Asymmetric Synthesis of a Series of Chiral AB2 Monomers for Dendrimer Construction

Article abstract of DOI:10.1021/jo961587w

Efficient preparation of a series of four chiral, nonracemic AB₂ monomers suitable for the construction of dendrimers is presented. Monomers 1-4 possess the common structural features of a diphenolic moiety and a benzylic or aliphatic hydroxyl which render these molecules suitable for convergent dendrimer synthesis. The same basic, high-yielding, five-step sequence is employed for 1-4. Stilbene derivatives 13 and 14 are prepared by a Horner-Wadsworth-Emmons modified Wittig reaction between 3,5- or 3,4-bis(benzyloxy)benzaldehyde (8 and 10) and an ester-substituted benzylphosphonate (11 or 12). Cinnamate derivatives 21 and 22 are prepared similarly from 8 and 10 and triethyl phosphonoacetate. Chirality is introduced in the form of a 1,2-diol unit by Sharpless asymmetric dihydroxylation (AD) (>97% ee in all cases). Protection of the 1,2-diols as their acetonide derivatives provides dioxolane intermediates 17, 18, 25, and 26. Reduction of the ester groups followed by hydrogenolysis of the benzyl ethers yields AB₂ monomers 1-4 in 57-67% overall yield from 8 and 10.

Full text of DOI:10.1021/jo961587w

908
J . Org. Chem. 1997, 62, 908-915
Asym m etr ic Syn th esis of a Ser ies of Ch ir a l AB2 Mon om er s for
Den d r im er Con str u ction
J ames R. McElhanon, Mu-J en Wu, Maya Escobar, Umer Chaudhry, Chun-Ling Hu, and
Dominic V. McGrath*
Department of Chemistry, University of Connecticut, 215 Glenbrook Road, Storrs, Connecticut 06269-4060
Received August 15, 1996X
Efficient preparation of a series of four chiral, nonracemic AB2 monomers suitable for the
construction of dendrimers is presented. Monomers 1-4 possess the common structural features
of a diphenolic moiety and a benzylic or aliphatic hydroxyl which render these molecules suitable
for convergent dendrimer synthesis. The same basic, high-yielding, five-step sequence is employed
for 1-4. Stilbene derivatives 13 and 14 are prepared by a Horner-Wadsworth-Emmons modified
Wittig reaction between 3,5- or 3,4-bis(benzyloxy)benzaldehyde (8 and 10) and an ester-substituted
benzylphosphonate (11 or 12). Cinnamate derivatives 21 and 22 are prepared similarly from 8
and 10 and triethyl phosphonoacetate. Chirality is introduced in the form of a 1,2-diol unit by
Sharpless asymmetric dihydroxylation (AD) (>97% ee in all cases). Protection of the 1,2-diols as
their acetonide derivatives provides dioxolane intermediates 17, 18, 25, and 26. Reduction of the
ester groups followed by hydrogenolysis of the benzyl ethers yields AB2 monomers 1-4 in 57-67%
overall yield from 8 and 10.
In tr od u ction
structural units. The work of Seebach6-8 uses chirality
from synthetic sourcesschiral triols are prepared for the
central core or linking units throughout the dendrimers
but these building blocks ultimately derive from the
natural biopolymer poly[(R)-3-hydroxybutanoate], thus
limiting the number of available stereoisomeric triols.15
In only one instance have chiral dendrimers been pre-
pared from materials outside the chiral pool. Chiral,
nonracemic 1,2-diols, introduced by osmium-catalyzed
asymmetric dihydroxylation (AD),20 are used as the
branching points to construct polyether dendrimers up
to the fourth generation.5
Dendrimers1 with chiral terminal groups2-4 or
interiors5-11 possess the potential for enantioselective
clathration of small, chiral molecules, leading to applica-
tions in chemical separations, sensor technology, and
asymmetric catalysis. The continued successful develop-
ment of new chiral dendritic structures depends on the
efficient preparation of appropriately functionalized (i.e.,
n-connected) monomers.12-15 Previous syntheses of chiral
dendrimers have relied on building blocks from natural
sources. The earliest example of a chiral dendrimer was
provided by Newkome, who modified an amine-termi-
nated dendrimer with tryptophan residues.4 Other ef-
forts include the use of nucleic acids,16 amino acids or
derivatives,2,9,17-19 and tartrates10,11 as either surface or
We seek to increase the structural diversity of chiral
dendrimers by preparing monomers for dendrimer con-
struction through asymmetric synthesis. A greater
structural diversity of monomers will facilitate the search
for configurationally induced chiral conformations, or
macromolecular asymmetry,21 in dendritic macromol-
ecules. Macromolecular asymmetry in linear macromol-
ecules is crucial for their application to, for example,
chiral chromatographic separations,22,23 preparation of
cholesteric liquid crystals,24 and the development of
organic materials for nonlinear optics.25,26 While much
is known of the effect of configuration on the conforma-
tion of linear polymers,27 systematic studies on dendritic
X Abstract published in Advance ACS Abstracts, February 1, 1997.
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Macromolecules; Newkome, G. R., Ed.; J AI Press: Greenwich, CT,
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S0022-3263(96)01587-3 CCC: $14.00 © 1997 American Chemical Society

