Steric control of organic transformation by a dendrimer cage: Organocobalt dendrimer porphyrins as novel coenzyme B12 mimics

Article abstract of DOI:10.1021/ja020687i

Cobalt(II) complexes of poly(aryl ester) dendrimer porphyrins (m-[Gn] TPP)Co^II and (p-[Gn]TPP)-Co^II (n = 0-3) underwent AIBN-initiated alkylation (AIBN = 2,2′-azobis(isobutyronitrile)) at the metal center with propargyl alcohol in CD

Full text of DOI:10.1021/ja020687i

Published on Web 08/29/2002
Steric Control of Organic Transformation by a Dendrimer
Cage: Organocobalt Dendrimer Porphyrins as Novel
Coenzyme B12 Mimics
Makoto Uyemura and Takuzo Aida*
Contribution from the JST ERATO Nanospace Project, National Museum of Emerging Science
and InnoVation Building, 2-41 Aomi, Koto-ku, Tokyo 135-0064, Japan, and Department of
Chemistry and Biotechnology, Graduate School of Engineering, The UniVersity of Tokyo, 7-3-1
Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
Received May 13, 2002
Abstract: Cobalt(II) complexes of poly(aryl ester) dendrimer porphyrins (m-[Gn]TPP)CoII and (p-[Gn]TPP)-
CoII (n ) 0-3) underwent AIBN-initiated alkylation (AIBN ) 2,2′-azobis(isobutyronitrile)) at the metal center
with propargyl alcohol in CDCl3 at 60 °C, where the dendritic substituents did not affect the overall conversion
rate but selectivity of the alkylation. With the largest (m-[G3]TPP)CoII, a single organocobalt(III) species
(CoIII-C(dCH2)CH2OH, 4) was selectively formed in 91% yield, due to a steric protection of 4 by the large
dendrimer cage from the access of another molecule of cobalt porphyrin species. In contrast, with other
cobalt(II) porphyrins, isomerized compounds such as CoIII-C(CH3)dCHOH (5) and CoIII-CH(CH3)CHO
(6) were formed in addition to 4. A stereochemical investigation with (m-[G3]TPP)CoII using AIBN-d12, in
place of nondeuterated AIBN, demonstrated that the alkylation (cobalt(III) hydride addition to propargyl
alcohol) is selective to a trans adduct. Results also indicated that this addition step does not involve external
activation of propargyl alcohol.
Introduction
selectivities of such artificial coenzymes are not high, and further
molecular design may be taken into consideration.
Adenosylcobalamin or coenzyme B12 has attracted great
attention, because of its interesting activity for selective
transformation of organic substrates via homolytic dissociation
of carbon-metal bonds.1,2 Structural aspects of the natural
holoenzymes3 suggest a possible contribution of the protein
matrix around the active site to the high selectivity of the
transformation.4 In this respect, several model studies related
to coenzyme B12, considering steric or site-isolation effects, have
been investigated with group IX transition metal complexes of
oximes, schiff bases, and porphyrins, and those embedded in
physically organized media such as micelles and bilayer
membranes.5-7 However, compared with the natural systems,
Here we report a novel artificial model of coenzyme B12,
having a cobalt(II) porphyrin functionality encapsulated within
a radical-tolerant, large poly(aryl ester) dendrimer cage (m-[G3]-
TPP)CoII (Figure 1D), and we highlight its high potential for
the steric control of AIBN-initiated transformation (AIBN )
2,2′-azobis(isobutyronitrile)) of alkynes.7 Dendrimers are well-
defined hyperbranched macromolecules with predictable three-
dimensional shapes8-10 and expected to possess an interesting
(5) Murakami, Y.; Kikuchi, J.; Hisaeda, Y.; Hayashida, O. Chem. ReV. 1996,
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Am. Chem. Soc. 1992, 114, 3982-3982. (j) Murakami, Y.; Hisaeda, Y.;
Kohno, H.; Ohno, Y.; Nishioka, T. J. Chem. Soc., Perkin Trans. 2 1995,
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T.; Murakami, Y. Inorg. Chim. Acta 1998, 273, 299-309.
* To whom correspondence should be addressed. E-mail: aida@macro.t.u-
tokyo.ac.jp.
(1) (a) B12; Dolphin, D., Ed.; Wiley: New York, 1982; Vols. 1 and 2. (b)
Enzyme Mechanisms; Page, M. I., Williams, A., Eds.; The Royal Society
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1979, 18, 417-426. (b) Halpern, J. Science 1985, 227, 869-875. (c)
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1997, 97, 1681-1712. (b) Bosman, A. W.; Janssen, H. M.; Meijer, E. W.
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J. AM. CHEM. SOC. 2002, 124, 11392-11403
10.1021/ja020687i CCC: $22.00 © 2002 American Chemical Society

Organic Transformation by a Dendrimer Cage
A R T I C L E S
potential as artificial substitutes for globular proteins.9 Core-
shell architectures of spherical dendrimers have also motivated
exploration of the possibility of spatial reactivity control of
active species encapsulated within such unique three-dimen-
sional cages.9,10 The AIBN-initiated alkylation of cobalt(II)
porphyrin 1 with an alkyne such as propargyl alcohol (eqs 1-5)7
involves the transient formation of an adduct (porphinato)CoIII-
CMe2CN (2; eq 2) with a tertiary radical originating from AIBN
(eq 1), which immediately undergoes â-hydride abstraction to
generate a (porphinato)CoIIIH (3)11 with elimination of an
unsaturated nitrile (eq 3). Subsequently, 3 undergoes addition
Scheme 1
retardation of the reaction, since the access of two cobalt
porphyrin centers must be sterically suppressed by the dendrimer
cage.9a,b On the other hand, as for the isomerization of alkylated
complex 4 (eq 5), an intramolecular 1,3-hydrogen shift mech-
anism has initially been considered a likely candidate (Scheme
2A).7b However, later, an alternative mechanism involving a
cobalt(II) or a cobalt(III) hydride species (Scheme 2B) has been
proposed to be more likely, since the isomerization is greatly
suppressed when sterically encumbered mesitylporphyrin (TMP)
is the ligand.7c Nevertheless, considering a large steric pressure
of the mesityl moieties to the active center, the intramolecular
1,3-hydrogen shift mechanism (Scheme 2A) may not be
excluded completely. From this point of view, studies with a
large dendrimer cobalt(II) porphyrin such as (m-[G3]TPP)CoII
(Figure 1D) are interesting, since it possibly bears a larger space
around the cobalt center than (TMP)CoII, due to the dendritic
growth of 1,3,5-trisubstituted aromatic building units.
In the present paper, we synthesized cobalt(II) complexes of
meta- and para-substituted series of poly(aryl ester) dendrimer
porphyrins, (m-[Gn]TPP)CoII and (p-[Gn]TPP)CoII, with dif-
ferent generation numbers (n ) 0-3) (Figure 1) and investigated
steric effects of the dendritic substituents on conversion rate
and selectivity of the AIBN-initiated alkylation at the cobalt-
(II) center with propargyl alcohol.
of propargyl alcohol to give 4 (eq 4), which gradually isomerizes
to 5 and 6 (eq 5). Since the cobalt hydride addition to alkynes
(eq 4), in most cases, is selective to trans adducts, a reaction
mechanism involving two cobalt porphyrin molecules7c has been
proposed by analogy to some related reactions,12 where cobalt-
(III) hydride 3 reacts with activated alkynes through coordinative
interaction with another cobalt porphyrin species (Scheme 1A).
