1,9-Bis(N,N-dimethylaminomethyl)dipyrromethanes in the synthesis of porphyrins bearing one or two meso substituents

Article abstract of DOI:10.1016/j.tet.2005.08.028

A synthesis of 5,15-disubstituted zinc-porphyrins has been developed that employs condensation of a 1,9-bis(N,N-dimethylaminomethyl)dipyrromethane+a dipyrromethane in refluxing ethanol containing zinc acetate followed by oxidation with DDQ. The N,N-dimethylaminomethylation of the dipyrromethane was achieved via Eschenmoser's reagent (N,N-dimethylmethyleneammonium iodide) in CH₂Cl₂ at room temperature. The synthesis is compatible with diverse substituents (e.g., alkyl, aryl, ester, acetal) and enables rapid synthesis of trans-AB-, A₂-, and A-porphyrins. The synthesis of >40 zinc porphyrins has been surveyed; 13 zinc porphyrins were isolated in yields of 5-20% without detectable scrambling.

Full text of DOI:10.1016/j.tet.2005.08.028

Tetrahedron 61 (2005) 10291–10302
1,9-Bis(N,N-dimethylaminomethyl)dipyrromethanes in the
synthesis of porphyrins bearing one or two meso substituents
*
Dazhong Fan, Masahiko Taniguchi, Zhen Yao, Savithri Dhanalekshmi and Jonathan S. Lindsey
Department of Chemistry, North Carolina State University, Raleigh, NC, 27695-8204, USA
Received 18 April 2005; revised 4 August 2005; accepted 5 August 2005
Available online 1 September 2005
Abstract—A synthesis of 5,15-disubstituted zinc-porphyrins has been developed that employs condensation of a 1,9-bis(N,N-
dimethylaminomethyl)dipyrromethaneCa dipyrromethane in refluxing ethanol containing zinc acetate followed by oxidation with DDQ.
The N,N-dimethylaminomethylation of the dipyrromethane was achieved via Eschenmoser’s reagent (N,N-dimethylmethyleneammonium
iodide) in CH2Cl2 at room temperature. The synthesis is compatible with diverse substituents (e.g., alkyl, aryl, ester, acetal) and enables rapid
synthesis of trans-AB-, A2-, and A-porphyrins. The synthesis of O40 zinc porphyrins has been surveyed; 13 zinc porphyrins were isolated in
yields of 5–20% without detectable scrambling.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
hydroxymethyl3) attached to a pyrrolic species or as added
reagents (formic acid,5 trimethyl orthoformate,6 formal-
dehyde,2 and imines7). A key consideration in the use of
dipyrromethanes is the possibility of acidolysis followed by
undesired recombination of dipyrromethane-derived
fragments, affording undesired porphyrin species (i.e.,
scrambling). The possibility of scrambling constrains the
nature of the reactive groups employed as C1 synthons (e.g.,
aldehyde or hydroxymethyl) and reaction conditions that
can be employed.
Porphyrins bearing only one or two substituents present a
compact architecture suitable for a wide variety of
applications or further synthetic elaboration. For sub-
stituents at the meso-positions, the methodology established
for preparing porphyrins bearing four distinct meso-
substituents would appear applicable. The route to such
ABCD-porphyrins entails condensation of a dipyrro-
methaneCdipyrromethane-1,9-dicarbinol, where the four
substituents are introduced via the meso-positions of both
dipyrromethane species and the carbinol units at the 1- and
9-positions.1 The corresponding synthesis of A-porphyrins,
trans-AB-porphyrins, and also trans-A2-porphyrins2
would employ meso-substituted dipyrromethanes with no
substituents at the carbinol sites. To our surprise,
condensations with dipyrromethanes bearing primary
carbinol groups proceeded poorly, giving a mixture of
porphyrins and overall low yields.3 No better alternatives
(other than statistical condensations) to A-porphyrins or
trans-AB-porphyrins have been developed. This limitation
prompted us to investigate C1 synthons having greater
reactivity than primary carbinol groups for the rational
synthesis of porphyrins bearing one or two meso-
substituents.
The aminomethyl group is an attractive candidate for the C1
synthon leading to porphyrinic macrocycles because of ease
of introduction, the possibility that reaction can be carried
out without added acid catalysts, and biomimetic analogy.
Indeed, an aminomethylpyrrole (porphobilinogen, A)8 is the
biosynthetic precursor of all naturally occurring porphyrinic
macrocycles (Chart 1). Aminomethylpyrroles have been
prepared by the condensation of pyrrole derivatives with
aldehydes and amines.9 The advent of N,N-dimethyl-
methyleneammonium iodide (Eschenmoser’s reagent),10
designed for reactions with corrins, also facilitated the
synthesis of aminomethylpyrrolic compounds. To construct
porphyrinic macrocycles from aminomethylpyrroles, three
different approaches have been investigated: (1) self-
condensation of an aminomethylpyrrole (e.g., B or C);11,12
(2) condensation of a bis(aminomethyl)pyrrole (e.g., D or E)
with a pyrrole derivative;11,13,14 and (3) 3C1 condensation
of a bis(aminomethyl)pyrrole D with a tripyrrane.14,15 These
approaches are attractive in their simplicity but have the
potential limitation of forming a mixture of porphyrin
A wide variety of C1 synthons have been employed in
porphyrin chemistry, either as functional groups (aldehyde,4
Keywords: Dipyrromethane; Aminomethylation; Porphyrin; Zinc.
*
Corresponding author. Tel.: C1 9195156406; fax: C1 9195132830;
e-mail: jlindsey@ncsu.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.08.028

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D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
regioisomers depending on the b-substitution pattern of the
pyrrolic substrates.
Although aminomethyl-dipyrromethanes can be attractive
precursors for porphyrinic macrocycles, aminomethyl-
dipyrromethane derivatives (F) have been mainly used for
the synthesis of expanded porphyrins, such as porpho-
cyanine.16 To our knowledge, the only previous example of
aminomethyl-dipyrromethane derivatives in porphyrin
chemistry is Hombrecher’s synthesis of meso-substituted
etioporphyrins:17 treatment of a dipyrromethane with a
Mannich reagent (CH2]NEt2Cl) gave the 1,9-bis(N,N-
diethylaminomethyl)dipyrromethane (not isolated), which
upon condensation with a dipyrromethane in situ afforded a
mixture including a trans-AB-porphyrin, A-porphyrins, and
etioporphyrin (Scheme 1).
In this paper, we report the synthesis of trans-AB-, trans-
A2-, and A-porphyrins via a [2C2] condensation of a
bis(aminomethyl)dipyrromethaneCa dipyrromethane. The
dipyrromethanes lack b-substituents. N,N-Dimethylamino-
methylation of a dipyrromethane is achieved with
Eschenmoser’s reagent. The survey of the scope of reaction
encompassed 14 dipyrromethanes and led to examination of
the synthesis of O40 zinc porphyrins.
Chart 1.
Scheme 1.
Scheme 2.

