (7)17 were prepared as previously reported. THF was distilled
l
max 677 (relative intensity, 0.58), 618 (0.08), 541 (0.10),
2
2
)
over CaH
2
before use. Other solvents and reagents were used as
2
2
Cl ) nmax 3299 (alkyne-
purchased without further purification. All synthetic procedures
were done in the dark.
ꢀ
1 1
1499 cm ; H NMR (CDCl
.62 (1H, s, 20-H), 5.31, 5.15 (each 1H, d, J¼19 Hz, 13 -CH
(1H, dq, J¼2, 7 Hz, 18-H), 4.34 (1H, dt, J¼8, 2 Hz, 17-H), 3.72 (2H, q,
3
) d 9.57 (1H, s, 10-H), 9.50 (1H, s, 5-H),
1
8
2
), 4.52
4
.2. Metallation of 3-ethynyl-chlorin
2
J¼8 Hz, 8-CH
(3H, s, 2-CH
2.61e2.54 (1H, m, 17 -CH), 2.35e2.28 (2H, m, 17-CHCH), 1.83 (3H, d,
2
), 3.70 (3H, s, 12-CH
3
), 3.62 (3H, s, 17 -CO
2 3
CH ), 3.48
Zinc- and copper-metallation of free-base 4 were done accord-
3
), 3.29 (3H, s, 7-CH
3
), 2.75e2.69 (1H, m, 17-CH),
2
0
1
ing to the reported procedure to give Zn-4 and Cu-4 in quanti-
tative yields.
1
J¼7 Hz, 18-CH
3
), 1.70 (3H, t, J¼8 Hz, 8 -CH
3
), 0.06, ꢀ1.98 (each 1H, s,
þ
NHꢁ2); MS (TOF) found: m/z 624, calcd for C34
H
33BrN
4
O
3
: M , 624.
4.2.1. Zinc methyl 3-devinyl-3-ethynyl-pyropheophorbide-a (Zn-
ꢂ
4
). Green solid; mp >300 C; VIS (CH
2
Cl
2
)
lmax 663 (relative in-
4.4. Synthesis of 3-cyano-chlorin
tensity, 0.83), 613 (0.11), 560 (0.06), 520 (0.04), 428 (1.00), 319 nm
1
(
(
0.21); H NMR (CDCl
3
)
d
9.18 (1H, s, 5-H), 9.15 (1H, s, 10-H), 8.42
4.4.1. Methyl 3-cyano-3-devinyl-pyropheophorbide-a (8). To a solu-
tion of chlorin 7 (30 mg, 0.053 mmol) in CH Cl (8 ml) was added
EtOPOCl (13 mg, 0.082 mmol), DBU (42 mg, 0.27 mmol), molecular
sieve 4 A, and the suspension was stirred for 6 h at room temper-
ature under nitrogen. The reaction mixture was poured into
1
1H, s, 20-H), 4.91, 4.81 (each 1H, d, J¼19 Hz, 13 -CH
2
), 4.44 (1H, dq,
2
2
1
J¼2, 7 Hz, 18-H), 4.22 (1H, dt, J¼8, 2 Hz, 17-H), 4.10 (1H, s, 3 -CH),
2
ꢀ
2
3
.52 (2H, q, J¼8 Hz, 8-CH
2
), 3.47 (3H, s, 12-CH
3
), 3.41 (3H, s, 17 -
CO CH ), 3.38 (3H, s, 2-CH
2
3
3
), 3.08 (3H, s, 7-CH ), 2.59e2.54 (1H, m,
3
1
1
2
7-CH), 2.49e2.43 (1H, m, 17 -CH), 2.31e2.26 (1H, m, 17-CH),
aqueous 2% HCl and extracted with Et
with brine, dried over anhydrous Na SO
in vacuo. The crude product was purified by FCC (Et
2
2
O. The extract was washed
, filtered and concentrated
O/
1
.24e2.19 (1H, m, 17 -CH), 1.86 (3H, d, J¼7 Hz, 18-CH
3
), 1.56 (3H, t,
2
4
1
J¼8 Hz, 8 -CH
3
); HRMS (FAB) found: m/z 608.1752, calcd for
Zn: M , 608.1766.