If this mechanism is really operative, use of a cobalt(II)
porphyrin encapsulated within a large dendrimer cage such as
(m-[G3]TPP)CoII (Figure 1D) should result in considerable
Results and Discussion
Synthesis of Dendrimer Cobalt(II) Porphyrins (m-[Gn]-
TPP)CoII and (p-[Gn]TPP)CoII (n ) 1-3) and Nondendritic
References (m-[G0]TPP)CoII and (p-[G0]TPP)CoII. Free-base
porphyrins, m-[Gn]TPPH2 and p-[Gn]TPPH2 (n ) 1-3), were
synthesized by DCC-mediated coupling of carboxylic acid-
terminated poly(aryl ester) dendrons or 3,5-dimethoxybenzoic
acid, in a manner similar to that reported by Suslick and co-
workers.10b The yields were all satisfactorily high. In particular,
m-[G3]TPPH2 and p-[G3]TPPH2, the largest homologues of the
meta- and para-substituted series, were obtained in 79 and 93%
yield, respectively. Nondendritic free-base porphyrins such as
m-[G0]TPPH2, p-[G0]TPPH2, and TMPH2 were synthesized by
the condensation of pyrrole with the corresponding benzaldehyde
derivatives.10c All the free-base porphyrins were unambiguously
characterized by means of MALDI-TOF-MS spectrometry
together with 1H and 13C NMR and electronic absorption
spectroscopies. Cobalt(II) porphyrins, (m-[Gn]TPP)CoII, (p-[Gn]-
TPP)CoII (n ) 0-3) (Figure 1), and (TMP)CoII, were prepared
by the reaction of the corresponding free-base porphyrins with
anhydrous Co(OAc)2 in CHCl3/EtOH, where complete meta-
lation was confirmed by the disappearance of the characteristic
(9) (a) Jiang, D.-L.; Aida, T. J. Chem. Soc., Chem. Commun. 1996, 1523-
1524. (b) Collman, J. P.; Fu, L.; Zing, A.; Diederich, F. J. Chem. Soc.,
Chem. Commun. 1997, 193-194. (c) Enomoto, M.; Aida, T. J. Am. Chem.
Soc. 1999, 121, 874-875. (d) Enomoto, M.; Aida, T. J. Am. Chem. Soc.
2002, 21, 6099-6108.
(10) (a) Brunner, H. J. Organomet. Chem. 1995, 500, 39-46. (b) Bhyrappa,
P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am. Chem. Soc. 1996,
118, 5708-5711. (c) Tomoyose, Y.; Jiang, D.-L.; Jin, R.-H.; Aida, T.;
Yamashita, T.; Horie, K.; Yashima, E.; Okamoto, Y. Macromolecules 1996,
29, 5236-5238. (d) Rheiner, P. B.; Seebach, D. Chem. Eur. J. 1999, 5,
3221-3236. (e) Sellner, H.; Seebach, D. Angew. Chem., Int. Ed. 1999, 38,
1918-1920. (f) Habicher, T.; Diederich, F.; Gramlich, V. HelV. Chim. Acta
1999, 82, 1066-1095. (g) Kimura, M.; Sugihara, Y.; Muto, T.; Hanabusa,
K.; Shirai, H.; Kobayashi, N. Chem. Eur. J. 1999, 5, 3495-3500. (h) Sen,
A.; Suslick, K. S. J. Am. Chem. Soc. 2000, 122, 11565-11566. (i) Kimura,
M.; Shiba, T.; Yamazaki, M.; Hanabusa, K.; Shirai, H.; Kobayashi, N. J.
Am. Chem. Soc. 2001, 123, 5636-5642. (j) Kimata, S.; Aida, T.
Tetrahedron Lett. 2001, 42, 4187-4190. (k) Hecht, S.; Fre´chet, J. M. J. J.
Am. Chem. Soc. 2001, 123, 6959-6960. (l) Weyermann, P.; Diederich, F.
HelV. Chim. Acta 2002, 85, 599-617.
(11) For selected examples of hydridocobalt(III) porphyrin-mediated transforma-
tions, see: (a) Fukuzumi, S.; Noura, S. J. Porphyrins Phthalocyanines 1997,
1, 251-258. (b) Watanabe, J.; Setsune, J. J. Organomet. Chem. 1999, 575,
21-32.
(12) (a) Ogoshi, H.; Setsune, J.; Yoshida, Z. J. Am. Chem. Soc. 1977, 99, 3869-
3870. (b) Zhang, X.-X.; Parks, G. F.; Wayland, B. B. J. Am. Chem. Soc.
1997, 119, 7938-7944.
9
J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002 11393

A R T I C L E S
Uyemura and Aida
Figure 1. Schematic structures of cobalt(II) porphyrins: (A) (m-[G0]TPP)CoII; (B) (m-[G1]TPP)CoII; (C) (m-[G2]TPP)CoII; (D) (m-[G3]TPP)CoII; (E)
(p-[G0]TPP)CoII; (F) (p-[G1]TPP)CoII; (G) (p-[G2]TPP)CoII; (H) (p-[G3]TPP)CoII.
free-base porphyrin fluorescence.13 The products, isolated by
chromatography on silica gel, showed a single molecular ion
peak in MALDI-TOF-MS spectrometry (Figure 2) and charac-
teristic absorption bands of cobalt(II) porphyrins in UV-vis
spectroscopy.
AIBN-Initiated Alkylation of (m-[G3]TPP)CoII with Pro-
pargyl Alcohol. We first investigated the alkylation of the
largest (m-[G3]TPP)CoII (Figure 1D). A CPK model study on
(m-[G3]TPP)CoII (Figure 3D) suggested that the four dendritic
substituents are capable of forming a cage-like envelope around
(13) Sanders, J. K. M.; Bampos, N.; Clyde-Watson, Z.; Darling, S. L.; Hawley,
J. C.; Kim, H.-J.; Mak, C. C.; Webb, S. J. In The Porphyrin Handbook;
Inorganic, Organometallic and Coordination Chemistry; Axial Coordination
Chemistry of Metalloporphyrins; Kadish, K. M., Smith, K. M., Guilard,
R., Eds.; Academic Press: New York, 2000; Vol. 3, p 23.
9
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Organic Transformation by a Dendrimer Cage
A R T I C L E S
Scheme 2
the cobalt(II) porphyrin focal core. For the alkylation of (m-
[G3]TPP)CoII, a CDCl3 solution (0.5 mL) of a mixture of (m-
[G3]TPP)CoII (4.7 µmol), AIBN (40 µmol), and propargyl
alcohol (450 µmol) was added to a NMR tube, which was then
degassed and sealed. Upon heating at 60 °C, 1H NMR
spectroscopy of the mixture (Figure 4) clearly indicated that
the cobalt(II) center within the large dendrimer cage is alkylated
with propargyl alcohol. At the initial stage, the reaction mixture
showed, e.g., a signal at δ 9.2 ppm (c) due to p-H of the meso-
Ar groups at the porphyrin macrocycle, which gradually
disappeared (b, Figure 5D) to give a new signal at δ 9.0 ppm
(a′), assignable to pyrrole-â-H of diamagnetic cobalt(III) por-
phyrin species.7 At the same time, a new set of signals appeared
at δ -0.2 (trans-H), -1.9 (CH2), and -2.4 (cis-H) ppm (see
also Figure 7B), which are assigned to an allyl alcohol
functionality at the axial position of (m-[G3]TPP)CoIII. As shown
in Figure 5D, such a spectral change subsided in 200 min, where
4 (O) was obtained in 91% spectral yield. After heating for 240
min, degassed MeOH (1 mL) was added to the reaction mixture,
whereupon a dark purple precipitate formed, which was isolated,
washed with MeOH, and dried under reduced pressure at room
temperature. When the residue, dissolved in CHCl3, was
subjected to preparative size-exclusion chromatography (SEC)
equipped with a multichannel detector, a single, sharp chro-
matogram exhibiting a similar absorption spectral profile to that
of (m-[G3]TPP)CoII was observed as the major component with
some very minor peaks. 1H NMR spectroscopy in CDCl3 (Figure
6) showed that this major fraction contains virtually a single
organocobalt(III) species 4 with a clear signal at δ -1.2 (t, 1H)
ppm due to the hydroxyl (OH) group of the axial allyl alcohol
functionality. Quite interestingly, no signals characteristic of
isomerized compounds7 such as 5 and 6 were detected even
upon prolonged heating.
Figure 2. MALDI-TOF-MS spectra of dendrimer cobalt(II) porphyrins:
(A) (p-[G1]TPP)CoII; (B) (m-[G1]TPP)CoII; (C) (p-[G2]TPP)CoII; (D) (m-
[G2]TPP)CoII; (E) (p-[G3]TPP)CoII; (F) (m-[G3]TPP)CoII.
TPP)CoII (91%), suggesting an interesting possibility that 4
derived from (m-[G3]TPP)CoII is protected against thermal
decomposition by the large dendrimer cage.