D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
10293
2. Results and discussion
(1) Oxidant. The condensation of 3aC1b in CH2Cl2/EtOH
3:1 under reflux for 16 h (without any oxidant other than air)
gave no porphyrin (Table 1, entry 1). However, further
treatment of the reaction mixture with DDQ afforded free
base porphyrin 5ab in 7% yield (entry 2). Smith employed
K3Fe(CN)6 as an oxidant for porphyrin formation from a
bis(aminomethyl)pyrrole.14 Inclusion of K3Fe(CN)6 in the
condensation of 3aC1b afforded porphyrin 5ab in 5% yield
(entry 3). The yield increased to 7% upon further oxidation
with DDQ (entry 4). No added catalyst is required for
formation of the putative porphyrinogen, however, oxi-
dation cannot be achieved with air or K3Fe(CN)6 but
requires use of DDQ.
2.1. Synthesis of aminomethyl derivatives of
5-phenyldipyrromethane
A series of aminomethyl derivatives of 5-phenyldipyrro-
methane was prepared as shown in Scheme 2. Treatment of
5-phenyldipyrromethane (1a)18 with Eschenmoser’s
reagent10 at room temperature smoothly gave the dipyrro-
methane-bis(ammonium iodide) 2a, which was easily
isolated by precipitation upon addition of ethyl ether.
Alternatively, treatment of the reaction mixture containing
2a with aqueous NaHCO3 quantitatively gave the corre-
sponding free amine, 1,9-bis(N,N-dimethylaminomethyl)-
dipyrromethane (3a). The reaction of 3a with methyl iodide
gave the quaternized ammonium salt 4a.
(2) Acid. Trifluoroacetic acid, trichloroacetic acid, acetic
acid, or propionic acid was examined as an acid catalyst
(entry 5). At room temperature, no porphyrin formation was
observed.
2.2. Optimization of the reaction conditions for
porphyrin formation
(3) Metal template. The condensation of 3aC1b in the
presence of Zn(OAc)2 in CH2Cl2/EtOH 3:1 under reflux
gave zinc porphyrin Zn5ab in 2% yield (entry 6).
Oxidation of the reaction mixture with DDQ afforded
Zn5ab in up to 13% yield without scrambling (entry 7). No
free base porphyrin was detected. This method provides a
simple procedure for the formation of a trans-AB-
porphyrin.
Porphyrin formation via a [2C2] condensation was first
examined by the reaction of free base bis(aminomethyl)
dipyrromethane 3aCdipyrromethane 1b19 under various
conditions. In each case, the yield of porphyrin was
determined by absorption spectroscopy and the occurrence
of scrambling was assessed by laser-desorption mass
spectrometry (LD-MS).20,21 Initially, several reagents
(oxidant, acid, and metal template) were examined for the
reaction in CH2Cl2/EtOH 3:1. The major findings are as
follows:
The required reagents for the porphyrin-forming
reaction from a bis(aminomethyl)dipyrromethane are
Zn(OAc)2 and DDQ. Further modification of the reaction
conditions was investigated by changing the following
factors:
Table 1. Effect of reagents in porphyrin formation via 3aC1ba
(4) Solvent. EtOH gave the best result out of six solvents that
were examined (THF, MeOH, toluene, CH2Cl2, CHCl3,
EtOH). In alcohol solvents, the reaction proceeded rapidly
and was complete in 1 h. A longer reaction time was
required with halogenated solvents.
(5) Amount of Zn(OAc)2. The highest yield of porphyrin was
obtained when 10 mol equiv of Zn(OAc)2 was used. The
yield decreased to one third with a stoichiometric amount of
Zn(OAc)2.
(6) Concentration. The effects of reactant concentration
were examined over the range from 1 to 316 mM. The
highest yield (w12% spectroscopic yield) was obtained at
10 mM (Fig. 1A).
Entry
Reagent 1
Reagent 2
Product
Yield (%)b
1
2
3
4
5
6
7
—
—
—
DDQc
—
—
5ab
5ab
5ab
—
Zn5ab
Zn5ab
0
7
5
7
0
2
13
(7) Reaction time. The yield of porphyrin as a function of
time upon condensation of 3a and 1b (to form porphyrin
Zn5ab) is shown in Figure 1B. The condensation was
essentially complete within w2 h.
K3Fe(CN)6
K3Fe(CN)6
Acidd
Zn(OAc)2
Zn(OAc)2
DDQc
DDQc
—
DDQc
a Reaction conditions: 10 mM reactants in CH2Cl2/EtOH 3:1 under reflux
exposed to air for 18 h in the presence or absence of reagents [K3Fe(CN)6
(0.1, 1, or 10 equiv) or Zn(OAc)2 (10 equiv)].
From these studies, the best conditions for porphyrin
formation are as follows: 3a (10 mM), 1b (10 mM), and
Zn(OAc)2 (10 equiv) in EtOH under reflux for w2 h,
followed by treatment with DDQ (3/4 equiv per pyrrolic
unit) at room temperature for 15 min. Application of this
method afforded trans-AB-porphyrin Zn5ab in 16% yield
without detectable scrambling.
b The yields of porphyrin were calculated upon absorption spectroscopy of
small aliquots from the reaction mixture.
c Following the general reaction condition, the reaction mixture was treated
with 3/4 equiv of DDQ per pyrrole unit (30 mM).
d Trifluoroacetic acid (TFA), trichloroacetic acid (TCA), acetic acid, or
propionic acid.

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D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
Figure 1. (A) Effect of concentration of dipyrromethane species in porphyrin formation (3aC1b). Reaction conditions were as follows: [Zn(OAc)2 (10 equiv)
in EtOH at reflux in air for 5 h, data points are at 1, 3.16, 10, 31.6, 100, and 316 mM], then treated with 3/4 equiv of DDQ per pyrrole unit. The yields of
porphyrin were determined using absorption spectroscopy by removing small aliquots from the reaction mixture; (B) the yield of porphyrin as a function of
time upon reaction of bis(N,N-dimethylaminomethyl)dipyrromethane 3aCdipyrromethane 1b with Zn(OAc)2 under reflux in EtOH (the concentration of each
reactant is 10 mM) exposed to air.
2.3. Reactivity of free base amine (3a) versus ammonium
salts (2a and 4a) of dipyrromethanes
were performed with free base 1,9-bis(N,N-dimethyl-
aminomethyl)dipyrromethane analogues of 3a.
