Synthesis of aryl/alkyl building blocks for dendrimer and hyperbranched polymer synthesis

Article abstract of DOI:10.1021/ol0356082

Several useful aryl/alkyl building blocks for dendrimer and hyperbranched polymer synthesis were prepared by Suzuki-Miyaura cross-coupling reactions and iododesilylation reactions. The iododesilylations were carried out with iodine monochloride (ICI) in m

Full text of DOI:10.1021/ol0356082

ORGANIC
LETTERS
2004
Vol. 6, No. 5
667-669
Synthesis of Aryl/Alkyl Building Blocks
for Dendrimer and Hyperbranched
Polymer Synthesis
,†
Zhishan Bo,* Jun Qiu,‡ Jing Li,† and A. Dieter Schlu1ter‡
State Key Laboratory of Polymer Physics and Chemistry, Joint Laboratory of Polymer
Science and Materials, Institute of Chemistry, Chinese Academy of Sciences,
Beijing, 100080, China, and Institut fu¨r Chemie/Organische Chemie,
Freie UniVersita¨t Berlin, Takustrasse 3, D-14195 Berlin, Germany
zsbo@iccas.ac.cn
Received August 26, 2003 (Revised Manuscript Received January 8, 2004)
ABSTRACT
Several useful aryl/alkyl building blocks for dendrimer and hyperbranched polymer synthesis were prepared by Suzuki−Miyaura cross-coupling
reactions and iododesilylation reactions. The iododesilylations were carried out with iodine monochloride (ICl) in methylene chloride and
diethyl ether (10:1). This solvent combination lowered the reagents electrophilicity to the point that the iododesilylation still proceeded absolutely
cleanly, but no direct iodination of alkyl-substituted aromatics occurred, which otherwise could not be avoided.
Dendrimers and hyperbranched polymers have attracted
considerable attention as a result of their unique structures
and properties. Dendrimers are highly branched macromol-
ecules prepared by divergent, convergent, and combined
divergent/convergent methods,1 whereas hyperbranched poly-
mers are irregularly branched macromolecules prepared by
one-step reactions.2 Dendrimers and hyperbranched polymers
with heteroatom linkages are readily available.1,2 Examples
of dendrimers and hyperbranched polymers based on non-
polar conjugated hydrocarbon skeletons have already been
reported by several groups.3 However all-hydrocarbon den-
drimers based on nonconjugated, flexible linkages, especially
of the aryl/alkyl type, are limited. Buildup of these macro-
molecules with a nonpolar inner environment is important
in cases where they are used as catalysts,4 unimolecular
micelles,5 etc.
Trimethylsilyl (TMS) is an ideal masking group for aryl
iodide in preparation of building blocks for such dendrimers
and hyperbranched polymers.6 Aryltrimethylsilanes are stable
(3) For examples: (a) Moore, J. S. Acc. Chem. Res. 1997, 30, 402. (b)
Xu, Z.; Moore, J. S. Angew. Chem., Int. Ed. 1993, 32, 246. (c) Xu, Z.;
Kahr, M.; Walker, K. L.; Willins, C. L.; Moore, J. S. J. Am. Chem. Soc.
1994, 116, 4537. (d) Bharathi, P.; Moore, J. S. Macromolecules 2000, 33,
3212. (e) Miller, T. M.; Neenan, T. X. Chem. Mater. 1990, 2, 346. (f) Miller,
T. M.; Neenan, T. X. Zayas, R.; Bair, H. E. J. Am. Chem. Soc. 1992, 114,
1018. (g) Kim, Y. H.; Webster, O. W. J. Am. Chem. Soc. 1990, 112, 4592.
(h) Deb, S. K.; Maddux, T. M.; Yu, L. J. Am. Chem. Soc. 1997, 119, 9079.
(i) Meier, H.; Lehmann, M. Angew. Chem., Int. Ed. 1998, 37, 643. (j) Pillow,
L. N. G.; Halim, M.; Lupton, J. M.; Burn, P. L.; Samuel, I. D. W.
Macromolecules 1999, 32, 5985. (k) Percec, V.; Barboiu, B.; Grigoras, C.;
Bera, T. K. J. Am. Chem. Soc. 2003, 125, 6503.
† Chinese Academy of Sciences.
‡ Freie Universita¨t Berlin.
(1) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendrimers and
Dendrons; Wiley-VCH: Weinheim, 2001. Fre´chet, J. M. J.; Tomalia, D.
A. Dendrimers and Other Dendritic Polymers; Wiley-VCH: Weinheim,
2001.
(2) (a) Kim, Y. H. J. Polym. Sci., Part A: Polym Chem. 1998, 36, 1685.
(b) Voit, B. J. Polym. Sci. Part A: Polym Chem. 2000, 38, 2505.
(4) Hecht, S.; Fre´chet, J. M. J. J. Am. Chem. Soc. 2001, 123, 6959.
(5) (a) Newkome, G. R.; Arai, S.; Fronczek, F. R.; Moorefield, C. N.;
Lin, X. F.; Weis, C. D. J. Org. Chem. 1993, 58, 898. (b) Newkome, G. R.;
Moorefield, C. N.; Baker, G. R.; Saunders: M. J.; Grossman, S. H. Angew.
Chem., Int. Et. 1991, 30, 1178. (c) Kim, Y.; Webster, O. W. J. Am. Chem.
Soc. 1990, 112, 4592.
10.1021/ol0356082 CCC: $27.50 © 2004 American Chemical Society
Published on Web 02/07/2004