AIBN-Initiated Alkylation of (m-[Gn]TPP)CoII (n ) 0-2)
with Propargyl Alcohol. To investigate effects of the generation
number of the dendritic substituents on the alkylation, cobalt-
(II) porphyrin complexes, such as (m-[G0]TPP)CoII, (m-[G1]-
TPP)CoII, and (m-[G2]TPP)CoII (Figure 1A-C) with lower
generation numbers than (m-[G3]TPP)CoII, were heated at 60
°C in the presence of AIBN and propargyl alcohol under
conditions identical to those given above. From the CPK models
in Figure 3A-C, it is obvious that these cobalt(II) porphyrins
have more open architectures than (m-[G3]TPP)CoII, where the
active centers of (m-[G0]TPP)CoII and (m-[G1]TPP)CoII, in
particular, are totally exposed to external environments. From
the time courses of the alkylation (Figure 5A-C), the conversion
rates of (m-[Gn]TPP)CoII (n ) 0-2) were almost comparable
to one another and even slightly smaller than that of (m-[G3]-
TPP)CoII (Figure 5D). Although, in every case, the reaction gave
compound 4 as the major product, it also afforded noticeable
amounts of several organocobalt species including isomerized
compounds 5 and 6.
For example, in the case of nondendritic (m-[G0]TPP)CoII
1
(Figure 1A), the reaction mixture showed a set of H NMR
signals at δ -0.1 (trans-H), -1.8 (CH2), and -2.3 (cis-H) ppm
due to the axial allyl alcohol functionality of 4, whose spectral
yield was increased to 69% within the first 100 min and then
decreased to 39% in the following 200 min (Figure 5A). The
1H NMR spectrum of the reaction mixture in, e.g., 300 min
(Figure 7A) showed another set of signals at δ -1.4 (q, vinyl-
H) and -3.8 (d, J ) 1.7 Hz, CH3) ppm, assigned to isomerized
compound 5. In the 1H NMR spectrum at a relatively early stage
of the reaction (40-230 min), a set of signals due to isomerized
compound 6 was also detected at δ -2.9 (m, CH) and -5.5 (d,
J ) 7.3 Hz, CH3) ppm, which gradually disappeared in the latter
stage. From these spectral change profiles, the yield of 5 was
found to increase gradually with time to reach 11% in 300 min,
while 6 was obtained in a maximum yield of 6% in 120 min.
Wayland and co-workers have reported that the cobalt(II)
complex of mesitylporphyrin (TMP)CoII is highly selectively
alkylated by alkynes in the presence of AIBN.7 For comparison,
we investigated alkylation of (TMP)CoII under the above-
mentioned conditions with propargyl alcohol as alkylating agent,
where 4 was observed in 75% yield in 220 min, but it gradually
disappeared upon prolonged heating to furnish the spectral yield
of 66% in 300 min. Isomerized compound 5 was formed in
3%, while compound 6 was not detected throughout the reaction.
Although the selectivity is satisfactorily high, the yield of 4 is
obviously lower than that in the alkylation of dendritic (m-[G3]-
9
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A R T I C L E S
Uyemura and Aida
Figure 3. CPK models of cobalt(II) porphyrins: (A) (m-[G0]TPP)CoII; (B) (m-[G1]TPP)CoII; (C) (m-[G2]TPP)CoII; (D) (m-[G3]TPP)CoII; (E) (p-[G0]-
TPP)CoII; (F) (p-[G1]TPP)CoII; (G) (p-[G2]TPP)CoII; (H) (p-[G3]TPP)CoII.
In addition to these signals, some unidentified signals (e.g., -0.3
(s) ppm, Figure 7A) also appeared in the latter stage, and the
spectrum became rather complicated.
example, in the case of (p-[G3]TPP)CoII (Figure 1H), the largest
homologue in this series, 1H NMR spectroscopy of the reaction
mixture (Figure 7D) clearly showed signals due to 5 at δ -1.4
(q, vinyl-H) and -3.8 (d, J ) 1.7 Hz, CH3) ppm. Although 6
was hardly detected throughout the reaction, the alkylation
profile (Figure 5H) was quite similar to that of (m-[G2]TPP)-
CoII (Figure 1C), the second largest homologue in the meta-
substituted series. On the other hand, the alkylation of nonden-
dritic (p-[G0]TPP)CoII (Figure 1E) was accompanied by the
formation of considerable amounts of isomerized compounds
Alkylation of (m-[G2]TPP)CoII (Figure 1C), a one-generation
smaller homologue of (m-[G3]TPP)CoII, proceeded rather
selectively, where the yield of 4 was increased to 82% in 200
min and remained almost unchanged thereafter (Figure 5C).
Nevertheless, similarly to the case of nondendritic (m-[G0]TPP)-
CoII, isomerized compounds 5 and 6 both formed in maximum
yields of 5% (300 min) and 3% (80 min), respectively. On the
other hand, the alkylation of (m-[G1]TPP)CoII (Figure 1B)
proceeded much less selectively than that of (m-[G3]TPP)CoII,
where 4, once formed in 78% yield in 220 min, disappeared
gradually to furnish 72% yield in 300 min (Figure 5B). In this
case, isomerized compounds 5 and 6 were formed in 6% (300
min) and 9% (120 min) maximum yields, respectively. In both
cases, 6 disappeared almost completely in the latter stage of
the reaction.
1
5 (17%, 300 min) and 6 (12%, 180 min) (Figure 5E; for H
NMR, see Figure 7C), while the maximum yield of 4 was only
as low as 46% (130 min).
For comparison, the spectral yields of 4 and those of
isomerization products (5 + 6) for the meta- and para-substituted
series are summarized in Figure 8. As expected from the CPK
models (Figure 3), the selectivities of the (p-[Gn]TPP)CoII series
are virtually comparable to those observed for the alkylation of
the corresponding one-generation lower compounds in the (m-
[Gn]TPP)CoII series. Here, it is clear that the large dendritic
cage of (m-[G3]TPP)CoII is quite essential for achieving both
high selectivity and high yield.
Mechanistic Aspects. As described in the Introduction, the
cobalt(III) hydride addition to alkynes (eq 4) has been proposed
to occur by the participation of another cobalt porphyrin
molecule for the activation of alkynes (Scheme 1A). However,
the alkylation of (m-[G3]TPP)CoII actually takes place at its
spatially encapsulated reaction center (Figure 5D), where the
overall conversion rate shows no sign of retardation compared
with those of the lower-generation homologues (Figure 5A-
C). The two cobalt porphyrin centers of (m-[G3]TPP)Co must
AIBN-Initiated Alkylation of (p-[Gn]TPP)CoII (n ) 0-3)
with Propargyl Alcohol. To obtain further insights into the
structural effects of the dendritic substituents, alkylation of (p-
[Gn]TPP)CoII (n ) 0-3), which bear dendritic substituents at
the para-positions of the meso-Ar groups (Figure 1E-H), was
investigated under conditions identical to those for the alkylation
of (m-[Gn]TPP)CoII (n ) 0-3). CPK model studies (Figure 3E-
H) suggested that the steric bulks of (p-[Gn]TPP)CoII (n ) 0-3)
are almost comparable to those of the corresponding one-
generation lower compounds in the meta-substituted series. In
the alkylation of (p-[Gn]TPP)CoII (n ) 0-3), isomerized
compounds 5 and 6 were detected, irrespective of the generation
number of the dendritic substituents (Figure 5E-H). For
9
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Organic Transformation by a Dendrimer Cage
A R T I C L E S
Figure 4. Reaction of (m-[G3]TPP)CoII (4.7 µmol) with propargyl alcohol (450 µmol) in the presence of AIBN (40 µmol) in CDCl3 (0.5 mL) at 60 °C. 1H
NMR spectral change profile over a period 300 min.
be hardly accessible to each other by the large dendritic cage.
We and other groups have found similar size-exclusion phe-
nomena in dioxygen binding of large dendrimer iron porphyrins,
where the dioxygen adducts are highly stabilized by the steric
protection against µ-oxo dimer formation.9a,b Furthermore, we
have also reported that, in the axial coordination of dendrimer-
appended imidazoles to dendrimer zinc porphyrins, the associa-
tion constant drops discretely when their generation numbers
both become high.10c Together with these related observations,
the cobalt(III) hydride addition step (eq 4) most likely proceeds
without external assistance for the activation of propargyl
alcohol.