þ
C
H
34 32
N
4
O
3
CH
2
Cl
2
¼7:93) followed by recrystallization from CH
2
Cl
2
and hexane
ꢂ
to give 8 as dark brown plates (20 mg, 67%): mp 218e219 C; VIS
4
4
C
.2.2. Copper methyl 3-devinyl-3-ethynyl-pyropheophorbide-a (Cu-
(CH
573 (0.02), 544 (0.13), 514 (0.12), 474 (0.04), 415 (1.00), 382 (0.74),
323 nm (0.22); IR (CH Cl max 2226 (C^N), 1734 (ester-C]O),
697 (keto-C]O), 1618, 1501, 1224, 1200, 1159, 977 cm ; H NMR
(CDCl 9.50 (1H, s,10-H), 9.42 (1H, s, 5-H), 8.76 (1H, s, 20-H), 5.35,
.20 (each 1H, d, J¼19 Hz, 13 -CH
4.37 (1H, dt, J¼9, 2 Hz,17-H), 3.63 (2H, q, J¼8 Hz, 8-CH
2 2
Cl ) lmax 685 (relative intensity, 0.81), 647 (0.08), 626 (0.08),
ꢂ
). Black crystals; mp >300 C; MS (TOF) found: m/z 607, calcd for
þ
H
34 32
N
4
O
3
Cu: M , 607.
2
2
) n
ꢀ1 1
1
4
.3. Synthesis of 3-bromoethynyl-chlorin
3
) d
1
5
2
), 4.58 (1H, dq, J¼7, 2 Hz, 18-H),
), 3.67 (3H, s,
2 3 3 3
CH ), 3.64 (3H, s, 2-CH ), 3.63 (3H, s, 12-CH ), 3.19 (3H, s, 7-
2
2
4
.3.1. Methyl 3 ,3 -dibromo-pyropheophorbide-a (5). Triphenylphos-
phine (980 mg, 3.7 mmol) and CBr (600 mg, 1.8 mmol) were dis-
(4 ml) and the mixture was stirred for 5 min at
2
2
4
17 -CO
CH ), 2.76e2.73 (1H, m, 17-CH), 2.64e2.58 (1H, m, 17 -CH),
2.35e2.28 (2H, m, 17-CHCH), 1.86 (3H, d, J¼7 Hz, 18-CH ), 1.66 (3H,
), ꢀ0.49, ꢀ2.38 (each 1H, s, NHꢁ2); MS (APCl)
1
solved in CH
2
Cl
2
3
ꢂ
0
C, then aldehyde 3 (300 mg, 0.54 mmol) was added. After
3
1
stirring for additional 5 min under nitrogen, the mixture was di-
luted with CH Cl and washed by aqueous saturated NaHCO . The
organic phase was dried over anhydrous Na SO , filtered and
concentrated in vacuo. The crude product was purified by FCC
t, J¼8 Hz, 8 -CH
3
þ
2
2
3
found: m/z 548, calcd for C33H N O : MH , 548.
34 5 3
2
4
2,4,6-Trichloro-1,3,5-triazine (12 mg, 0.067 mmol) was dis-
solved in anhydrous DMF (1 ml) and the solution was stirred for
20 min at room temperature under nitrogen, then chlorin 7 (14 mg,
0.025 mmol) in anhydrous DMF (4 ml) was added and the mixture
(
Et
2
O/CH
2
Cl
2
¼7:93) followed by recrystallization from CH
2
Cl
2
and
ꢂ
hexane to give 5 (192 mg, 50%) as a black solid: mp 212e214 C
15
ꢂ
(
6
(
(
lit. 205e208 C); VIS (CH
11 (0.09), 537 (0.10), 507 (0.12), 413 (1.00), 320 nm (0.23); H NMR
CDCl 9.48 (1H, s, 10-H), 9.01 (1H, s, 5-H), 8.58 (1H, s, 20-H), 8.45
1H, s, 3 -H), 5.27, 5.12 (each 1H, d, J¼19 Hz, 13 -CH
2
Cl
2
)
lmax 668 (relative intensity, 0.48),
was stirred for 6 h. The reaction mixture was poured into H
2
O and
1
extracted with CH
2
Cl
2
. The extract was washed with brine, dried
3
)
d
1
over anhydrous Na
2
4
SO , filtered and concentrated in vacuo. The
1
2
), 4.50 (1H, dq,
crude product was purified as mentioned above to afford 8 (6.0 mg,
44%).
