The synthesis and characterization of phenylacetylene tripodal compounds containing boroxine cores

Article abstract of DOI:10.1016/j.tetlet.2005.10.033

A convergent synthesis of phenylacetylene tripodal compounds containing boroxine cores has been accomplished. The boroxine cores are assembled in high yield either by chemical dehydration or ligand-facilitated trimerization of the corresponding monomeric

Full text of DOI:10.1016/j.tetlet.2005.10.033

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8753–8756
The synthesis and characterization of phenylacetylene
tripodal compounds containing boroxine cores
Emily K. Perttu, Matthew Arnold and Peter M. Iovine*
Department of Chemistry, University of San Diego, 5998 Alcala Park, San Diego, CA 92110, USA
Received 27 September 2005; accepted 11 October 2005
Available online 26 October 2005
Abstract—A convergent synthesis of phenylacetylene tripodal compounds containing boroxine cores has been accomplished. The
boroxine cores are assembled in high yield either by chemical dehydration or ligand-facilitated trimerization of the corresponding
monomeric boronic acids.
Ó 2005 Elsevier Ltd. All rights reserved.
The tripodal molecular architecture is a common struc-
tural motif found in such diverse areas as dendrimers,1
hyperbranched polymers,2 receptors for small molecule
recognition,3 and catalysts.4 Boroxines, the dehydration
product of boronic acids, have found commercial use in
such diverse areas as flame retardant materials,5 dopants
that enhance lithium ion transference in polymer
electrolytes,6 and recently as boronic acid alternatives
in Suzuki–Miyaura coupling reactions.7 Our group is
interested in utilizing boroxine rings to construct conju-
gated C3-symmetric materials. From a molecular design
perspective, boroxine-based organic materials8 are of
interest because they provide rapid synthetic entry into
tripodal architectures. Furthermore, the boroxineꢀs
Lewis acidity9 and rich ligand chemistry provides
additional opportunities to functionalize boroxine
based-materials through noncovalent interactions. In
this work, we have synthesized conjugated boronic acid
monomers that are efficiently converted to boroxine
containing materials (Fig. 1). In addition, we investigate
ligand-facilitated boroxine formation as an alternative
to dehydration in the construction of the central borox-
ine ring.
boronic acid is dehydrated to the boroxine. As an alter-
native to dehydration, arylboronic acids can rapidly be
converted to boroxineÆligand adducts by stirring at
room temperature with a suitable ligand.10,11 Although
binding of Lewis bases with preformed boroxines is well
established, utilizing the low temperature conversion of
monomeric boronic acids to boroxineÆligand adducts as
a means of assembling tripodal architectures has not
been demonstrated. Ligand-facilitated formation of
boroxine takes advantage of the high thermodynamic
stability of the boroxineÆligand complex relative to the
monomeric boronic acid.12
The synthesis of boroxine 1 and 1Æpyridine is shown in
Scheme 1. Using standard Sonogashira–Hagihara cou-
pling methodology,13 commercially available 4-tert-
butylphenyl acetylene was coupled to pinacol protected
4-iodophenyboronic acid. Exchange of the pinacol
group for diethanolamine followed by acidic hydrolysis
afforded the boronic acid.14 The addition of a drying
agent, calcium chloride, to a toluene solution of the
boronic acid promotes dehydration to boroxine.
The syntheses of branched boroxines 2 and 3 are out-
lined in Schemes 2 and 3. 1,3,5-Tribromobenzene is
converted to disubstituted derivative 7. Compound 7 is
borylated with bis(pinacolato)diboron to yield com-
pound 8 in 46% isolated yield. Conversion of 8 to borox-
ine 2 was inefficient. After drying a toluene solution of
boronic acid 9 over calcium chloride, NMR analysis
shows a mixture of 2 and 9. Boroxine formation is facil-
itated by the addition of pyridine (1.5 equiv relative to
the theoretical yield of boroxine). After stirring, excess
The conjugated synthetic precursors are synthesized
convergently with the boron functionality being intro-
duced late in the synthesis. The boronate ester is con-
verted to a boronic acid, and upon workup, the
Keywords: Boroxine; Boronic acid; Phenylacetylene; Tripodal.
*
Corresponding author. Tel.: +1 619 2604208; fax: +1 619 260
2211; e-mail: piovine@sandiego.edu
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.033