In relation to this mechanism, we examined the alkylation
of (m-[G3]TPP)CoII with propargyl alcohol by using deuterated
AIBN-d12, which allows investigation of the stereochemistry
of the hydride addition step.7c As already described, when
nondeuterated AIBN is the hydride source, the adduct 4 shows
the trans-H signal of the axial allyl alcohol moiety at δ -0.2
ppm (Figure 9B). In sharp contrast, when AIBN-d12 was used,
the corresponding signal was hardly detected, while relative
intensities of the other signals remained virtually intact (Figure
9A). Furthermore, the doublet signal due to cis-H of 4 (Figure
9B) was observed as a singlet signal in Figure 9A. These spectral
profiles demonstrate that the cobalt(III) hydride species (3)
9
J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002 11397

A R T I C L E S
Uyemura and Aida
Figure 5. Time courses of the reaction of cobalt(II) porphyrins (4.7 µmol) with propargyl alcohol (450 µmol) in the presence of AIBN (40 µmol) in CDCl3
(0.5 mL) at 60 °C: (A) (m-[G0]TPP)CoII; (B) (m-[G1]TPP)CoII; (C) (m-[G2]TPP)CoII; (D) (m-[G3]TPP)CoII; (E) (p-[G0]TPP)CoII; (F) (p-[G1]TPP)CoII;
(G) (p-[G2]TPP)CoII; (H) (p-[G3]TPP)CoII.
undergoes trans-addition to propargyl alcohol.7c This is quite
interesting, since the trans-selectivity has been considered an
indication for the mechanism involving external activation of
alkynes (Scheme 1A). Here, one may also have to consider that
cobalt hydride species in porphyrin macrocycles are thermally
dissociative. Chen and co-workers have suggested a rapid and
reversible cobalt-to-ligand hydrogen migration,7c by analogy to
the chemistry of hydridorhodium(III) phthalocyanines.14 This
possibility may account for the trans-selectivity of the hydride
addition in the large dendrimer cage of (m-[G3]TPP)CoIIIH,
where external assistance cannot be expected for the activation
of alkynes (Scheme 1B).
(14) Chen, M. J.; Nunez, L.; Ratheke J. W.; Rogers, R. D. Organometallics
1996, 15, 2338-2344.
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Organic Transformation by a Dendrimer Cage
A R T I C L E S
Figure 6. Reaction of (m-[G3]TPP)CoII (4.7 µmol) with propargyl alcohol
(450 µmol) in the presence of AIBN (40 µmol) in CDCl3 (0.5 mL) at 60
°C. 1H NMR spectral profile in CDCl3 at 20 °C of a MeOH-insoluble part
of the reaction mixture in 240 min (SEC-isolated fraction based on electronic
absorption spectroscopy).
Figure 8. Reaction of cobalt(II) porphyrins (4.7 µmol) with propargyl
alcohol (450 µmol) in the presence of AIBN (40 µmol) in CDCl3 (0.5 mL)
at 60 °C. 1H NMR spectral yields (%) of nonisomerized 4 and isomerization
products (5 + 6) in 300 min.
at 60 °C both in the absence and presence of AIBN. On the
other hand, one might also consider that no isomerization
activity of 4, derived from (m-[G3]TPP)CoII, is due to the steric
suppression of the 1,3-hydrogen shift (Scheme 2A). However,
the isomerization via this intramolecular process seems unlikely
for the following consideration. Figure 8 shows that the
selectivities of the alkylation of (p-[G3]TPP)CoII and (m-[G2]-
TPP)CoII are almost comparable to each other. Their dendritic
substituents are also comparable in size to each other, but the
former has a larger interior space around the cobalt center than
the latter (Figure 3C,H), since the dendrons are attached to the
para-positions of the meso-Ar groups. If the isomerization of 4
takes place via the intramolecular 1,3-hydrogen shift (Scheme
2A), and if this process is sterically suppressed by the dendrimer
cage, one can expect a higher probability of isomerization in
the alkylation of (p-[G3]TPP)CoII than that of (m-[G2]TPP)-
CoII. Therefore, once again, it is more likely that no isomer-
ization with the largest (m-[G3]TPP)CoII is due to the steric
suppression of the mechanism in Scheme 2B, which requires
two spatially encapsulated cobalt(II) centers to come in close
proximity to each other.
Figure 7. Reaction of cobalt(II) porphyrins (4.7 µmol) with propargyl
alcohol (450 µmol) in the presence of AIBN (40 µmol) in CDCl3 (0.5 mL)
at 60 °C. 1H NMR spectral profiles (δ -6 to 0 ppm, 60 °C) of the reaction
mixtures in 300 min: (A) (m-[G0]TPP)CoII; (B) (m-[G3]TPP)CoII; (C) (p-
[G0]TPP)CoII; (D) (p-[G3]TPP)CoII.
The mechanism involving two cobalt porphyrin molecules
(Scheme 2B) has also been proposed for the isomerization of
adduct 4 (eq 5). This possibility is quite reasonable, since the
alkylation of the cobalt(II) center of large (m-[G3]TPP)CoII is
not accompanied by the isomerization of 4 (Figure 5D).
Compound 4, isolated from the reaction mixture with (m-[G3]-
TPP)CoII, also showed no sign of isomerization upon heating
Finally, it is interesting to note that the dendrimer cage does
not affect the overall conversion rate but product selectivity
(isomerization activity) in the alkylation of the cobalt(II) center.
9
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A R T I C L E S
Uyemura and Aida
77.00) as internal standard. MALDI-TOF-MS spectra were recorded
on a Bruker model Reflex III. Preparative size-exclusion chromatog-
raphy (SEC) was performed at room temperature on a Japan Analytical
Industry model LC-918 recycling preparative HPLC equipped with a
JASCO model MD-1510 multichannel photodiode array detector, using
CHCl3 as eluent at a flow rate of 3.5 mL min-1. The column set
consisted of two Polystyragel columns (20 (i.d.) × 600 mm (L)) of
JAIGEL-1H (exclusion limit 1 × 103)/JAIGEL-2H (5 × 103) or
JAIGEL-2H/JAIGEL-3H (3 × 104). Electronic absorption spectra were
recorded on a JASCO model V-570 spectrophotometer. Fluorescence
spectra were recorded on a JASCO model FP-777W spectrofluorometer.
Materials. CH2Cl2 was washed successively with concentrated H2-
SO4, water, and aqueous NaHCO3, dried over CaCl2, and distilled over
CaH2 under Ar. Tetrahydrofuran (THF) was distilled under Ar over
sodium benzophenone ketyl just before use. MeOH was distilled over
Mg coupled with iodine under Ar. CDCl3 was passed through alumina
just before use. Propargyl alcohol was distilled before use. 4-(Dim-
ethylamino)pyridinium 4-toluenesulfonate (DPTS) and 2′,2′,2′-trichlo-
roethyl 3,5-dihydroxybenzoate were synthesized according to literature
methods.10b,16 2,2′-Azobis(isobutyronitrile) (AIBN) was purchased from
Wako Chemicals and used as received. Deuterium labeled AIBN-d12
was synthesized according to a literature method, using acetone-d6 and
D2O, which were purchased from Merck.17 4-(Dimethylamino)pyridine
(DMAP) and 1,3-dicyclohexylcarbodiimide (DCC) were purchased from
Tokyo Chemical Industry and used as received. Anhydrous cobalt
acetate (Co(OAc)2) was purchased from Nakarai Chemicals and used
as received.
Figure 9. Azo-initiated reaction of (m-[G3]TPP)CoII (4.7 µmol) and
propargyl alcohol (450 µmol) in CDCl3 (0.5 mL) at 60 °C. 1H NMR spectral
profiles (δ -3 to 0 ppm) in CDCl3 at 20 °C of MeOH-insoluble parts of
the reaction mixtures in 240 min with (A) AIBN-d12 (40 µmol) and (B)
AIBN (40 µmol) (SEC-isolated fractions based on electronic absorption
spectroscopy).