The reactivity of free base amine (3a) versus amine salt (2a
or 4a) was examined under the optimized conditions
described above and also in the absence of Zn(OAc)2 and/
or DDQ (Table 2). The highest yields were obtained for all
three substrates (2a, 3a, 4a) upon use of both Zn(OAc)2 and
DDQ. This result was somewhat surprising, because we
anticipated that the quaternized ammonium salt might react
in the absence of Zn(OAc)2. With either Zn(OAc)2 or DDQ
present, the bis(ammonium) salts of the dipyrromethane
(2a, 4a) exhibited reactivity comparable to each other and
greater than that of the free base amine 3a. However, the
highest yield overall was observed with the free base amine
derivative 3a. All subsequent porphyrin-forming reactions
2.4. Synthesis of trans-AB-, trans-A2-, and A-porphyrins.
Probing aryl/alkyl/H substituents
A series of known dipyrromethanes (1a–n)1,18,19,22–31 was
prepared by application of a new solventless synthesis that
entails treatment of an aldehyde dissolved in 100 equiv of
pyrrole with a mild Lewis acid (InCl3) at room tempera-
ture.32 Each dipyrromethane (1a–n) was reacted with
Eschenmoser’s reagent at room temperature followed by
workup with aqueous NaHCO3 (aqueous K2CO3 was used
for the synthesis of 3i), affording the corresponding free
base 1,9-bis(N,N-dimethylaminomethyl)dipyrromethane
(3a–n) in 43–91% yield (Table 3).
Table 2. Effect of reagents and amine [free amine (3a) versus amine salt (2a or 4a)] in porphyrin formationa
Substrate
Yield (%)b
Step (1):
Step (2):
—
—
—
DDQ
Zn(OAc)2
—
Zn(OAc)2
DDQ
2a
3a
4a
1 (5ab)
0
!1 (5ab)
6 (5ab)
0
6 (5ab)
4 (Zn5ab)c
0
2 (Zn5ab)
10 (Zn5ab)
13 (Zn5ab)
8 (Zn5ab)
a Reaction conditions: 10 mM reactants and 10 equiv of Zn(OAc)2 in EtOH under reflux exposed to air for 18 h, then treated with 3/4 equiv of DDQ per pyrrole
unit (30 mM).
b The yields of porphyrin were calculated using absorption spectroscopy by removing small aliquots from the reaction mixture.
c LD-MS showed the presence of free base porphyrin 5ab.

D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
10295
Table 3. Synthesis of 5-substituted-1,9-bis(N,N-dimethylaminomethyl)dipyrromethanes 3a–na
R
Yield (%)b
68
R
Yield (%)b
83
a
h
b
c
91
64
85
i
63
75
43
j
d
k
e
87
l
81
f
68
87
m
n
66
86
g
a Reaction conditions: 100 mM dipyrromethane 1a–n and 2 equiv of Eschenmoser’s reagent in CH2Cl2 at room temperature for 1 h, then washed with saturated
aqueous NaHCO3 (K2CO3 for 1i).
b Isolated yield.
The scope of porphyrin formation was examined using
the 1,9-bis(N,N-dimethylaminomethyl)dipyrromethanes
(Scheme 3, Table 4). Emphasis was placed on (1) variation
of the substituents; (2) assessment of any scrambling
processes; and (3) yields of porphyrin. Altogether, the
preparation of 28 trans-AB-porphyrins was examined. The
yields of porphyrin were determined spectroscopically and
ranged from !1 to 19% depending on the substituents and
combination of the dipyrromethane precursors. Note that a
given porphyrin can be made in two ways by switching the
combination of the 1,9-bis(N,N-dimethylaminomethyl)-
dipyrromethane (3) and dipyrromethane (1). For example,
1eC3d afforded the zinc porphyrin Zn5de in !1% yield
while 1dC3e gave Zn5de in 15% yield. In all cases where
the better of the two possible combinations was employed,
the yields ranged from 12 to 19%. In those cases where the
porphyrin was isolated (Zn5ab and Zn5ac), the isolated
yields compared well with the spectroscopic yield.
Scrambling was observed only in the reaction of
5-(pentafluorophenyl)dipyrromethane (1e)C1,9-bis(N,N-
dimethylaminomethyl)-5-pentyldipyrromethane (3g) (8%
yield, level 2 scrambling). The scrambling problem could
be overcome by reversal of the substituents; thus, reaction of
1gC3e afforded the same target porphyrin in 15% yield
with no detectable scrambling. In general, the reaction of
5-(pentafluorophenyl)dipyrromethane (1e) proceeded in
low yield and/or scrambling whereas the same meso-
substituent could be well accommodated upon use of 1,9-
bis(N,N-dimethylaminomethyl)-5-(pentafluorophenyl)-
dipyrromethane (3e). Taken together, the results upon
condensation of a dipyrromethaneC1,9-bis(N,N-dimethyl-
aminomethyl)dipyrromethane are superior to those of the
reaction of a 1,9-bis(hydroxymethyl)-5-substituted-dipyrro-
methaneCa 5-substituted-dipyrromethane, which resulted
in extensive scrambling.3
The results illustrate the effects of substituents (alkyl or
aryl) on the yields of the trans-AB-porphyrins and the
relative reactivity of those groups when present on the
dipyrromethane (1) versus 1,9-bis(dimethylaminomethyl)-
dipyrromethane (3). The yields of porphyrin are insensitive
to the presence of an alkyl versus aryl group on either
dipyrromethane or 1,9-bis(dimethylaminomethyl)dipyrro-
methane reactants. However, in the synthesis of porphyrins
bearing only one meso-substituent (A-porphyrin), the
combination of unsubstituted dipyrromethane and 5-sub-
stituted 1,9-bis(dimethylaminomethyl)dipyrromethane
affords higher yields than the reverse combination.
Scheme 3.

Table 4. Formation of trans-AB- and A-porphyrins Zn5 via 3a–g,iC1a–g,ia
3a
3b
3c
3d
3e
3f
3g
3i
Methyl
n-Pentyl
H
1a
1b
—
13
—
11
11
11
9
18
13
7
6
15
16
5
5
14 (16)b
1c
18 (15)b
18
13
—
12
10
—
18
15
12
6
16
14
6
5
1d
12
1e
!1
6c
!1
!1
—
4
8c
2
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
16
1f
Methyl
13
13
16
12
12
—
4
1g
n-Pentyl
18
16
16
15
15
11
—
8
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1i 13 19 14 11 16
H
8
9
—
a The yields of porphyrin were determined by absorption spectroscopy of small aliquots from the reaction mixture. All reactions gave level 0 scrambling (detected by LD-MS analysis) unless noted otherwise. Reaction
conditions: 10 mM reactants and 10 equiv of Zn(OAc)2 in EtOH under reflux exposed to air for 3 h, then treated with 3/4 equiv of DDQ per pyrrole unit (30 mM). The combination that gives the better yield of
porphyrin is underlined.
b Isolated yield.
c Level 2 scrambling.

D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
Table 5. Synthesis of trans-AB-, A2-, and A-porphyrins Zn5 with diverse substituentsa
10297
Bis(aminomethyl)dipyrromethane
Dipyrromethane
Porphyrin
Yield (%)b
trans-AB-porphyrin
3j
1b
1b
Zn5bj
Zn5bk
10
14
3k
3l
1b
Zn5bl
15
3m
1b
Zn5bm
5
3g
3a
1h
1n
Zn5gh
Zn5an
17
6
3j
1n
Zn5jn
1
A-porphyrin
3j
1i
1i
Zn5ij
Zn5ik
12
17
3k
3l
1i
1i
Zn5il
20
3m
Zn5im
5
trans-A2-porphyrin
3l
1l
Zn5ll
15
a All reactions give level 0 scrambling (assessed by LD-MS analysis). Reaction conditions: 10 mM reactants and 10 equiv of Zn(OAc)2 in refluxing EtOH
exposed to air for 2 h, then treated with 3/4 equiv of DDQ per pyrrole unit (30 mM).
b Isolated yields.
