Constitution, configuration, and the optical activity of chiral dendrimers

Article abstract of DOI:10.1021/ja970150i

Three series of zeroth to second generation chiral dendrimers, 7-9, 10-12, and 13-15, were prepared by convergent methods using chiral, nonracemic AB₂ monomers 1, 2, and 3, respectively. Chiroptical data revealed a significant change in molar r

Full text of DOI:10.1021/ja970150i

VOLUME 120, NUMBER 8
MARCH 4, 1998
© Copyright 1998 by the
American Chemical Society
Constitution, Configuration, and the Optical Activity of Chiral
Dendrimers
James R. McElhanon and Dominic V. McGrath*
Contribution from the Department of Chemistry, UniVersity of Connecticut,
Storrs, Connecticut 06269-4060
ReceiVed January 17, 1997
Abstract: Three series of zeroth to second generation chiral dendrimers, 7-9, 10-12, and 13-15, were prepared
by convergent methods using chiral, nonracemic AB2 monomers 1, 2, and 3, respectively. Chiroptical data
revealed a significant change in molar rotation per subunit ([Φ]D/n) as dendrimer generation increased for
dendrimers 7-9 and 10-12, but not for dendrimers 13-15, a possible indication of chiral conformational
order in the former two series of dendrimers, but not in the last. However, the optical activities ([Φ]D) of
low-molecular-weight model compounds 16 (+262) and 17 (+122), prepared to simulate different regions of
the dendrimer structure, suggest that as generation size increases slight constitutional changes have a strong
effect on the chiroptical properties of the dendrimer subunits. Using the [Φ]D values of these and other (18-
23) low-molecular-weight model compounds, we calculated [Φ]D values for dendrimers 7-15 that agree within
14% of the observed values. Agreement between the optical activity of the model compounds and the dendrimers
leads to the conclusion that the conformational equilibria of the dendrimer subunits are not perturbed relative
to those of the model compounds. Therefore, we interpreted the change in [Φ]D/n as dendrimer generation
increased for dendrimers 7-12 to be based solely on constitutional changes in the dendritic structure and not
chiral conformational order.
Introduction
leading to applications in separation, catalysis, and sensor
technology. While much is known of the effects of stereoregu-
larity4 and chirality5 on the conformation of linear macromol-
ecules,6 research on the effect of configurational stereochemistry
on the conformational order of chiral dendritic macromolecules
is still progressing.3
Asymmetric conformational order, or macromolecular asym-
metry,7 in linear macromolecules8 is crucial for their application
to, for example, chiral chromatographic separations,9 preparation
Dendrimers, well-defined macromolecules with highly branched
structures, have attracted increasing interest.1 However, while
the diversity of dendritic structures reported has grown quite
rapidly, corresponding studies on the conformation of dendrim-
ers have been more limited.2 The conformation of chiral
dendritic macromolecules3 is of particular interest because these
materials have the potential for enantioselective clathration,
(1) (a) Zheng, F.; Zimmerman, S. C. Chem. ReV. 1997, 97, 1681-1712.
(b) Tomalia, D. A.; Esfand, R. Chem. Ind. (London) 1997, 416-420. (c)
Fre´chet, J. M. J. Science 1994, 263, 1710-1715. (d) Newkome, G. R.;
Moorefield, C. N.; Vo¨gtle, F. Dendritic Molecules. Concepts, Syntheses,
PerspectiVes; VCH: Cambridge, 1996.
(2) For the distinctions among constitution, configuration, and conforma-
tion used here, see: Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic
Compounds; Wiley: New York, 1994; pp 18-24.
(3) For an excellent review of chirality and dendrimers, see: Peerlings,
H. W. I.; Meijer, E. W. Chem. Eur. J. 1997, 3, 1563-1570.
(4) Vogl, O.; Jaycox, G. D. Polymer 1987, 28, 2179-2182.
(5) Green, M. M.; Peterson, N. C.; Sato, T.; Teramoto, A.; Cook, R.;
Lifson, S. Science 1995, 268, 1860-1866.
(6) Farina, M. Top. Stereochem. 1987, 17, 1.
(7) Vogl, O.; Jaycox, G. D. CHEMTECH 1986, 698-703.
S0002-7863(97)00150-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 02/11/1998

1648 J. Am. Chem. Soc., Vol. 120, No. 8, 1998
McElhanon and McGrath
of cholesteric liquid crystals,5 and the development of organic
materials for nonlinear optics.10 Likewise, the utility of
dendrimers, as well as other well-defined macromolecules, will
depend on our ability to drive their properties and function
through their 3-dimensional organization.11 It is important,
therefore, to delineate the factors which govern macromolecular
asymmetry in dendrimers as well as standard methods for
assessment of dendritic conformational order.
conformational order in a distal portion of the molecule.22 In
the second study, dendrimers with fully chiral branches were
observed to undergo changes in the sign of optical rotation on
increasing generation, a possible indication of conformationally
chiral substructures in the dendrimer branches.15
The conclusions in these studies are largely based on the
assumption, similar to that made in the study of linear
macromolecules,6 that the contribution of a chiral subunit to
the overall optical activity of a dendrimer is relatively inde-
pendent of the subunit’s position within the structure. Hence,
information concerning polymer conformation can be obtained
by comparing the optical activity of the polymer with that of a
single low-molecular-weight model compound.23-25 Any dis-
parity in optical activity is attributed to different positions of
the respective conformational equilibria for the model compound
and the monomeric units of the polymer.23,26 In a recent
chiroptical study of chiral dendrons prepared convergently from
nonracemic, synthetic AB2 monomers 1-3,27 we illustrated that
Efforts by Newkome,12 Meijer,13,14 Seebach,15-17 Chow,18,19
and Sharpless20 have established that macromolecular asym-
metry is, at this point, rare in dendrimers.21 Both Newkome
and Meijer have shown that chiral terminal groups have little
to no effect on macromolecular asymmetry with too densely
packed a surface, in concert with hydrogen bonding, actually
resulting in destruction of optical activity.12,13 Current evidence
also indicates that dendrimers with fully chiral branches based
on tartaric acid subunits19 or chiral ethers20 do not adopt chiral
conformations, the observed rotations being the sum of the
rotations for the individual chiral subunits. Two reports by
Seebach and co-workers, however, present chiroptical data that
suggests chiral conformations. In the first, dendrimers with
chiral central cores and achiral branches exhibit anomalous
chiroptical behavior depending on the size (generation) of the
achiral branch.16,17 This study is significant in that it suggests
that a single chiral subunit, in this case the core, can impart
(8) Macromolecular asymmetry in linear polymers can be induced by
either (i) stereogenic centers in the main or side chains or (ii) conformational
constraints inherent in the primary structure. Typical examples of the former
class of materials are polypeptides and polysaccharides. Examples of the
latter class are polychloral, poly(triphenylmethyl methacrylate), poly-
(isocyanides), and poly(isocyanates). See (a) Poland, D.; Scheraga, H. A.
Theory of Helix-Coil Transitions in Biopolymers; Academic Press: New
York, 1970. (b) Corley, L. S.; Vogl, O. Polym. Bull. 1980, 3, 211-217. (c)
Okamoto, Y.; Suzuki, K.; Ohta, K.; Hatada, K.; Yuki, H. J. Am. Chem.
Soc. 1979, 101, 4763-4765. (d) van Beijen, A. J. M.; Nolte, R. J. M.;
Naaktgeboren, A. J.; Zwikker, J. W.; Drenth, W.; Hezemans, A. M. F.
Macromolecules 1983, 16, 1679-1689. (e) Green, M. M.; Reidy, M. P.;
Johnson, R. J.; Darling, G.; O’Leary, D. J.; Willson, G. J. Am. Chem. Soc.
1989, 111, 6452-6454.
(9) For leading references, see: (a) Okamoto, Y.; Nakano, T. Chem. ReV.
1994, 94, 349-372. (b) A Practical Approach to Chiral Separations by
Liquid Chromatography; Subramanian, G., Ed.; VCH: New York, 1994;
p 405.
(10) (a) Kapitza, H.; Poths, H.; Zentel, R. Makromol. Chem., Makromol.