(1) Synthesis of Nondendritic Porphyrin Free Bases and Cobalt-
(II) Complexes. 5,10,15,20-Tetrakis(4′-hydroxyphenyl)-21H,23H-por-
phine (T(p-[HO]Ar)PH2), 5,10,15,20-tetrakis(3′,5′-dihydroxyphenyl)-
21H,23H-porphine (T(m-[HO]2Ar)PH2), [5,10,15,20-tetrakis(4′-methoxy-
phenyl)-21H,23H-porphinato]cobalt(II) ((p-[G0]TPP)CoII), [5,10,15,-
20-tetrakis(3′,5′-dimethoxyphenyl)-21H,23H-porphinato]cobalt(II) ((m-
[G0]TPP)CoII), and [5,10,15,20-tetrakis(2′,4′,6′-trimethylphenyl)-21H,-
23H-porphinato]cobalt(II) ((TMP)CoII) were synthesized according to
literature methods.10c,13
The dendrimer cage may serve as a molecular sieve to exclude
large dendritic macromolecules but allow small molecules
(propargyl alcohol and AIBN fragment) to have substantially a
nonrestricted access to the interior active site.10b,h,i,k
Conclusion
By using a novel cobalt(II) porphyrin encapsulated by a
radical-tolerant, large poly(aryl ester) dendritic cage ((m-[G3]-
TPP)CoII), we succeeded in demonstrating steric control of the
AIBN-initiated alkylation of cobalt(II) porphyrin with an alkyne
such as propargyl alcohol. Here, the dendritic cage sterically
prohibits the access of two cobalt porphyrin molecules, thereby
protecting the interior alkylated product (4) from subsequent
isomerization. Although the alkylation has been proposed to
involve additional cobalt porphyrin species for the activation
of alkynes, the results with (m-[G3]TPP)CoII also indicated that
the reaction does not involve such an external activation of
alkynes. Organic transformations involving free-radical species
are of great importance both from biological and synthetic
viewpoints.1,2,5-7,15 In this sense, the present finding not only
indicates the high potential of designer dendritic catalysts9,10
but may also provide a new strategy toward precision organic
synthesis involving free-radical species.
(2) Synthesis of Poly(aryl ester) Dendrons. [Gn]poly(aryl ester)-
CO2H dendrons were prepared by a method with a slight modification
of the reported procedure.10b
(i) Preparation of [G1]poly(aryl ester)-CO2CH2CCl3 Dendron.
To a distilled CH2Cl2 solution (220 mL) of a mixture of 3,5-
dimethoxybenzoic acid (45.5 g, 250 mmol), 2′,2′,2′-trichloroethyl 3,5-
dihydroxybenzoate (28.6 g, 100 mmol), and DPTS (8.24 g, 28 mmol)
was added DCC (51.6 g, 250 mmol) under Ar at 0 °C. The reaction
mixture was stirred overnight at room temperature, then filtered off
from insoluble substances through Celite, washed with water (500 mL),
and extracted with AcOEt and Et2O. The combined extract was dried
over anhydrous MgSO4 and evaporated to dryness under reduced
pressure at room temperature, and the residue was chromatographed
on silica gel with CH2Cl2 as eluent, to give after evaporation 2′,2′,2′-
trichloroethyl 3,5-bis(3′,5′-dimethoxybenzoyloxy)benzoate ([G1]poly-
(aryl ester)-CO2CH2CCl3 dendron) as white powder quantitatively (61.4
1
g). H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ 3.85 (s, 12H),
4.98 (s, 2H), 6.72 (t, 2H, J ) 2.4 Hz), 7.32 (d, 4H, J ) 2.4 Hz), 7.45
(t, 1H, J ) 2.2 Hz), 7.89 (d, 2H, J ) 2.2 Hz). 13C NMR (67.80 MHz;
CDCl3; 20 °C; ppm): δ 55.7, 74.6, 94.6, 106.7, 107.7, 120.8, 121.5,
130.3, 130.8, 151.3, 160.6, 163.1, 164.2. MALDI-TOF-MS (dithranol)
m/z [M + Na]+. Calcd: 635.0. Found: 634.9.
(ii) Preparation of [G1]poly(aryl ester)-CO2H Dendron. To a
THF/AcOH solution (70/80 mL) of [G1]poly(aryl ester)-CO2CH2CCl3
dendron (33.1 g, 54 mmol) was slowly added zinc powder (22.2 g)
under Ar at 0 °C. The reaction mixture was vigorously stirred for 15
min at room temperature, then filtered off from insoluble substances
Experimental Section
General Methods. 1H spectroscopies were performed in CDCl3 using
a JEOL type GSX-270 spectrometer operating at 270.05 MHz, where
the chemical shifts were determined with respect to CHCl3 (δ 7.24) as
internal standard. 13C NMR spectroscopies were performed in CDCl3
using a JEOL type GSX-270 spectrometer and a JEOL type EXcalibur-
500 spectrometer operating at 67.80 and 125.65 MHz, respectively,
where the chemical shifts were determined with respect to CDCl3 (δ
(15) (a) Pattenden, G. Chem. Soc. ReV. 1988, 17, 361-382. (b) Wayland, B.
B.; Mukerjee, S.; Poszmik, G.; Woska, D. C.; Basickes, L.; Gridnev, A.
A.; Fryd, M.; Ittel, S. D. ACS Symp. Ser. 1998, 15, 305-315. (c) Gridnev,
A. A.; Ittel, S. D. Chem. ReV. 2001, 101, 3611-3660.
(16) Moore, J. S.; Stupp, S. I. Macromolecules 1990, 23, 65-70.
(17) Overberger, C. G.; Huang, P.-T.; Berenbaum, M. B. In Organic Syntheses;
Wiley: New York, 1963; Collective Vol. 4, pp 66-67 and 274-275.
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Organic Transformation by a Dendrimer Cage
A R T I C L E S
1
through Celite, and extracted with AcOEt and Et2O. The combined
extract was evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3 was washed with water
(1 L) and evaporated to dryness under reduced pressure at room
temperature. The residue was dissolved in CHCl3/2-PrOH (10%) and
crystallized with hexane, to give 3,5-bis(3′,5′-dimethoxybenzoyloxy)-
benzoic acid ([G1]poly(aryl ester)-CO2H dendron) as white powder
phine (p-[G1]TPPH2) as a purple powder in 78% yield (278 mg). H
NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ -2.79 (s, 2H), 3.40 (s,
24H), 6.80 (t, 4H, J ) 2.4 Hz), 7.52 (d, 8H, J ) 2.4 Hz), 7.62 (d, 8H,
J ) 8.4 Hz), 8.28 (d, 8H, J ) 8.4 Hz), 8.93 (s, 8H). 13C NMR (125.65
MHz; CDCl3; 45 °C; ppm): δ 55.8, 106.6, 107.9, 119.2, 119.9, 131.4,
135.2, 139.6, 150.8, 160.8, 164.8. MALDI-TOF-MS (dithranol) m/z
[M]+. Calcd: 1335.4. Found: 1335.2. UV-vis (CHCl3; λmax (nm)):
257, 309 (sh), 419, 515, 552, 590, 647.
1
in 96% yield (25.0 g). H NMR (270.05 MHz; CDCl3; 20 °C; ppm):
δ 3.85 (s, 48H), 6.72 (t, 8H, J ) 2.4 Hz), 7.32 (d, 16H, J ) 2.4 Hz),
7.45 (t, 4H, J ) 2.4 Hz), 7.89 (d, 8H, J ) 2.4 Hz). 13C NMR (67.80
MHz; CDCl3; 20 °C; ppm): δ 55.7, 106.8, 107.7, 121.0, 121.2, 130.5,
131.3, 151.2, 160.7, 164.2, 169.0. MALDI-TOF-MS (dithranol) m/z
[M + Na]+. Calcd: 505.1. Found: 505.5.
