A R T I C L E S
Percec et al.
of conformationally flexible AB2 building blocks.13 The syn-
thesis of the AB4 building block 13 is outlined in Scheme 1.
The first step involves the acylation of 4-chlorophenylacetic acid
(1) with veratrole (2) in freshly prepared polyphosphoric acid14
at 75 °C to yield ketone 3 in 96% yield. This procedure was
previously employed in our laboratory13 since it replaces the
need to form the acid chloride required for Friedel-Crafts
acylations. Bromination of 3,4-dimethoxybenzyl alcohol (4) with
PBr3 in Et2O15 generated bromide 5 in 83% yield. The enolate
alkylation of 3 with 3,4-dimethoxybenzyl bromide (5) under
phase-transfer conditions13 gave ketone 6, which was reduced
Scheme 1. Synthesis of the AB4 Building Block
(5) For selected recent reviews on supramolecular dendrimers self-organized
into periodic arrays, see: (a) Zimmerman, S. C. Curr. Opin. Colloid
Interface Sci. 1997, 2, 89-99. (b) Matthews, O. A.; Shipway, A. N.;
Stoddart, J. F. Prog. Polym. Sci. 1998, 23, 1-56. (c) Fischer, M.; Vo¨gtle,
F. Angew. Chem., Int. Ed. 1999, 38, 885-905. (d) Emrick, T.; Fre´chet, J.
M. J. Curr. Opin. Colloid Interface Sci. 1999, 4, 15-23. (e) Schlenk, C.;
Frey, H. Monatsh. Chem. 1999, 130, 3-14. (f) Smith, D. K.; Diederich, F.
Top. Curr. Chem. 2000, 210, 183-227. (g) Ponomarenko, S. A.; Boiko,
N. I.; Shibaev, V. P. Polym. Sci. Ser. C 2001, 43, 1-45. (h) Guillon, D.;
Deschenaux, R. Curr. Opin. Solid State Mater. Sci. 2002, 6, 515-525. (i)
Tschierske, C. Curr. Opin. Colloid Interface Sci. 2002, 7, 69-80. (j) Diele,
S. Curr. Opin. Colloid Interface Sci. 2002, 7, 333-342. (k) Caminade,
A.-M.; Turrin, C.-O.; Sutra, P.; Majoral, J.-P. Curr. Opin. Colloid Interface
Sci. 2003, 8, 282-295. (l) Smith, D. K.; Hirst, A. R.; Love, C. S.; Hardy,
J. G.; Brignell, S. V.; Huang, B. Prog. Polym. Sci. 2005, 30, 220-293.
(m) Percec, V. Philos. Trans. R. Soc. London, Ser. A 2006, 364, 2709-
2719. (n) Rudick, J. C.; Percec, V. New J. Chem. 2007, 31, 1083-1096.
(o) Donnio, B.; Guillon, D. AdV. Polym. Sci. 2006, 201, 45-155.
(6) For selected examples of amphiphilic self-assembling dendrons and self-
organizing dendrimers based on AB3 repeat units, see: (a) Percec, V;
Johansson, G.; Heck, J.; Ungar, G.; Batty, S. V. J. Chem. Soc., Perkin
Trans. 1 1993, 1411-1420. (b) Johansson, G.; Percec, V.; Ungar, G.;
Abramic, D. J. Chem. Soc., Perkin Trans. 1 1994, 447-459. (c) Percec,
V.; Johansson, G.; Ungar, G.; Zhou, J. J. Am. Chem. Soc. 1996, 118, 9855-
9866. (d) Balagurusamy, V. S. K.; Ungar, G.; Percec, V.; Johansson, G. J.
Am. Chem. Soc. 1997, 119, 1539-1555. (e) Hudson, S. D.; Jung, H.-T.;
Percec, V.; Cho, W.-D.; Johansson, G.; Ungar, G.; Balagurusamy, V. S.
K. Science 1997, 278, 449-452. (f) Percec, V.; Cho, W.-D.; Mosier, P.
E.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc. 1998, 120, 11061-
11070. (g) Ungar, G.; Percec, V.; Holerca, M. N.; Johannson, G.; Heck, J.
A. Chem.-Eur. J. 2000, 6, 1258-1266. (h) Percec, V.; Cho, W.-D.; Mo¨ller,
M.; Prokhorova, S. A.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc.
2000, 122, 4249-4250. (i) Percec, V.; Cho, W.-D.; Ungar, G. J. Am. Chem.
Soc. 2000, 122, 10273-10281. (j) Dukeson, D. R.; Ungar, G.; Balaguru-
samy, V. S. K.; Percec, V.; Johansson, G. A.; Glodde, M. J. Am. Chem.