J¼2, 7 Hz, 18-H), 4.31 (1H, dt, J¼8, 2 Hz, 17-H), 3.67 (2H, q, J¼8 Hz,
2
8
-CH
-CH
2
), 3.65 (3H, s, 12-CH
), 3.22 (3H, s, 7-CH
3
), 3.62 (3H, s, 17 -CO
2 3
CH ), 3.30 (3H, s,
2
3
3
), 2.71e2.68 (1H, m, 17-CH), 2.59e2.55
4.5. Coupling reactions of (zinc) 3-ethynyl-chlorin (Zn)-4
1
(
1
1H, m, 17 -CH), 2.31e2.25 (2H, m, 17-CHCH), 1.83 (3H, d, J¼7 Hz,
1
8-CH
3
), 1.69 (3H, t, J¼8 Hz, 8 -CH
3
), 0.26, ꢀ1.86 (each 1H, s,
4.5.1. Methyl 3-devinyl-3-phenylethynyl-pyropheophorbide-a (9). To
þ
NHꢁ2); MS (TOF) found: m/z 704, calcd for C34
H34Br
2
N
4
O
3
: M ,
a solution of 4 (20 mg, 0.037 mmol) in toluene (8 ml) and Et
(2 ml) was added iodobenzene (200 mg, 0.99 mmol), Pd (dba)
8.9 mg, 0.010 mmol), P(o-tolyl) (11 mg, 0.036 mmol) and the
3
N
7
04.
2
3
(
3
ꢂ
4
.3.2. Methyl 3-bromoethynyl-3-devinyl-pyropheophorbide-a (6). To
mixture was stirred for 12 h at 60 C under nitrogen. The reaction
mixture was poured into aqueous saturated NaHCO , and extracted
with CH Cl . The extract was washed with H O, dried over anhy-
drous Na SO , filtered, and concentrated in vacuo. The crude
product was purified by FCC (Et O/CH Cl
¼7:93) followed by re-
crystallization from CH Cl and hexane to afford 9 (16 mg, 70%) as
a solution of 5 (20 mg, 0.028 mmol) in anhydrous DMF (8 ml) was
added tetrabutylammonium fluoride trihydrate (16 mg, 0.05
mmol) and the mixture was stirred at room temperature under
nitrogen. The reaction was monitored by visible spectrometry for
3
2
2
2
2
4
2
2
2
2
h until the Q
y
peak (668 nm) of 5 completely disappeared. The
2
2

S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
6071
5
ꢂ
4
4
4
4
a black solid: mp 221e223 C; VIS (CH
2
Cl
2
)
l
max 679 (
3
, 6.3ꢁ10 ),
628 (1.5ꢁ10 ), 552 (2.7ꢁ10 ), 519 (2.6ꢁ10 ), 419 (1.52ꢁ10 ),
3
4
4
5
4
6
20 (8.6ꢁ10 ), 542 (1.1ꢁ10 ), 513 (1.2ꢁ10 ), 419 (1.11ꢁ10 ), 324 nm
326 nm (3.6ꢁ10 ); IR (CH
C]O), 1618, 1551, 1498, 1222 cm
NMR (CDCl
9.50 (2H, s, 5-Hꢁ2), 9.29 (2H, s, 10-Hꢁ2), 8.65 (2H, s,
20-Hꢁ2), 5.28, 5.13 (each 2H, d, J¼19 Hz, 13 -CH
dq, 18-Hꢁ2), 4.35 (2H, br dt, 17-Hꢁ2), 3.65 (6H, s, 2-CH
2 2
Cl ) nmax 1734 (ester-C]O), 1693 (keto-
