ROM polymerization-capture-release: Application to the synthesis of unsymmetrical porphyrazinedithiols and peripherally metalated derivatives

Article abstract of DOI:10.1021/jo050369c

Crossover Linstead macrocyclization of a doubly norbornenyl-functionalized dimercaptomaleonitrile with dipropylmaleonitrile gave a crude mixture of porphyrazines containing the hexapropylporphyrazinedithiol magnesium complex. The mixture was subjected to

Full text of DOI:10.1021/jo050369c

ROM Polymerization-Capture-Release: Application to the
Synthesis of Unsymmetrical Porphyrazinedithiols and
Peripherally Metalated Derivatives
Matthew J. Fuchter,† Brian M. Hoffman,*,‡ and Anthony G. M. Barrett*,†
Department of Chemistry, Imperial College London, London SW7 2AZ, U.K., and Department of
Chemistry, Northwestern University, Evanston, Illinois 60208
agmb@imperial.ac.uk
Received February 28, 2005
Crossover Linstead macrocyclization of a doubly norbornenyl-functionalized dimercaptomaleonitrile
with dipropylmaleonitrile gave a crude mixture of porphyrazines containing the hexapropylpor-
phyrazinedithiol magnesium complex. The mixture was subjected to ring-opening metathesis
polymerization to yield the insoluble porphyrazinedithiol-functionalized polymers. Cleavage from
the polymer backbone using mercury(II) acetate followed by reaction with electrophiles gave access
to a range of thioporphyrazinedithiol derivatives including solitaire porphyrazines. Studies into
the possible uses of hexapropyl-2,3-di-(carboxymethylthio)porphyrazine in sensing metal cations
in solution are described.
Introduction
have published extensively on the synthesis of porphyra-
zines bearing thiols, amines, or alcohols as ring substit-
uents and with the conversion of these polydentate
ligands into a variety of coordination complexes.5,6
Porphyrazines containing peripheral thiols constitute
an important subclass of these immensely flexible
macrocycles. Since our initial publication in 1980,1
we have demonstrated the synthesis of numerous
porphyrazinedithiol, -tetrathiol, -hexathiol, and -octathi-
ols and their multimetallic complexes, including star
porphyrazines,7-9 Gemini porphyrazines,10 solitaire sys-
tems,11-13 octathioporphyrazine crown ethers,14-16 and
Compounds possessing tetrapyrrolic macrocyclic ring
systems can be divided into two distinct categories,
namely porphyrins and tetraazaporphyrins. The latter
differ merely by the presence of meso nitrogen atoms and
can be further divided into porphyrazines and phthalo-
cyanines. Porphyrazines present a unique opportunity in
respect to the other two tetrapyrrolic systems in that
direct heteroatom substitution of the â-pyrrole positions
is possible.1 meso-Aza-substitution has a strong influence
on the chemical behavior2 and the overall aromaticity and
the size of the central cavity.3 In addition, peripheral
heteroatom substitution has profound effects on the
electronic structure and optical properties of the por-
phyrazine framework.4 Barrett, Hoffman, and co-workers
(5) Michel, S. L.; Baum, S.; Barrett, A. G. M.; Hoffman, B. M.
Progress in Inorganic Chemistry; Karlin, K. D., Ed.; J. Wiley & Sons:
New York, 2001; Vol. 50, p 473.
(6) Stuzhin, P. A.; Ercolani, C. In The Porphyrin Handbook; Kadish,
K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York,
2003; Vol. 15, p 263.
(7) Vela´zquez, C. S.; Broderick, W. E.; Sabat, M.; Barrett, A. G. M.;
Hoffman, B. M. J. Am. Chem. Soc. 1990, 112, 7408.
(8) Vela´zquez, C. S.; Fox, G. A.; Broderick, W. E.; Anderson, K. A.;
Anderson, O. P.; Barrett, A. G. M.; Hoffman, B. M. J. Am. Chem. Soc.
1992, 114, 7416.
(9) Vela´zquez, C. S.; Baumann, T. F.; Olmstead, M. M.; Hope, H.;
Barrett, A. G. M.; Hoffman, B. M. J. Am. Chem. Soc. 1993, 115, 9997.
(10) Sibert, J. W.; Baumann, T. F.; Williams, D. J.; White, A. J. P.;
Barrett, A. G. M.; Hoffman, B. M. J. Am. Chem. Soc. 1996, 118, 10487.
† Imperial College London.
‡ Northwestern University.
(1) Schramm, C. J.; Hoffman, B. M. Inorg. Chem. 1980, 19, 383.
(2) Stuzhin, P. A.; Khelevina, O. G.; Berezin, B. D. In Phthalocya-
nines: Properties and Applications; VCH Publishers: Weinheim, 1993;
p 23.
(3) Ghosh, A.; Gassman, P. G.; Almlo¨f, J. J. Am. Chem. Soc. 1994,
116, 1932.