8754
E. K. Perttu et al. / Tetrahedron Letters 46 (2005) 8753–8756
Figure 1. Conjugated boroxine core compounds 1Æpyridine, 2Æpyridine, and 3Æpyridine.
Scheme 1. Synthesis of compound 1Æpyridine.
pyridine is removed under vacuum leaving the 1:1
acid or boroxine that has precipitated from a chloro-
boroxine 2Æpyridine adduct.
form solution, results in a homogeneous solution
consisting of boroxineÆpyridine adduct. The introduc-
tion of the pyridine ligand drives the formation of the
boroxine adduct and this adduct shows a concomitant
increase in solubility. As in other boroxineÆpyridine
adducts,8b,10a,d,11 the pyridine ligand is in fast
exchange on the NMR timescale and the observed
chemical shift of the ortho protons are a weighted
average of the ligated and unligated forms.
Compound 7 can be further elaborated using 2-methyl-
3-butyn-2-ol. After deprotection under basic condi-
tions,15 acetylene 11 is coupled to 4-iodophenylboronic
acid pinacol ester 4 giving compound 12 in 37% isolated
yield (Scheme 3). After deprotection of 12, the boronic
acids are taken up in toluene and smoothly converted
to the boroxine 3 by drying over calcium chloride.
The solubility of these compounds is noteworthy.
Boroxines 1 and 3 are initially soluble in chloroform
but precipitate on standing. This is likely due to the for-
mation of p-stacked aggregates.16 In contrast, the
boroxineÆpyridine adducts are highly soluble in chloro-
form. Addition of a stoichiometric volume of pyridine
to a heterogeneous mixture of either monomeric boronic
The UV–vis absorption spectra of boronate ester 8, in
the presence of pyridine, and 2Æpyridine are shown in
Figure 2. As can be seen from the data, there is no
broadening or red shifting of the absorption maxima
(291 nm, 308 nm) going from a boronate ester to the
tripodal boroxine. This suggests that there are no signifi-
cant electronic perturbations caused by boroxine ring

E. K. Perttu et al. / Tetrahedron Letters 46 (2005) 8753–8756
8755
3
2.5
Compound 2 + pyridine
2
1.5
1
Compound 8
+ pyridine
0.5
0
250
300
350
400
450
Wavelength (nm)
Figure 2. UV–vis absorption spectra of boronate ester 8 (in the
presence of pyridine) and boroxineÆpyridine adduct 2Æpyridine in
dichloromethane. The spectra are normalized to 15 lM.
Scheme 2. Synthesis of compound 2Æpyridine.
methods, dehydration or ligand-facilitated trimeriza-
tion, and functions as a tripodal scaffold.
Acknowledgments
This research was supported by an award from Research
Corporation.
Supplementary data
Experimental procedures and full spectroscopic data for
all new compounds. This material is available free of
charge via the Internet. Supplementary data associated
with this article can be found, in the online version, at
doi:10.1016/j.tetlet.2005.10.033.
References and notes
´
1. (a) Frechet, J. M. J. J. Polym. Sci. Part A: Polym. Chem.
2003, 41, 3713–3725; (b) Grayson, S. M.; Frechet, J. M. J.
Chem. Rev. 2001, 101, 3819–3868; (c) Ruiz, J.; Lafuente,
G.; Marcen, S.; Ornelas, C.; Lazare, S.; Cloutet, E.; Blais,
J.-C.; Astruc, D. J. Am. Chem. Soc. 2003, 125, 7250–7257;
(d) Devadoss, C.; Bharathi, P.; Moore, J. S. J. Am. Chem.
Soc. 1996, 118, 9635–9644.
2. (a) Gittins, P. J.; Twyman, L. J. J. Am. Chem. Soc. 2005,
127, 1646–1647; (b) Pan, Y.; Lu, M.; Peng, Z.; Melinger,
J. S. J. Am. Chem. Soc. 2003, 68, 6952–6958.
Scheme 3. Synthesis of compound 3Æpyridine.
3. (a) Dai, Z.; Xu, X.; Canary, J. W. Chirality 2005, 17,
S227–S233; (b) Seong, H. R.; Kim, D.-S. K.; Kim, S.-G.;
Choi, H.-J.; Ahn, K. Tetrahedron Lett. 2004, 45, 723–
727; (c) Fan, J.; Gan, L.; Kawaguchi, H.; Sun, W.-Y.; Yu,
K.-B.; Tang, W.-X. Chem. Eur. J. 2003, 9, 3965–3973; (d)
Yun, S.; Kim, Y.-O.; Kim, D.; Kim, H. G.; Ihm, H.; Kim,
J. K.; Lee, C.-W.; Lee, W. J.; Yoon, J.; Oh, K. S.; Yoon,
J.; Park, S.-M.; Kim, K. S. Org. Lett. 2003, 5, 471–474.
4. Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999,
527–538.
incorporation as compared to the corresponding boro-
nate ester. As expected, the molar extinction coefficient
of 2Æpyridine tripodal assembly increases relative to the
monomeric boronate ester.
In conclusion, a series of phenylacetylene boroxine core
compounds have been convergently synthesized. The
boroxine core is easily formed by one of two synthetic
5. Morgan, A. B.; Jurs, J. L.; Tour, J. M. Polym. Prepr. 1999,
40, 553.

