Regioselecitive huisgen cycloaddition within porous coordination networks

Article abstract of DOI:10.1002/anie.201000018

(Figure Presented) Pore it on: Huisgen 1,3-dipolarcycloaddition reactions of 2-(azidomethyl)triphenylene and alkynes (see scheme) took place within the pores of a porous coordination network in a single-crystal-tosingle-crystal fashion. Columnar ? stacks and nanosized pores in the network complex enforce a particular orientation of the reactants such that the 1,4-substituted isomer of the 1,2,3-triazole product is selectively produced.

Full text of DOI:10.1002/anie.201000018

Angewandte
Chemie
DOI: 10.1002/anie.201000018
Porous Networks
Regioselecitive Huisgen Cycloaddition within Porous Coordination
Networks**
Takehide Kawamichi, Yasuhide Inokuma, Masaki Kawano, and Makoto Fujita*
Chemical reactivity within porous coordination networks is a
current topic of significant interest.[1] Recently, we and others
have shown that the pores of coordination networks can be
used as “crystalline molecular flasks” wherein pseudo solu-
tion state organic reactions, even those involving surprisingly
bulky reagents, can smoothly occur while crystallinity is
maintained throughout.[2,3] Reaction centers are held at fixed
geometries in the crystalline state, and with this close
proximity, restricted motion can be exploited to obtain high
regio- and stereoselectivity. Herein we report that regiose-
lective 1,3-dipolar cycloadditions between azides and alkynes
(Huisgen reaction) proceed within the pores of the coordi-
nation network 1 (Scheme 1). Typically, the Huisgen reaction
gives two regioisomers (i.e. 1,4- and 1,5-substituted-1,2,3-
triazoles) in solution, with a slight excess of the 1,5-isomer.
Within the pores of network 1, however, the 1,4-regioisomers
are obtained with high selectivity. The robust structure of the
coordination network facilitates reaction monitoring by using
in situ single crystal X-ray analysis, which not only provides
structural information about the product but can also
elucidate the structural basis of reaction selectivity. There
exist a few reports on Huisgen reactions within porous
coordination networks, but none have discussed the regiose-
lectivity and, hence, achieved an understanding of the
structural aspects of network pores and how they relate to
the reaction selectivity.[4]
Coordination network
1
was
obtained when ZnI2 and tri(4-pyri-
dyl)triazine (2) were mixed in the
presence of azide 3 in nitrobenzene/
methanol (4:1).[5] From elemental
analysis, the molecular formula of
the as-synthesized network 1 was
shown to be [{(ZnI2)3(2)2(3)}·x
(C6H5NO2)]n (x = ca. 4.0). After
replacing the nitrobenzene in the
pores with ethyl acetate the crystal
structure of 1 was unambiguously
determined by X-ray crystallographic
analysis (Figure 1, and see the Sup-
porting Information). As in similar
previous networks, guest
3
was
embedded within a columnar stack
of ligand 2. The structure of 1 exhib-
ited two distinct pores and the azido
groups point into the larger of the two
Scheme 1. a) Preparation of network 1. b) Huisgen cycloaddition reactions.
cylindrical pores (Figure 1).
[*] T. Kawamichi, Dr. Y. Inokuma, Prof. Dr. M. Fujita
Department of Applied Chemistry, School of Engineering
The University of Tokyo
Crystals of network 1 (20 mg) were immersed in a small
amount of methyl propiolate (4a; 0.1 mL) at 108C. The
reaction proceeded and was monitored by using single-crystal
microscopic IR methods. The strong N3 stretching band of 3 at
n = 2099 cmÀ1 gradually disappeared, and 3 was completely
consumed after three days. The crystals of robust network 1
retained crystallinity and the product of the single-crystal-to-
single-crystal transformation was determined by X-ray dif-
fraction. By X-ray analysis, 1,4-substituted-1,2,3-triazole 5a
selectively formed in the pores of network 1. The network
complex was decomposed with [D6]DMSO, and 1H NMR
analysis revealed a small amount of the 1,5-adduct (11%),
which was not detected by X-ray analysis.
Hongo, Bunkyo-ku, Tokyo 113-8656 (Japan)
Fax: (+81)3-5841-7257
E-mail: mfujita@appchem.t.u-tokyo.ac.jp
Prof. Dr. M. Kawano
Department of Chemistry, POSTECH
San 31 Hyojadong, Pohang 790-784 (South Korea)
[**] This research was supported by the CREST project of the Japan
Science and Technology Agency (JST), for which M.F. is the principal
investigator, and also in part by KAKENHI (20044006), JSPS, and
the Global COE Program (Chemistry Innovation through Cooper-
ation of Science and Engineering), MEXT (Japan). This work has
been approved by Photon Factory Program Advisory Committee
(Proposal No. 2008G052).
High 1,4-regioselectivity was also observed for phenyl-
acetylene derivatives 4b–4h (Figure 2). The observed 1,4-
selectivity warrants additional discussion because the Huis-