(4) Guo, L.; Ellis, D. E.; Hoffman, B. M.; Ishikawa, Y. Inorg. Chem.
1996, 35, 5304.
10.1021/jo050369c CCC: $30.25 © 2005 American Chemical Society
Published on Web 05/17/2005
5086
J. Org. Chem. 2005, 70, 5086-5091

ROM Polymerization-Capture-Release
trimetallic porphyrazine dimers.17 Furthermore, we have
attached porphyrazinedithiol and -tetrathiol derivatives
to gold surfaces and investigated the effect of orientation
on the porphyrazine redox potential.18 Many of the
porphyrazinedithiols and -tetrathiols are fluorescent and
are of potential use as biomedical agents.19,20 Following
our studies on purification-minimized parallel synthesis
using ring-opening metathesis (ROM) polymerization21
and impurity annihilation22 and related studies by Han-
son,23,24 we sought to use ROM polymerization methods
to improve the syntheses of polyfunctional porphyrazines.
The principle of employing a norbornenyl-functionalized
dinitrile with solution-phase Linstead macrocyclization
and subsequent selective capture of the desired por-
phyrazine by ROM polymerization is appealing. Cleavage
of the macrocycle from the ROM polymer should deliver
the pure porphyrazine without the need for extensive
chromatography. Ruthenium alkene metathesis cata-
lysts, developed by Grubbs,25,26 have been previously
applied to the synthesis of polymeric porphyrazine struc-
tures27 and, therefore, should be ideal for this application.
Recently, we published initial studies on a ROM polym-
erization-capture-release strategy for the chromatog-
raphy-free synthesis of amino-porphyrazines.28 We now
report an significant extension of the method for the
preparation of unsymmetrical porphyrazinedithiols. This
new procedure should assist in the parallel synthesis of
novel multimetallic porphyrazines, with possible applica-
tions in electronic and magnetic materials and as chemi-
cal sensors, nanomaterials, and biomedical agents.
SCHEME 1a
a Reagents and conditions: (a) NaBH4, MeOH, (97%); (b) SOCl2,
Tol, 0 °C to ∆(96%); (c) 5, Me2CO, cat. NaI, ∆(68%).
suitable protected derivative of dimercaptomaleonitrile,
tagged with a norbornenyl linker was needed. Simmons
and co-workers reported the synthesis of the monosodium
salt of mercapto(methylthio)maleonitrile,29 in two steps
from the readily available disodium dimercaptomaleoni-
trile (Na-mnt) 5,30 a starting material frequently em-
ployed in the synthesis of porphyrazinedithiols.5 How-
ever, in our hands, monofunctionalization of 5 gave low
yields and mixtures of mono-, di-, and unsubstituted
compounds. We therefore focused on the synthesis of
doubly norbornenyl-functionalized mercaptomaleonitrile
4. Aldehyde 128 was reduced using sodium borohydride
to provide alcohol 2 (97%). Although preparation of the
tosylate proved problematic due to its facile solvolysis,
conversion of alcohol 2 into the corresponding chloride 3
proceeded smoothly by treatment with thionyl chloride.
Subsequent reflux of an acetone solution containing
dinitrile 5 and chloride 3 catalyzed by sodium iodide
resulted in the formation of dinitrile 4 (68% yield)
(Scheme 1).
Mixed Linstead macrocyclization of dinitrile 4 with
dipropylmaleonitrile 6 (10 equiv)31 gave a crude mixture
of dyes containing the porphyrazines 7 and 8, as identi-
fied by FAB mass spectrometry. Filtration of this crude
mixture, followed by treatment with Grubbs’ second-
generation catalyst 1325,26 and cross-linker 14, under the
previously reported conditions,28 resulted in the forma-
tion of ROM polymer 9 as an insoluble blue solid (Scheme
2).
Results and Discussion
To extend the ROM polymerization-capture-release
strategy to the synthesis of porphyrazinedithiols, a
(11) Baumann, T. F.; Nasir, M. S.; Sibert, J. W.; White, A. J. P.;
Olmstead, M. M.; Williams, D. J.; Barrett, A. G. M.; Hoffman, B. M.
J. Am. Chem. Soc. 1996, 118, 10479.
(12) Baumann, T. F.; Sibert, J. W.; Olmstead, M. M.; Barrett, A. G.
M.; Hoffman, B. M. J. Am. Chem. Soc. 1994, 116, 2639.
(13) Goldberg, D. P.; Michel, S. L.; White, A. J. P.; Williams, D. J.;
Barrett, A. G. M.; Hoffman, B. M. Inorg. Chem. 1998, 37, 2100.
(14) Sibert, J. W.; Lange, S. J.; Stern, C. L.; Barrett, A. G. M.;
Hoffman, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 2020.
(15) Lange, S. J.; Sibert, J. W.; Barrett, A. G. M.; Hoffman, B. M.
Tetrahedron 2000, 56, 7371.
(16) Michel, S. L.; Barrett, A. G. M.; Hoffman, B. M. Inorg. Chem.
