Synthesis of cored dendrimers with internal cross-links

Article abstract of DOI:10.1002/1521-3773(20010518)40:10<1962::AID-ANIE1962>3.0.CO;2-J

Hydrolytic removal of the core unit and cross-linking of their wedges enables dendrimers to be "cored" (see schematic representation). By internalizing the alkenes, the ring-closing metathesis reaction will "stitch" the dendritic wedges to gather intramolecularly, even at dendrimer concentrations of 10^-3M. In contrast peripheral alkenes react intermolecularly at this concentration.

Full text of DOI:10.1002/1521-3773(20010518)40:10<1962::AID-ANIE1962>3.0.CO;2-J

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the partial separation of the pure diastereomers, which were obtained in a
combined yield of 75%. Removal of the protecting groups with trimethyl-
silyl triflate,[19] N-acylation with octanoyl chloride[20] and final chromatog-
raphy afforded erythro-1 in 14% overall yield from pentadecyne.
[15] J. R. Clark, H. W. Kircher, Lipids 1972, 7, 769 ± 772.
[16] R. J. Aldulayymi, M. S. Baird, M. J. Simpson, S. Nyman, G. R. Port,
Tetrahedron 1996, 52, 12509 ± 12520.
[17] P. Herold, Helv. Chim. Acta 1988, 71, 354 ± 362.
[18] G. Niel, F. Roux, Y. Maisonnasse, I. Maugras, J. Poncet, P. Jouin, J.
Chem. Soc. Perkin Trans. 1 1994, 1275 ± 1280.
[19] M. Sakaitani, Y. Ohfune, J. Org. Chem. 1990, 55, 870 ± 876.
[20] P. De Ceuster, G. P. Mannaerts, P. P. Van Veldhoven, Biochem. J. 1995,
311, 139 ± 146.
[21] K. Raith, J. Darius, R. H. Neubert, J. Chromatogr. A 2000, 876, 229 ±
233.
erythro-1: [a]D ˆ ‡3.0 (c ˆ 0.8 in CHCl3); IR (NaCl): nÄ ˆ 1550, 1644, 3010,
3287 cm 1; 1H NMR (300 MHz, CDCl3): d ˆ 0.87 (t, 6H, J ˆ 6.2 Hz), 1.01 (s,
2H), 1.25 (s, 28H), 1.60 (m, 4H), 2.24 (t, 2H, J ˆ 7.2 Hz), 2.45 (dt, 2H, J ˆ
7.6, J' ˆ 1.2 Hz), 3.02 (brs, 1H), 3.37 (brs, 1H), 3.71 (dd, 1H, J ˆ 11.4, J' ˆ
3.4 Hz), 3.87 (dd, 1H, J ˆ 11.2, J' ˆ 4 Hz), 4.18 (m, 1H), 4.85 (s, 1H), 6.37
(brd, 1H); 13C NMR (75 MHz, CDCl3): d ˆ 8.36, 14.04, 14.10, 22.58, 22.66,
25.70, 25.82, 27.27, 28.99, 29.19, 29.33, 29.37, 29.44, 29.57, 29.63, 29.64, 29.64,
29.67, 31.65, 31.89, 36.77, 53.74, 63.12, 70.52, 107.52, 115.40, 174.00. HR-MS
calcd for C27H51NO3: 437.386895; found: 437.387000.