2.5. Synthesis of trans-AB-, trans-A2-, and A-porphyrins.
Scope with diverse substituents
change was obtained upon use of the TMS-ethynyl unit in
the bis(N,N-dimethylaminomethyl)dipyrromethane species.
We examined the synthesis of a series of trans-AB-, trans-
A2-, and A-porphyrins bearing diverse substituents
(Table 5). Each porphyrin was purified by short passage
over a pad of silica. 5-(p-Tolyl)dipyrromethane (1b) was
reacted with a series of 1,9-bis(dimethylaminomethyl)-
dipyrromethanes bearing diverse substituents 3j–m, includ-
ing acetal,27 allyl,28 swallowtail,29 and carboethoxy30
groups. In each case, no scrambling was observed and the
isolated yields of the trans-AB-porphyrins ranged from 5 to
15%. In the same manner, a trans-AB-porphyrin (Zn5gh)
bearing two alkyl groups was prepared in 17% yield. When
a 5-TMS-ethynyldipyrromethane (1n) was employed, the
yield of porphyrin was low (Zn5an and Zn5jn). Very little
A similar series of reactions was performed with unsub-
stituted dipyrromethane (1i) and 5-substituted 1,9-bis(N,N-
dimethylaminomethyl)dipyrromethanes 3j–m. The corre-
sponding A-porphyrins (Zn5ij, Zn5ik, Zn5il, and Zn5im)
were obtained in yields of 5–20%. trans-AB-porphyrins
bearing a single swallowtail substituent (Zn5bl and Zn5il)
were obtained smoothly. A trans-A2-porphyrin (Zn5ll) was
obtained by using a dipyrromethane and a bis(N,N-
dimethylaminomethyl)dipyrromethane each bearing
swallowtail substituents at the 5-position. The success of
these approaches is in contrast to the failure encountered
upon attempted reaction of a dipyrromethane-1-carbinol
bearing a swallowtail substituent at the 1-position.29

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D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
In general, the substituents that can be introduced with this
method are quite diverse and open up a number of
applications. The acetal group (Zn5bj, Zn5ij) can be
converted to an aldehyde,27 the allyl group (Zn5bk, Zn5ik)
can be used for surface attachment,28 the swallowtail group
(Zn5bl, Zn5il, Zn5ll) can suppress aggregation and thereby
increase the solubility of the porphyrin,29 and the ester
(Zn5bm, Zn5im) provides a motif for apical coordination in
self-assembly processes.
with THF (500 mL, 21 times dilution), then 50 mL of this
diluted reaction mixture was added to a 1-cm pathlength
cuvette containing 3.00 mL of THF (61 times dilution) and
the absorption spectrum was recorded (total dilution 1281
times). The yield of the porphyrin was determined by the
intensity of the Soret band (412 nm, 3Z500,000 MK1 cmK1
)
measured from the apex to the base of the red edge of the
band. In this manner, a Soret band absorption of 1.00
corresponded to a porphyrin yield of 26%.
4.4. Standard procedures
3. Outlook
4.4.1. Aminomethylation of a dipyrromethane, exempli-
fied for 1,9-bis(N,N-dimethylaminomethyl)-5-phenyl-
dipyrromethane (3a). A solution of 1a (667 mg,
3.00 mmol) in CH2Cl2 (30 mL) at room temperature was
treated with N,N-dimethylmethyleneammonium iodide
(Eschenmoser’s reagent; employed as a fine powder;
1.17 g, 6.30 mmol). After 1 h, CH2Cl2 (100 mL) and
aqueous NaHCO3 (100 mL) were added to the reaction
mixture. The organic phase was dried (Na2SO4) and then
concentrated to dryness. Addition of hexanes/CH2Cl2
afforded a precipitate, which upon filtration was obtained
The synthesis of porphyrins bearing one or two meso-
substituents (A-porphyrin, trans-AB-porphyrin) requires
use of a C1 synthon that provides greater reactivity than
that of a primary carbinol group. The N,N-dimethylamino-
methyl group serves as an effective C1 synthon owing to the
ease of introduction, reactivity in the absence of an added
Brønsted acid, and reaction under mild conditions without
detectable acidolysis. The method described herein affords
rather modest yields of zinc porphyrins. The low yields are
offset by the absence of scrambling, the broad scope, and the
ease of implementation.
1
as a pale yellow solid (600 mg, 59%): mp 76–78 8C; H
NMR d 2.17 (s, 12H), 3.33 (s, 4H), 5.37 (s, 1H), 5.72–5.74
(m, 2H), 5.89–5.91 (m, 2H), 7.19–7.31 (m, 5H), 8.07–8.18
(br, 2H); 13C NMR d 44.3, 45.0, 56.7, 106.8, 107.3, 126.7,
128.36, 128.48, 128.9, 132.5, 142.4. Anal. Calcd for
C21H28N4: C, 74.96; H, 8.39; N, 16.65. Found: C, 74.76;
H, 8.63; N, 16.27.
4. Experimental
4.1. General
1
All H NMR (400 MHz) and 13C NMR (100 MHz) spectra
were obtained in CDCl3 unless noted otherwise. Porphyrins
were analyzed by laser desorption mass spectrometry
without a matrix (LD-MS).21 Fast atom bombardment
mass spectrometry (FAB-MS) data are reported for the
molecule ion or protonated molecule ion. Column chroma-
tography was performed with flash silica. Each new
compound (except salt 4a) was O95% pure as determined
by 1H NMR spectroscopy. For each zinc porphyrin, only the
principal absorption maxima are reported.
4.4.2. Porphyrin formation from 1,9-bis(N,N-dimethyl-
aminomethyl)dipyrromethanes, exemplified for Zn(II)-
5-mesityl-15-phenylporphyrin (Zn5ac) via 3aC1c. A
solution of 3a (168 mg, 0.500 mmol) and 5-mesityldipyrro-
methane (1c, 132 mg, 0.500 mmol) in ethanol (50 mL) at
room temperature was treated with Zn(OAc)2 (917 mg,
5.00 mmol). The mixture was heated to reflux. After 2 h, the
reaction mixture was allowed to cool to room temperature.