2003, 42, 814.
(17) Baumann, T. F.; Barrett, A. G. M.; Hoffman, B. M. Inorg. Chem.
1997, 36, 5661.
(18) Vesper, B. J.; Salaita, K.; Zong, H.; Mirkin, C. A.; Barrett, A.
G. M.; Hoffman, B. M. J. Am. Chem. Soc. 2004, 126, 16653.
(19) Lee, S.; Stackow, R.; Foote, C. S.; Barrett, A. G. M.; Hoffman,
B. M. Photochem. Photobiol. 2003, 77, 18.
(20) Hammer, N. D.; Lee, S.; Vesper, B. J.; Elseth, K.; Hoffman, B.
M.; Barrett, A. G. M.; Radosevich, J. Charge Dependence of Cellular
Uptake and Selective Anti-Tumour Activity of Porphyrazines. Submit-
ted for publication.
(21) Barrett, A. G. M.; Hopkins, B. T.; Ko¨bberling, J. Chem. Rev.
2002, 102, 3301.
(22) Barrett, A. G. M.; Smith, M. L.; Zecri, F. Chem. Commun. 1998,
2317.
(23) Harned, A. M.; Hanson, P. R. Org. Lett. 2002, 4, 1007.
(24) Mukherjee, S.; Poon, K. W. C.; Flynn, D. L.; Hanson, P. R.
Tetrahedron Lett. 2003, 44, 7187.
(25) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
(26) Bielawski, C. W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2000,
39, 2903.
(27) Montalban, A. G.; Steinke, J. H. G.; Anderson, M. E.; Barrett,
A. G. M.; Hoffman, B. M. Tetrahedron Lett. 1999, 40, 8151.
(28) Fuchter, M. J.; Vesper, B. J.; Murphy, K. A.; Collins, H. A.;
Philips, D.; Hoffman, B. M.; Barrett, A. G. M. J. Org. Chem. 2005, 70,
2793.
ROM polymer 9 was stable to the previously estab-
lished cleavage acidic system (10% TFA in dichlo-
romethane).28 This is not too surprising since the analo-
gous p-methoxybenyl protecting group has been reported
to be relatively stable to TFA when used as a protecting
group for cysteine amino acids.32 However, treatment of
ROM polymer 9 under more potent Brønsted acidic
(29) Simmons, H. E.; Blomstrom, D. C.; Vest, R. D. J. Am. Chem.
Soc. 1962, 84, 4756.
(30) Ba¨hr, S. Chem. Ber. 1955, 88, 1771.
J. Org. Chem, Vol. 70, No. 13, 2005 5087

Fuchter et al.
SCHEME 2a
a Reagents and conditions: (a) Mg(OnBU)2, nBuOH, ∆; (b) 1 mol % of 13, 14, CH2Cl2, 40 °C; (c) Hg(OAc)2, CH2Cl2, MeOH, 20 °C;
HOCH2CH2SH, 20 °C; (d) Ni(dppe)Cl2, EtN, CH2Cl2, 20 °C, 24 h, 15%; (e) Z(OAc)2, PhMe, DMF, 85 °C (98%).
conditions (1 M triflic acid, 2 M TFA)28 resulted in the
formation of the purple pigment 10, which was not
characterized but allowed to react with (diphos)NiCl2 and
triethylamine. This resulted in the formation of solitaire
porphyrazine 11 in 6% overall yield (from 4) (Scheme 2).
Unfortunately, significant decomposition was observed
throughout the reaction and the isolation of the highly
air-sensitive macrocycle 10 was not conducive to isolation
of the product in reasonable yield. Therefore, an alterna-
tive cleavage strategy was examined. Recently, the
4-methoxybenyl protecting group has been utilized in the
synthesis of porphyrazinedithiols, with subsequent cleav-
age by mercury(II) acetate, to give the air-sensitive free
porphyrazinedithiolate complex.33 With this in mind,
ROM polymer 9 was allowed to react sequentially with
mercury(II) acetate, 2-hydroxyethanethiol, and (diphos)-
NiCl2 in the presence of triethylamine in a one-pot
reaction. Purification by chromatography on a single
flash column gave the solitaire porphyrazine 11. Opti-
mization showed that use of an excess of mercury(II)
acetate was important and resulted in the production of
11 in good yield (15% from 4) (Scheme 2). This result
compares favorably with a structurally related nickel
solitaire porphyrazine, which was obtained by the stan-
dard solution phase methods in approximately 5% overall
yield from the maleonitrile.11 The product contained
traces of dppe/dppe oxide from the excess (dppe)NiCl2
utilized. Likewise, the synthesis of a molybdocene soli-
taire porphyrazine, using the p-methoxybenyl protecting
group was achieved in a low 5% yield from the precursor
dinitrile.33
Excess mercury(II) acetate was presumably needed to
compensate for oxymercuration of the unsaturated ROMP
backbone and the slow rates commonly observed for solid
supported reactions. However, interestingly, hydrogena-
tion of the ROM polymer backbone34 or demetalation (1:1
acetic acid/dichloromethane) of the polymer supported
macrocycle 9 failed to increase the yield of the cleavage
reaction. The unexpected in situ demetalation of 9
observed, giving the delicate porphyrazinedithiol 10,
arose from acetic acid mediated demetalation. Remeta-
lation of the free-base solitaire 11 furnished the pure
(31) Fitzgerald, J.; Taylor, W.; Owen, H. Synthesis 1991, 686.