[22] The activities of dihydroceramide desaturase were 1.4 Æ
1
0.3 nmolh 1 mg in microsomes incubated with threo-1 and 1.3 Æ
1
0.2 nmolh 1 mg in control microsomes (average Æ standard devia-
The dihydroceramide desaturase inhibition assay was performed by using
rat liver microsomes, which were prepared as reported.[5] The activity of
dihydroceramide desaturase was determined in phosphate buffer (0.1m,
pH 7.4), with d-erythro-N-octanoylsphingosine as substrate. The inhibitor
(at the indicated concentrations) and the substrate (15 nmol) were
solubilized (15 nmol of BSA in phosphate buffer/ethanol 9:1 v/v, 100 mL),
combined with the microsome suspension (1 mg of protein) and NADH
(30 mL, 1 mm in phosphate buffer), and made up to a final volume of 300 mL
with phosphate buffer. The suspension was incubated for 30 min at 378C,
and the reactions were terminated by the addition of CHCl3 (0.5 mL)
containing d-erythro-N-hexanoylsphingosine (1 nmol) as an internal stan-
dard for quantification. The lipids were extracted with CHCl3 (2 Â 250 mL),
the combined organic layers were evaporated under a stream of nitrogen,
and the residue was derivatized with bistrimethylsilyltrifluoroacetamide
(50 mL, 258C, 60 min). After derivatization, CHCl3 (50 mL) was added and
the samples were stored at 808C. Instrumental analyses were carried out
by gas chromatography coupled to electron impact (70 eV) mass spec-
trometry using a Fisons gas chromatograph (8000 series) coupled to a
Fisons MD-800 mass-selective detector. The system was equipped with a
nonpolar Hewlett ± Packard HP-1 capillary column (30 m  0.20 mm i.d.),
which was programmed from 1008C to 3408C at 78Cmin 1. Analyses were
carried out in the selected ion monitoring mode. Selected ions were m/z ˆ
311, 313, 230, and 258. Dwell (time for which a given mass is monitored)
was set at 0.02 s and the mass span at 0.5.
tion, n ˆ 3).
[23] R. H. Unger, L. Orci, Int. J. Obes. 2000, 24(Suppl. 4), S28 ± S32.
Synthesis of Cored Dendrimers with Internal
Cross-Links**
Laura G. Schultz, Yan Zhao, and
Steven C. Zimmerman*
The physical properties of a dendrimer may be manipulated
by post-synthetic modification of its periphery, core, or
interior. Such alterations can tune the bulk properties of the
dendritic system and frequently convert simple dendrimers
into functional macromolecules. For example, incorporation
of molecular recognition elements on the periphery of a
dendrimer produces multivalent receptors capable of ligand
binding or supramolecular assembly.[1] Organometallic func-
tional groups can also be added to the periphery, thus creating
macromolecular catalysts.[1±3] In contrast to the many reports
of end-group functionalization, there are only a few examples
of covalent modification of the interior of the dendrimer.[4]
We recently reported[5] the ªcoringº of dendrimer 1 by ring-
closing metathesis (RCM) of the peripheral homoallyl ether
groups[6] using ruthenium benzylidene catalyst 2[7] followed by
hydrolytic removal of the core. In some respects, ªcoredº
dendrimers resemble hollow, polymeric nanospheres or core-
shell nanoparticles.[8] Consequently, the potential of ªcoredº
dendrimers to encapsulate or complex substances makes them
outstanding candidates for delivery agents or molecular
sensors.
Received: January 31, 2001
Revised: March 8, 2001 [Z16535]
[1] T. Kolter, K. Sandhoff, Angew. Chem. 1999, 111, 1632 ± 1670; Angew.
Chem. Int. Ed. 1999, 38, 1532 ± 1568.
[2] T. Kolter, K. Sandhoff, Chem. Soc. Rev. 1996, 25, 371 ± 381.
[3] C. Arenz, A. Giannis, Angew. Chem. 2000, 112, 1498 ± 1500; Angew.
Chem. Int. Ed. 2000, 39, 1440 ± 1442.
[4] The synthesis of two fluorinated dihydroceramide analogues that have
a marginal activity as inhibitors of dihydroceramide desaturase has
been reported recently: S. De Jonghe, I. Van Overmeire, S. Van
Calenbergh, C. Hendrix, R. Busson, D. De Keukeleire, P. Herdewijn,
Eur. J. Org. Chem. 2000, 3177 ± 3183.
[5] C. Michel, G. van Echten-Deckert, J. Rother, K. Sandhoff, E. Wang,
A. H. Merrill, Jr., J. Biol. Chem. 1997, 272, 22432 ± 22437.
[6] C. Michel, G. van Echten-Deckert, FEBS Lett. 1997, 416, 153 ± 155.
[7] J. W. Kok, M. Nikolova-Karakashian, K. Klappe, C. Alexander, A. H.
Merrill, Jr., J. Biol. Chem. 1997, 272, 21128 ± 21136.
Our reported synthesis of cored dendrimers[5] is limited in
its scalability by the requirement of high dilution (about
[8] L. Geeraert, G. P. Mannaerts, P. P. van Veldhoven, Biochem. J. 1997,
327, 125 ± 132.