4
ꢀ1
1
(
2.3ꢁ10 ); IR (CH
2
Cl
2
)
n
max 2209 (C^C), 1734 (ester-C]O), 1694
[n(C^C) was not observed]; H
ꢀ1 1
(
keto-C]O), 1620, 1551, 1498 cm ; H NMR (CDCl
3
)
d
9.40 (1H, s,
3
) d
1
5
3
3
-H), 9.38 (1H, s,10-H), 8.55 (1H, s, 20-H), 7.88 (2H, d, J¼7 Hz, 2-H of
2
ꢁ2), 4.53 (2H, br
ꢁ2), 3.64
ꢁ2), 3.55 (6H, s, 12-
ꢁ2), 2.75e2.71 (2H, m, 17-CHꢁ2),
2.63e2.57 (2H, m, 17 -CHꢁ2), 2.34e2.28 (4H, m, 17-CHCHꢁ2), 1.90
2
2
2
-Ph), 7.56 (2H, t, J¼7 Hz, 3-H of 3 -Ph), 7.51 (1H, t, J¼7 Hz, 4-H of
3
1
2
-Ph), 5.26, 5.11 (each 1H, d, J¼19 Hz, 13 -CH
2
), 4.48 (1H, br dq, 18-
CH ), 3.62 (3H, s, 12-
), 3.47 (3H, s, 2-CH ), 3.16 (3H, s,
), 2.73e2.68 (1H, m, 17-CH), 2.60e2.55 (1H, m, 17 -CH),
.32e2.27 (2H, m, 17-CHCH), 1.83 (3H, d, J¼7 Hz, 18-CH ), 1.65 (3H,
), 0.17, ꢀ1.98 (each 1H, s, NHꢁ2); C NMR (CDCl
(6H, s, 17 -CO
2
CH
3
ꢁ2), 3.58 (4H, br q, 8-CH
2
2
H), 4.30 (1H, br dt, 17-H), 3.63 (3H, s, 17 -CO
CH
2
3
CH
3
ꢁ2), 3.27 (6H, s, 7-CH
3
1
3
), 3.59 (2H, q, J¼8 Hz, 8-CH
2
3
1
1
7
2
-CH
3
(6H, d, J¼7 Hz, 18-CH
3
ꢁ2), 1.66 (6H, t, J¼8 Hz, 8 -CH ꢁ2), ꢀ0.17,
3
1
3
1
3
ꢀ2.17 (each 2H, s, NHꢁ2ꢁ2); C NMR (CDCl
3
)
d
196.1 (C13 ꢁ2),
1
13
3
t, J¼8 Hz, 8 -CH
3
3
)
173.5 (C17 ꢁ2), 170.6 (C19ꢁ2), 161.0 (C16ꢁ2), 154.6 (C6ꢁ2), 151.3
(C9ꢁ2), 148.8 (C14ꢁ2), 145.0 (C8ꢁ2), 140.0, 139.7 (C1ꢁ2, C2ꢁ2),
138.9, 129.4 (C11ꢁ2, C12ꢁ2), 137.1 (C4ꢁ2), 136.7 (C7ꢁ2), 131.3
(C13ꢁ2), 120.1 (C3ꢁ2), 106.6 (C15ꢁ2), 103.7 (C10ꢁ2), 98.1 (C5ꢁ2),
1
3
d
196.8 (C13 ), 174.1 (C17 ), 171.5 (C19), 161.1 (C16), 155.4 (C6), 151.6
(
C9), 149.4 (C14), 145.6 (C8), 141.4, 137.7 (C1, C2), 139.0, 129.4 (C11,
4
6
C12), 137.4 (C4), 136.9 (C7), 132.5 (C3 ꢁ2), 131.5 (C13), 129.6 (C3 ),
5
2
3
2
1
5
1
(
(
1
29.3 (C3 ꢁ2), 124.0, 100.8 (C3 , C3 ), 122.6 (C3), 106.9 (C15), 104.5
94.0 (C20ꢁ2), 84.5 (C3 ꢁ2), 78.6 (C3 ꢁ2), 52.1 (C17 ꢁ2), 51.9
2 2 1
1
5
C10), 98.4 (C5), 94.1 (C20), 83.7 (C3 ), 52.5 (C17), 52.4 (C17 ), 50.4
(C17ꢁ2), 49.7 (C18ꢁ2), 48.2 (C13 ꢁ2), 31.0 (C17 ꢁ2), 29.9 (C17 ꢁ2),
2 1 1 1
2
2
1
1
1
C18), 48.8 (C13 ), 31.6 (C17 ), 30.5 (C17 ), 23.9 (C18 ), 20.0 (C8 ),
23.4 (C8 ꢁ2), 19.5 (C8 ꢁ2), 17.5 (C18 ꢁ2), 13.1 (C2 ꢁ2), 12.1