Soc. 2003, 125, 15974-15980. (k) Percec, V.; Glodde, M.; Johansson, G.;
Balagurusamy, V. S. K.; Heiney, P. A. Angew. Chem., Int. Ed. 2003, 42,
4338-4342. (l) Maltheˆte, J. New J. Chem. 1996, 20, 925-928. (m) Percec,
V.; Peterca, M.; Sienkowska, M. J.; Ilies, M. A.; Aqad, E.; Smidrkal, J.;
Heiney, P. A. J. Am. Chem. Soc. 2006, 128, 3324-3334. (n) Percec, V.;
Holerca, M. N.; Nummelin, S.; Morrison, J. L.; Glodde, M.; Smidrkal, J.;
Peterca, M.; Rosen, B. M.; Uchida, S.; Balagurusamy, V. S. K.; Sienkowska,
M. J.; Heiney, P. A. Chem.-Eur. J. 2006, 12, 6216-6241.
(7) For selected examples of amphiphilic self-assembling dendrons based on
AB2 repeat units, see: (a) Percec, V.; Cho. W.-D.; Ungar, G.; Yeardley,
D. J. P. Angew. Chem., Int. Ed. 2000, 39, 1598-1602. (b) Percec, V.; Cho,
W.-D.; Ungar, G.; Yeardley, D. J. P. J. Am. Chem. Soc. 2001, 123, 1302-
1315. (c) Sua´rez, M.; Lehn, J.-M.; Zimmerman, S. C.; Skoulios, A.;
Heinrich, B. J. Am. Chem. Soc. 1998, 120, 9526-9532.
(8) For examples of amphiphilic self-assembling dendrons based on combina-
tions of AB, AB2, and AB3 benzyl ether and other hybrid dendrons, see:
(a) Percec, V.; Mitchell, C. M.; Cho, W.-D.; Uchida, S.; Glodde, M.; Ungar,
G.; Zeng, X.; Liu, Y.; Balagurusamy, V. S. K.; Heiney, P. A. J. Am. Chem.
Soc. 2004, 126, 6078-6094. (b) Percec, V.; Smidrkal, J.; Peterca, M.;
Mitchell, C. M.; Nummelin, S.; Dulcey, A. E.; Sienkowska, M. J.; Heiney,
P. A. Chem.-Eur. J. 2007, 13, 3989-4007.
(9) For examples of dendrons that self-assemble and co-assemble into
supramolecular lattices and/or complex supramolecules, see: (a) Percec,
V.; Ahn, C.-H.; Bera, T. K.; Ungar, G.; Yeardley, D. J. P. Chem.-Eur. J.
1999, 5, 1070-1083. (b) Percec, V.; Bera, T. K.; Glodde, M.; Fu, Q.;
Balagurusamy, V. S. K.; Heiney, P. A. Chem.-Eur. J. 2003, 9, 921-935.
(c) Percec, V.; Imam, M. R.; Bera, T. K.; Balagurusamy, V. S. K.; Peterca,
M.; Heiney, P. A. Angew. Chem., Int. Ed. 2005, 44, 4739-4745.
(10) For new periodic and quasi-periodic lattices self-organized from supramo-
lecular dendrimers, see: (a) Ungar, G.; Liu, Y.; Zeng, X.; Percec, V.; Cho,
W.-D. Science 2003, 299, 1208-1211. (b) Zeng, X.; Ungar, G.; Liu, Y.;
Percec, V.; Dulcey, A. E.; Hobbs, J. K. Nature 2004, 428, 157-160. (c)
Chvalun, S. N.; Shcherbina, M. A.; Yakunin, A. N.; Blackwell, J.; Percec,
V. Polym. Sci. Ser. A 2007, 49, 158-167.
(11) For additional examples of self-assembling amphiphilic dendrons, see: (a)
Kim, C.; Kim, K. T.; Chang, Y.; Song, H. H.; Cho, T.-Y.; Jeon, H.-J. J.
Am. Chem. Soc. 2001, 123, 5586-5587. (b) Cho, B.-K.; Jain, A.; Gruner,
S. M.; Wiesner, U. Science 2004, 305, 1598-1601. (c) Cho, B.-K.; Jain,
A.; Mahajan, S.; Ow, H.; Gruner, S. M.; Wiesner, U. J. Am. Chem. Soc.
2004, 126, 4070-4071.
directly to the methylene group by using a LiAlH4/AlCl3‚Et2O
complex.13,16 The aryl chloride 7 was obtained in 43% yield.