[9] T. Mikami, M. Kashiwagi, K. Tsuchihashi, T. Akino, S. Gasa, J.
Biochem. Tokyo 1998, 123, 906 ± 911.
[10] C. Causeret, L. Geeraert, G. Van der Hoeven, G. P. Mannaerts, P. P.
Van Veldhoven, Lipids 2000, 35, 1117 ± 1125.
[11] A. R. Johnson, J. A. Pearson, F. S. Shenstone, A. C. Fogerty, Nature
1967, 214, 1244 ± 1245.
[*] Prof. S. C. Zimmerman, L. G. Schultz, Y. Zhao
Department of Chemistry
University of Illinois
600 S. Mathews Ave., Urbana, IL 61801 (USA)
Fax : (‡1)217-244-9919
E-mail: sczimmer@uiuc.edu
[**] This work was supported by the National Institute of Health (GM
39782). L.G.S. acknowledges the Department of Chemistry, University
of Illinois, and Pharmacia & Upjohn for fellowship support.
[12] J. Quintana, M. Barrot, G. Fabrias, F. Camps, Tetrahedron 1998, 54,
10187 ± 10198, and references therein.
[13] A. R. Johnson, A. C. Fogerty, J. A. Pearson, F. S. Shenstone, A. M.
Bersten, Lipids 1968, 4, 265 ± 269.
Supporting information for this article is available on the WWW under
http://www.angewandte.com or from the author.
[14] A. C. Fogerty, A. R. Johnson, J. A. Pearson, Lipids 1972, 7, 335 ± 338.
1962
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Angew. Chem. Int. Ed. 2001, 40, No. 10

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OR
RO
O
O
O
O
O
O
OR
RO
O
O
O
O
O
O
O
O
O
O
O
O
O
O
OR
OR
O
RO
RO
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
RO
OR
O
O
O
O
O
O
RO
OR
O
O
O
O
3a : R =
, 3b : R = Me
CH2
PCy3
Cl
Cl
O
O
1
Ru
Ph
PCy3
2
10 5 m) to effect intramolecular cross-linking. By internalizing
the alkenes there is a possibility that intermolecular cross-
linking will be disfavored, as one dendrimer would need to
interpenetrate another. Armes and co-workers used a similar
strategy in the synthesis of shell-cross-linked knedel (SCK)
micelles.[9] To test the idea that internalizing the cross-linking
groups would favor RCM reactions at higher concentration
three new dendrimers (3a, 3b, and 4) were designed and
synthesized. Dendrimers 3a and 3b are identical except that
the latter, a control compound, lacks the additional dendritic
layer so the allyl groups reside on the surface. In both cases,
the dendrimer contains labile ester linkages to the core.
Dendrimers 3a and 3b were synthesized using the con-
vergent approach[10] employing either the Mitsunobu ether-
ification[11] or phenol ± bromide coupling[10] as shown by
Scheme 1. The synthesis of 6, required for the synthesis of
3a, is shown in Equation (1) (Ms ˆ mesyl ˆ methanesulfan-
yl).[12] Bromide 6 was then coupled with phenol 7 and
converted into bromide 8a. Phenol 7 was obtained by
reduction of the corresponding aldehyde, a compound first
reported by Claisen and Eisleb.[13] The coupling of bromide 8a
with commercially available ester 9 afforded the second
generation ester which was reduced to alcohol 10a. Mitsuno-
bu coupling of 10a with 9 followed by reduction yielded third
generation alcohol 11a. Treatment of 12 with alcohol 11a
under Dean ± Stark conditions afforded dendrimer 3a.[14, 15]
Dendrimer 3b was synthesized in an analogous manner
(Scheme 1).
With the desired dendrimers in hand, attention was turned
to the cross-linking experiments. The critical question was
whether cross-linking would occur, and, if so, to what extent
(both intra- and intermolecularly). Although 1 can be cross-
linked completely,[5] the alkenes are more hindered in 3b and
especially congested in 3a. The sensitivity of some RCM
catalysts to steric hindrance is well documented.[16] All the
dendrimers were cross-linked by ring-closing metathesis using
Grubbꢁs catalyst 2 in benzene (Scheme 2).[7, 16] The catalyst
was removed after the RCM reactions using a modification of
a reported protocol in which the metathesis solution was
treated with tris(hydroxymethyl)phosphane and then silica.[17]
Subsequent purification of all compounds by preparative size-
exclusion chromatography (SEC) in toluene afforded almost
quantitative recovery of the cross-linked products.