(ii) Preparation of p-[G2]TPPH2. To a distilled THF solution (5
mL) of a mixture of [G1]poly(aryl ester)-CO2H dendron (724 mg,
1.50 mmol), 5,10,15,20-tetrakis(4′-hydroxyphenyl)-21H,23H-porphine
(182 mg, 0.268 mmol), and DPTS (1.32 g, 4.5 mmol) was added DCC
(330 mg, 1.6 mmol) under Ar at room temperature. The reaction mixture
was stirred overnight at room temperature and then evaporated to
dryness under reduced pressure at room temperature, and the residue
was chromatographed on silica gel with CHCl3 as eluent and subjected
to SEC with CHCl3 as eluent. A fraction containing the desired product
was isolated and evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3 containing 2-PrOH
(10%) was crystallized with hexane, to give 5,10,15,20-tetrakis{4′-
[3′′,5′′-bis(3′′′,5′′′-dimethoxybenzoyloxy)benzoyloxy]pheny l}-21H,-
23H-porphine (p-[G2]TPPH2) as a purple powder in 96% yield (654
(iii) Preparation of [G2]poly(aryl ester)-CO2CH2CCl3 Dendron.
To a distilled CH2Cl2 solution (50 mL) of a mixture of [G1]poly(aryl
ester)-CO2H dendron (19.3 g, 40 mmol), 2′,2′,2′-trichloroethyl 3,5-
dihydroxybenzoate (5.43 g, 19 mmol), and DPTS (1.35 g, 4.5 mmol)
was added DCC (9.29 g, 45 mmol) under Ar at 0 °C. The reaction
mixture was stirred overnight at room temperature, then filtered off
from insoluble substances through Celite, washed with water (200 mL),
and extracted with AcOEt and Et2O. The combined extract was dried
over anhydrous MgSO4 and evaporated to dryness under reduced
pressure at room temperature, and the residue was chromatographed
on silica gel with CH2Cl2 as eluent, to give after evaporation 2′,2′,2′-
trichloroethyl3,5-bis[3′,5′-bis(3′′,5′′-dimethoxybenzoyloxy)benzoyloxy]-
benzoate ([G2]poly(aryl ester)-CO2CH2CCl3 dendron) as white powder
1
mg). H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ -2.80 (s, 2H),
3.89 (s, 48H), 6.76 (t, 8H, J ) 2.2 Hz), 7.38 (d, 16H, J ) 2.2 Hz),
7.56 (t, 4H, J ) 2.2 Hz), 7.65 (d, 8H, J ) 8.1 Hz), 8.18 (d, 8H, J )
2.2 Hz), 8.28 (d, 8H, J ) 8.1 Hz), 8.93 (s, 8H). 13C NMR (125.65
MHz; CDCl3; 45 °C; ppm): δ 55.8, 106.9, 107.9, 119.1, 119.8, 121.0,
121.2, 130.6, 131.9, 135.3, 139.8, 150.6, 151.5, 160.8, 163.4, 164.2.
MALDI-TOF-MS (dithranol) m/z [M + Na]+. Calcd: 2534.7. Found:
2534.6. UV-vis (CHCl3; λmax (nm)): 257, 307 (sh), 419, 515, 550,
590, 647.
1
in 98% yield (22.7 g). H NMR (270.05 MHz; CDCl3; 20 °C; ppm):
δ 3.85 (s, 24H), 4.98 (s, 2H), 6.72 (t, 4H, J ) 2.4 Hz), 7.32 (d, 8H, J
) 2.4 Hz), 7.48 (t, 1H, J ) 2.2 Hz), 7.50 (t, 2H, J ) 2.2 Hz), 7.92 (d,
2H, J ) 2.2 Hz), 7.99 (d, 4H, J ) 2.2 Hz). 13C NMR (125.65 MHz;
CDCl3; 20 °C; ppm): δ 55.7, 74.7, 94.6, 106.7, 107.6, 120.6, 120.9,
121.0, 121.5, 130.3, 130.7, 130.9, 150.9, 151.3, 160.5, 162.6, 162.8,
164.0. MALDI-TOF-MS (dithranol) m/z [M + Na]+. Calcd: 1235.2.
Found: 1235.0.
(iii) Preparation of p-[G3]TPPH2. To a distilled THF solution (2
mL) of a mixture of [G2]poly(aryl ester)-CO2H dendron (812 mg,
0.75 mmol), 5,10,15,20-tetrakis(4′-hydroxyphenyl)-21H,23H-porphine
(91 mg, 0.134 mmol), and DPTS (12.2 mg, 0.10 mmol) was added
DCC (165 mg, 0.80 mmol) under Ar at room temperature. The reaction
mixture was stirred for 90 min at room temperature and then evaporated
to dryness under reduced pressure at room temperature. The residue
was chromatographed on silica gel with CHCl3 as eluent and subjected
to SEC with CHCl3 as eluent. A fraction containing the desired product
was isolated and evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3 containing 2-PrOH
(10%) was crystallized with hexane, to give 5,10,15,20-tetrakis(4′-
{3′′,5′′-bis[3′′′,5′′′-bis(3′′′′,5′′′′-dimethoxybenzoyloxy)benzoyloxy]-
benzoyloxy}phenyl)-21H,23H-porphine (p-[G3]TPPH2) as a purple
(iv) Preparation of [G2]poly(aryl ester)-CO2H Dendron. To a
THF/AcOH solution (50/45 mL) of [G2]poly(aryl ester)-CO2CH2CCl3
dendron (34.0 g, 28 mmol) was slowly added zinc powder (13.5 g)
under Ar at 0 °C. The reaction mixture was vigorously stirred for 10
min at 60 °C, then filtered off from insoluble substances through Celite,
and extracted with AcOEt and Et2O. The combined extract was
evaporated to dryness under reduced pressure at room temperature, and
the residue dissolved in CHCl3 was washed with water (500 mL) and
evaporated to dryness under reduced pressure at room temperature. The
residue was dissolved in CHCl3/2-PrOH (10%) and crystallized with
hexane, to give 3,5-bis[3′,5′-bis(3′′,5′′-dimethoxybenzoyloxy)benzoy-
loxy]benzoic acid ([G2]poly(aryl ester)-CO2H dendron) as white
powder in 92% yield (28.0 g). 1H NMR (270.05 MHz; CDCl3; 20 °C;
ppm): δ 3.85 (s, 24H), 6.72 (t, 4H, J ) 2.4 Hz), 7.32 (d, 8H, J ) 2.4
Hz), 7.49 (t, 1H, J ) 2.2 Hz), 7.50 (t, 2H, J ) 2.2 Hz), 7.91 (d, 2H,
J ) 2.2 Hz), 7.99 (d, 4H, J ) 2.2 Hz). 13C NMR (67.80 MHz; CDCl3;
45 °C; ppm): δ 55.7, 106.9, 107.9, 120.8, 120.8, 121.0, 121.4, 130.6,
131.0, 131.6, 151.1, 151.5, 160.8, 162.7, 164.2, 168.7. MALDI-TOF-
MS (dithranol) m/z [M + Na]+. Calcd: 1105.2. Found: 1106.0.
(3) Synthesis of Dendrimer Porphyrins Free Bases. (i) Prepara-
tion of p-[G1]TPPH2. To a distilled THF solution (5 mL) of a mixture
of 3,5-dimethoxybenzoic acid (273 mg, 1.5 mmol), 5,10,15,20-tetrakis-
(4′-hydroxyphenyl)-21H,23H-porphine (182 mg, 0.268 mmol), and
DPTS (44.2 mg, 0.15 mmol) was added DCC (330 mg, 1.6 mmol)
under Ar at room temperature. The reaction mixture was stirred
overnight at room temperature and then evaporated to dryness under
reduced pressure at room temperature, and the residue was chromato-
graphed on silica gel with CHCl3 as eluent. A fraction containing the
desired product was isolated and evaporated to dryness under reduced
pressure at room temperature, and the residue dissolved in CHCl3
containing 2-PrOH (10%) was crystallized with hexane, to give 5,10,-
15,20-tetrakis[4′-(3′′,5′′-dimethoxybenzoyloxy)phenyl]-21H,23H-por-
1
powder in 93% yield (618 mg). H NMR (270.05 MHz; CDCl3; 20
°C; ppm): δ -2.81 (s, 2H), 3.86 (s, 96H), 6.73 (t, 16H, J ) 2.4 Hz),
7.35 (d, 32H, J ) 2.4 Hz), 7.53 (t, 8H, J ) 2.2 Hz), 7.61 (t, 4H, J )
2.2 Hz), 7.65 (d, 8H, J ) 8.5 Hz), 8.07 (d, 16H, J ) 2.2 Hz), 8.28 (d,
8H, J ) 8.5 Hz), 8.92 (s, 8H). 13C NMR (125.65 MHz; CDCl3; 45 °C;
ppm): δ 55.8, 106.9, 107.9, 119.1, 119.7, 120.8, 121.1, 121.1, 121.5,
130.5, 131.0, 132.1, 135.3, 139.8, 150.5, 151.2, 151.5, 160.7, 162.7,
163.1, 164.1. MALDI-TOF-MS (dithranol) m/z [M]+. Calcd: 4938.4.