1 1
2
1
1
1
8.1 (C8 ), 13.2 (C2 ), 12.7 (C12 ), 11.7 (C7 ); HRMS (FAB) found: m/z
(C12 ꢁ2), 11.3 (C7 ꢁ2); MS (FAB) found: m/z 1091.4, calcd for
þ
þ
6
23.2999, calcd for C40
To a solution of Zn-4 (11 mg, 0.017 mmol) in Et
added iodobenzene (100 mg, 0.50 mmol), Cu(OAc)
.11 mmol), Pd(PPh Cl (60 mg, 0.086 mmol), and the mixturewas
stirred for 12 h at room temperature under nitrogen. The reaction
mixture was poured into aqueous saturated NaHCO solution and
extracted with CH Cl . The extract was washed with H O and con-
centrated. The residue was dissolved in CH Cl ,18% aqueous HCl was
added, and stirred for 1 h at room temperature. The mixture was
then poured into H O, and the organic phase was washed succes-
sively with saturated aqueous NaHCO and H O, dried over anhy-
drous Na SO , filtered and concentrated in vacuo. The crude product
was purified as mentioned above to give 9 (4.0 mg, 38%).
H
39
N
4
O
3
: MH , 632.3022.
C
68
H N
67 8
O
6
: MH , 1091.5.
3
N (10 ml) was
$H O (22 mg,
Similar to the synthesis of 9, reaction of Zn-4 (23 mg, 0.037 mmol)
in the presence of Cu(OAc) $H O (22 mg, 0.11 mmol) in pyridine
(12 ml) and successive demetallation gave 11 (13 mg, 58%).
2
2
2
2
0
3
)
2
2
3
4.5.4. Chlorin-dyad 12. Similar to the synthesis of 11, reaction of 4
(20 mg, 0.037 mmol) with 1,2-diiodobenzene (6.2 mg, 0.019 mmol)
at 80 C for 2 days gave 12 (6.7 mg, 32%) as a black solid: mp
2
2
2
ꢂ
2
2
ꢂ
>300 C; VIS (CH
2
Cl
2
)
l
max 683 (relative intensity, 0.53), 628 (0.10),
Cl max 2201 (C^C),
1734 (ester-C]O), 1693 (keto-C]O), 1618, 1499 cm
(CDCl
9.25 (2H, s, 5-Hꢁ2), 8.46 (2H, s, 20-Hꢁ2), 8.16, 7.69 (each
2H, m, 3 -C
2
545 (0.12), 514 (0.13), 411 nm (1.00); IR (CH
2
2
) n
ꢀ
1
1
3
2
; H NMR
2
4
3
) d
2
6
H
4
), 8.00 (2H, s, 10-Hꢁ2), 5.36, 5.19 (each 2H, d,
J¼19 Hz, 13 -CH ꢁ2), 4.47 (2H, br q, 18-Hꢁ2), 4.32 (2H, br d, 17-
Hꢁ2), 3.68 (6H, s, 17 -CO
(6H, s, 12-CH
ꢁ2), 2.78e2.74 (2H, m, 17-CHꢁ2), 2.67e2.60 (2H, m,
17 -CHꢁ2), 2.44e2.30 (4H, m, 17-CHCHꢁ2), 1.91 (6H, s, 7-CH ꢁ2),
ꢁ2), 0.67
1
2
2
4
.5.2. Methyl 3-devinyl-3-phenylbutadiynyl-pyropheophorbide-a (10).