(32) Erickson, B. W.; Merrifield, R. B. J. Am. Chem. Soc. 1973, 95,
3750.
(33) Kimura, S.; Barrett, A. G. M.; Hoffman, B. M. Unpublished
results, 2004.
(34) Arnauld, T.; Barrett, A. G. M.; Hopkins, B. T. Tetrahedron Lett.
2002, 43, 1081.
5088 J. Org. Chem., Vol. 70, No. 13, 2005

ROM Polymerization-Capture-Release
SCHEME 3a
a Reagents and conditions: (a) Hg(OAc)2, CH2Cl2, MeOH, 20
°C; HOCH2CH2SH, 20 °C; (d) Cp2MoCl2 or MeI or BrCH2CO2Et,
Et3N, CH2Cl2, 20 °C (4-6%); (c) Ni(OAc)2, DMF, 100 °C (80%).
zinc(II) macrocycle 12 (98%), highlighting both the stabil-
ity of the solitaire porphyrazines and the usefulness in
this methodology in the synthesis of multi-metallic
systems (Scheme 2). The range of functionalized por-
phyrazines obtained from the above cleavage reaction
was extended by reaction of the porphyrazinedithiol 10
with a variety of electrophiles to provide pure samples
of the solitaire porphyrazine 15, methylated macrocycle
16 and porphyrazine diester 17 (4%, 6% and 6% overall
yield respectively) (Scheme 3). Macrocycle 17 was sub-
sequently metalated using nickel(II) acetate to yield
porphyrazine 18 (80%).
Previously, we have demonstrated the binding and
sensing of various cationic metal salts using octathiopor-
phyrazine crown ethers,14-16 porphyrazine-appended thia-
crown ethers,15 and polyetherol appended porphyra-
zines.35 For these reasons, we examined the binding of
soft metal ions within the binding pocket of nickel
porphyrazine 18. A solution of macrocycle 18 was titrated
against silver(I) tetrafluoroborate, mercury(II) perchlo-
rate, lead(II) nitrate, cadmium(II) chloride, and cad-
mium(II) perchlorate. No evidence of binding was ob-
served for lead(II) or cadmium(II); however, in the case
of silver(I) and mercury(II) changes in the UV-vis
spectra were apparent (Figure 1).
The results from the titration indicate complex binding
behavior. In the case of titration with Ag+ there was
initially no significant change in the UV-vis spectrum
(0-2.5 equiv AgBF4). At higher concentrations (>2.5
equiv), the Soret band (325 nm) gradually increased in
intensity and the small band at 385 nm disappeared. The
Q-band exhibited complex behavior; the peak at 600 nm
underwent broadening with a blue shift, whereas the
peak at 618 nm underwent sharpening with a red shift.
No further changes were observed at greater than 10
equiv. The initial minimal effects on the spectrum have
been previously observed for certain porphyrazine ap-
pended crown and thiacrown ethers.36 The authors sug-
gested a cooperative binding process was in operation.
Alternatively, binding to the carboxyl groups without
FIGURE 1. UV-vis spectra during titration of 18 in CHCl3
and MeOH (3:1) using (a) AgBF4, (b) Hg(ClO4)2.
binding to the ring sulfur atoms may have been occur-
ring, which would have been UV-vis invisible. As with
AgBF4, Hg(ClO4)2 displayed more complex binding be-
havior than expected, although the observable changes
appeared qualitatively similar to those of Ag(I). With Hg-
(II), spectroscopic changes were observed from the start
of the titration (<1 equiv Hg(II)) with the changes
complete at around 5 equivalents. No real change was
observed for the Soret band (325 nm) whereas the Q-band
exhibited complex behavior. The peak at 600 nm was
broadened and blue shifted whereas the peak at 618 nm
was sharpened and red shifted. From these initial results
it is difficult to draw any firm conclusions regarding the
binding of metal cations by porphyrazine 18, apart from
the fact that Hg2+ is bound more strongly than Ag+. The
exact nature the binding has yet to be established and
further studies are underway.
Conclusions
An extension to the ROM polymerization-capture-
release strategy for the synthesis of novel porphyra-
zinedithiols and derived solitaire complexes is described.