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201000018.
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Communications
strates influenced the selectivity. When the steric bulk of the
para substituents increased (H < F < Br< OMe) the 1,4-
selectivity increased (67% < 77% < 79% < 87%, respec-
tively). Phenylacetylene 4g having the Br groups in the
ortho position to the alkyne, and 4h having a terminal methyl
group, both showed only moderate 1,4-selectivity (60:40 and
63:37, respectively) despite the closer proximity of the bulky
substituents to the reaction center. Thus, in the confining
pores of 1, the steric effects of the para position play a greater
role in controlling the regioselectivity. In addition, the result
with internal alkyne 4h can exclude a possibility of copper
contamination, which can catalyze regioselective cycloaddi-
tions.[7] There is, however, a size limit and no additional
increase in the regioselectivity was obtained with 4-tert-
butylphenylacetylene (4 f). The steric demand of 4 f actually
inhibited the reaction (most likely because of product
inhibition; see the Supporting Information) and only approx-
imately 65% conversion was obtained, even under forced
conditions.
X-ray crystal analyses of 1 both before and after the
reaction, provided a better understanding for the 1,4-selec-
tivity and the steric effects of the para substituent. The azide
group in 3 is pointed towards the center of the pore, and to
furnish the 1,5-substituted triazole 6, phenylacetylenes 4b–h
would need to direct their pendant aryl groups towards the
column or side wall of 2 (see Figure S7 in the Supporting
Information). In this case, bulky para substituents will pre-
vent the ethynyl group from adopting favorable orientations
for the 1,5-cycloaddition. In contrast, the orientations leading
to the 1,4-substituted triazoles 5b–h align well within the
space provided by the network pores.
In summary, we have demonstrated that the typically
disfavored 1,4-regioselective Huisgen cycloaddition between
2-(azidomethyl)triphenylene (3) and alkynes 4a–h does occur
within the pores of coordination network 1. Whereas
regioselective Huisgen reactions without transition metal
catalysts have been achieved in cavitand molecules, polymers,
and supramolecular assemblies,[8] porous coordination net-
works have not yet been successfully used as regioselective
reaction media. Unlike other molecular hosts, coordination
network 1 possesses a robust crystallinity and a porous pseudo
solution state which enables monitoring of reactions by using
Figure 1. a) Crystal structure of network complex 1. In the highlighted
region, azide 3 stacks alternatively with triazine ligand 2. ORTEP
drawings (30% probability) of a triphenylene unit before (b) and after
(c) the reaction between 3 and 4a (solvent molecules were omitted for
clarity).
gen reaction of these substrates under standard
solution conditions displays no selectivity or a slight
selectivity for the 1,5-regioisomer. For example, when
p-methoxyphenylacetylene (4b) was treated with
crystals of 1, the 1,4-regioisomer was selectively
formed (1,4-isomer/1,5-isomer= 87:13) in the network
pores. In solution, however, there is only a minor
preference (45:55) for the 1,5-isomer. The Huisgen
cycloadditions of alkynes 4c–4h in the porous net-
work 1 showed similar selectivities (good to high) for
the 1,4-regioisomer. Again, the solution state regiose-
lectivities were trivial (Figure 2). Only 4a shows latent
high 1,4-selectivity in solution most likely due to the
electronic effect of COOMe.[6]
Figure 2. Alkynes 4a–h employed for Huisgen cycloaddition. Results given for
products obtained using a) the network complex 1 and b) neat conditions. See
Though far away from the reaction center, the size
of the para substituents of the phenylacetylene sub- the Experimental section for details.
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Angewandte
Chemie
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Experimental Section
General procedure for Huisgen reaction in the pore of 1: Crystals of 1
were dipped in liquid alkynes at 108C (for 4a), 508C (for 4b–d, f–h)
˚
and 70 C (for 4e) for 7 d. Elemental analyses of the resulting crystals
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were carried out after filtration. The NMR spectra were obtained
after decomposing crystals by the addition of [D6]DMSO.
General procedure for Huisgen reaction under neat conditions:
Azide 3 (30 mg, 0.11 mmol) was dissolved in 1 g of an alkyne. The
solution was stirred at 1008C for 2 d (see the Supporting Information
for more detail).
Received: January 4, 2010 [Z18]
Published online: February 23, 2010
Keywords: azides · cycloaddition · solid-state structures ·
.
huisgen reactions
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