Symp. 1991, 44, 117-125. (b) Firestone, M. A.; Park, J.-W.; Minami, N.;
Ratner, M. A.; Marks, T. J.; Lin, W.; Wong, G. K. Macromolecules 1995,
28, 2247-2259.
this assumption for dendritic molecules has a distinct limita-
tion.28 Subunits closer to the core of a dendrimersor focal point
of a dendronsare different in constitution from subunits nearer
the periphery, necessitating the use of several low-molecular-
weight model compounds to account for the optical activity of
the entire dendritic structure. Thus, anomalies in optical activity
of the dendrons with increasing generation were shown to arise
from the nature of the dendritic structure (constitution), not chiral
conformations or perturbation of conformational equilibria.28
In the present paper, we report a chiroptical study of the
corresponding chiral dendrimers and an investigation of the role
of molecular constitution on their optical activity.29 The
dendrimers reported here are part of our recently initiated
program to develop strategies for the incorporation of asym-
metric units into dendrimers,28-31 which aims toward the
development of materials active for the selective clathration of
(11) Stupp, S. I. J. Macromol. Sci.sChem. 1991, A28, 1255-1265.
(12) Newkome, G. R.; Lin, X.; Weis, C. D. Tetrahedron: Asymmetry
1991, 2, 957-960.
(13) Jansen, J. F. G. A.; Peerlings, H. W. I.; de Brabander-van den Berg,
E. M. M.; Meijer, E. W. Angew. Chem., Int. Ed. Engl. 1995, 34, 1206-
1209.
(22) For other examples of dendrimers with stereogenic cores and achiral
branches, see: (a) Kremers, J. A.; Meijer, E. W. J. Org. Chem. 1994, 59,
4262-4266. (b) Struijk, M. P.; Peerlings, H. W. I.; Meijer, E. W. Am. Chem.
Soc., DiV. Polym. Chem., Preprints 1996, 37(2), 497-498. (c) Peerlings,
H. W. I.; Trimbach, D.; Meijer, E. W. Polym. Mater. Sci. Eng. 1997, 77,
73-74.
(23) Pino, P.; Salvadori, P.; Chiellini, E.; Luisi, P. L. Pure Appl. Chem.
1968, 16, 469-490.
(24) Low-molecular-weight model compounds are no longer appropriate
when the optically active electronic transitions of the polymer are modified
by mutual interactions among the chromophoric systems existing in different
monomeric units, e.g., in polypeptides or polyacetylenes. See previous
reference.
(14) Jansen, J. F. G. A.; de Brabander-van den Berg, E. M. M.; Meijer,
E. W. Recl. TraV. Chim. Pays-Bas 1995, 114, 225-230.
(15) Murer, P.; Seebach, D. Angew. Chem., Int. Ed. Engl. 1995, 34,
2116-2119.
(16) Seebach, D.; Lapierre, J.-M.; Skobridis, K.; Greivelkinger, G. Angew.
Chem., Int. Ed. Engl. 1994, 33, 440-442.
(17) Seebach, D.; Lapierre, J.-M.; Greiveldinger, G.; Skobridis, K. HelV.
Chim. Acta 1994, 77, 1673-1688.
(25) For a recent example, see: Coates, G. W.; Waymouth, R. M. J.
Am. Chem. Soc. 1991, 113, 6270.
(18) Chow, H.-F.; Mak, C. C. Pure Appl. Chem. 1997, 69, 483-488.
(19) Chow, H.-F.; Mak, C. C. J. Chem. Soc., Perkin Trans. 1 1994,
2223-2228.
(26) Perturbation of the conformational equilibria can imply a helical
sense of the main chain. However, additional data is usually warranted before
such a conclusion can be drawn. See: Ciardelli, F. In Encyclopedia of
Polymer Science and Engineering; Mark, H. F., Bikales, N. M., Overberger,
C. G., Menges, G., Kroschwitz, J. I., Eds.; Wiley: New York, 1985; Vol.
10, pp 463-493.
(27) McElhanon, J. R.; Wu, M.-J.; Escobar, M.; Chaudhry, U.; Hu, C.-
L.; McGrath, D. V. J. Org. Chem. 1997, 62, 908-915.
(28) McElhanon, J. R.; Wu, M.-J.; Escobar, M.; McGrath, D. V.
Macromolecules 1996, 29, 8979-8982.
(29) For a preliminary account see: McElhanon, J. R.; McGrath, D. V.
Am. Chem. Soc., DiV. Polym. Chem., Preprints 1997, 38(1), 278-279.
(30) McElhanon, J.; Wu, M.-J.; Escobar, M.; McGrath, D. V. Am. Chem.
Soc., DiV. Polym. Chem., Preprints 1996, 37(2), 495-496.
(20) Chang, H.-T.; Chen; C.-T.; Kondo, T.; Siuzdak, G.; Sharpless, K.
B. Angew. Chem., Int. Ed. Engl. 1996, 35, 182-186.
(21) The majority of chiral dendrimers have consisted of amino acid,
carbohydrate, and other naturally derived building blocks, but only those
with reported chiroptical properties are mentioned here. For other examples,
see ref 3 and (a) Chapman, T. M.; Hillyer, G. L.; Mahan, E. J.; Shaffer, K.
A. J. Am. Chem. Soc. 1994, 116, 11195-11196. (b) Page´, D.; Aravind, S.;
Roy, R. Chem. Commun. 1996, 1913-1914. (c) Ranganathan, D.; Kurur,
S. Tetrahedron Lett. 1997, 38, 1265-1268. (d) Mulders, S. J. E.; Brouwer,
A. J.; Liskamp, R. M. J. Tetrahedron Lett. 1997, 38, 3085-3088. (e)
Jayaraman, N.; Nepogodiev, S. A.; Stoddart, J. F. Chem. Eur. J. 1997, 3,
1193-1199.

Chiral Dendrimers
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1649
small guest molecules. Hence, these materials contain not only
chiral, nonracemic subunits in the interior for shape selectivity,
but also vicinal diol moieties, here in protected form, capable
of specific interactions with encapsulated guests.32 Once
unmasked in the final dendrimer, the vicinal diol moieties should
be capable of engaging in hydrogen bonding interactions with
small clathrated guest molecules33 or acting as chiral auxilia-
ries34,35 or ligands for transition metals36 in catalytic asymmetric
synthesis.37,38
considered the molar rotation per chiral subunit ([Φ]D/n, Figure
2). From these data there was revealed a significant change in
[Φ]D/n as dendrimer generation increased for dendrimers 7-9
and 10-12, but not for dendrimers 13-15, a possible indication
of chiral conformational order in the former two series of
dendrimers, but not in the last. Indeed, the closer packing of
subunits in dendrimers 7-12, relative to that in 13-15,40
suggests that intramolecular communication between chiral
subunits might result in conformational order in the former
dendrimers, but not the latter.
Results and Discussion
However, slight changes in constitution, rather than confor-
mation, could also be responsible for the observed changes in
optical activity. Indeed, the optical activities of neither
monomer units 1 and 2, nor zero generation monodendrons 4
and 5, correlate with the observed optical activities of the
corresponding dendrimers (cf. Table 1, column 5 and Table 2,
column 4). Considering the chiral dioxolane rings in the
subunits of 7-12, we noted that those in the zeroth generation
shell, adjacent to the central linker, are constitutionally dissimilar
to those in the outer generational shells. The former dioxolane
rings are flanked by benzoyloxymethyl and bis(benzyloxy)-
phenyl groups, while the latter are flanked by phenoxymethyl
and bis(benzyloxy)phenyl groups. In contrast, the chiral diox-
olane rings in the subunits of dendrimers 13-15 are all in a
more constant environment, flanked by 4-(oxymethyl)phenyl
and bis(benzyloxy)phenyl groups throughout the structure.
Accordingly, compounds 16 and 17 (Chart 3) were prepared
as low-molecular-weight model compounds for the subunits of
dendrimers 7-9. While compound 16 models subunits in the
outer shells, including those on the periphery, 17 models
subunits directly attached to the central linker. As can be seen
from polarimetry data in Table 3, small changes in constitution
distal to the dioxolane ring do indeed greatly affect the optical
activity of the model compounds. The simple replacement of
a proton with a phenyl group at the focal point of zeroth
generation dendron 4 ([Φ]D ) -17) to give phenyl ether 16
(+262) results in a change in sign of the [Φ]D value. In
addition, the [Φ]D value of phenyl ether 16 (+262) is more
than twice that of benzoyl derivative 17 (+122).