This synthetic strategy therefore has potential for ap-
plication to the synthesis of novel electronic and magnetic
materials. In addition, the nickel(II) porphyrazine 18
showed complex binding behavior with silver(I) and
mercury(II) salts in solution, whereas no binding was
(35) Ehrlich, L. A.; Skrdla, P. J.; Jarell, W. K.; Sibert, J. W.;
Armstrong, N. R.; Saavendra, S. S.; Barrett, A. G. M.; Hoffman, B. M.
Inorg. Chem. 2000, 39, 3963.
(36) Van Nostrum, C. F.; Benneker, F. B. G.; Brussaard, H.;
Kooijamn, H.; Veldman, N.; Spek, A. L.; Schoonman, J.; Feiters, M.
C.; Nolte, R. J. M. Inorg. Chem. 1996, 35, 959.
J. Org. Chem, Vol. 70, No. 13, 2005 5089

Fuchter et al.
ROM Polymer-Supported [7,8,12,13,17,18-Hexapropyl-
2,3-di((4-(norborn-2-en-5-yl)methoxy)benzylthio)por-
phyrazinato]magnesium(II) (9). Mg (91 mg, 3.75 mmol) and
I2 (ca. 1 crystal) in 1-butanol (20 mL) were heated to reflux
for 24 h under N2. The mixture was allowed to cool when
dinitrile 4 (0.16 g, 0.28 mmol) and dipropylmaleonitrile 624
(0.45 g, 2.8 mmol) in 1-butanol (10 mL) were added, and the
mixture was heated to reflux for a further 24 h. Rotary
evaporation and subsequent azeotrope with PhMe (2 × 50 mL)
gave a residue, which was preabsorbed onto silica and added
to additional silica. Elution with hexanes/EtOAc (8:2) was
carried out until the intensity of the initial blue extract had
decreased. After rotary evaporation, the residue was dissolved
in degassed CH2Cl2 (2 mL) under N2 and cross-linker 14 (8.1
mg, 0.031 mmol) in CH2Cl2 (0.5 mL) was added followed by
catalyst 13 (2.4 mg, 2.8 µmol) and the mixture heated to 40
°C for 12 h. CH2Cl2 (2 mL), MeCN (1 mL), and ethyl vinyl ether
(1 mL) were added, and the mixture was heated to 40 °C for
1 h. The polymer gel was filtered off and washed sequentially
with CH2Cl2 (3 × 20 mL) and further extracted with CH2Cl2
(Soxhlet) for 12 h to leave the insoluble ROM polymer 9 (87
mg) as a blue solid.
[1,2-(Diphenylphosphino)ethyl)nickel(II)]-7,8,12,13,-
17,18-hexapropyl-2,3-dithiolatoporphyrazine (11). Hg-
(OAc)2 (36 mg, 0.11 mmol) was added to a suspension of ROM
polymer 9 (10 mg) in degassed CH2Cl2 (3 mL) and MeOH (1
mL) under N2. The suspension was stirred at 20 °C for 24 h.
2-Hydroxyethanethiol (48 µL, 0.68 mmol) in degassed CH2Cl2
(0.5 mL) was added and the resultant suspension stirred at
20 °C for 10 min. (Diphos)NiCl2 (70 mg, 0.13 mmol) was added,
followed by Et3N (27 µL, 0.195 mmol) in degassed CH2Cl2 (0.5
mL). The resulting suspension was stirred under N2 for 24 h
and rotary evaporated. Chromatography (SiO2, CHCl3) gave
solitaire 11 (5.3 mg, 15%) as a blue solid: Rf 0.41 (CHCl3); IR
(neat) 1481, 1462, 1435, 1104, 734 cm-1; UV-vis (CH2Cl2) λmax
(log ꢀ) 339 (4.68), 549 (4.38), 587 (4.44), 661 (4.34) nm; 1H NMR
(500 MHz, CHCl3) δ 1.17-1.29 (m, 18H), 2.13-2.39 (m, 8H),
2.53 (m, 4H), 2.69 (m, 4H), 3.74-4.01 (m, 12H), 7.46 (m, 4H),
7.72 (m, 8H), 8.06 (m, 8H); 13C NMR (125 MHz, CHCl3) δ 14.9,
25.0, 27.2, 28.4, 29.7, 128.7, 129.3, 130.8, 131.0, 131.1, 132.4,
133.5, 134.0, 143.3, 165.5; MS (FAB) m/z 1085 [M + H]+;
HRMS (FAB) calcd for C60H69N8NiP2S2 [M + H]+ 1085.3915,
found [M + H]+ 1085.3942.
observed for cadmium(II) and lead(II). Therefore, deriva-
tives of 18 could find application in the production of
selective chemical sensors. Further applications of this
methodology will be the subject of future reports.