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
Dendrimers 1 and 3b were cross-linked using 7 mol% of
catalyst per alkene at three concentrations (1 Â 10 , 1 Â 10 ,
5
4
4
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1963

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1
and 1 Â 10 3 m). Both H NMR and mass
HO
spectrometric analysis clearly indicated
Br
HO
that cross-linking of the allyl groups in 3b
had occurred. Thus, the H NMR signals
3,4
1,2
O
O
1
O
OCH3
OH
broadened significantly and the alkene
methine signal shifted upfield from d ˆ
5.98 to 5.73, which is consistent with the
conversion of monosubstituted into disub-
stituted alkenes. Matrix-assisted laser-de-
sorption/ionization time-of-flight spec-
trometry (MALDI-TOF) analysis showed
the average loss of 11 molecules of ethyl-
ene, thus indicating the formation of 11 out
of 12 possible cross-links.[18] Similar results
were seen in the cross-linking of den-
drimer 1.
OR
OH
OR
RO
7
8a,b
HO
10a,b
9
HO
O
5,6
7
O
3a,b
O
O
COCl
O
O
RO
OR
ClOC
COCl
Dendrimer 3a was cross-linked at two
12
5
and 1 Â 10 3 m)
OR
concentrations (1 Â 10
RO
using 4 mol% of 2 per alkene. Indeed,
cross-linking did occur at the concentra-
tions examined which indicated that the
catalyst could access the internal alkenes.
11a,b
CH2
a : R =
b : R = CH3
O
O
1
The same H NMR and MALDI analyses
used for 1 and 3b showed the cross-linking
of 3a to be less advanced. In particular, the
MALDI-TOF peak assignments indicate
the average formation of 8 ± 9 out of 12
possible cross-links at 10 3 m and 10 out of
12 cross-links at 10 5 m.[18] The degree of
cross-linking did not increase when higher
catalyst loadings were used. Grubbs and
co-workers recently reported the develop-
ment of a new ruthe-
Scheme 1. Syntheses of dendrimers 3a and 3b. Reaction conditions: 1) a. 6, K2CO3, 2-butanone
(79%); b. CH3I, K2CO3, acetone (71%); 2) CBr4, PPh3, THF (a: 75%, b: 82%); 3) a. 9, K2CO3,
acetone, [18]crown-6 (77%); b. 9, K2CO3, acetone (81%); 4) LiAlH4, THF (a: 96%, b: 81%);
5) PPh3, DEAD, THF, 9 (a: 70%, b: 79%); 6) LiAlH4, THF (a: 94%, b: 93%); 7) 12, DMAP,
benzene (a: 34%, b: 71%). DEAD ˆ diethylazodicarboxylate, DMAP ˆ 4-dimethylaminopyri-
dine.
Br
O
OCH3
O
nium benzylideneimi-
1. LiAlH4, THF, 97%
Mes
N
N Mes
O
O
dazol-2-ylidene cata-
lyst 17 (mes ˆ mesityl)
capable of cross-link-
ing sterically hin-
dered olefins.[19] Grat-
ifyingly, metathesis of
O
2. MsCl, Et3N, CH2Cl2
3. NaBr, acetone
79% (two steps)
(1)
Cl
Cl
Ru
P(Cy)3
Ph
6
5
17
Scheme 2. Synthesis of cored dendrimers.
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3a with 17 at both 10 3 m and 10 5 m resulted in greater than
95% cross-linking based on H NMR analysis.
Table 1. A comparative SEC analysis of intermolecular cross-linking in 1,
3a, and 3b with 2.