The significantly higher [Φ]D value of 16, relative to 17,
suggests that the addition of subunits of this approximate
constitution to a dendritic structure consisting of subunit 17,
such as zeroth generation dendrimer 7, would result in a higher
overall [Φ]D per subunit for the larger structure, as was observed
for first generation dendrimer 8 (Figure 2). Indeed, using the
individual [Φ]D values obtained for 16 and 17, calculated molar
rotations for dendrimers 7-9 agree within 15% of the observed
values (Table 1, column 6). Interestingly, the optical activities
of dendrimers 10-12 are also successfully modeled with low-
molecular-weight compounds 16 and 17 within 16% of the
observed values (Table 1, column 6), indicating that the change
in constitution from 3,5- to 3,4-linkages does not significantly
Zeroth, first, and second generation dendrimers 7-15 (Charts
1 and 2) were prepared from chiral, nonracemic AB2 monomers
1-327 via the corresponding monodendrons.28 The monoden-
drons were allowed to react with C3-symmetric central linker
1,3,5-benzenetricarbonyl trichloride in refluxing benzene or
toluene under Dean-Stark conditions (eq 1).20 Dendrimers
(1)
7-15 were isolated as colorless, glassy solids in 37-80% yield
after purification by flash chromatography on silica gel. The
chiral vicinal diol unit of each dendritic subunit in 7-15, masked
as an acetonide derivative for synthetic purposes, was readily
introduced during the preparation of 1-3 by the asymmetric
dihydroxylation reaction.27,39 All dendrimers were characterized
1
by H/13C NMR, MALDI MS, and combustion analysis for
confirmation of primary structure. 13C NMR analysis was
particularly useful, especially for nonsymmetrically 3,4-linked
dendrimers 10-12, since overlapping resonances limited the
utility of 1H NMR. Full assignment of all 13C NMR spectra of
7-15 was possible using the information provided by chemical
shift calculations and resonance intensity, which confirmed
generational growth (Figure 1).
Specific and molar rotations for dendrimers 7-15 are reported
in Table 1 (columns 4 and 5). In initial comparisons of optical
activity of the dendrimers as a function of generation, we
(31) McGrath, D. V.; Wu, M.-J.; Chaudhry, U. Tetrahedron Lett. 1996,
37, 6077-6080.
(32) For dendrimers with specific recognition sites, see: (a) Newkome,
G. R.; Woosley, B. D.; He, E.; Moorefield, C. N.; Gu¨ther, R.; Baker, G.
R.; Escamilla, G. H.; Merrill, J.; Luftmann, H. Chem. Commun. 1996, 2737-
2738. (b) Baars, M. W. P. L.; Meijer, E. W. Polym. Mater. Sci. Eng. 1997,
77, 149-150.
(33) (a) Hanessian, S.; Simard, M.; Roelens, S. J. Am. Chem. Soc. 1995,
117, 7630-7645. (b) Ermer, O.; Eling, A. J. Chem. Soc., Perkin Trans. 2
1994, 925-944.
(34) Tomioka, K.; Shindo, M.; Koga, K. J. Am. Chem. Soc. 1989, 111,
8266-8268.
(35) Rosini, C.; Fansini, L.; Pini, D.; Salvadori, P. Tetrahedron:
Asymmetry 1990, 1, 587-588.
(36) For dendrimers with metal-binding sites, see ref 1d, Chapter 8,
and: (a) Bhyrappa, P.; Young, J. K.; Moore, J. S.; Suslick, K. S. J. Am.
Chem. Soc. 1996, 118, 5708-5711. (b) Tzalis, D.; Tor, Y. Tetrahedron
Lett. 1996, 37, 8293-8296. (c) Bosman, A. W.; Schenning, A. P. H. J.;
Janssen, R. A. J.; Meijer, E. W. Chem. Ber. 1997, 130, 725-728. (d)
Newkome, G. R.; Gross, J.; Moorefield, C. N.; Woosley, B. D. Chem.
Commun. 1997, 515-516. (e) Chow, H. F.; Mak, C. C. J. Org. Chem. 1997,
62, 5116-5127. (f) Bardaji, M.; Kustos, M.; Caminade, A.-M.; Majoral,
J.-P.; Chaudret, B. Organometallics 1997, 16, 403-410 and references
therein. (g) Issberner, J.; Vo¨gtle, F.; De Cola, L.; Balzani, V. Chem. Eur.
J. 1997, 3, 706-712. (h) Constable, E. C. Chem. Commun. 1997, 1073.
(37) Sawamura, M.; Ito, Y. In Catalytic Asymmetric Synthesis; Ojima,
I., Ed.; VCH: New York, 1993; pp 367-388.
(40) Monte Carlo conformational searches (Macromodel 5.0) were carried
out on model subunits A and B, derived from monomers 1 and 3,
respectively, and convergence was found on a series of low-energy
conformations for each subunit. The distance between the “focal” and
“branching” oxygens of the two model subunits in these low-energy
conformations exhibited the ranges shown below.
(38) Devine, P. N.; Oh, T. J. Org. Chem. 1992, 57, 396-399.
(39) Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. ReV.
1994, 94, 2483-2547.

1650 J. Am. Chem. Soc., Vol. 120, No. 8, 1998
McElhanon and McGrath
Chart 1
affect the optical activity of the subunits in this system.
Individual model compounds with a 3,4-substitution pattern were
not prepared.
Low-molecular-weight model compounds which more ac-
curately match the constitution of dendrimers 7-9 were also
prepared. Model compounds 18 and 19 were prepared as
potential improvements over 17 and 16, respectively. It was
anticipated that the strong electronic influence of the additional
ester groups in 18 and the m-methoxy group in 19 might affect
the observed optical activities. Both 18 (+134) and 19 (+271)
exhibit slightly different [Φ]D values than 17 (+122) and 16
(+262), respectively, and result in a marginal increase in
accuracy in calculating the rotation of first and second generation
dendrimers 8, 9, 11, and 12 (Table 1, columns 7 and 8). Model
This quite general agreement between the optical activity of
the model compounds and the dendrimers leads to the conclusion
that the conformational equilibria of the dendrimer subunits are
not perturbed relative to those of the model compounds.23
Therefore, we interpret the chiroptical changes in dendrimers
7-12 as dendrimer generation increases to be based solely on
constitutional changes in the dendritic structure and not chiral
conformational order.

Chiral Dendrimers
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1651
Chart 2

1652 J. Am. Chem. Soc., Vol. 120, No. 8, 1998
McElhanon and McGrath
interactions.42 The magnitudes of the Cotton effects for all
compounds are proportional to the number of chromophores
contained.
That we can accurately predict the optical activity of
dendrimers 7-12 based on two low-molecular-weight model
compounds and dendrimers 13-15 with one low-molecular-
weight model compound indicates that the conformational
equilibria for the model compound(s) and the monomeric units
of the dendrimers are similar. This conclusion might also
suggest that (a) few conformations are available to the subunits
and model compounds and/or (b) the different available
conformations have similar optical properties. We propose that
both (a) and (b) are most likely the case here. The subunits in
dendrimers 7-15 are indeed fairly rigid. The acetonide
protecting moiety restricts rotation about the bond between the
asymmetric centers and precludes any conformations in which
the oxygen atoms attached to the asymmetric centers are
anything but synperiplanar. As a result, while the conformation
of the subunits with respect to each other could potentially vary,
the conformation of the subunits themselves, and their individual
optical activities, is relatively invariable. In addition, the
dependence of the rotations of 7-15 on temperature were
measured and found to be <0.5% per °C over the range 10-
25 °C.43
Figure 1. 13C NMR (CDCl3) spectrum of second generation dendrimer
9. Insets show regions where the 4:2:1 ratio of nuclei in a second
generation dendrimer with a branching ratio of 2:1 are evident.
compound 20b was prepared from first generation monodendron
20a.28 The relative [Φ]D values of 20a (+625) and 20b (+837)
mimic the same positive trend also seen for compounds 4 (-17)
and 16 (+262) on replacement of a proton with a phenyl group
at the focal point of the dendron (vide supra). Using the [Φ]D
value of 20b, the optical activities of second generation
dendrimers 9 and 12 are calculated within 10% (Table 2, column
8). An oligomeric model compound, 20b could contain the
same possible interactions between chromophoric systems as
in the dendrimers. That its optical activity can be also predicted
with reasonable accuracy (+804, within 3.9% using models 16
and 19) is further evidence for the lack of ordered conformation
in this system.23
In dendrimers with more flexible subunits, e.g., 7-15 after
deprotection of the vicinal diol moieties, analysis using low-
molecular-weight model compounds, as presented in this paper,
is more likely to reveal perturbation of conformational equilibria.
Two other systems in the literature are of interest in this regard.
First, the work of Seebach and co-workers on fully chiral
dendrimers with subunits of type 24a,b revealed [Φ]D values
The constant optical activity of dendrimers 13-15 in relation
to number of subunits implies that the conformational equilibria
of the subunits in these dendrimers is similar to that of a single
low-molecular-weight model compound. We found it curious,
however, that the average [Φ]D/n value for 13-15 (ca. +540)
was significantly different than the [Φ]D value of zeroth
generation dendron 6 (+468). Hence, we prepared model
compounds 21-23, analogous to 16-18, to investigate the
influence of constitutional environment on subunit optical
activity in these dendrimers. Substitution distal to the chiral
dioxolane moiety again affects the [Φ]D values, although not
as dramatically as above. The [Φ]D values of 21-23 are all
rather similar (Table 3, column 4), and quite close to the average
[Φ]D/n value for 13-15. Calculated [Φ]D/n values for 13-15
using these compounds now agree within 6.0% of the observed
values (Table 1, columns 6 and 7), but use of the different model
compounds here is not as critical as in the above system.