Experimental Section
5-(4-(Hydroxymethyl)phenoxymethyl)bicyclo[2.2.1]hept-
2-ene (2). Aldehyde 128 (5.0 g, 21.9 mmol) in MeOH (10 mL)
was added slowly to NaBH4 (2.0 g, 52.9 mmol) in MeOH (30
mL) at 0 °C under N2, and the mixture was allowed to warm
to 20 °C over 30 min. HCl (1 M, 30 mL) was added, and the
resulting solution extracted with Et2O (3 × 50 mL). The
combined organic extracts were dried (MgSO4), filtered, and
rotary evaporated. Chromatography (SiO2, hexanes/EtOAc,
6:4) gave alcohol 2 (4.89 g, 97%), a clear oil, as a mixture of
isomers: Rf 0.44 (hexanes/EtOAc 6:4); IR (neat) 3339, 1612,
1
1513, 1468, 1243, 1173, 1029, 826 cm-1; H NMR (300 MHz,
CDCl3) 0.62 (m, 1H), 1.26-1.51 (m, 2H), 1.91 (m, 1H), 2.56
(m, 1H), 2.86 (s, 1H) 3.05 (s, 1H), 3.55 (t, J ) 9.0 Hz, 1H),
3.72 (t, J ) 9.0 Hz, 1H), 4.60 (s, 2H), 5.96-6.18 (m, 2H), 6.88
(d, J ) 8.0 Hz, 2H), 7.27 (d, J ) 8.0 Hz, 2H); 13C NMR (75
MHz, CDCl3) δ 29.1, 38.4, 42.3, 43.9, 49.5, 65.1, 71.6, 114.6,
128.7, 132.4, 132.9, 137.6, 158.8; MS (CI) m/z 230 [M]+; HRMS
(CI) calcd for C15H18O2 [M+•] 230.1307, found [M+•] 230.1300.
Anal. Calcd for C15H17ClO: C, 78.23; H, 7.88. Found: C, 78.05;
H, 7.75.
5-(4-(Chloromethyl)phenoxymethyl)bicyclo[2.2.1]hept-
2-ene (3). Thionyl chloride (0.62 mL, 8.6 mmol) in PhMe (5
mL) was added dropwise with vigorous stirring to alcohol 2
(1.0 g, 4.3 mmol) and Et3N (0.6 mL, 4.5 mmol) in PhMe (20
mL) at 0 °C under N2. Once the addition was complete, the
mixture was allowed to warm to 20 °C and stirred for 2 h.
Finally, the mixture was heated at reflux for 30 min to
complete the transformation. The solution was allowed to cool
to 20 °C and further cooled to 0 °C, and H2O (20 mL) was
slowly added. The resulting layers were separated, and the
organic layer was washed with 10% 2 M HCl (20 mL) and
saturated aqueous NaHCO3 (20 mL). The combined organic
extracts were dried (MgSO4), filtered, and rotary evaporated.
Chromatography (SiO2, hexanes/EtOAc, 9:1) gave chloride 3
(1.03 g, 96%), a clear oil, as a mixture of isomers: Rf 0.67
(hexanes/EtOAc, 9:1); IR (neat) 1611, 1513, 1467, 1246, 1175,
1025, 830 cm-1; 1H NMR (300 MHz, CDCl3) 0.64 (m, 1H), 1.28-
1.53 (m, 2H), 1.95 (m, 1H), 2.58 (m, 1H), 2.89 (s, 1H), 3.07 (s,
1H), 3.57 (t, J ) 9.0 Hz, 1H), 3.74 (t, J ) 9.0 Hz, 1H), 4.60 (s,
2H), 5.97-6.22 (m, 2H), 6.89 (d, J ) 8.0 Hz, 2H), 7.29 (d, J )
8.0 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 29.1, 38.6, 42.3, 43.9,
46.1, 49.5, 71.5, 114.7, 129.4, 130.1, 132.4, 137.6, 159.3; MS
[1,2-(Diphenylphosphino)ethyl)nickel(II)][7,8,12,13,-
17,18-hexapropyl-2,3-dithiolatoporphyrazinato]zinc-
(II) (12). Porphyrazine 11 (3.6 mg, 3.3 µmol), Zn(OAc)2‚2H2O
(3.0 mg, 13 µmol), dry DMF (0.5 mL), and PhMe (2 mL) were
heated to 85 °C for 16 h under N2. Rotary evaporation and
chromatography (SiO2, CHCl3) gave solitaire 12 (3.7 mg, 98%)
as a green solid: Rf 0.10 (CHCl3); IR (neat) 1454, 1435, 1148,
947, 875 cm-1; UV-vis (CH2Cl2) λmax (log ꢀ) 346 (4.48), 572
(CI) m/z 248 [M]+; HRMS (CI) calcd for C15H17ClO [M+•
]
1
248.0968, found [M+•] 248.0964. Anal. Calcd for C15H17ClO:
C, 72.43; H, 6.89. Found: C, 72.29; H, 6.73.
(4.03), 622 (4.41), 668 (3.93) nm; H NMR (500 MHz, CHCl3)
δ 1.11-1.25 (m, 18H), 2.12 (m, 12H), 2.54 (m, 4H), 3.58 (m,
8H), 3.75 (m, 4H), 7.47 (m, 4H), 7.63 (m, 8H), 8.03 (m, 8H);
13C NMR (125 MHz, CHCl3) δ 14.8, 25.4, 27.2, 28.2, 29.7, 128.8,
129.2, 131.8, 132.0, 133.6, 133.9, 144.6; MS (FAB) m/z 1146
[M+•].