1
Conc. of RCM [m]
Relative amount of oligomer formed [%]
The extent of intermolecular cross-linking, namely, oligo-
mer formation, was determined by both MALDI-TOF
analysis and size-exclusion chromatography (SEC) using
toluene as eluent. Each SEC trace consisted of two signals
corresponding to formation of the monomer and oligomer
(Figure 1). The relative areas of these two signals were used to
1
3a
3b
5
1 Â 10
0
7
0
±
0
7
4
1 Â 10
3
1 Â 10
38
< 5
29
intramolecular metathesis had occurred. As the concentration
of the RCM reaction was increased to 1 Â 10 4 m, an additional
peak evident in the SEC traces of 1 and 3b (Figure 1a and 1b)
revealed the formation of small amounts of oligomer, which
MALDI-TOF analysis showed to be dimer. Substantial
oligomer formation occurred with both 1 and 3b at a RCM
reaction concentration of 10 3 m. However, dendrimer 3a
underwent more than 95% intramolecular cross-linking at
10 3 m ([alkene] ˆ 0.024m) with both catalysts 2 and 17, the
latter giving greater than 95% cross-linking based on 1H NMR
analysis. This result is consistent with a model wherein the
alkene groups are sterically blocked from intermolecular
metathesis.
For these dendritic systems to be useful, the cross-linked
dendrimer must remain intact when the core is removed.
Scheme 2 also depicts the ªcoringº procedure. Hydrolysis of
14a and 14b led to complete core removal as evidenced by the
loss of the aromatic signal at d ˆ 8.95 in the 1H NMR spectrum
and a reduction of m/z 159 (C9H3O3) in the MALDI-TOF
spectrum.[18] Whereas dendrimer 14b produced 16b fully
intact, the MALDI-TOF and SEC data for 16a revealed a
minor amount of cross-linked mono- and didendron formed in
the hydrolysis of 14a.[18]
The ability to fully cross-link dendrimer 3a intramolecu-
larly at 10 3 m makes this cross-linking-coring approach
suitable for further development. It was considered to be
particularly important to develop a system wherein the end
groups could ultimately be conjugated with targeting or
reporter groups or converted into groups that provide water
solubility. For these reasons, a synthesis of 4 was developed
(Scheme 3). Bromide 18, prepared by bromination of 4-meth-
ylacetophenone with N-bromosuccinimide (NBS), was cou-
pled with alcohol 19 to afford 20, which was purified as its 3,5-
dinitrobenzoate derivative. Conversion of 20 into the bro-
mide, coupling with 7, and treatment with mesyl chloride/
sodium bromide afforded 21. Coupling of 21 with tBDPS-
protected 22[20] yielded 23, which was treated with acid
chloride 12 to afford dendrimer 4. Preliminary cross-linking
studies of dendrimer 4 indicated the formation of 11 of 12
cross-links at 10 3 m in dichloromethane using 4 mol% of
catalyst 2 per alkene.
Figure 1. Comparison of cross-linked dendrimers by SEC. a) 3b; b) 1;
c) 3a.
The previously reported synthesis of cored dendrimers was
limited by the high-dilution conditions required for intra-
molecular metathesis. The current work solves this problem.
Thus, larger quantities of cored dendrimers can now be
produced, thus making it possible to develop a range of
applications. Efforts in this direction have been successful and
will be reported in due course.
calculate the percentage of oligomer formation (Table 1). The
molecular weights of dendrimers, pre- and post-cross-linking,
were determined using both MALDI-TOF and SEC analy-
ses.[18] No oligomer formation was evident in either the
MALDI-TOF spectra or SEC traces of dendrimers 1, 3a, and
3b cross-linked at 10 5 m, thus indicating that complete
Received: February 5, 2001 [Z16560]
Angew. Chem. Int. Ed. 2001, 40, No. 10
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1965

COMMUNICATIONS
5468 ± 5470; b) L. J. Twyman, Tetrahe-
dron Lett. 2000, 41, 6875 ± 6878; intra/
interdendrimer cross-linking: M. Zhao,
Y. Liu, R. M. Crooks, D. E. Bergbreiter, J.
Am. Chem. Soc. 1999, 121, 923 ± 930;
incorporation of hydroxyl groups:
c) J. R. McElhanon, M.-J. Wu, M. Esco-
bar, D. V. McGrath, Macromolecules
1996, 29, 8979 ± 8982; d) A. W. Freeman,
Br
HO
Br
HO
1–3
4 –7
O
O
O
HO
OH
O
19
18
O
O
O
O
20
Â
L. A. J. Chrisstoffels, J. M. J. Frechet, J.
Org. Chem. 2000, 65, 7612 ± 7617; poly-
lithiation/addition: L. Lochmann, K. L.