A sample of DDQ (340 mg, 1.50 mmol) was added and the
mixture was stirred for 15 min. Triethylamine (355 mL,
2.50 mmol) was added and the reaction mixture was
concentrated to dryness. Column chromatography [silica,
hexanes/CH2Cl2 1:1] afforded a purple solid (42.4 mg,
4.2. Noncommercial compounds
The dipyrromethanes 1a,18 1b,19 1c,22 1d,23 1e,24 1f,25 1g,19
1h,1 1i,26 1j,27 1k,28 1l,29 1m,30 1n31 were prepared using a
new method that entails reaction of an aldehyde in
100 equiv of pyrrole containing a Lewis acid (e.g., InCl3).32
1
15%); H NMR d 1.85 (s, 6H), 2.68 (s, 3H), 7.34 (s, 2H),
7.80–7.82 (m, 3H), 8.25–8.28 (m, 2H), 9.00 (d, JZ4.4 Hz,
2H), 9.14 (d, JZ4.4 Hz, 2H), 9.41 (d, JZ4.4 Hz, 2H), 9.45
(d, JZ4.4 Hz, 2H), 10.30 (s, 2H); 13C NMR d 21.7, 22.0,
106.1, 118.7, 120.2, 126.9, 127.7, 128.0, 131.6, 131.9, 132.5,
132.7, 134.8, 137.8, 139.0, 139.6, 142.9, 149.65, 149.74,
150.17, 150.31. Anal. Calcd for C35H26N4Zn: C, 74.01; H,
4.61; N, 9.86. Found: C, 74.27; H, 4.72; N, 9.53; LD-MS obsd
565.9, calcd 566.14 (C35H26N4Zn); labs 412, 544 nm.
4.3. Spectroscopic yield determinations
Yields of porphyrin-forming reactions were determined by
removal of aliquots from the reaction mixture, treatment
with DDQ, followed by absorption spectroscopy of the
oxidized product. For example, an ethanol solution of 3a
(1.00 mL, 20.0 mM stock solution, 20.0 mmol of 3a) and an
ethanol solution of 1b (1.00 mL, 20.0 mM stock solution,
20.0 mmol of 1b) were combined and treated with Zn(OAc)2
(36.6 mg, 200 mmol), affording [3a]Z[1a]Z10 mM. The
reaction mixture was refluxed for a designated period. A
sample of DDQ (13.6 mg, 60.0 mmol) was added and the
mixture was stirred for 10 min at room temperature, then
triethylamine (13 mL, 100 mmol) was added. An aliquot
(25 mL) of the reaction mixture was removed and diluted
4.5. Synthesis of 1,9-dialkylated dipyrromethanes
4.5.1. Hydroiodide salt of 1,9-bis(N,N-dimethylamino-
methyl)-5-phenyldipyrromethane (2a). A solution of 1a
(222 mg, 1.00 mmol) in CH2Cl2 (10 mL) at room tempera-
ture was treated with N,N-dimethylmethyleneammonium
iodide (fine powder form; 389 mg, 2.10 mmol). After 1 h,
the mixture was diluted with ethyl ether (30 mL), causing
formation of a precipitate. A pale yellow solid (542 mg,

D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
10299
91%) was collected by filtration: mp 138–140 8C; 1H NMR
d 2.97 (d, JZ5.2 Hz, 12H), 4.54 (d, JZ5.2 Hz, 4H), 5.45 (s,
1H), 5.79–5.81 (m, 2H), 6.19–6.21 (m, 2H), 7.20–7.29 (m,
5H), 8.90–9.10 (br, 2H), 10.40 (s, 2H); 13C NMR d 43.03,
43.08, 44.6, 55.2, 108.9, 113.6, 118.2, 126.7, 128.43,
128.54, 135.0, 143.0; FAB-MS obsd 465.18, calcd 465.16
[(MKI)C] (MZC21H30IN4).
146.4 (m); FAB-MS obsd 426.1825, calcd 426.1843
(C21H23F5N4).
4.5.7. 1,9-Bis(N,N-dimethylaminomethyl)-5-methyl-
dipyrromethane (3f). Following the standard procedure,
reaction of 1.00 mmol of 1f afforded a pale yellow solid
1
(140 mg, 51%): mp 113–115 8C; H NMR d 1.57 (d, JZ
8.0 Hz, 3H), 2.16 (s, 12H), 3.32 (s, 4H), 4.07–4.12 (m, 1H),
5.87–5.91 (m, 4H), 8.12–8.24 (br, 2H); 13C NMR d 20.6,
32.1, 45.1, 56.8, 104.2, 107.4, 128.4, 135.2; FAB-MS obsd
274.31, calcd 274.22 (C16H26N4).
4.5.2. Hydroiodide salt of 1,9-bis(N,N-trimethylamino-
methyl)-5-phenyldipyrromethane (4a). A solution of 3a
(336 mg, 1.00 mmol) in dry CH2Cl2 (10 mL) was treated
with CH3I (3.00 mmol) at room temperature in 1 h. The
reaction mixture was filtered, washed with a small amount
of cold THF, and concentrated to dryness, affording a pale
yellow solid (400 mg, 65%, O80% pure): mp 186–188 8C;
1H NMR (DMSO-d6) d 3.37 (s, 18H), 4.80 (s, 4H), 5.90 (s,
1H), 6.18 (s, 2H), 6.69 (s, 2H), 7.60–7.76 (m, 5H), 11.50–
11.68 (br, 2H); 13C NMR (DMSO-d6) d 43.2, 51.4, 54.37,
54.41, 61.8, 107.9, 113.6, 118.1, 126.7, 128.1, 128.4, 135.8,
1425.4; FAB-MS obsd 493.21, calcd 493.18 [(MKI)C]
(MZC23H34IN4).
4.5.8. 1,9-Bis(N,N-dimethylaminomethyl)-5-n-pentyl-
dipyrromethane (3g). Following the standard procedure,
reaction of 1.00 mmol of 1g afforded a brown oil (290 mg,
1
87%); H NMR d 0.85 (t, JZ6.4 Hz, 3H), 1.27 (s, 6H),
1.92–1.94 (m, 2H), 2.37 (s, 12H), 3.59–3.67 (m, 4H), 3.92–
3.95 (m, 1H), 5.89–5.90 (m, 2H), 5.97–5.98 (m, 2H), 9.10–
9.24 (br, 2H); 13C NMR d 14.3, 22.8, 27.5, 31.9, 34.8, 38.2,
45.2, 56.9, 105.0, 107.4, 128.5, 134.1; FAB-MS obsd
330.2774, calcd 330.2783 (C20H34N4).
4.5.9. 1,9-Bis(N,N-dimethylaminomethyl)-5-n-hexyl-
dipyrromethane (3h). Following the standard procedure,
reaction of 1.00 mmol of 1h afforded a yellow solid
(278 mg, 80%): mp 88–90 8C; 1H NMR d 0.85 (t, JZ
6.4 Hz, 3H), 1.24–1.29 (m, 8H), 1.89–1.91 (m, 2H), 2.16 (s,
12H), 3.29–3.37 (m, 4H), 3.88 (t, JZ7.6 Hz, 1H), 5.87–5.90
(m, 4H), 8.10–8.20 (br, 2H); 13C NMR d 14.3, 22.8, 27.8,
29.4, 31.9, 34.7, 38.1, 45.2, 56.9, 105.0, 107.4, 128.4, 134.1;
FAB-MS obsd 344.2859, calcd 344.2940 (C21H36N4).