2,3-Di((4-(norborn-2-en-5-yl)methoxy)benzylthio)ma-
leonitrile (4). A mixture containing dinitrile 5 (0.3 g, 1.65
mmol), chloride 3 (0.82 g, 3.3 mmol), and NaI (0.1 g, 0.7 mmol)
in Me2CO (10 mL) was heated to reflux for 18 h. The
suspension was allowed to cool, filtered, and rotary evaporated.
The residue was dissolved in CH2Cl2 (20 mL) and washed with
H2O (4 × 30 mL) to remove residual salts. The organic extract
was dried (MgSO4), filtered, and rotary evaporated. Chroma-
tography (SiO2, CH2Cl2) gave sulfide 4 (0.64 g, 68%), a viscous
bright yellow oil, which crystallized over time as a mixture of
isomers: Rf 0.74 (CH2Cl2); IR (neat) 2209, 1609, 1511, 1467,
[1,1′-Di(cyclopentadienyl)molybdenum(II)]-7,8,12,13,-
17,18-hexapropyl-2,3-dithiolatoporphyrazine (15).13 Hg-
(OAc)2 (36 mg, 0.11 mmol) was added to ROM polymer 9 (10
mg) in degassed CH2Cl2 (3 mL) and MeOH (1 mL) under N2
and the suspension stirred at 20 °C for 24 h. 2-Hydroxy-
ethanethiol (48 µL, 0.68 mmol) in degassed CH2Cl2 (0.5 mL)
was added and the resultant suspension stirred at 20 °C for
10 min. Cp2MoCl2 (39 mg, 0.13 mmol) was added, followed by
Et3N (27 µL, 0.195 mmol) in degassed CH2Cl2 (0.5 mL). The
resulting suspension was stirred under N2 for 24 h and rotary
evaporated. Chromatography (SiO2, CHCl3) gave solitaire 15
(1.2 mg, 4%) as a blue solid: Rf 0.13 (CHCl3); UV-vis (CH2-
Cl2) λmax (log ꢀ) 345 (3.87), 576 (3.76), 636 (3.56) nm; MS (FAB)
m/z 856 [M+•]; HRMS (FAB) calcd for C44H55MoN8S2 [M + H+]
857.3045, found [M + H+] 857.3075.
1
1241, 1171, 1023, 832 cm-1; H NMR (300 MHz, CDCl3) 0.64
(m, 2H), 1.28-1.51 (m, 4H), 1.93 (m, 2H), 2.56 (m, 2H), 2.87
(s, 2H), 3.05 (s, 2H), 3.55 (t, J ) 9.0 Hz, 2H), 3.71 (t, J ) 9.0
Hz, 2H), 4.28 (s, 4H), 5.96-6.21 (m, 4H), 6.84 (d, J ) 8.0 Hz,
4H), 7.23 (d, J ) 8.0 Hz, 4H); 13C NMR (75 MHz, CDCl3) δ
29.1, 38.3, 39.1, 42.3, 43.9, 49.5, 71.5, 115.0, 125.9, 130.4, 132.3,
137.7, 159.2; MS (FAB) m/z 567 [M + H]+; HRMS (FAB) calcd
for C34H35N2O2S2 [M + H]+ 567.2140, found [M + H]+ 567.2156.
5090 J. Org. Chem., Vol. 70, No. 13, 2005

ROM Polymerization-Capture-Release
7,8,12,13,17,18-Hexapropyl-2,3-di(methylthio)porphyra-
zine (16). Hg(OAc)2 (36 mg, 0.11 mmol) was added to a
suspension of ROM polymer 9 (10 mg) in degassed CH2Cl2 (3
mL) and MeOH (1 mL) under N2. The suspension was stirred
at 20 °C for 24 h. A solution of 2-hydroxyethanethiol (48 µL,
0.68 mmol) in degassed CH2Cl2 (0.5 mL) was added and the
resultant suspension stirred at 20 °C for 10 min. MeI (8 µL,
0.13 mmol) was added, followed by Et3N (27 µL, 0.195 mmol)
in degassed CH2Cl2 (0.5 mL). The resulting suspension was
stirred under N2 for 24 h, rotary evaporated and chromato-
graphed (SiO2, hexanes/CH2Cl2, 1:1) to give sulfide 16 (1.5 mg,
6%) as a blue solid: Rf 0.89 (hexanes/CH2Cl2, 1:1); IR (neat)
1489, 1463, 1147, 991, 755, 717 cm-1; UV-vis (CH2Cl2) λmax
(log ꢀ) 348 (4.39), 550 (3.84), 584 (4.16), 634 (4.21) nm; 1H NMR
(500 MHz, CHCl3) δ 0.89 (m, 2H), 1.28 (m, 18H), 2.33 (m, 12H),
NMR (125 MHz, CHCl3) δ 14.0, 14.7, 25.4, 25.7, 28.1, 28.3,
37.0, 61.4, 139.0, 142.0, 142.4, 145.4, 145.9, 147.2, 158.1, 164.3,
169.8; MS (FAB) m/z 803 [M + H]+; HRMS (FAB) calcd for
C42H59N8O4S2 [M + H]+ 803.4101, found [M + H]+ 803.4097.