Actually, using 21, 22, or 23 as the sole model compound for
dendrimers 13-15 results in calculated [Φ]D values all within
8.4% of those observed.
that change with generation.15 The preparation of several low-
molecular-weight model compounds and their [R]D values were
reported, although a detailed analysis using [Φ]D values was
not undertaken;44 it remains unclear whether the observed optical
activities in this system reflect contributions from perturbed
conformational equilibria. What also remains to be elucidated
is the nature of the intriging chiroptical anomalies observed in
dendrimers with chiral cores of type 24b and achiral branches.16,17
While suggestive of conformational order in the achiral branches,
these observations may simply reflect a perturbation of the
conformational equilibria of the flexible central linker as a
function of achiral branch size. Second, in the work of Chow
and co-workers, while the [Φ]D values of a series of tartrate-
derived dendrimers and dendrons were roughly proportional to
the number of (L)- and (D)-tartrate units (25a and b) in the
structure,18,19 CD data suggested that subunits in inner layer
of the first generation dendrimers have different chiroptical
properties than those in the outer layer.18 Again, it remains
Circular dichroism (CD) and absorption spectra have been
obtained for all dendrimers reported. Representative examples
are shown in Figure 3. All exhibit positive Cotton effects
throughout the absorption range. The null at ca. 203 nm arises
from a weak excitonic coupling also evident in the CD spectra
of monomeric units.41 No additional exciton coupling is
observed. The absence of excitonic coupling in the CD traces
of the dendrimers can be interpreted as the dendrimer arms in
solution adopting no prevailing conformation suitable for exciton
(41) McGrath, D. V., et al. Unpublished results.
(42) Altomare, A.; Ciardelli, F.; Tirelli, N.; Solaro, R. Macromolecules
1997, 30, 1298-1303.
(43) See ref 2, p 1076.
(44) The best evidence for preferred conformations in Seebach’s den-
drimers may be, in fact, spectacular cases of diastereoselectivity observed
in coupling reactions, representing molecular recognition events among
chiral dendritic molecules. See: Murer, P. K.; Lapierre, J.-M.; Greiveldinger,
G.; Seebach, D. HelV. Chim. Acta 1997, 80, 1648-1681.

Chiral Dendrimers
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1653
Table 1. Observed and Calculated Chiroptical Data for Dendrimers 7-15
observeda
calculatedb
d
e
classc
gener.
FW
[R]26
[Φ]D
[Φ]D (% error)f
[Φ]D (% error)g
[Φ]D (% error)h
[Φ]D (% error)i
D
3,5-Cinn
0 (7)
1 (8)
2 (9)
0 (10)
1 (11)
2 (12)
0 (13)
1 (14)
2 (15)
1417.61
3291.81
7040.19
1417.61
3291.81
7040.19
1645.91
3976.69
8638.24
+25.1
+66.9
+84.5
+26.7
+67.8
+85.8
+97.1
+125.5
+129.3
+356
+2204
+5948
+379
+2232
+6039
+1598
+4992
+11172
+366 (2.8)
+1938 (12)
+5082 (15)
+366 (3.4)
+1938 (13)
+5082 (16)
+1623 (1.6)
+5031 (0.8)
+11847 (6.0)
+402 (13)
+1974 (10)
+5118 (14)
+402 (6.1)
+1974 (12)
+5118 (15)
+1524 (4.6)
+4932 (1.2)
+11748 (5.2)
+2028 (8.0)
+5280 (11)
+5424 (8.8)
+5424 (10)
3,4-Cinn
3,5-Stil
+2028 (9.1)
+5280 (13)
a All rotations measured in CH2Cl2. b Arithmatic sum of the [Φ]D values of the appropriate model compounds. c Dendrimer class name derives
from the linkage geometry (3,4 or 3,5) and the subunit synthetic presursor (stilbene or cinnamate derivatives). d Specific rotation in 10-1 deg cm2
-1
g-1
.
e Molar rotation in 10 deg cm2 mol
.
f Calculated using model compounds 16 and 17 (Cinn) or 21 and 22 (Stil). g Calculated using model
compounds 16 and 18 (Cinn) or 21 and 23 (Stil). h Calculated using model compounds 18 and 19. iCalculated using model compounds 18 and 20b.
Chart 3
Figure 2. Molar optical rotations (Φ) per chiral unit (n) for zeroth (n
) 3), first (n ) 9), and second (n ) 21) generation dendrimers 7-15.
3,5-Cinn ) 7-9; 3,4-Cinn ) 10-12; 3,5-Stil ) 13-15.
Table 2. Chiroptical Data for Monomer Units and Zeroth
Generation Monodendrons27
a,b
c
cmpd
FW
[R]26
[Φ]D
D
1
2
3
4
5
6
240.26
240.26
316.35
420.50
420.50
496.60
-7.08
-18.0d
+122
-4.05
-8.31
+94.2
-17.0
-43.2
+355
-17.0
-34.9
+468
a Specific rotation in 10-1 deg cm2 g-1
.
b 1-3 in EtOH, 4-6 in
-1
CH2Cl2. c Molar rotation in 10 deg cm2 mol
in ref 27.
.
d Incorrectly reported
unclear whether this difference is constitutionally or confor-
mationally based.
Summary and Conclusion
Table 3. Chiroptical Data for Model Compounds
We have prepared and explored the chiroptical properties of
three series of chiral dendrimers. Although we observed
dramatic changes in optical activity with increasing generation
in two of these series, we have determined that chiral conforma-
tions do not contribute to this enhancement. Rather, slight
constitutional changes appear to have a strong effect on the
chiroptical properties of these dendrimers as generation size
increases, as revealed by the demonstrated effect of molecular
constitution on the optical activity of several low-molecular-
weight model compounds. In exploring dendrimer conformation
using chiroptical properties, we found it necessary to consider
the immediate constitutional environment of the chiral subunits
in order to assess the relative contributions of constitution,
configuration, and conformation to optical activity.
a,b
c
cmpd
FW
[R]26
[Φ]D
D
16
17
18
19
20a
20b
21
22
23
496.60
524.61
668.74
526.63
1045.24
1121.33
572.70
600.71
744.84
+52.7
+23.2
+20.0
+51.4
+59.8
+74.6
+99.2
+90.1
+68.2
+262
+122
+134
+271
+625
+837
+568
+541
+508
a Specific rotation in 10-1 deg cm2 g-1
.
b All in CH2Cl2. c Molar
rotation in 10 deg cm2 mol
.
-1
comparing the chiroptical properties of the dendrimers with
those of appropriate low-molecular-weight model compounds,
similar to the approach used in the study of linear polymers.23
Although two different model compounds, at most, were
In general terms, we conclude that it is indeed possible to
gain information on the conformation of chiral dendrimers by

1654 J. Am. Chem. Soc., Vol. 120, No. 8, 1998
McElhanon and McGrath
3H), 1.53 (s, 9H), 1.49 (s, 9H); 13C NMR: δ 164.5, 160.2, 139.7, 136.6,
134.9, 131.0, 128.5, 128.0. 127.5, 110.1, 105.6, 101.9, 80.8, 79.5, 70.1,
64.0, 27.0; MS (MALDI) m/z 1439.3 (M + Na), 1456.3 (M + K);
[R]26 ) +25.1 (c ) 0.62, CH2Cl2). Anal. Calcd for C87H84O18: C,
D
73.71; H, 5.97. Found: C, 73.81; H, 6.26.
3,5-[G1]-Cinn Dendrimer (8): colorless glassy solid, 80% (SiO2,
9:1 methylene chloride-ethyl acetate); 1H NMR: δ 8.83 (s, 3H), 7.36-
7.25 (m, 60H), 6.61 (d, J ) 2.2 Hz, 12 H), 6.57 (d, J ) 2.2 Hz, 6H),
6.52 (t, J ) 2.2 Hz, 6H), 6.40 (t, J ) 2.2 Hz, 3H), 4.96 (s, 24 H), 4.82
(d, J ) 8.2 Hz, 6H), 4.70 (d, J ) 8.6 Hz, 3H), 4.50 (br d, J ) 11.5 Hz,
3H), 4.39 (dd, J ) 12.3, 5.7 Hz, 3H), 4.10-4.00 (m, 21H), 1.52-1.45
(m, 54H); 13C NMR: δ 164.5, 160.2, 160.0, 140.3, 139.8, 136.7, 134.9,
130.9, 128.5, 128.0, 127.5, 110.1, 109.9, 105.7, 101.8, 101.6, 81.5,
80.9, 79.4, 79.1, 70.1, 67.2, 63.8, 27.1, 27.04, 27.01; MS (MALDI)
3211.9 (M + Na), 3229.5 (M + K); [R]26D ) +66.9 (c ) 0.79, CH2Cl2).