to air, various bases, acids, nucleophiles such as Grignard
and organolithium reagents, common oxidants, and reducing
reagents. The transformation to iodo is commonly achieved
by ipso-substitution with electrophilic reagents such as ICl
or iodine in methylene chloride.7 However, these conditions
cannot be applied in all cases. Some aromatics are sensitive
to ICl and undergo direct iodination or other reactions.8
Herein, we report the synthesis of valuable building blocks
for dendrimer and hyperbranched polymer synthesis (1-4),
which uses slightly modified reaction conditions for the
iododesilylation steps. This way the side reaction can be
completely suppressed, and all products can be easily
obtained in pure form.
Scheme 1 a
Compounds 1-3 (Scheme 1) have alkylene linkages
between the peripheral benzenes and the central one and,
thus, potential as multifunctional core for dendrimer con-
struction. Compound 4 (Scheme 2) with its one boronic
pinacol ester group and two iodo functions is an AB2 type
monomer for hyperbranched polymers. The synthetic routes
to these compounds rely on (a) Suzuki-Miyaura cross-
coupling (SCC) reactions9 between bromoaromatics and
alkylboranes or arylboronic acids and (b) conversion of
aryltrimethylsilanes into their corresponding aryl iodides by
treatment with ICl. The synthesis of compound 1 started from
a TMS-masked allylbenzene 5,6a whose hydroboration with
9-BBN was essentially quantitative. Subsequent SCC of the
resulting 96a with 1,3,5-tribromobenzene was carried out in
a biphasic system of aqueous NaOH/THF with Pd(PPh3)4
as a catalyst precursor. Compound 10 was obtained as a
colorless oil in a yield of 92%. Conversion of 10 to its
corresponding triiodide 1 was done in a mixture of methylene
chloride and diethyl ether (10:1) at 0 °C for 1 h. The addition
of some ether as donor solvent tuned the reactivity of ICl to
the point that the side reaction was suppressed. In the
following these conditions are referred to as mild iododesi-
lylation. The use of 1 equiv of pyridine per iodochloride was
tried but turned out not to be an alternative because the
iododesilylation did not work anymore. Similarly hydrobo-
ration of 66b with 9-BBN afforded borane 11, whose reaction
with 1,3,5- tribromobenzene furnished 12 as a colorless oil
in a 76% yield. Conversion of 12 to its corresponding
(6) (a) Bo, Z. S.; Schlu¨ter, A. D. J. Org. Chem. 2002, 67, 5327. (b) Bo,
Z. S.; Schlu¨ter, A. D. Chem. Commun. 2003, 2354. (c) Beinhoff, M.;
Karakaya, B. Schlu¨ter, A. D. Synthesis 2003, 79.
(7) (a) Pray, B. O.; Sommer, L. H.; Goldberg, G. M.; Kerr, G. T.; Di
Giorgio, P. A. J. Am. Chem. Soc. 1948, 70, 433. (b) Stock, L. M.; Spector,
A. R. J. Org. Chem. 1963, 28, 3272. (c) Aalbersberg, W. G. L.; Barkovich,
A. J.; Funk, R. L.; Hillard, R. L.; Vollhardt, K. P. C. J. Am. Chem. Soc.
1975, 97, 5600. (d) Hillard, R. L.; Vollhardt, K. P. C. J. Am. Chem. Soc.
1977, 99, 4058. (e) Fe´lix, G.; Dunogue´s, J.; Pisciotti, F.; Calas R. Angew.
Chem., Int. Ed. Engl. 1977, 16, 488. (f) Fe´lix, G.; Dunogue´s, J.; Calas R.
Angew. Chem., Int. Ed. Engl. 1979, 18, 402. (g) Wilson, S. R.; Jacob, L.
A. J. Org. Chem. 1986, 51, 4833. (h) Jacob, J. A.; Chen, B. L.; Stec, D.
Synthesis 1993, 611. (i) Effenberger, F.; Krebs, A. J. Org. Chem. 1984,
49, 4687. (j) Hensel, V.; Schlu¨ter, A. D. Chem. Eur. J. 1999, 5, 421. (k)
Hensel, V.; Lu¨tzow, K.; Jakob, J. Gessler, K.; Saenger, W.; Schlu¨ter, A.
D. Angew. Chem., Int. Ed. Engl. 1997, 36, 2654. (l) Nitschke, J. R.; Zurcher,
S.; Tilley, T. D. J. Am. Chem. Soc. 2000, 122, 10345. (m) Zhu, Z. G.;
Swager, T. M. Org. Lett. 2001, 3, 3471. (n) Zhang, W.; Luo, Z. Y.; Chen,
C. H. T., Curran, D. P. J. Am. Chem. Soc. 2002, 124, 8337.
a Reagents and conditions: (a) THF, rt, 2 d; (b) THF, Pd(PPh3)4,
aq NaOH, reflux, 2 d; (c) ICl, CH2Cl2, ether, 0 °C, 1 h; (d) THF,
Pd(PPh3)4, aq NaHCO3, reflux, 3 d.
(8) For examples: (a) Andrews, L. J.; Keefer, R. M. J. Am. Chem. Soc.
1957, 79, 1412. (b) Andrews, L. J.; Keefer, R. M. J. Am. Chem. Soc. 1964,
86, 4158.
hexaiodide 2 was achieved under the above mild conditions,
whereas when normal conditions were applied, a mixture
(9) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
668
Org. Lett., Vol. 6, No. 5, 2004