Similar to the synthesis of 9, reaction of 4 with phenylacetylene
instead of iodobenzene gave 10 in 67% yield as a black solid: mp
2
CH
3
ꢁ2), 3.47 (6H, s, 2-CH ꢁ2), 3.44
3
3
1
3
ꢂ
4
3
1
(
(
22e124 C; VIS (CH
2
Cl
2
)
l
max 686 (
1.1ꢁ10 ), 517 (1.1ꢁ10 ), 423 (9.4ꢁ10 ), 327 nm (2.2ꢁ10 ); IR
CH Cl max 2212 (C^C), 1730 (ester-C]O), 1694 (keto-C]O),
618, 1501 cm ; H NMR (CDCl
3
, 6.3ꢁ10 ), 626 (7.8ꢁ10 ), 546
1.80 (4H, q, J¼8 Hz, 8-CH
2
ꢁ2), 1.79 (6H, d, J¼7 Hz, 18-CH
3
4
4
4
4
1
(6H, t, J¼8 Hz, 8 -CH
3
ꢁ2), ꢀ0.47, ꢀ2.25 (each 2H, s, NHꢁ2ꢁ2); MS
þ
2
2
)
n
(TOF) found: m/z 1167, calcd for C74
H
70
N
8
O
6
: M , 1167.
ꢀ
1 1
1
3
) d 9.38 (1H, s, 10-H), 9.33 (1H, s, 5-
4
H), 8.58 (1H, s, 20-H), 7.74 (2H, d, J¼7 Hz, 2-H of 3 -Ph), 7.47e7.37
4.5.5. Chlorin-dyad 13. Similar to the synthesis of 12, reaction of 4
with 1,3-diiodobenzene gave 13 in 57% yield as a black solid after FCC
4
1
(
3H, m, 3-, 4-H of 3 -Ph), 5.29, 5.14 (each 1H, d, J¼19 Hz, 13 -CH
2
3
3
),
),
),
2
4
3
3
.51 (1H, br dq, 18-H), 4.33 (1H, br dt, 17-H), 3.63 (3H, s, 17 -CO
.62 (3H, s, 12-CH ), 3.49 (3H, s, 2-CH
), 3.59 (2H, q, J¼8 Hz, 8-CH
.17 (3H, s, 7-CH
2
CH
(Et
CH
2
O/MeOH/CH
Cl
2
Cl
2
¼10:1:89) followed by recrystallization from
ꢂ
3
2
2
2
ehexane: mp >300 C; VIS (CH
2
Cl
2
)
l
max 681 (relative in-
3
), 2.72e2.68 (1H, m, 17-CH), 2.58e2.54 (1H, m,
),
) 0.03, ꢀ2.18 (each 1H, s, NHꢁ2); C NMR
tensity, 0.59), 621 (0.08), 545 (0.12), 515 (0.12), 420 (1.00), 324 nm
(0.22); IR (CH Cl max 2219(C^C),1734(ester-C]O),1693 (keto-C]
O),1619,1499 cm ; H NMR (CDCl
1
1
7 -CH), 2.30e2.26 (2H, m, 17-CHCH), 1.85 (3H, d, J¼7 Hz, 18-CH
3
2
2
)n
1
13
ꢀ1 1
1
.64 (3H, t, J¼8 Hz, 8 -CH
3
3
)
d
9.70 (2H, s, 5-Hꢁ2), 9.57 (2H, s,
1
3
(CDCl
3
)
d
196.7 (C13 ), 174.0 (C17 ), 171.1 (C19), 161.3 (C16), 155.7
10-Hꢁ2), 8.66(2H, s,20-Hꢁ2), 8.47(1H, t, J¼1 Hz,2-HofPh), 8.07(2H,
(
C6), 151.6 (C9), 149.3 (C14), 145.5 (C8), 140.6, 140.3 (C1, C2), 139.3,
dd, J¼8, 1 Hz, 4-, 6-H of Ph), 7.77 (1H, t, J¼8 Hz, 5-H of Ph), 5.32, 5.16
6
1
1
1
29.8 (C11, C12), 137.5 (C4), 137.2 (C7), 133.2 (C3 ꢁ2), 131.7 (C13),
(each 2H, d, J¼19 Hz,13 -CH
2
ꢁ2), 4.54 (2H, br q,18-Hꢁ2), 4.36 (2H, br
8
7
5
30.2 (C3 ), 129.2 (C3 ꢁ2), 122.3 (C3 ), 120.8 (C3), 107.0 (C15), 104.4
t,17-Hꢁ2), 3.73 (4H, q, J¼8 Hz, 8-CH
2
ꢁ2), 3.70 (6H, s,12-CH
3
ꢁ2), 3.63
ꢁ2),
1
2