HO
O
O
21
Â
Wooley, P. T. Ivanova, J. M. J. Frechet, J.
Am. Chem. Soc. 1993, 115, 7043 ± 7044;
O
O
electrophile addition: J.-P. Majoral, C.
HO
Â
Larre, R. Laurent, A.-M. Caminade,
OR
RO
Coord. Chem. Rev. 1999, 192, 3 ± 18;
metal ion coordination: G. R. Newkome,
C. N. Moorefield, J. M. Keith, G. R. Bak-
er, G. H. Escamilla, Angew. Chem. 1994,
106, 701 ± 703; Angew. Chem. Int. Ed.
Engl. 1994, 33, 666 ± 668.
OR
RO
O
O
22 : R = tBDPS
9
4
O
O
8
O
O
O
O
[5] M. S. Wendland, S. C. Zimmerman, J.
Am. Chem. Soc. 1999, 121, 1389 ± 1390.
[6] Reports detailing surface-oligomeriza-
tion methods without coring: C. O. No-
bel IV, R. L. McCarley, J. Am. Chem. Soc.
2000, 122, 6518 ± 6519; J. Wang, X. Jia, H.
Zhong, H. Wu, Y. Li, X. Xu, M. Li, Y.
Wei, J. Polym. Sci. Part A 2000, 38, 4147 ±
4153; M. Tominaga, K. Konishi, T. Aida,
Chem. Lett. 2000, 4, 374 ± 375.
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
[7] E. L. Dias, S. T. Nguyen, R. H. Grubbs, J.
Am. Chem. Soc. 1997, 119, 3887 ± 3897.
[8] J. Ding, G. Liu, Chem. Mater. 1998, 10,
537 ± 542; F. Caruso, Chem. Eur. J. 2000,
6, 413 ± 419; J. Hotz, W. Meier, Langmuir
1998, 14, 1031 ± 1036; Q. Zhang, E. E.
Remsen, K. L. Wooley, J. Am. Chem. Soc.
2000, 122, 3642 ± 3651; T. K. Mandal,
M. S. Fleming, D. R. Walt, Chem. Mater.
23
Scheme 3. Synthesis of dendrimer 4. Reaction conditions: 1) K2CO3, 2-butanone (76%); 2) 3,5-
dinitrobenzoyl chloride, pyridine, DMAP (53%); 3) K2CO3, MeOH (62%); 4) MsCl, Et3N, CH2Cl2;
5) NaBr, acetone (92%); 6) 7, K2CO3, 2-butanone (85%); 7) MsCl, Et3N, CH2Cl2; NaBr, acetone (80%);
8) 22, KF, [18]crown-6, 2-butanone (57%); 9) 12, DMAP, benzene (52%). Ms ˆ mesyl ˆ methanesul-
fonyl.
[1] Selected recent reviews: K. Inoue, Prog. Polym. Sci. 2000, 25, 453 ±
571; D. K. Smith, F. Diederich, Top. Curr. Chem. 2000, 210, 183 ± 227;
M. W. P. L. Baars, E. W. Meijer, Top. Curr. Chem. 2000, 210, 131 ± 182;
S. C. Zimmerman, Curr. Opin. Coll. Interf. Sci. 1997, 2, 89 ± 99; F. W.
Zeng, S. C. Zimmerman, Chem. Rev. 1997, 97, 1687 ± 1712; G. R.
Newkome, E. He, C. N. Moorefield, Chem. Rev. 1999, 99, 1681 ± 1746;
V. Balzani, S. Campagna, G. Denti, A. Juris, S. Serroni, M. Venturi,
Acc. Chem. Res. 1998, 31, 26 ± 34.
2000, 12, 3481 ± 3487; M. Iijima, Y. Nagasaki, T. Okada, M. Kato, K.
Kataoka, Macromolecules 1999, 32, 1140 ± 1146; V. Bütün, A. B. Lowe,
N. C. Billingham, S. P. Armes, J. Am. Chem. Soc. 1999, 121, 4288 ±
4289.