Anal. Calcd for C201H204O42: C, 73.34; H, 6.25. Found: C, 73.66;
H, 6.61.
3,5-[G2]-Cinn Dendrimer (9): colorless glassy solid, 45% (SiO2,
9:1 methylene chloride-ethyl acetate); 1H NMR: δ 8.87 (s, 3H), 7.34-
7.22 (m, 120H), 6.59 (d, J ) 2.2 Hz, 24H), 6.57 (d, J ) 2.0 Hz, 12 H),
6.51-6.50 (m, 18H), 6.42 (br, 3H), 6.37 (br t (unresolved), 6H), 4.94
(s, 48H), 4.83 (d, J ) 8.4 Hz, 6H), 4.80 (d, J ) 8.1 Hz, 12H), 4.69 (d,
J ) 8.4 Hz, 3H), 4.51-4.48 (br, 3H), 4.40-4.35 (br, 3H), 4.06-3.96
(m, 57H), 1.55-1.44 (m, 126H); 13C NMR: δ 164.6, 160.12, 160.10,
160.0, 140.4, 140.3, 139.7, 136.6, 131.0, 128.5, 128.0, 127.5, 110.1,
109.93, 109.87, 105.9, 105.8, 105.6, 101.7, 101.3, 81.6, 81.4, 80.8,
79.4, 79.1, 70.1, 67.1, 27.0; MS (MALDI) 7065.3 (M + Na), 7082.5
Figure 3. CD (top) and UV (bottom) spectra of dendrimers 7-9 in
CH2Cl2.
(M + K); [R]26 ) +84.5 (c ) 0.67, CH2Cl2). Anal. Calcd for
D
necessary and sufficient in our studies, a greater or fewer number
of model compounds may be required in different sys-
temssdendrimers with chiral cores, branching units, and
peripheral units may require three or more low-molecular-weight
model compounds. If perturbation of conformational equilibria
is revealed by a disparity in optical activity, determination of
the exact nature of that perturbation will require additional
information.26
C429H444O90: C, 73.19; H, 6.36. Found: C, 73.36; H, 6.54.
3,4-[G0]-Cinn Dendrimer (10): colorless glassy solid, 70% (SiO2,
1
3:2 petroleum ether-ethyl acetate); H NMR: δ 8.79 (s, 3H), 7.41-
7.25 (m, 30H), 6.96 (br s, 3H), 6.87 (br s, 6H), 5.14 (s, 6H), 5.11 (s,
6H), 4.71 (d, J ) 8.7 Hz, 3H), 4.47 (dd, J ) 12.0, 3.0 Hz, 3H), 4.39
(dd, J ) 12.1, 5.4 Hz, 3H), 4.03 (ddd, J ) 8.7, 5.4, 3.0 Hz, 3H), 1.52
(s, 9H), 1.48 (s, 9H); 13C NMR: δ 164.5, 149.3, 149.1, 137.1, 134.9,
130.9, 130.0, 128.4, 127.82, 127.80, 127.3, 127.2, 119.9, 114.9, 113.9,
109.8, 80.7, 79.5, 71.4, 71.2, 64.0, 27.1, 27.0; MS (MALDI) 439.3 (M
+ Na), 1454.5 (M + K); [R]26 ) +26.7 (c ) 1.46, CH2Cl2). Anal.
D
Experimental Section
Calcd for C87H84O18: C, 73.71; H, 5.97. Found: C, 73.46; H, 6.28.
3,4-[G1]-Cinn Dendrimer (11): colorless glassy solid, 69% (SiO2,
9:1 methylene chloride-ethyl acetate); 1H NMR: δ 8.87 (s, 3H), 7.38-
7.24 (m, 60H), 7.00-6.81 (m, 27H), 5.07-5.05 (m, 24H), 4.91 (d, J
) 8.3 Hz, 3H), 4.88 (d, J ) 8.2 Hz, 3H), 4.73 (d, J ) 8.6 Hz, 3H),
4.50 (dd, J ) 12.4, 2.4 Hz, 3H), 4.40 (dd, J ) 12.1, 5.6 Hz, 3H),
4.16-3.94 (m, 21H), 1.55 (s, 9H), 1.54 (s, 9H), 1.48 (s, 9H), 1.47 (s,
9H), 1.46 (s, 9H), 1.45 (s, 9H); 13C NMR: δ 164.6, 149.33, 149.28,
149.10, 149.07, 149.05, 137.17, 135.0, 131.0, 130.85, 130.80, 130.3,
128.42, 128.40, 127.8, 127.4, 127.3, 127.2, 120.0, 119.93, 119.88, 114.9,
114.5, 113.53, 113.50, 113.0, 109.9, 109.4, 81.83, 81.76, 80.9, 79.1,
79.00, 78.95, 71.3, 71.2, 68.0, 67.8, 63.89, 27.2, 27.1, 27.0, 26.9; MS
(MALDI) 3313.2 (M + Na), 3328.2 (M + K), 3223.1 (M - Bn +
Materials and Methods. Optical rotations and high performance
liquid chromatography (HPLC) were performed on commercially
available instrumentation. All NMR spectra were measured at 400 MHz
1H and 100 MHz 13C and in CDCl3 unless otherwise specified.
Elemental analyses were performed by NuMega Resonance Labs of
San Diego, CA. Mass spectrometry was performed at the University
of Illinois School of Chemical Sciences Mass Spectrometry Labora-
tories. Tetrahydrofuran (sodium-benzophenone), toluene (sodium),
methylene chloride (calcium hydride), and dimethylformamide (3 Å
molecular sieves, reduced pressure) were distilled under N2. Acetone
was dried over crushed 3 Å molecular sieves. Potassium carbonate
(granular, J. T. Baker) was dried at 150 °C at reduced pressure for at
least 12 h and stored in a desiccator. Compounds 1-6,27 20a,28 and
the diethyl ester of benzene-1,3,5-tricarboxylic acid45 were prepared
according to the literature. All other reagents were purchased from
commercial suppliers and used as received. Flash chromatography was
performed by the method of Still et al.46 using silica gel (32-63µ,
Scientific Adsorbants, Inc., Atlanta, GA). Thin-layer chromatography
(TLC) was performed on precoated TLC plates (Silica Gel HLO, F-254,
Scientific Adsorbants, Inc.).
Na); [R]26 ) +67.8 (c ) 1.54, CH2Cl2). Anal. Calcd for
D
C201H204O42: C, 73.34; H, 6.25. Found: C, 73.44; H, 6.48.
3,4-[G2]-Cinn Dendrimer (12): colorless glassy solid, 37% (SiO2,
1
1:1 petroleum ether-ethyl acetate); H NMR: δ 8.90 (s, 3H), 7.36-
7.20 (m, 120H), 7.00-6.76 (m, 63H), 5.06 (s, 24H), 5.04 (s, 24H),
5.00 (d, J ) 8.3 Hz, 3H), 4.97 (d, J ) 8.2 Hz, 3H), 4.90 (d, J ) 9.5
Hz, 6H), 4.88 (d, J ) 8.4 Hz, 6H), 4.73 (d, J ) 8.4 Hz, 3H), 4.52-
4.49 (br d, J ) 11.2 Hz, 3H), 4.41-4.37 (br dd, J ) 12.4, 6.0 Hz,
3H), 4.22-3.91 (m, 57H), 1.56-1.43 (m, 126); 13C NMR: δ 164.6,
149.3, 149.2, 149.10,149.07, 149.05, 149.02,137.2,135.0, 131.1, 131.04,
131.01, 130.90, 130.86, 130.83, 130.3, 128.4, 127.7, 127.34, 127.31,
127.2, 120.12, 120.05, 119.9, 119.8, 114.9, 114.5, 114.4, 113.50, 113.48,
113.47, 113.05, 113.00, 112.89, 112.87, 109.8, 109.5, 109.40, 109.38,
81.9, 81.79, 81.75, 80.88, 80.85, 79.0, 78.9, 78.74, 78.70, 71.3, 71.2,
68.0, 67.8, 67.6, 27.22, 27.20, 27.1, 27.0, 26.9; MS (MALDI) 7066.8
Preparation of Dendrimers 7-15. Dendrimers were prepared from
the corresponding monodendrons28 and benzene-1,3,5-tricarbonyl trichlo-
ride using a procedure adapted from the literature.20
3,5-[G0]-Cinn Dendrimer (7): colorless glassy solid, 76% (SiO2,
1
1:1 petroleum ether-ethyl acetate); H NMR: δ 8.82 (s, 3H), 7.39-
7.26 (m, 30H), 6.61 (d, J ) 2.2 Hz, 6H), 6.53 (t, J ) 2.2 Hz, 3H),
5.02 (s, 12H), 4.74 (d, J ) 8.6 Hz, 3H), 4.54 (dd, J ) 12.1, 2.9 Hz,
3H), 4.41 (dd, J ) 12.1, 5.4 Hz, 3H), 4.09 (ddd, J ) 8.6, 5.4, 2.9 Hz,
(M + Na); [R]26 ) +85.8 (c ) 1.39, CH2Cl2). Anal. Calcd for
D
C429H444O90: C, 73.19; H, 6.36. Found: C, 72.88; H, 6.44.