3
4
1
2
(
5
2
C10), 98.5 (C5), 94.4 (C20), 85.1, 74.5 (C3 , C3 ), 84.6 (C3 ), 76.0 (C3 ),
(6H, s, 17 -CO
2
CH
3
ꢁ2), 3.62 (6H, s, 2-CH ꢁ2), 3.37 (6H, s, 7-CH
3
3
5
2
2
1
2.5 (C17), 52.4 (C17 ), 50.2 (C18), 48.8 (C13 ), 31.5 (C17 ), 30.4 (C17 ),
2.76e2.71 (2H, m, 17-CHꢁ2), 2.62e2.58 (2H, m, 17 -CHꢁ2),
1
1
2
1
1
1
3.9 (C18 ), 20.0 (C8 ), 18.0 (C8 ), 13.4 (C2 ), 12.7 (C12 ), 11.8 (C7 );
2.34e2.27 (4H, m, 17-CHCHꢁ2), 1.86 (6H, d, J¼7 Hz, 18-CH
3
ꢁ2), 1.72
þ
1
HRMS (FAB) found: m/z 647.3035, calcd for C42
47.3022.
Similar to the alternative synthesis of 9, reaction of Zn-4 with
39
H N
4
O
3
: MH ,
(6H, t, J¼8 Hz, 8 -CH
3
ꢁ2), 0.31, ꢀ1.81 (each2H, s, NHꢁ2ꢁ2); MS(TOF)
þ
6
found: m/z 1167, calcd for C74
H
70
8
N O
6
: M , 1167.
phenylacetylene in pyridine and successive demetallation gave 10
4.5.6. Chlorin-dyad 14. Similar to the synthesis of 12, reaction of 4
in 50% yield.
with 1,4-diiodobenzene gave 14 in 58% yield as a black solid: mp
ꢂ
>
300 C; VIS (CH
2
Cl
2
)
l
max 685 (relative intensity, 0.68), 624 (0.09),
Cl
2202 (C^C), 1733 (ester-C]O), 1694 (keto-C]O), 1619, 1504 cm
4
.5.3. Chlorin-dyad 11. Similar to the synthesis of 9, homocoupling
of 4 (20 mg, 0.037 mmol) in the presence of Pd (dba) (8.4 mg,
.009 mmol) and P(o-tolyl) (11 mg, 0.036 mmol) in toluene (8 ml)
and Et N (2 ml) gave 11 (18 mg, 88%) as a black solid after FCC
Et O/MeOH/CH
CH Cl -hexane: mp >300 C; VIS (CH
545 (0.14), 516 (0.14), 419 (1.00), 324 nm (0.26); IR (CH
2
2 max
) n
ꢀ
1
2
3
;
1
0
3
H NMR (CDCl
3
)
d
9.65 (2H, s, 5-Hꢁ2), 9.55 (2H, s, 10-Hꢁ2), 8.65
2
3
(2H, s, 20-Hꢁ2), 8.11 (4H s, 3 -C
6
H
4
), 5.31, 5.16 (each 2H, d, J¼19 Hz,
ꢁ2), 4.54 (2H, br q, 18-Hꢁ2), 4.35 (2H, br d, 17-Hꢁ2), 3.73
(4H, q, J¼8 Hz, 8-CH ꢁ2), 3.69 (6H, s, 12-CH ꢁ2), 3.64 (6H, s,
1
(
2
2
Cl
2
¼10:1:89) followed by recrystallization from
13 -CH
2
ꢂ
5
2
2
2
Cl
2
)
l
max 696 (
3
, 1.46ꢁ10 ),
2
3

6072
S.-i. Sasaki et al. / Tetrahedron 67 (2011) 6065e6072
1
2
2
72-CO
2
CH
3
ꢁ2), 3.60 (6H, s, 2-CH
3
ꢁ2), 3.35 (6H, s, 7-CH
3
ꢁ2),
Commun. 2007, 4407; (c) Kelley, R. F.; Lee, S. J.; Wilson, T. M.; Nakamura, Y.;
Tiede, D. M.; Osuka, A.; Hupp, J. T.; Wasielewski, M. R. J. Am. Chem. Soc. 2008,
1
.76e2.70 (2H, m, 17-CHꢁ2), 2.63e2.57 (2H, m, 17 -CHꢁ2),
130, 4277; (d) Gunderson, V. L.; Conron, S. M. M.; Wasielewski, M. R. Chem.