bis(trimethylsilyl)benzene (8).6c Treatment of 8 with ICl
readily afforded 14 in quantitative yield. Alkylboranes react
at a higher rate with iodoaromatics than with bromoaromat-
ics. Coupling of 9 and 14 afforded 15 in a 64% yield;
Subsequent halo-lithium exchange and quenching with
trimethyl borate afforded the corresponding boronic acid,
which was converted with pinacol in CH2Cl2 into its cyclic
ester 16 (yield 77%). Mild iododesilylation of 16 successfully
led to the corresponding diiodide 4 in quantitative yield.
Scheme 2 a
In summary, several useful building blocks for dendrimer
and hyperbranched polymer synthesis were prepared by using
Suzuki-Miyaura cross-coupling and iododesilylation reac-
tions. In the iododesilylation step, using a solvent mixture
of methylene chloride and diethyl ether (10:1) instead of pure
methylene chloride was the key to tune the reactivity of ICl
and suppress the side reactions.
a Reagents and conditions: (a) ICl, CH2Cl2, diethyl ether, 0 °C,
1 h; (b) THF, Pd(PPh3)4, aq NaOH, reflux, 2 d; (c) (i) n-BuLi,
ether/THF, -78 °C, 1 h (ii) B(OMe)3, 1 d (iii) pinacol, CH2Cl2,
reflux, 6 h.
Acknowledgment. Financial support from The Chinese
Academy of Sciences, the National Natural Science Founda-
tion of China, the Major State Basic Research Development
Program 973, the Deutsche Forschungsgemeinschaft (Sfb
448, TP A1), and the Fonds der Chemischen Industrie is
greatly acknowledged
formed. Further separation of the desired product from it
proved very complicated and time-consuming. Compound
13 was synthesized by coupling of boronic acid 76b with
1,3,5-tribromobenzene using standard SCC conditions.9 Mild
iododesilylation gave 3 as a colorless solid in a 95% yield,
whereas iododesilylation under ICl/CH2Cl2 condition did not
give any of the desired product but rather a complex mixture.
Compound 4 was prepared in four steps from 1-bromo-3,5-
Supporting Information Available: Detailed experi-
mental procedures and characterization of all compounds.
This material is available free of charge via Internet at
http://pubs.acs.org.
OL0356082
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