Found: 4938.5. UV-vis (CHCl3; λmax (nm)): 312 (sh), 419, 515, 550,
590, 647.
(iv) Preparation of m-[G1]TPPH2. To a distilled THF solution (5
mL) of a mixture of 3,5-dimethoxybenzoic acid (1.63 g, 1.5 mmol),
5,10,15,20-tetrakis(3′,5′-dihydroxyphenyl)-21H,23H-porphine (100 mg,
0.134 mmol), and DPTS (44 mg, 0.15 mmol) was added DCC (330
mg, 1.6 mmol) under Ar at room temperature. The reaction mixture
was stirred overnight at room temperature and then evaporated to
dryness under reduced pressure at room temperature. The residue was
chromatographed on silica gel with CH2Cl2 as eluent and then subjected
to SEC with CHCl3 as eluent. A fraction containing the desired product
was isolated and evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3/2-PrOH (10%) was
9
J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002 11401

A R T I C L E S
Uyemura and Aida
crystallized with hexane, to give 5,10,15,20-tetrakis[3′,5′-bis(3′′,5′′-
dimethoxybenzoyloxy)phenyl]-21H,23H-porphine (m-[G1]TPPH2) as
a purple powder in 80% yield (221 mg). 1H NMR (270.05 MHz; CDCl3;
20 °C; ppm): δ -2.90 (s, 2H), 3.84 (s, 48H), 6.70 (t, 8H, J ) 2.4 Hz),
7.41 (d, 16H, J ) 2.4 Hz), 7.66 (t, 4H, J ) 2.2 Hz), 8.04 (d, 8H, J )
2.2 Hz), 9.15 (s, 8H). 13C NMR (125.65 MHz; CDCl3; 45 °C; ppm):
δ 55.7, 106.9, 107.8, 115.3, 118.3, 125.7, 131.1, 143.8, 149.8, 160.8,
164.7. MALDI-TOF-MS (dithranol) m/z [M]+. Calcd: 2054.6. Found:
2053.9. UV-vis (CHCl3; λmax (nm)): 259, 310, 420, 515, 551, 589,
645.
(i) Preparation of (p-[G1]TPP)CoII. Using p-[G1]TPPH2 (20 mg,
15 µmol), {5,10,15,20-tetrakis[4′-bis(3′′,5′′-dimethoxybenzoyloxy)-
phenyl]porphinato}cobalt(II) ((p-[G1]TPP)CoII) was obtained in 72%
1
yield (15 mg). H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ 4.33
(s, 24H), 7.16 (s, 4H), 8.33 (s, 8H), 9.81 (s, 8H), 13.20 (br s, 8H),
15.98 (br s, 8H). MALDI-TOF-MS (dithranol) m/z [M]+. Calcd: 1392.3.
Found: 1392.2. UV-vis (CHCl3; λmax (nm)): 259, 309 (sh), 412, 530.
(ii) Preparation of (p-[G2]TPP)CoII. Using p-[G2]TPPH2 (205 mg,
80.8 µmol), (5,10,15,20-tetrakis{4′-bis[3′′,5′′-bis(3′′′,5′′′-dimethoxy-
benzoyloxy)benzoyloxy]phenyl}porphinato)cobalt(II) ((p-[G2]TPP)CoII)
was obtained in 83% yield (173.9 mg). 1H NMR (270.05 MHz; CDCl3;
20 °C; ppm): δ 4.04 (s, 48H), 6.84 (s, 8H), 7.62 (s, 16H), 7.93 (s,
4H), 9.01 (d, 8H, J ) 1.4 Hz), 9.84 (s, 8H), 13.18 (br s, 8H), 15.97 (br
s, 8H). MALDI-TOF-MS (dithranol) m/z [M]+. Calcd: 2591.6.
Found: 2591.3. UV-vis (CHCl3; λmax (nm)): 260, 309 (sh), 412, 528.
(iii) Preparation of (p-[G3]TPP)CoII. Using p-[G3]TPPH2 (130 mg,
26.0 µmol), [5,10,15,20-tetrakis(4′-{3′′,5′′-bis[3′′′,5′′′-bis(3′′′′,5′′′′-
dimethoxybenzoyloxy)benzoyloxy]benzoyloxy}phenyl)porphinato]cobalt-
(II) ((p-[G3]TPP)CoII) was obtained in 91% yield (120 mg). 1H NMR
(270.05 MHz; CDCl3; 20 °C; ppm): δ 3.94 (s, 96H), 6.80 (t, 16H, J
) 2.4 Hz), 7.49 (d, 32H, J ) 2.4 Hz), 7.70 (t, 8H, J ) 2.2 Hz), 7.98
(t, 4H, J ) 1.9 Hz), 8.36 (d, 16H, J ) 2.2 Hz), 9.01 (d, 8H, J ) 1.9
Hz), 9.81 (s, 8H), 13.16 (br s, 8H), 15.91 (br s, 8H). MALDI-TOF-
MS (dithranol) m/z [M]+. Calcd: 4995.4. Found: 4995.3. UV-vis
(CHCl3; λmax (nm)): 311 (sh), 412, 523.
(v) Preparation of m-[G2]TPPH2. To a distilled THF solution (5
mL) of a mixture of [G1]poly(aryl ester)-CO2H dendron (724 mg,
1.5 mmol), 5,10,15,20-tetrakis(3′,5′-dihydroxyphenyl)-21H,23H-por-
phine (100 mg, 0.134 mmol), and DPTS (1.32 g, 4.5 mmol) was added
DCC (330 mg, 1.6 mmol) under Ar at room temperature. The reaction
mixture was stirred overnight at room temperature and then evaporated
to dryness under reduced pressure at room temperature. The residue
was chromatographed on silica gel with CH2Cl2 as eluent and subjected
to SEC with CHCl3 as eluent. A fraction containing the desired product
was isolated and evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3/2-PrOH (10%) was
crystallized with hexane, to give 5,10,15,20-tetrakis{3′,5′-bis[3′′,5′′-
bis(3′′′,5′′′-dimethoxybenzoyloxy)benzoyloxy] phenyl}-21H,23H-por-
1
phine (m-[G2]TPPH2) as a purple powder in 88% yield (523 mg). H
NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ -2.90 (s, 2H), 3.79 (s,
96H), 6.66 (t, 16H, J ) 2.4 Hz), 7.28 (d, 32H, J ) 2.4 Hz), 7.48 (t,
8H, J ) 2.2 Hz), 7.70 (t, 4H, J ) 2.2 Hz), 8.06 (m, 24H), 9.11 (s, 8H).
13C NMR (125.65 MHz; CDCl3; 45 °C; ppm): δ 55.7, 106.9, 107.7,
114.9, 118.0, 120.9, 121.2, 125.5, 130.5, 131.4, 143.9, 149.4, 151.4,
160.6, 163.0, 164.0. MALDI-TOF-MS (dithranol) m/z [M + H]+.
Calcd: 4458.1. Found: 4458.1. UV-vis (CHCl3; λmax (nm)): 256, 309
(sh), 420, 514, 548, 589, 647.
(iv) Preparation of (m-[G1]TPP)CoII. Using m-[G1]TPPH2 (20.5
mg, 10 µmol), {5,10,15,20-tetrakis[3′,5′-bis(3′′,5′′-dimethoxybenzoyloxy)-
phenyl]porphinato}cobalt(II) ((m-[G1]TPP)CoII) was obtained quanti-
1
tatively (21.5 mg). H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ
3.91 (s, 48H), 6.74 (s, 8H), 7.96 (s, 16H), 9.53 (s, 4H), 12.8 (br s, 8H),
15.9 (br s, 8H). MALDI-TOF-MS (dithranol) m/z [M]+. Calcd: 2111.5.
Found: 2110.9. UV-vis (CHCl3; λmax (nm)): 262, 308, 413, 528.