.34e2.28 (4H, m, 17-CHCHꢁ2), 1.86 (6H, d, J¼7 Hz, 18-CH
3
ꢁ2), 1.74
Commun. 2010, 401; (e) Lee, J.-E.; Yang, J.; Gunderson, V. L.; Wasielewski, M. R.;
Kim, D. J. Phys. Chem. Lett. 2010, 1, 284.
8. pep interactive covalently-linked chlorin dimers as a model of special pair in
photosynthetic reaction center: (a) Wasielewski, M. R.; Svec, W. A.; Cope, B. T. J.
Am. Chem. Soc. 1978, 100, 1961; (b) Bucks, R. R.; Boxer, S. G. J. Am. Chem. Soc.
1982, 104, 340; (c) Osuka, A.; Wada, Y.; Shinoda, S. Tetrahedron 1996, 52, 4311;
1
(
(
6H, t, J¼8 Hz, 8 -CH
3
ꢁ2), 0.29, ꢀ1.83 (each 2H, s, NHꢁ2ꢁ2); MS
þ
70 8 6
TOF) found: m/z 1167, calcd for C74H N O : M , 1167.
Acknowledgements
(d) Kosaka, N.; Tamiaki, H. Eur. J. Org. Chem. 2004, 232; (e) Sasaki, S.; Tamiaki, H.
Tetrahedron Lett. 2006, 47, 4965; (f) Tamiaki, H.; Fukai, K.; Shimazu, H.; Nishide,
K.; Shibata, Y.; Itoh, S.; Kunieda, M. Photochem. Photobiol. Sci. 2008, 7, 1231; (g)
Nikkonen, T.; Haavikko, R.; Helaja, J. Org. Biomol. Chem. 2009, 7, 2046.
. (a) Osuka, A.; Marumo, S.; Wada, Y.; Yamazaki, I.; Yamazaki, T.; Shirakawa, Y.;
Nishimura, Y. Bull. Chem. Soc. Jpn. 1995, 68, 2909; (b) Kelley, R. F.; Tauber, M. J.;
Wasielewski, M. R. J. Am. Chem. Soc. 2006, 128, 4779; (c) Kelley, R. F.; Goldsmith,
R. H.; Wasielewski, M. R. J. Am. Chem. Soc. 2007, 129, 6384; (d) Gunderson, V. L.;
Wilson, T. M.; Wasielewski, M. R. J. Phys. Chem. C 2009, 113, 11936.
This work was partially supported by Grants-in-Aid for Scientific
Research (A) (No. 2245030) (to H.T.) from the Japan Society for the
Promotion of Science (JSPS) and for Young Scientists (B) (No.
9
21750154) (to S.S.) from the Ministry of Education, Culture, Sports,
Science and Technology (MEXT) of the Japanese Government.
1
0. (a) Tamiaki, H.; Kouraba, M. Tetrahedron 1997, 53, 10677; (b) Sasaki, S.; Tamiaki,
H. J. Org. Chem. 2006, 71, 2648; (c) Sasaki, S.; Yoshizato, M.; Kunieda, M.; Ta-
Supplementary data
miaki, H. Eur. J. Org. Chem. 2010, 5287.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.06.020.
11. Sasaki, S.; Mizutani, K.; Kunieda, M.; Tamiaki, H. Tetrahedron Lett. 2008, 49, 4113.
12. Tamiaki, H.; Amakawa, M.; Shimono, Y.; Tanikaga, R.; Holzwarth, A. R.;
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1
3. (a) Smith, K. M.; Goff, D. A.; Simpson, D. J. J. Am. Chem. Soc. 1985, 107, 4946; (b)
Li, G.; Graham, A.; Chen, Y.; Dobhal, M. P.; Morgan, J.; Zheng, G.; Kozyrev, A.;
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7