4.5.3. 1,9-Bis(N,N-dimethylaminomethyl)-5-(p-tolyl)
dipyrromethane (3b). Following the standard procedure,
reaction of 1.00 mmol of 1b afforded a pale yellow solid
1
(320 mg, 91%): mp 62–64 8C; H NMR d 2.17 (s, 12H),
2.32 (s, 3H), 3.29–3.38 (m, 4H), 5.34 (s, 1H), 5.74–5.75 (m,
2H), 5.90–5.91 (m, 2H), 7.09 (s, 4H), 8.27–8.35 (br, 2H);
13C NMR d 21.3, 44.1, 45.2, 56.9, 106.8, 107.6, 128.4,
128.9, 129.4, 133.1, 136.5, 139.6; FAB-MS obsd 350.2483,
calcd 350.2470 (C22H30N4).
4.5.10. 1,9-Bis(N,N-dimethylaminomethyl)dipyrro-
methane (3i). Following the standard procedure with slight
modification (K2CO3 was used instead of NaHCO3),
reaction of 1.00 mmol of 1i afforded a pale yellow solid
4.5.4. 1,9-Bis(N,N-dimethylaminomethyl)-5-mesityl-
dipyrromethane (3c). Following the standard procedure,
reaction of 1.00 mmol of 1c afforded a pale yellow solid
(240 mg, 64%): mp 43–45 8C; 1H NMR d 2.09 (s, 6H), 2.18
(s, 12H), 2.27 (s, 3H), 3.34 (s, 4H), 5.77–5.79 (m, 2H), 5.82
(s, 1H), 5.92–5.93 (m, 2H), 6.83 (s, 2H), 8.18–8.34 (br, 2H);
13C NMR d 20.91, 21.03, 38.9, 45.1, 56.8, 106.4, 108.0,
127.9, 130.4, 131.7, 135.1, 136.4, 137.7; FAB-MS obsd
378.2785, calcd 378.2783 (C24H34N4).
1
(152 mg, 63%): mp 74–76 8C; H NMR d 2.17 (s, 12H),
3.33 (s, 4H), 3.84 (s, 2H), 5.82–5.83 (m, 2H), 5.88–5.90 (m,
2H), 8.55–8.70 (br, 2H); 13C NMR d 27.0, 45.2, 56.9, 105.9,
107.8, 128.6, 129.7; FAB-MS obsd 261.2091, calcd
261.2079 (C15H24N4).
4.5.11.
1,9-Bis(N,N-dimethylaminomethyl)-5-(5,5-
4.5.5. 1,9-Bis(N,N-dimethylaminomethyl)-5-(4-methoxy-
phenyl)dipyrromethane (3d). Following the standard
procedure, reaction of 1.00 mmol of 1d afforded a pale
yellow solid (310 mg, 85%): mp 65–66 8C; 1H NMR d 2.15
(s, 12H), 3.28–3.36 (m, 4H), 3.77 (s, 3H), 5.30 (s, 1H), 5.71–
5.73 (m, 2H), 5.90–5.91 (m, 2H), 6.80–6.82 (m, 2H), 7.09–
7.11 (m, 2H), 8.30–8.45 (br, 2H); 13C NMR d 43.6, 45.2,
55.5, 56.9, 106.9, 107.6, 114.0, 128.9, 129.6, 133.3, 134.8,
158.5; FAB-MS obsd 366.2411, calcd 366.2420
(C22H30N4O).
dimethyl-1,3-dioxan-2-yl)dipyrromethane (3j). Following
the standard procedure, reaction of 1.00 mmol of 1j afforded
a colorless solid (280 mg, 75%): mp 92–94 8C; H NMR d
0.72 (s, 3H), 1.12 (s, 3H), 2.18 (s, 12H), 3.32 (d, JZ
13.2 Hz, 2H), 3.41 (d, JZ13.2 Hz, 2H), 3.48 (d, JZ
13.2 Hz, 2H), 3.72 (d, JZ13.2 Hz, 2H), 4.30 (d, JZ4.0 Hz,
1H), 4.80 (d, JZ4.0 Hz, 1H); 5.79–5.81 (m, 2H), 5.88–5.89
(m, 2H), 8.80–8.90 (br, 2H); 13C NMR d 22.0, 23.2, 30.5,
42.6, 45.2, 57.0, 103.7, 107.0, 107.2, 128.8, 129.5; FAB-MS
obsd 374.2680, calcd 374.2682 (C21H34N4O2).
1
4.5.6. 1,9-Bis(N,N-dimethylaminomethyl)-5-(penta-
fluorophenyl)dipyrromethane (3e). Following the stan-
dard procedure, reaction of 1.00 mmol of 1e afforded a
yellow solid (370 mg, 87%): mp 38–40 8C; 1H NMR d 2.19
(s, 12H), 3.30–3.41 (m, 4H), 5.82 (s, 1H), 5.87–5.88 (m,
2H), 5.94–5.95 (m, 2H), 8.50–8.60 (br, 2H); 13C NMR d
33.5, 45.2, 56.8, 107.3, 107.9, 116.2–116.5 (m), 128.3,
129.8, 136.5–136.8 (m), 139.0–139.3 (m, two peaks were
overlapped), 141.5–141.8 (m), 143.8–144.0 (m), 146.3–
4.5.12. 5-Allyl-1,9-bis(N,N-dimethylaminomethyl)dipyr-
romethane (3k). Following the standard procedure,
reaction of 1.00 mmol of 1k afforded a brown oil
1
(130 mg, 43%); H NMR d 2.14 (s, 12H), 2.68–2.72 (m,
2H), 3.32–3.33 (m, 4H), 4.00–4.03 (m, 1H), 4.98–5.08 (m,
2H), 5.76–5.83 (m, 1H), 5.89–5.90 (m, 4H), 8.20–8.40 (br,
2H); 13C NMR d 38.2, 39.3, 45.2, 56.9, 105.2, 107.5, 116.7,
128.6, 133.4, 136.8; FAB-MS obsd 300.2308, calcd
300.2314 (C18H28N4).

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D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
4.5.13. 1,9-Bis(N,N-dimethylaminomethyl)-5-(tridec-7-
yl)dipyrromethane (3l). Following the standard procedure,
reaction of 1.00 mmol of 1l afforded a brown oil (180 mg,
(d, JZ8.0 Hz, 2H), 8.15 (d, JZ8.0 Hz, 2H), 9.13 (d, JZ
4.0 Hz, 2H), 9.36–9.37 (m, 4H), 9.59 (d, JZ4.0 Hz, 2H),
10.13 (s, 2H); 13C NMR (THF-d8) d 21.8, 40.0, 106.12,
106.18, 115.5, 116.6, 120.1, 128.1, 130.4, 132.2, 132.72,
132.81, 135.7, 137.7, 141.7, 143.7, 150.26, 150.44, 151.26,
151.42; LD-MS obsd 501.9; FAB-MS obsd 502.1118, calcd
502.1136 (C30H22N4Zn); labs 412, 545 nm.