(45) Leon, J. W.; Kawa, M.; Fre´chet, J. M. J. J. Am. Chem. Soc. 1996,
3,5-[G0]-Stil Dendrimer (13): colorless glassy solid, 76% (SiO2,
118, 8847-8859.
1
1:1 petroleum ether-ethyl acetate); H NMR: δ 8.81 (s, 3H), 7.37-
(46) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923-
2925.
7.21 (m, 42H), 6.53 (t, J ) 2.2 Hz, 3H), 6.44 (d, J ) 2.2 Hz, 6H), 5.34

Chiral Dendrimers
J. Am. Chem. Soc., Vol. 120, No. 8, 1998 1655
(s, 6H), 4.92 (s, 12H), 4.66 (dd, J ) 14.9, 8.4 Hz, 6H), 1.62 (s, 9H),
1.60 (s, 9H); 13C NMR: δ 164.6, 159.9, 139.2, 137.4, 136.7, 135.4,
134.7, 131.2, 128.5, 128.4, 128.0, 127.4, 127.0, 109.5, 105.9, 101.9,
85.1, 84.7, 70.0, 67.0, 27.12, 27.10; MS (MALDI) m/z 1668.2 (M +
Na), 1685.5 (M + K); [R]26D ) +97.1 (c ) 1.68, CH2Cl2). Anal. Calcd
for C105H96O18: C, 76.62; H, 5.88. Found: C, 76.57; H, 6.08.
3,5-[G1]-Stil Dendrimer (14): colorless glassy solid, 80% (SiO2,
purification by flash chromatography (SiO2, 7:3 petroleum ether-ethyl
acetate) of the resulting residue gave 17 (217 mg, 71%) as a colorless
oil: 1H NMR (400 MHz, CDCl3) δ 8.00-7.97 (m, 2H), 7.55-7.52
(m, 1H), 7.42-7.28 (m, 12H), 6.65 (d, J ) 2.2 Hz, 2H), 6.55 (t, J )
2.2 Hz, 1H), 5.00 (s, 4H), 4.81 (d, J ) 8.5 Hz, 1H), 4.54 (dd, J )
12.0, 3.8 Hz, 1H), 4.41 (dd, J ) 12.0, 4.7 Hz, 1H), 4.08 (ddd
(unresolved), 1H), 1.55 (s, 3H), 1.50 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 166.2, 160.2, 140.0, 136.7, 133.1, 129.74, 129.71, 128.6,
128.4, 128.0, 127.6, 109.9, 105.7, 101.9, 80.9, 79.9, 70.2, 63.1, 27.04,
1
1:1 petroleum ether-ethyl acetate); H NMR: δ 8.81 (s, 3H), 7.19-
7.35 (m, 96H), 6.53 (t, J ) 2.1 Hz, 6H), 6.50 (t, 3H), 6.45 (d, J ) 2.1
Hz, 6H), 6.44 (d, J ) 2.2 Hz, 12H), 5.30 (s, 6H), 4.93 (s, 24H), 4.90
(s, 12H), 4.72 (d, J ) 8.4 Hz, 3H), 4.69 (d, J ) 8.4 Hz, 6H), 4.62 (d,
J ) 8.3 Hz, 3H), 4.61 (d, J ) 8.4 Hz, 6H), 1.60 (s, 54H); 13C NMR:
δ 164.6, 159.9, 139.4, 139.3, 137.5, 136.8, 136.7, 135.5, 134.7, 131.2,
128.5, 128.4, 128.3, 127.9, 127.52, 127.47, 127.0, 126.95, 109.54,
109.48, 105.9, 101.9, 101.8, 85.2, 85.1, 84.8, 84.7, 70.1, 69.8, 67.0,
27.2, 27.1; MS (MALDI) m/z 3998.6 (M + Na), 4016.1 (M + K);
27.02; [R]26 ) +23.2 (c ) 3.02, CH2Cl2). Anal. Calcd for
D
C33H32O6: C, 75.55; H, 6.15. Found: C, 75.69; H, 6.20.
(R,R)-4-(3′,5′-Dicarbethoxybenzoyloxymethyl)-5-[3′,5′-bis(ben-
zyloxy)phenyl]-2,2-dimethyl-1,3-dioxolane (18). A solution of the
diethyl ester of benzene-1,3,5-tricarboxylic acid (501 mg, 1.88 mmol),
SOCl2 (8 mL), and 2 drops of DMF was heated to reflux for 4 h, after
which time it was cooled to room temperature, concentrated, and dried
under high vacuum. The resulting acid chloride (536 mg, 100%) was
used without further purification. In a flask fitted with a Dean-Stark
trap (filled with 3 Å sieves) and a reflux condenser, a solution of alcohol
4 (778 mg, 1.85 mmol), DMAP (693 mg, 5.67 mmol), and benzene
(20 mL) was maintained at reflux for 1.5 h and then allowed to cool
to room temperature. A solution of crude acid chloride (536 mg, 1.88
mmol) and benzene (5 mL) was added and the reaction was maintained
at reflux for an additional 30 min, after which time TLC (SiO2, 3:2
petroleum ether-ethyl acetate) indicated consumption of 4. The
reaction mixture was evaporated to dryness and the resulting residue
taken up in CH2Cl2 (200 mL). The solution was washed successively
with 1N HCl (60 mL), saturated NaHCO3 (100 mL), and brine (100
mL), dried (MgSO4), and concentrated. Purification of the residue by
flash chromatography (85:15 petroleum ether-ethyl acetate) gave 18
(564 mg, 46%) as a clear pale yellow oil: 1H NMR (400 MHz, CDCl3)
δ 8.84 (t, J ) 1.6 Hz, 1H), 8.82 (d, J ) 1.6 Hz, 2H), 7.40-7.28 (m,
10H), 6.62 (d, J ) 2.2 Hz, 2H), 6.53 (t, J ) 2.2 Hz, 1H), 5.00 (s, 4H),
4.79 (d, J ) 8.6 Hz, 1H), 4.57 (dd, J ) 12.1, 3.1 Hz, 1H), 4.44 (dd
(unresolved), 1H), 4.40 (q, J ) 7.1 Hz, 4H), 4.12-4.09 (m, 1H), 1.55
(s, 3H), 1.52 (s, 3H), 1.40 (t, J ) 7.1 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 164.7, 164.6, 160.1, 139.6, 136.6, 134.6, 134.4, 131.5, 128.4,
127.9, 127.4, 125.7, 109.9, 105.5, 101.8, 80.7, 79.4, 70.0, 63.5, 61.6,
27.0, 26.9, 14.2; [R]26D ) +20.0 (c ) 5.64, CH2Cl2). Anal. Calcd for
C39H40O10: C, 70.05; H, 6.03. Found: C, 69.98; H, 6.30.
(R,R)-4-[(3′-Methoxyphenoxy)methyl]-5-[3′,5′-bis(benzyloxy)-
phenyl]-2,2-dimethyl-1,3-dioxolane (19). Following the procedure for
16, alcohol 4 (189 mg, 0.45 mmol), Et3N (100 µL, 0.75 mmol),
methanesulfonyl chloride (38 µL, 0.50 mmol), and CH2Cl2 (25 mL)
yielded the corresponding mesylate (224 mg, 100%) as a colorless oil.