8756
E. K. Perttu et al. / Tetrahedron Letters 46 (2005) 8753–8756
6. (a) Mehta, M. A.; Fujinami, T. Chem. Lett. 1997, 26, 915–
Snyder, H. R.; Konecky, M. S.; Lennarz, W. J. J. Am.
Chem. Soc. 1958, 80, 3611; (d) Das, M. K.; Mariategui,
J. F.; Niedenzu, K. Inorg. Chem. 1987, 26, 3114–3116.
11. (a) Beckmann, J.; Dakternieks, D.; Duthie, A.; Lim, A. E.
K.; Tiekink, E. R. T. J. Organomet. Chem. 2001, 633, 149;
(b) Yalpani, M.; Boese, R. Chem. Ber. 1983, 116, 3347; (c)
Beckett, M. A.; Brassington, D. S.; Owen, P.; Hursthouse,
M. B.; Light, M. E.; Malik, K. M. A.; Varma, K. S. J.
Organomet. Chem. 1999, 585, 7.
12. Kua, J.; Iovine, P. M. J. Phys. Chem. A 2005, 109, 8938–
8943.
13. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron
Lett. 1975, 16, 4467–4470; (b) Sonogashira, K. In Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: New York, 1998.
916; (b) Yang, Y.; Inoue, T.; Fujinami, T.; Mehta, M. A.
J. Appl. Polym. Sci. 2002, 84, 17–21; (c) Forsyth, M.; Sun,
J.; Zhou, F.; MacFarlane, D. R. Electrochim. Acta 2003,
48, 2129–2136.
7. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–
2483.
8. (a) Alcaraz, G.; Euzenat, L.; Mongin, O.; Katan, C.;
Ledoux, I.; Zyss, J.; Blanchard-Desce, M.; Vaultier, M.
Chem. Commun. 2003, 2766–2767; (b) Wu, Q. G.; Wu, G.;
Brancaleon, L.; Wang, S. Organometallics 1999, 18, 2553–
2556.
9. Farfan, N.; Contreras, R. J. Chem. Soc., Perkin Trans. 2
1987, 771–773.
10. For examples of boroxines binding nitrogen containing
Lewis bases, see: (a) Beckett, M. A.; Strickland, G. C.;
Varma, K. S.; Hibbs, D. E.; Hursthouse, M. B.; Malik, K.
J. Organomet. Chem. 1997, 535, 33–41; (b) Ritchey, J. M.
Ph.D. Thesis (Synthesis and Properties of Addition
Complexes of Boroxines and Other Selected Boron-
Containing Systems), University of Colorado, 1968; (c)
14. Jung, M. E.; Tsvetelina, L. I. J. Org. Chem. 1999, 64,
2976–2977.
15. Melissaris, A.; Litt, M. H. J. Org. Chem. 1994, 59, 5818–
5821.
16. Li, Y.; Ding, J.; Day, M.; Tao, Y.; Lu, J.; Dꢀiorio, M.
Chem. Mater. 2003, 15, 4936–4943.