7,8,12,13,17,18-Hexapropyl-2,3-di((ethoxycarbonyl)-
methylthio)porphyrazinato]nickel (II) (18). Porphyrazine
17 (2.4 mg, 0.003 mmol), Ni(OAc)2 (5.0 mg, 0.03 mmol), and
dry DMF (3 mL) were heated to 100 °C for 16 h under N2.
Rotary evaporation and chromatography (SiO2, CH2Cl2) gave
porphyrazine 18 (2.0 mg, 80%) as a deep blue solid: Rf 0.19
(hexanes/CH2Cl2, 1:1); IR (neat) 1732, 1454, 1284, 1155, 1026,
979, 764 cm-1; UV-vis (CH2Cl2) λmax (log ꢀ) 325 (4.57), 385
1
(4.02), 600 (4.53), 618 (4.55) nm; H NMR (500 MHz, CHCl3)
δ 1.04 (t, J ) 7 Hz, 6H), 1.26 (m, 18H), 2.26 (m, 12H), 3.77 (t,
J ) 7 Hz, 12H), 4.08 (q, J ) 7 Hz, 4H), 4.96 (s, 4H); 13C NMR
(125 MHz, CHCl3) δ 14.0, 14.7, 25.3, 25.5, 28.1, 28.2, 37.1, 61.4,
138.0, 145.0, 145.2, 145.5, 146.1, 149.2, 151.1, 151.2, 169.6;
MS (FAB) m/z 859 [M + H]+; HRMS (FAB) calcd for C42H57N8-
NiO4S2 [M + H]+ 859.3298, found [M + H]+ 859.3313.
3.55 (s, 6H), 3.80 (t, J ) 7 Hz, 4H), 3.97 (t, J ) 7 Hz, 8H); 13
C
NMR (125 MHz, CHCl3) δ 14.7, 25.4, 25.6, 28.1, 28.3, 29.6,
140.2, 141.9, 142.2, 145.6, 146.0, 147.4, 158.3, 163.3; MS (FAB)
m/z 658 [M+•]; HRMS (FAB) calcd for C36H50N8S2 [M+•
]
658.3600, found [M+•] 658.3587.
7,8,12,13,17,18-Hexapropyl-2,3-di((ethoxycarbonyl)-
Acknowledgment. We thank GlaxoSmithKline for
the generous endowment (to A.G.M.B.), the Royal
Society and the Wolfson Foundation for a Royal Society
Wolfson Research Merit Award (to A.G.M.B.), the Wolf-
son Foundation for establishing the Wolfson Centre for
Organic Chemistry in Medical Sciences at Imperial
College, and the Engineering and Physical Sciences
Research Council, the National Science Foundation and
Schering AG for generous support of our studies.
methylthio)porphyrazine (17). Hg(OAc)2 (36 mg, 0.11
mmol) was added to ROM polymer 9 (10 mg) in degassed CH2-
Cl2 (3 mL) and MeOH (1 mL) under N2. The suspension was
stirred at 20 °C for 24 h and 2-hydroxyethanethiol (48 µL, 0.68
mmol) in degassed CH2Cl2 (0.5 mL) was added and the
resultant suspension stirred at 20 °C for 10 min. EtO2CCH2-
Br (14 µL, 0.13 mmol) was added, followed by Et3N (27 µL,
0.195 mmol) in degassed CH2Cl2 (0.5 mL). The resulting
suspension was stirred under N2 for 24 h, rotary evaporated,
and chromatographed (SiO2, CH2Cl2) to give sulfide 17 (1.5
mg, 6%) as a blue solid: Rf 0.19 (hexanes/CH2Cl2, 1:1); IR
(neat) 1732, 1463, 1286, 1143, 1033, 758, 722 cm-1; UV-vis
Supporting Information Available: General experimen-
tal procedures and structural data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
(CH2Cl2) λmax (log ꢀ) 348 (4.20), 592 (4.04), 632 (4.11) nm; H
NMR (500 MHz, CHCl3) δ -2.23 (br s, 2H), 1.06 (t, J ) 7 Hz,
6H), 1.29 (m, 18H), 2.33 (m, 12H), 3.80 (t, J ) 7 Hz, 4H), 3.97
(t, J ) 7 Hz, 8H). 4.10 (q, J ) 7 Hz, 4H), 5.07 (s, 4H); 13C
JO050369C
J. Org. Chem, Vol. 70, No. 13, 2005 5091