Crude mesylate (224 mg, 0.45 mmol), K2CO3 (190 mg, 1.38 mmol),
3-methoxyphenol (56 mg, 0.46 mmol), 18-crown-6 (28 mg, 0.11 mmol)
and dry acetone (15 mL) yielded, after purification by flash chroma-
tography (SiO2, 9:1 petroleum ether-ethyl acetate), 19 (155 mg, 65%)
as a colorless glassy solid: 1H NMR (400 MHz, CDCl3) δ 7.40-7.26
(m, 10H), 7.15 (t, J ) 8.1 Hz, 1H), 6.63 (d, J ) 2.2 Hz, 2H), 6.55 (t,
J ) 2.2 Hz, 1H), 6.52-6.43 (m, 3H), 5.00 (s, 4H), 4.85 (d, J ) 7.8
Hz, 1H), 4.12-4.04 (m, 3H), 3.73 (s, 3H), 1.55 (s, 3H), 1.53 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 160.8, 160.2, 159.8, 140.4, 136.7, 129.8,
128.6, 128.0, 127.5, 106.8, 106.7, 105.7, 101.8, 101.2, 81.6, 79.6, 70.2,
67.1, 55.2, 27.1, 27.0; [R]26D ) +51.4 (c ) 0.80, CH2Cl2). Anal. Calcd
for C33H34O6: C, 75.26; H, 6.51. Found: C, 75.24; H, 6.69.
[R]26 ) +125.5 (c ) 1.85, CH2Cl2). Anal. Calcd for C255H240O42:
D
C, 77.02; H, 6.08. Found: C, 76.72; H, 6.41.
3,5-[G2]-Stil Dendrimer (15): colorless glassy solid, 34% (SiO2,
19:1 methylene chloride-ethyl acetate); 1H NMR: δ 8.81 (s, 3H),
7.34-7.19 (m, 204 H), 6.52 (t, J ) 2.3 Hz, 12H), 6.50 (t, J ) 2.3 Hz,
9H), 6.45 (d, J ) 2.1 Hz, 18H), 6.44 (d, J ) 2.2 Hz, 24H), 5.30 (s,
6H), 4.92 (s, 48 H), 4.90 (s, 24 H), 4.88 (s, 12 H), 4.72 (d, J ) 8.4 Hz,
9H), 4.68 (d, J ) 8.4 Hz, 12H), 4.64-4.60 (m, 21H), 1.61-1.54 (m,
126H); 13C NMR: δ 164.6, 159.9, 139.5, 139.3, 137.5, 136.9, 136.80,
136.77, 135.5, 134.7, 131.2, 128.52, 128.47, 127.9, 127.55, 127.51,
127.46, 127.05, 127.00, 109.5, 109.4, 105.9, 101.9, 101.8, 85.2, 85.1,
85.0, 84.82, 84.77, 84.70, 70.0, 69.8, 27.14, 27.10; MS (MALDI) m/z
8663.8 (M + Na); [R]26D ) +129.2 (c ) 0.705, CH2Cl2). Anal. Calcd
for C555H528O90: C, 77.16; H, 6.16. Found: C, 76.99; H, 6.35.
(R,R)-4-(Phenoxymethyl)-5-[3′,5′-bis(benzyloxy)phenyl]-2,2-di-
methyl-1,3-dioxolane (16). To a cold (0 °C) solution of 4 (347 mg,
0.83 mmol) and CH2Cl2 (20 mL) was added Et3N (173 µL, 1.24 mmol)
followed by methanesulfonyl chloride (72 µL, 0.93 mmol) which was
added dropwise via syringe over a 10 min period. The reaction was
allowed to stir at 0 °C until TLC (SiO2, 3:2 petroleum ether-ethyl
acetate) indicated consumption of starting material (10 min). The
reaction mixture was quenched with ice (20 g), diluted with CH2Cl2
(80 mL), and the resulting organic layer was washed successively with
saturated NH4Cl (30 mL), saturated NaHCO3 (2 × 30 mL), and brine
(50 mL). After drying (MgSO4), concentration gave the corresponding
mesylate (367 mg, 89%) as a colorless oil: 1H NMR (270 MHz, CDCl3)
δ 7.29-7.42 (m, 10H), 6.61 (d, J ) 8.5 Hz, 2H), 6.55 (t, J ) 2.2 Hz,
1H), 5.02 (s, 4H), 4.62 (d, J ) 8.5 Hz, 1H), 4.39 (dd, J ) 2.7, 7.3 Hz,
1H), 4.22 (dd, J ) 4.3, 7.3 Hz, 1H), 3.90 (ddd, J ) 2.8, 4.3, 7.2 Hz,
1H), 3.04 (s, 3H), 1.53 (s, 3H), 1.49 (s, 3H). A slurry of crude mesylate
(367 mg, 0.74 mmol), K2CO3 (504 mg, 3.64 mmol), phenol (71 mg,
0.74 mmol), 18-crown-6 (30 mg, 0.11 mmol), and dry acetone (15 mL)
was heated at reflux. After TLC (SiO2, 9:1 petroleum ether-ethyl
acetate) indicated consumption of starting material, the reaction mixture
was concentrated to dryness, dissolved in CH2Cl2 (50 mL) and water
(50 mL), and separated; the aqueous layer was extracted with CH2Cl2
(2 × 20 mL). The combined organic layers were dried (MgSO4) and
concentrated. Flash chromatography (SiO2, 9:1 petroleum ether-ethyl
acetate) of the residue yielded 16 (251 mg, 69%) as a pale yellow
solid: 1H NMR (400 MHz, CDCl3) δ 7.40-7.24 (m, 12H), 6.94 (m,
1H), 6.88 (m, 2H), 6.63 (d, J ) 2.2 Hz, 2H), 6.55 (t, J ) 2.2 Hz, 1H),
5.00 (s, 4H), 4.87 (d, J ) 7.7 Hz, 1H), 4.13-4.04 (m, 3H), 1.55 (s,
3H), 1.54 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.1, 158.6, 140.4,
136.7, 129.4, 128.5, 127.9, 127.4, 121.1, 114.6, 109.8, 105.6, 101.8,
81.6, 79.5, 70.1, 66.9, 27.0, 26.9; [R]26D ) +52.7 (c ) 2.36, CH2Cl2).
Anal. Calcd for C32H32O5: C, 77.40; H, 6.49. Found: C, 77.60; H,
6.64.
(R,R,R,R,R,R)-4-(Phenoxymethyl)-5-[3′,5′-bis({5′′-[3′′′,5′′′-bis(ben-
zyloxy)phenyl]-2′′,2′′-dimethyl-1′′,3′′-dioxolan-4′′-yl}methoxy)phenyl]-
2,2-dimethyl-1,3-dioxolane (20b). Following the procedure for 16,
monodendron 20a28 (405 mg, 0.39 mmol), Et3N (80 µL, 0.60 mmol),
methanesulfonyl chloride (36 µL, 0.47 mmol), and CH2Cl2 (20 mL)
yielded the corresponding mesylate (415 mg, 95%) as a colorless glassy
solid: 1H NMR (400 MHz, CDCl3) δ 7.39-7.28 (m, 20H), 6.62 (d, J
) 2.2 Hz, 4H), 6.57 (d, J ) 2.2 Hz, 2H), 6.54 (t, J ) 2.2 Hz, 2H),
6.41 (t, J ) 2.2 Hz, 1H), 5.00 (s, 8H), 4.83 (d, J ) 8.2 Hz, 2H), 4.77
(d, J ) 8.5 Hz, 1H), 4.32-4.25 (m, 2H), 4.10-3.90 (m, 7H), 2.94 (s,
3H), 1.54-1.51 (m, 18H). Crude mesylate (415 mg, 0.37 mmol),
K2CO3 (256 mg, 1.85 mmol), phenol (35 mg, 0.37 mmol), 18-crown-6
(22 mg, 0.08 mmol), and dry acetone (10 mL) yielded, after purification
by flash chromatography (SiO2, 7:3 petroleum ether-ethyl acetate),
(R,R)-4-(Benzoyloxymethyl)-5-[3′,5′-bis(benzyloxy)phenyl]-2,2-
dimethyl-1,3-dioxolane (17). Benzoyl chloride (80 µL, 0.69 mmol)
was added to a solution of alcohol 4 (246 mg, 0.58 mmol), DMAP
(219 mg, 1.8 mmol), and toluene (20 mL) at room temperature. The
reaction was left at room temperature until TLC (SiO2, 7:3 petroleum
ether-ethyl acetate) indicated consumption of starting material. The
reaction was diluted with ethyl acetate (100 mL), washed with 1N HCl
(50 mL) and brine (50 mL), and dried (MgSO4). Concentration and

1656 J. Am. Chem. Soc., Vol. 120, No. 8, 1998
McElhanon and McGrath
20b (344 mg, 83%) as a colorless glassy solid: 1H NMR (400 MHz,
CDCl3) δ 7.38-7.20 (m, 22H), 6.92-6.84 (m, 3H), 6.61 (d, J ) 2.2
Hz, 4H), 6.58 (d, J ) 2.1 Hz, 2H), 6.54 (t, J ) 2.3 Hz, 2H), 6.40 (t,
J ) 2.1 Hz, 1H), 4.98 (s, 8H), 4.85 (d, 8.2 Hz, 1H), 4.82 (d, J ) 8.0
Hz, 2H), 4.12-4.00 (m, 9H), 1.54-1.50 (m, 18H); 13C NMR (100 MHz,
CDCl3) δ 160.2, 159.9, 158.5, 140.4, 140.2, 136.6, 129.4, 128.6, 128.0,
127.5, 121.1, 114.6, 109.92, 109.90, 105.8, 105.7, 101.7, 101.4, 81.52,
(R,R)-4-[4′-(Benzoyloxymethyl)phenyl]-5-[3′,5′-bis(benzyloxy)-
phenyl]-2,2-dimethyl-1,3-dioxolane (22). Following the procedure for
17, benzoyl chloride (85 µL, 0.73 mmol), alcohol 6 (232 mg, 0.47
mmol), DMAP (173 mg, 1.4 mmol), and toluene (15 mL) gave, after
purification by flash chromatography (SiO2, 7:3 petroleum ether-ethyl
acetate), 22 (241 mg, 86%) as a colorless solid: 1H NMR (400 MHz,
CDCl3) δ 8.09-8.06 (m, 2H), 7.58-7.54 (m, 1H), 7.44-7.26 (m, 16H),
6.58 (t, J ) 2.2 Hz, 1H), 6.49 (d, J ) 2.2 Hz, 2H), 5.38 (s, 2H), 4.98
(s, 4H), 4.74 (d, J ) 8.4 Hz, 1H), 4.67 (d, J ) 8.4 Hz, 1H), 1.67 (s,
3H), 1.65 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.4, 160.0, 139.3,
137.0, 136.8, 136.1, 133.0, 130.1, 129.6, 128.6, 128.4, 128.2, 128.0,
127.5, 127.0, 109.5, 105.8, 102.0, 85.2, 84.8, 70.1, 66.3, 27.2, 27.1;
81.50, 79.5, 79.4, 70.1, 67.1, 67.0, 27.1, 27.03, 27.00, 26.9; [R]26
)