(v) Preparation of (m-[G2]TPP)CoII. Using m-[G2]TPPH2 (200 mg,
44.8µmol),(5,10,15,20-tetrakis{3′,5′-bis[3′′,5′′-bis(3′′′,5′′′-dimethoxybenzoyloxy)-
benzoyloxy]phenyl}porphinato)cobalt(II) ((m-[G2]TPP)CoII) was ob-
tained in 69% yield (140 mg). 1H NMR (270.05 MHz; CDCl3; 20 °C;
ppm): δ 3.66 (s, 96H), 6.48 (s, 16H), 7.15 (s, 32H), 7.53 (s, 8H), 8.58
(s, 16H), 9.53 (s, 4H), 12.73 (br s, 8H), 15.86 (br s, 8H). MALDI-
TOF-MS (dithranol) m/z [M + H]+. Calcd: 4515.2. Found: 4515.1.
UV-vis (CHCl3; λmax (nm)): 257, 311 (sh), 414, 527.
(vi) Preparation of m-[G3]TPPH2. To a distilled THF solution (10
mL) of a mixture of [G2]poly(aryl ester)-CO2H dendron (3.25 g, 3.0
mmol), 5,10,15,20-tetrakis(3′,5′-dihydroxyphenyl)-21H,23H-porphine
(200 mg, 0.268 mmol), and DMAP (49 mg, 0.40 mmol) was added
DCC (660 mg, 3.2 mmol) under Ar at room temperature. The reaction
mixture was stirred for 45 min at room temperature and then evaporated
to dryness under reduced pressure at room temperature. The residue
was chromatographed on silica gel with CH2Cl2 as eluent and subjected
to SEC with CHCl3 as eluent. A fraction containing the desired product
was isolated and evaporated to dryness under reduced pressure at room
temperature, and the residue dissolved in CHCl3/2-PrOH (10%) was
crystallized with hexane, to give 5,10,15,20-tetrakis(3′,5′-bis{3′′,5′′-
bis[3′′′,5′′′-bis(3′′′′,5′′′′-dimethoxybenzoyloxy)benzoyloxy]benzoyloxy}-
phenyl)-21H,23H-porphine (m-[G3]TPPH2) as a purple powder in 79%
yield (3.12 g). 1H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ -2.90
(s, 2H), 3.75 (s, 192H), 6.62 (t, 32H, J ) 2.2 Hz), 7.22 (d, 64H, J )
2.2 Hz), 7.43 (t, 16H, J ) 2.2 Hz), 7.49 (t, 8H, J ) 2.2 Hz), 7.73 (t,
4H, J ) 2.2 Hz), 7.91 (m, 24H), 8.07 (d, 16H, J ) 2.2 Hz), 9.11 (s,
8H). 13C NMR (125.65 MHz; CDCl3; 45 °C; ppm): δ 55.6, 106.7,
107.7, 114.9, 118.1, 120.7, 120.8, 120.9, 121.2, 125.6, 130.4, 130.8,
131.5, 143.8, 149.3, 151.0, 151.2, 160.5, 162.4, 162.7, 163.8. MALDI-
TOF-MS (dithranol) m/z [M]+. Calcd: 9262.3. Found: 9262.1. UV-
vis (CHCl3; λmax (nm)): 312 (sh), 421, 516, 550, 589, 646.
(4) Synthesis of Cobalt(II) Porphyrin Complexes. General
Procedure. To a CHCl3 solution of a free-base porphyrin (1.3 mM)
and a saturated EtOH solution of anhydrous Co(OAc)2 were mixed at
a 1:0.15 volume ratio, and the solution was stirred at room temperature
until it became nonfluorescent. Then, the reaction mixture was
evaporated to dryness under reduced pressure at room temperature, and
the residue was chromatographed on silica gel with CHCl3 as eluent,
where a fraction containing the desired product was isolated and
evaporated to dryness under reduced pressure at room temperature. The
residue was dissolved in CHCl3 and crystallized with 2-PrOH, to give
a dendrimer porphyrin cobalt(II) complex as a dark purple powder.
(vi) Preparation of (m-[G3]TPP)CoII. Using m-[G3]TPPH2 (648
mg, 70.0 µmol), [5,10,15,20-tetrakis(3′,5′-bis{3′′,5′′-bis[3′′′,5′′′-bis-
(3′′′′,5′′′′-dimethoxybenzoyloxy)benzoyloxy]benzoyloxy}phenyl)-
porphinato]cobalt(II) ((m-[G3]TPP)CoII) was obtained in 91% yield (596
1
mg). H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ 3.68 (s, 192H),
6.54 (br s, 32H), 7.14 (br s, 64H), 7.39 (br s, 16H), 7.57 (br s, 8H),
7.90 (d, J ) 1.4 Hz, 32H), 8.65 (br s, 16H), 9.60 (br s, 4H), 12.90 (br
s, 8H), 15.89 (br s, 8H). MALDI-TOF-MS (dithranol) m/z [M]+.
Calcd: 9319.2. Found: 9319.3. UV-vis (CHCl3; λmax (nm)): 311 (sh),
413, 530.
(5) Reaction of Cobalt(II) Porphyrins with Propargyl Alcohol
in the Presence of AIBN. As a typical example, a CDCl3 solution
(0.5 mL) of a mixture of [5,10,15,20-tetrakis(3′,5′-bis{3′′,5′′-bis[3′′′,5′′′-
bis(3′′′′,5′′′′-dimethoxybenzoyloxy)benzoyloxy]benzoyloxy}phenyl)-
porphinato]cobalt(II) ((m-[G3]TPP)CoII, 43.7 mg, 4.7 µmol), propargyl
alcohol (26.2 µL, 450 µmol), and AIBN (6.57 mg, 40 µmol) was
transferred to a NMR tube. After three freeze-pump-thaw cycles, the
NMR tube was sealed off under reduced pressure and subjected to 1H
NMR spectroscopy at 60 °C. Alkylation products were identified by
analogy to the 1H NMR spectral profiles reported in ref 7. After heating
for 240 min, degassed MeOH (1 mL) was added to the reaction mixture,
and the resulting dark purple precipitate was isolated, washed with
degassed MeOH, and dried under reduced pressure at room temperature.
Then, the residue was subjected to SEC with CHCl3 as eluent, where
a fraction containing the desired product was isolated and evaporated
to dryness under reduced pressure at room temperature to give 2-(1-
9
11402 J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002

Organic Transformation by a Dendrimer Cage
A R T I C L E S
hydroxy-2-propenyl)[5,10,15,20-tetrakis(3′,5′-bis{3′′,5′′-bis[3′′′,5′′′-bis-
(3′′′′,5′′′′-dimethoxybenzoyloxy)benzoyloxy]benzoyloxy}phenyl)-
porphinato]cobalt(III) ((m-[G3]TPP)CoIII-C(dCH2)CH2OH) as a dark
purple powder. 1H NMR (270.05 MHz; CDCl3; 20 °C; ppm): δ -2.41
(br d, J ) 2.7 Hz, 1H), -1.88 (d, J ) 6.5 Hz, 2H), -1.24 (t, J ) 6.5
Hz, 1H, OH), -0.22 (br d, J ) 2.7 Hz, 1H), 3.76 (s, 192H), 6.62 (t, J
) 2.2 Hz, 32H), 7.23 (d, J ) 2.2 Hz, 64H), 7.44 (t, J ) 2.2 Hz, 16H),
7.51 (t, J ) 2.2 Hz, 8H), 7.73 (t, J ) 2.2 Hz, 4H), 7.92 (br s, 32H),
8.07 (m, 24H), 9.10 (s, 8H). UV-vis (CHCl3; λmax (nm)): 310 (sh),
414, 531.
(6) Reaction of (m-[G3]TPP)CoII with Propargyl Alcohol in the
Presence of AIBN-d12. The reaction was carried out with AIBN-d12
(7.05 mg, 40 µmol) under otherwise identical conditions to the above.
A fraction containing cobalt porphyrin species was isolated from the
reaction mixture by precipitation with degassed MeOH, followed by
SEC with CHCl3 as eluent, in a manner similar to the case using
nondeuterated AIBN.
JA020687I
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J. AM. CHEM. SOC. VOL. 124, NO. 38, 2002 11403