ORGANIC LETTERS
Synthesis of Aryl/Alkyl Building Blocks for Dendrimer and Hyperbranched Polymer Synthesis
2004 Vol. 6, No. 5 667-669
Zhishan Bo,*,† Jun Qiu,‡ Jing Li,† and A. Dieter Schlu1 ter‡ 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
[email protected] 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 macromolecules prepared by divergent, convergent, and combined divergent/convergent methods,1 whereas hyperbranched polymers 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 nonpolar conjugated hydrocarbon skeletons have already been reported by several groups.3 However all-hydrocarbon dendrimers based on nonconjugated, flexible linkages, especially of the aryl/alkyl type, are limited. Buildup of these macro†
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. ‡
10.1021/ol0356082 CCC: $27.50 Published on Web 02/07/2004
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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. (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.
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. Compounds 1-3 (Scheme 1) have alkylene linkages between the peripheral benzenes and the central one and, thus, potential as multifunctional core for dendrimer construction. 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 crosscoupling (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 iododesilylation. 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 hydroboration 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. (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. (9) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. 668
Scheme 1 a
a Reagents and conditions: (a) THF, rt, 2 d; (b) THF, Pd(PPh ) , 3 4 aq NaOH, reflux, 2 d; (c) ICl, CH2Cl2, ether, 0 °C, 1 h; (d) THF, Pd(PPh3)4, aq NaHCO3, reflux, 3 d.
hexaiodide 2 was achieved under the above mild conditions, whereas when normal conditions were applied, a mixture Org. Lett., Vol. 6, No. 5, 2004
Scheme 2 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. a
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-
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 bromoaromatics. 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. In summary, several useful building blocks for dendrimer and hyperbranched polymer synthesis were prepared by using Suzuki-Miyaura cross-coupling and iododesilylation reactions. 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. Acknowledgment. Financial support from The Chinese Academy of Sciences, the National Natural Science Foundation 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 Supporting Information Available: Detailed experimental 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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