D
+74.6 (c ) 0.84, CH2Cl2). Anal. Calcd for C70H72O13: C, 74.98; H,
6.47. Found: C, 74.69; H, 6.55.
(R,R)-4-[4′-(Phenoxymethyl)phenyl]-5-[3′,5′-bis(benzyloxy)-
phenyl]-2,2-dimethyl-1,3-dioxolane (21). To a solution of alcohol 6
(1.04 g, 2.09 mmol), CBr4 (1.06 g, 3.20 mmol), and THF (50 mL) was
added PPh3 (830 mg, 3.17 mmol). The reaction mixture was allowed
to stir at room temperature, and additional portions of CBr4 and PPh3
in the initial amounts were added until TLC (SiO2, 9:1 petroleum ether-
ethyl acetate) indicated consumption of starting material. The reaction
was diluted with CH2Cl2 (200 mL) and quenched with water (100 mL).
The organic layer was separated, and the aqueous layer was extracted
with CH2Cl2 (3 × 50 mL). The combined organic extracts were dried
(MgSO4) and concentrated. Purification of the residue by flash
chromatography (SiO2, 7:3 petroleum ether-ethyl acetate) gave the
corresponding bromide (1.08 g, 92%) as a colorless solid: 1H NMR
(400 MHz, CDCl3) δ 7.37-7.29 (m, 12H), 7.20-7.18 (m, 2H), 6.54
(t, J ) 2.3 Hz, 1H), 6.43 (d, J ) 2.3 Hz, 2H), 4.95 (s, 4H), 4.67 (d, J
) 8.5 Hz, 1H), 4.60 (d, J ) 8.5 Hz, 1H), 4.47 (s, 2H), 1.62 (s, 3H),
1.61 (s, 3H). A slurry of bromide (195 mg, 0.35 mmol), K2CO3 (307
mg, 2.2 mmol), phenol (68 mg, 0.72 mmol), 18-crown-6 (34 mg, 0.13
mmol), and dry acetone (10 mL) was heated at reflux. After TLC (SiO2,
95:5 petroleum ether-ethyl acetate) indicated consumption of starting
material, the reaction mixture was concentrated to dryness, dissolved
in Et2O (50 mL) and water (50 mL), and separated; the aqueous layer
was extracted with Et2O (3 × 50 mL). The residue was purified by
flash chromatography (SiO2, 9:1 petroleum ether-CH2Cl2 gradient to
CH2Cl2), and the resulting product was dissolved in CH2Cl2 (20 mL),
washed with NaOH (1.25 N), dried over MgSO4, and concentrated to
yield 21 (165 mg, 82%) as a colorless solid: 1H NMR (400 MHz,
CDCl3) δ 7.38-7.22 (m, 16H), 6.95-6.90 (m, 3H), 6.54 (t, J ) 2.2
Hz, 1H), 6.45 (d, J ) 2.2 Hz, 2H), 5.04 (s, 2H), 4.95 (s, 4H), 4.70 (d,
J ) 8.4 Hz, 1H), 4.64 (d, J ) 8.4 Hz, 1H), 1.63 (s, 3H), 1.61 (2, 3H);
13C NMR (100 MHz, CDCl3) δ 159.9, 158.7, 139.3, 137.2, 136.8, 136.6,
129.4, 128.6, 128.0, 127.52, 127.47, 127.0, 121.0, 114.8, 109.5, 105.8,
[R]26 ) +90.1 (c ) 1.14, CH2Cl2). Anal. Calcd for C39H36O6: C,
D
77.98; H, 6.04. Found: C, 77.74; H, 6.23.
(R,R)-4-[4′-(3′′,5′′-Dicarbethoxybenzoyloxymethyl)phenyl]-5-[3′,5′-
bis(benzyloxy)phenyl]-2,2-dimethyl-1,3-dioxolane (23). A solution
of the diethyl ester of benzene-1,3,5-tricarboxylic acid (181 mg, 0.68
mmol), SOCl2 (8 mL), and 2 drops of DMF was heated to reflux for
4 h, after which time it was cooled to room temperature, concentrated,
and dried under high vacuum. The resulting acid chloride (194 mg,
100%) was used without further purification. Following the procedure
for 17, crude acid chloride (194 mg, 0.68 mmol), alcohol 6 (345 mg,
0.70 mmol), DMAP (254 mg, 2.08 mmol), and toluene (25 mL) gave,
after purification by flash chromatography (SiO2, 7:3 petroleum ether-
ethyl acetate), 23 (420 mg, 81%) as a colorless solid: 1H NMR (400
MHz, CDCl3) δ 8.84 (d, J ) 1.6 Hz, 2H), 8.82 (t, J ) 1.6 Hz, 1H),
7.41-7.26 (m, 14H), 6.54 (t, J ) 2.2 Hz, 1H), 6.46 (d, J ) 2.2 Hz,
2H), 5.39 (s, 2H), 4.95 (s, 4H), 4.71 (d, J ) 8.4 Hz, 1H), 4.63 (d, J )
8.4 Hz, 1H), 4.40 (q, J ) 7.1 Hz, 4H), 1.63 (s, 3H), 1.62 (s, 3H), 1.40
(t, J ) 7.1 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ 165.0, 164.9,
159.9, 139.2, 137.4, 136.7, 135.5, 134.6, 134.5, 131.5, 131.0, 128.5,
128.4, 128.0, 127.5, 127.0, 109.6, 105.9, 101.9, 85.1, 84.7, 70.1, 67.0,
61.7, 27.17, 27.12, 14.3; [R]26 ) +68.2 (c ) 1.24, CH2Cl2). Anal.
D
Calcd for C45H44O10: C, 72.57; H, 5.95. Found: C, 72.31; H, 6.06.
Acknowledgment. We are grateful to Jeffrey Moore, Bert
Meijer, Rob Peerlings, Peter Murer, and Mark Green for helpful
discussions and Mu-Jen Wu for assistance in the preparation
of compounds 13 and 14. Acknowledgment is made to the
National Science Foundation (CAREER Award 9702123), the
donors of the Petroleum Research Fund (29720-G7), adminis-
tered by the American Chemical Society, and the University of
Connecticut Research Foundation for support of this research.
101.9, 85.2, 84.9, 70.1, 69.6, 27.2, 27.1; [R]26 ) +99.2 (c ) 0.78,
D
CH2Cl2). Anal. Calcd for C38H36O5: C, 79.70; H, 6.34. Found: C,
79.89; H, 6.54.
JA970150I