1
81%); H NMR d 0.86 (t, JZ7.2 Hz, 6H), 1.13–1.35 (m,
20H), 1.81–1.91 (m, 1H), 2.16 (s, 12H), 3.30 (d, JZ
13.2 Hz, 2H), 3.39 (d, JZ13.2 Hz, 2H), 3.97 (d, JZ6.4 Hz,
2H), 5.85–5.86 (m, 2H), 5.89–5.90 (m, 2H), 8.15–8.33 (br,
2H); 13C NMR d 14.3, 22.9, 27.2, 29.9, 31.6, 32.1, 41.8,
42.1, 45.1, 56.9, 105.9, 107.5, 127.9, 132.9; FAB-MS obsd
442.4033, calcd 442.4035 (C28H50N4).
4.6.4. Zn(II)-5-(4-methylphenyl)-15-(tridec-7-yl)por-
phyrin (Zn5bl) via 3lC1b. Following the standard
procedure, reaction of 1.00 mmol of 3l and 1b afforded a
purple solid (100 mg, 15%); 1H NMR d 0.69–0.72 (m, 6H),
1.06–1.11 (m, 12H), 1.33–1.42 (m, 2H), 1.58–1.66 (m, 2H),
2.75 (s, 3H), 2.80–2.89 (m, 2H), 3.00–3.10 (m, 2H), 5.38–
5.42 (m, 1H), 7.60 (d, JZ7.6 Hz, 2H), 8.13 (d, JZ7.6 Hz,
2H), 9.12–9.14 (m, 2H), 9.39–9.40 (m, 2H), 9.50–9.53 (m,
2H), 9.90 (d, JZ4.8 Hz, 1H), 9.99 (d, JZ4.8 Hz, 1H), 10.26
(s, 2H); 13C NMR d 14.2, 21.8, 22.7, 29.9, 31.9, 43.0, 47.4,
105.7, 106.0, 119.7, 125.0, 127.6, 130.3, 131.3, 131.69,
131.72, 132.1, 132.5, 132.74, 134.77, 137.3, 139.9, 147.7,
149.1, 149.4, 149.72, 149.74, 150.53, 150.58, 152.0; LD-
MS obsd 644.7; FAB-MS obsd 644.2899, calcd 644.2857
(C40H44N4Zn); labs 412, 545 nm.
4.5.14. 1,9-Bis(N,N-dimethylaminomethyl)-5-(ethoxy-
carbonyl)dipyrromethane (3m). Following the standard
procedure, reaction of 1.00 mmol of 1m afforded a brown
oil (230 mg, 69%); 1H NMR d 1.27 (t, JZ7.2 Hz, 3H), 2.17
(s, 12H), 3.28 (d, JZ12.0 Hz, 2H), 3.45 (d, JZ12.0 Hz,
2H), 4.20 (q, JZ7.2 Hz, 2H), 4.99 (s, 1H), 5.89–5.93 (m,
4H), 8.80–9.00 (br, 2H); 13C NMR d 14.3, 44.6, 45.1, 56.7,
61.8, 106.9, 107.8, 127.2, 129.4, 171.6; FAB-MS obsd
333.2291, calcd 332.2212 (C18H28N4O2).
4.5.15. 1,9-Bis(N,N-dimethylaminomethyl)-5-[2-(tri-
methylsilyl)ethynyl]dipyrromethane (3n). Following the
standard procedure, reaction of 1.00 mmol of 1n afforded a
brown solid (290 mg, 81%): mp 73–76 8C; 1H NMR d 0.19
(s, 9H), 2.18 (s, 12H), 3.35 (d, JZ3.2 Hz, 4H), 5.15 (s, 1H),
5.90–5.91 (m, 2H), 5.96–5.97 (m, 2H), 8.30–8.40 (br, 2H);
13C NMR d 0.2, 31.6, 45.2, 56.8, 87.7, 104.1, 106.0, 107.6,
129.1, 129.4.
4.6.5. Zn(II)-5-ethoxycarbonyl-15-(4-methylphenyl)por-
phyrin (Zn5bm) via 3mC1b. Following the standard
procedure, reaction of 1.00 mmol of 3m and 1b afforded a
1
purple solid (25.0 mg, 5%); H NMR (THF-d8) d 1.82 (t,
JZ7.2 Hz, 3H), 2.73 (s, 3H), 5.08 (q, JZ7.2 Hz, 2H), 7.61
(d, JZ8.0 Hz, 2H), 8.11 (d, JZ7.6 Hz, 2H), 9.04 (d, JZ
4.4 Hz, 2H), 9.38 (d, JZ4.4 Hz, 2H), 9.49 (d, JZ4.4 Hz,
2H), 9.66 (d, JZ4.8 Hz, 2H), 10.30 (s, 2H); 13C NMR
(THF-d8) d 14.4, 20.8, 62.2, 106.71, 106.83, 107.3, 127.2,
131.11, 131.15, 132.40, 132.53, 134.7, 137.1, 140.4, 149.2,
149.70, 149.77, 150.1, 172.2; LD-MS obsd 535.6; FAB-MS
obsd 534.1059, calcd 534.1034 (C30H22N4O2Zn); labs 410,
541 nm.
4.6. Synthesis of Zn(II)porphyrins
4.6.1. Zn(II)-5-(4-methylphenyl)-15-phenylporphyrin
(Zn5ab) via 3aC1b. Following the standard procedure,
reaction of 0.500 mmol of 3a and 1b afforded a purple solid
(43 mg, 16%); 1H NMR (THF-d8) d 2.75 (s, 2H), 7.58–7.62
(m, 2H), 7.77–7.83 (m, 2H), 8.13–8.18 (m, 2H), 8.26–8.29
(m, 2H), 9.11–9.15 (m, 2H), 9.15–9.19 (m, 2H), 9.41–9.47
(m, 2H), 10.31 (s, 2H); 13C NMR (THF-d8) d 21.7, 106.6,
120.3, 120.6, 127.4, 128.1, 128.2, 132.2, 132.3, 132.7,
132.9, 135.7, 135.8, 137.8, 141.6, 144.6, 150.61, 150.64,
151.0, 151.2; LD-MS obsd 538.5; FAB-MS obsd 538.1150,
calcd 538.1136 (C33H22N4Zn); labs 413, 539 nm.
4.6.6. Zn(II)-5-hexyl-15-n-pentylporphyrin (Zn5gh)
from 3gC1h. Following the standard procedure, reaction
of 0.600 mmol of 3g and 1h afforded a purple solid
1
(80.0 mg, 17%); H NMR d 0.94–1.03 (m, 6H), 1.40–1.46
(m, 2H), 1.51–1.61 (m, 4H), 1.83–1.88 (m, 4H), 2.54–2.59
(m, 4H), 4.94–4.98 (m, 4H), 9.34 (d, JZ4.4 Hz, 4H), 9.58
(d, JZ4.4 Hz, 4H), 10.00 (s, 2H); 13C NMR (THF-d8) d
13.7, 13.8, 22.9, 23.0, 30.4, 32.3, 32.9, 35.28, 35.34, 39.1,
39.4, 104.5, 118.81, 118.82, 128.8, 131.6, 148.9, 150.3; LD-
MS obsd 526.6; FAB-MS obsd 526.2088, calcd 526.2075
(C31H34N4Zn); labs 411, 546 nm.