The boronic acid 11 was prepared by the formation of the
Grignard reagent of bromotoluene (8), followed by addition of
trimethylborate to generate tolylboronic acid (9)17 in 72% yield.
Benzylic oxidation of 9 with KMnO4 in aqueous NaOH yielded,
after acidification, the carboxylic acid 10,18 which was esterified
under acidic conditions with methanol to give 1119 in 74% yield.
Nickel-catalyzed Suzuki coupling20 of aryl chloride 7 and
(12) For examples of functions mediated via the 3-D structures generated by
self-assembling dendrons, see: (a) Percec, V.; Heck, J.; Tomazos, D.;
Falkenberg, F.; Blackwell, H.; Ungar, G. J. Chem. Soc., Perkin Trans. 1
1993, 2799-2811. (b) Percec, V.; Heck, J. A.; Tomazos, D.; Ungar, G. J.
Chem. Soc., Perkin Trans. 2 1993, 2381-2388. (c) Percec, V.; Tomazos,
D.; Heck, J.; Blackwell, H.; Ungar, G. J. Chem. Soc., Perkin Trans. 2 1994,
31-44. (d) Percec, V.; Ahn, C.-H.; Barboiu, B. J. Am. Chem. Soc. 1997,
119, 12978-12979. (e) Percec, V.; Ahn, C.-H.; Ungar, G.; Yeardley, D. J.
P.; Mo¨ller, M.; Sheiko, S. S. Nature 1998, 391, 161-164. (f) Percec, V.;
Glodde, M.; Bera, T. K.; Miura, Y.; Shiyanovskaya, I.; Singer, K. D.;
Balagurysamy, V. S. K.; Heiney, P. A.; Schnell, I.; Rapp, A.; Spiess, H.-
W.; Hudson, S. D.; Duan, H. Nature 2002, 419, 384-387. (g) Percec, V.;
Dulcey, A. E.; Balagurusamy, V. S. K.; Miura, Y.; Smidrkal, J.; Peterca,
M.; Nummelin, S.; Edlund, U.; Hudson, S. D.; Heiney, P. A.; Duan, H.;
Magonov, S. N.; Vinogradov, S. A. Nature 2004, 430, 764-768. (h) Percec,
V.; Rudick, J. G.; Peterca, M.; Wagner, M.; Obata, M.; Mitchell, C. M.;
Cho. W.-D.; Balagurusamy, V. S. K.; Heiney, P. A. J. Am. Chem. Soc.
2005, 127, 15257-15264.
(13) (a) Percec, V.; Kawasumi, M. Macromolecules 1991, 24, 6318-6324. (b)
Percec, V.; Kawasumi, M. Macromolecules 1992, 25, 3843-3850. (c)
Percec, V.; Chu, P. W.; Kawasumi, M. Macromolecules 1994, 27, 4441-
4453. (d) Percec, V.; Chu, P.; Ungar, G.; Zhou, J. J. Am. Chem. Soc. 1995,
117, 11441-11454.
(14) (a) Napolitano, E.; Giannone, E.; Fiaschi, R.; Marsili, A. J. Org. Chem.
1983, 48, 3653-3657. (b) Alesso, E. N.; Tombari, D. G.; Iglesias, G. Y.
M.; Aguirre, J. M. Can. J. Chem. 1987, 65, 2568-2574.
(15) Zumbrunn, A. Synthesis 1998, 9, 1357-1361.
(16) (a) Nystrom, R. F.; Berger, C. R. J. Am. Chem. Soc. 1958, 80, 2896-
2898. (b) Albrecht, W. L.; Gustafson, D. H.; Horgan, S. W. J. Org. Chem.
1972, 37, 3355-3357.
(17) (a) Seeman, W.; Johnson, J. R. J. Am. Chem. Soc. 1931, 53, 711-723. (b)
Chan, K. S.; Zhou, X. A.; Au, M. T.; Tam, C. Y. Tetrahedron 1995, 51,
3129-3136.
(18) (a) Michaelis, A.; Richter, E. Justus Liebigs Ann. Chem. 1901, 315, 26-
40. (b) Matsubara, H.; Seto, K. J.; Tahara, T.; Takahashi, S. Bull. Chem.
Soc. Jpn. 1989, 62, 3896-3901.
(19) Tong, A. J.; Yamauchi, A.; Hayashita, T.; Zhang, Z. Y.; Smith, B. D.;
Teramae, N. Anal. Chem. 2001, 73, 1530-1536.
9
11266 J. AM. CHEM. SOC. VOL. 129, NO. 36, 2007