Â
Ä
[9] V. Bütün, X.-S. Wang, M. V. de Paz Banez, K. L. Robinson, N. C.
Billingham, S. P. Armes, Z. Tuzar, Macromolecules 2000, 33, 1 ± 3.
Â
[10] C. J. Hawker, J. M. J. Frechet, J. Am. Chem. Soc. 1990, 112, 7638 ±
7647.
[2] Selected examples: H. Brunner, J. Organomet. Chem. 1995, 500, 39 ±
46; D. K. Smith, F. Diederich, Chem. Eur. J. 1998, 4, 1353 ± 1361; E.
de Wolf, G. van Koten, B.-J. Deelman, Chem. Soc. Rev. 1999, 28, 37 ±
41; R. A. Gossage, L. A. van de Kuil, G. van Koten, Acc. Chem. Res.
1998, 31, 423 ± 431; O. A. Mathews, A. N. Shipway, J. F. Stoddart, Prog.
Polym. Sci. 1998, 23, 1 ± 56.
[3] [Co(salen)] (salen ˆ N,N'-bis(salicylidene)ethylenediamine dianion)
units for asymmetric ring opening of epoxides: R. Breinbauer, E. N.
Jacobsen, Angew. Chem. 2000, 112, 3750 ± 3753; Angew. Chem. Int.
Ed. 2000, 39, 3604 ± 3607; RhI complexes for hydroformylation:
a) S. C. Bourque, F. Maltais, W.-J. Xiao, O. Tardif, H. Alper, P. Arya,
L. E. Manzer, J. Am. Chem. Soc. 1999, 121, 3035 ± 3038; b) A. Gong,
Q. Fan, Y. Chen, H. Liu, C. Chen, F. Xi, J. Mol. Catal. A 2000, 159,
225 ± 232; Sc-poly(amidoamine) (Sc-PAMAM) dendrimers for catal-
ysis of the Diels ± Alder and aldol reactions: M. T. Reetz, D. Giebel,
Angew. Chem. 2000, 112, 2614 ± 2617; Angew. Chem. Int. Ed. 2000, 39,
2498 ± 2501; nickel(ii) complexes for Kharasch additions: G. van Ko-
ten, J. T. B. H. Jastrzebski, J. Mol. Catal. A 1999, 146, 317 ± 323;
palladium(ii) moieties for hydrogenation: T. Mizugaki, M. Ooe, K.
Ebitani, K. Kaneda, J. Mol. Catal. 1999, 145, 329 ± 333.
[11] F. Zeng, S. C. Zimmerman, J. Am. Chem. Soc. 1996, 118, 5326 ± 5327;
O. Mitsunobu, Synthesis 1981, 1, 1 ± 28.
[12] S. C. Zimmerman, F. Zeng, D. E. C. Reichert, S. V. Kolotuchin,
Science 1996, 271, 1095 ± 1098.
[13] L. Claisen, O. Eisleb, Liebigs Ann. Chem. 1913, 401, 107.
[14] H.-T. Chang, C.-T. Chen, T. Kondo, G. Siuzdak, K. B. Sharpless,
Angew. Chem. 1996, 108, 202 ± 206; Angew. Chem. Int. Ed. Engl. 1996,
35, 182 ± 186.
1
[15] Dendrimer purity was estimated to be >95% by both H NMR and
SEC analysis. All compounds had spectroscopic properties in accord
with the proposed structures.
[16] T. A. Kirkland, R. H. Grubbs, J. Org. Chem. 1997, 62, 7310 ± 7318.
[17] H. D. Maynard, R. H. Grubbs, Tetrahedron Lett. 1999, 40, 4137 ± 4140.
[18] Data presented in the Supporting Information.
[19] M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs, Org. Lett. 1999, 1, 953 ±
956.
Â
[20] G. Lꢁabbe, B. Forier, W. Dehaen, Chem. Commun. 1996, 2143 ± 2144.
[4] Selected examples: nitro group reduction: G. R. Newkome, V. V.
Narayanan, L. A. Godínez, J. Org. Chem. 2000, 65, 1643 ± 1649; amine
quaternization: a) Y. Pan, W. T. Ford, Macromolecules 1999, 32,
1966
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