4.6.2. Zn(II)-5-(5,5-dimethyl-1,3-dioxan-2-yl)-15-(4-
methylphenyl)porphyrin (Zn5bj) via 3jC1b. Following
the standard procedure, reaction of 1.00 mmol of 3j and 1b
afforded a purple solid (58.0 mg, 10%); 1H NMR (THF-d8)
d 1.17 (s, 3H), 2.00 (s, 3H), 2.74 (s, 3H), 4.30–4.39 (m, 4H),
7.60 (d, JZ8.0 Hz, 2H), 8.07 (s, 1H), 8.14 (d, JZ8.0 Hz,
2H), 9.18 (d, JZ4.0 Hz, 2H), 9.43 (d, JZ4.0 Hz, 2H), 9.56
(d, JZ4.0 Hz, 2H), 10.18 (d, JZ4.0 Hz, 2H), 10.34 (s, 2H);
13C NMR (THF-d8) d 21.7, 23.0, 31.7, 80.8, 106.4, 108.0,
113.2, 121.5, 128.1, 131.8, 132.0, 132.5, 132.9, 135.6,
137.8, 141.6, 150.36, 150.48, 150.51, 151.3; LD-MS obsd
575.9; FAB-MS obsd 576.1519, calcd 576.1504
(C33H28N4O2Zn); labs 409, 541 nm.
4.6.7. Zn(II)-5-phenyl-15-[2-(trimethylsilyl)ethynyl]por-
phyrin (Zn5an) from 3aC1n. Following the standard
procedure, reaction of 1.00 mmol of 3a and 1n afforded a
1
purple solid (30.1 mg, 6%); H NMR (THF-d8) d 0.69 (s,
9H), 7.79–7.81 (m, 3H), 8.22–8.24 (m, 2H), 8.79 (d, JZ
4.4 Hz, 2H), 9.34 (d, JZ4.4 Hz, 2H), 9.45 (d, JZ4.4 Hz,
2H), 9.85 (d, JZ4.4 Hz, 2H), 10.22 (s, 2H); 13C NMR
(THF-d8) d 0.8, 98.5, 100.2, 106.0, 107.7, 122.5, 127.5,
128.4, 131.9, 132.3, 133.13, 133.24, 135.6, 135.8, 144.3,
150.5, 150.8, 151.0, 153.6; LD-MS obsd 545.5; FAB-MS
obsd 544.1061, calcd 544.1062 (C31H24N4SiZn); labs 424,
556, 595 nm.
4.6.3. Zn(II)-5-allyl-15-(4-methylphenyl)porphyrin
(Zn5bk) via 3kC1b. Following the standard procedure,
reaction of 1.00 mmol of 3k and 1b afforded a purple solid
1
(70.0 mg, 14%); H NMR (THF-d8) d 2.75 (s, 3H), 5.15–
5.20 (m, 2H), 5.73–5.75 (m, 2H), 6.81–6.88 (m, 1H), 7.61

D. Fan et al. / Tetrahedron 61 (2005) 10291–10302
10301
4.6.8. Zn(II)-5-(5,5-dimethyl-1,3-dioxan-2-yl)-15-[2-(tri-
methylsilyl)ethynyl]porphyrin (Zn5jn) from 3jC1n.
Following the standard procedure, reaction of 1.00 mmol
of 3j and 1n afforded a purple solid (5.70 mg, 1%); 1H NMR
d 7.98 (s, 2H), 9.30 (d, JZ4.8 Hz, 2H), 9.40 (d, JZ4.8 Hz,
2H), 9.75 (d, JZ4.0 Hz, 2H), 10.08 (d, JZ4.0 Hz, 2H),
10.11 (s, 2H); LD-MS obsd 583.406; FAB-MS obsd
582.1473, calcd 582.1429 (C31H30N4O2SiZn); labs 417,
551, 587 nm.
2.97–3.07 (m, 4H), 5.32–5.37 (m, 2H), 9.46–9.50 (m, 4H),
9.84–9.86 (m, 2H), 9.92–9.94 (m, 2H), 10.21 (s, 2H); 13C
NMR d 14.2, 22.7, 29.8, 31.9, 42.8, 47.2, 104.93, 105.21,
105.49, 124.0, 130.02, 130.25, 130.95, 131.17, 131.50,
131.82, 147.12, 147.37, 149.18, 149.45, 149.72, 149.76,
152.04, 152.10; LD-MS obsd 736.0; FAB-MS obsd
736.4412, calcd 736.4422 (C46H64N4Zn); labs 412, 548 nm.
Acknowledgements
4.6.9. Zn(II)-5-(5,5-dimethyl-1,3-dioxan-2-yl)porphyrin
(Zn5ij) from 3jC1i. Following the standard procedure,
reaction of 1.00 mmol of 3j and 1i afforded a purple solid
(56.0 mg, 12%); 1H NMR d 1.17 (s, 3H), 2.01 (s, 3H), 4.30–
4.40 (m, 4H), 8.09 (s, 1H), 9.41 (s, 4H), 9.53 (d, JZ4.0 Hz,
2H), 10.15 (s, 1H), 10.19 (d, JZ4.0 Hz, 2H), 10.25 (s, 2H);
13C NMR (THF-d8) d 21.6, 30.3, 79.4, 104.4, 104.6, 106.6,
108.8, 112.1, 129.6, 130.5, 130.9, 131.1, 131.4, 132.3,
133.7, 148.52, 148.59, 148.87, 148.90, 149.1, 149.5, 150.3,
152.6; LD-MS obsd 485.6; FAB-MS obsd 486.1057, calcd
486.1034 (C26H22N4O2Zn); labs 403, 535 nm.
This research was supported by a grant from the NIH
(GM36238). Mass spectra were obtained at the Mass
Spectrometry Laboratory for Biotechnology. Partial funding
for the facility was obtained from the North Carolina
Biotechnology Center and the National Science Foundation.
References and notes
4.6.10. Zn(II)-5-allylporphyrin (Zn5ik) from 3kC1i.
Following the standard procedure, reaction of 1.00 mmol
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1
of 3k and 1i afforded a purple solid (71.2 mg, 17%); H
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(m, 1H), 9.46–9.47 (m, 6H), 9.72–9.73 (m, 2H), 10.17 (s,
1H), 10.19 (s, 2H); 13C NMR (THF-d8) d 41.0, 105.51,
105.54, 106.42, 106.46, 116.4, 117.9, 131.2, 133.56, 133.63,
133.65, 144.6, 151.1, 151.4, 151.91, 152.03; LD-MS obsd
412.1; FAB-MS obsd 412.0632, calcd 412.0666
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