Chiral AB2 Monomers for Dendrimer Construction
J . Org. Chem., Vol. 62, No. 4, 1997 909
macromolecules are few.6,7,10,18,28 Although the use of
synthetic monomers for chiral dendrimer construction is
rare possibly due to the absence of sufficiently function-
alized chiral, nonracemic building blocks, synthetic tech-
niques for stereoselectively introducing chirality into
prochiral organic substrates are abundant.29,30
both enantiomers, and (c) contain functionality suitable
for enthalpic interactions with guest molecules but not
used to link the monomer units together. Monomers 1-4
fulfill these requirements. The common structural fea-
tures of a diphenolic moiety and a benzylic or aliphatic
hydroxyl render these molecules suitable for convergent
dendrimer synthesis.42 The central chiral 1,2-diol unit,
masked in 1-4 as an acetonide derivative for synthetic
Our recently initiated program to develop strategies
for the incorporation of asymmetric units into den-
drimers31-33 focuses on the development of materials
active for the selective clathration of small guest mol-
ecules. We anticipate that for selectivity with regards
to shape and functionality of the guest, a dendrimer must
consist of chiral, nonracemic subunits in the interior for
shape selectivity, as well as interior moieties capable of
engaging in strong hydrogen bonding with encapsulated
guests.9,17,34 Appropriate functionality at the surface or
within the interior of dendrimers also avails the op-
portunity to anchor well-defined transition metal moi-
eties for catalysis applications.19,35-39 The monomeric
units necessary for preparing dendritic materials must
also have the requisite functionality for construction of
a highly branched structure; with rare exception,40,41
dendrimers are constructed by formation of heteroatomic
linkages through SN2 or acyl transfer pathways.1 In this
paper, the preparation and characterization of a series
of four new chiral AB2 monomers are reported. All four
monomers contain two phenolic residues and a benzylic
or aliphatic hydroxyl group, making them suitable for
convergent dendrimer synthesis, and a protected 1,2-diol
moiety, which can serve, after deprotection, as a hydrogen
bond donor or an anchor point for transition metal
moieties in a dendritic structure.
purposes, can be readily introduced by the AD reaction
in either enantiomeric sense.20 Once unmasked in the
final dendrimer, the 1,2-diol should be capable of hydro-
gen bonding interactions with small clathrated guest
molecules, especially 1,2-diamines.43,44 In addition, the
ability for 1,2-diols, particularly hydrobenzoins, to act as
chiral auxiliaries and ligands for transition metals in
catalytic asymmetric synthesis is well precedented. Lewis-
acidic metal centers with hydrobenzoin ligands have been
used to catalyze the aldol45 and Diels-Alder reactions.46
The hydrobenzoin moiety has also been used as a chiral
auxiliary for conjugate additions of organolithiums to R,â-
unsaturated aldimines47 and the enantioselective alky-
lation of prochiral aldehydes by diethylzinc.48
Syn th esis of AB2 Mon om er s. A logical pathway to
monomers 1-4 proceeds through a Wittig preparation
of the appropriately substituted olefin AD substrates.
This Wittig strategy requires bis(benzyloxy)benzalde-
hydes 8 and 10. While commercially available, both are
prohibitively expensive. Fortunately, efficient routes to
8 from R-resorcylic acid esters have been reported.49-51
We have made modifications to these routes to avoid the
use of benzyl bromide and 18-crown-6 as well as chro-
matography (Scheme 1). Thus, benzylation of methyl 3,5-
dihydroxybenzoate (5) with benzyl chloride proceeded
smoothly in K2CO3/DMF to provide 6 in yields consis-
tently exceeding 90% after recrystallization. Reduction
to benzyl alcohol 7, followed by oxidation (PCC/CH2Cl2),
provided 8 in 77% overall yield from 5. Benzylation of
Resu lts a n d Discu ssion
Mon om er Design . Our primary goal was to prepare
AB2 monomers for chiral dendrimer synthesis in a simple,
efficient manner from inexpensive starting materials. In
addition, we required the monomers to (a) possess
appropriate functionality to allow incorporation into a
convergent growth process, (b) be preparable by an
asymmetric technique which allows the preparation of
(28) J ansen, J . F. G. A.; de Brabander-van den Berg, E. M. M.;
Meijer, E. W. Recl. Trav. Chim. Pays-Bas 1995, 114, 225.
(29) No´gra´di, M. Stereoselective Synthesis: A Practical Approach;
VCH Publishers: New York, 1995.
(30) Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH Publish-
ers: New York, 1993.
(31) McElhanon, J .; Wu, M.-J .; Escobar, M.; McGrath, D. V. Am.
Chem. Soc., Div. Polym. Chem., Prepr. 1996, 37(2), 495.
(32) McGrath, D. V.; Wu, M.-J .; Chaudhry, U. Tetrahedron Lett.
1996, 37, 6077.
(33) McElhanon, J . R.; Wu, M.-J .; Escobar, M.; McGrath, D. V.
Macromolecules 1996, 29, 8979.
(34) While several workers have introduced chirality into the interior
of dendritic structures, only those structures reported by Mitchell and
Chapman possess moieties (amide linkages) capable of providing strong
enthalpic contributions to guest binding. See references 9 and 17.
(35) Newkome, G. R.; Guther, R.; Moorefield, C. N.; Cardullo, F.;
Echegoyen, L.; Perez-Cordero, E.; Luftmann, H. Angew. Chem., Int.
Ed. Engl. 1995, 34, 2023.
(42) Hawker, C. J .; Fre´chet, J . M. J . J . Am. Chem. Soc. 1990, 112,
7638.
(43) Hanessian, S.; Simard, M.; Roelens, S. J . Am. Chem. Soc. 1995,
117, 7630.
(36) Knapen, J . W. J .; van der Made, A. W.; de Wilde, J . C.; van
Leeuwen, P. W. N. M.; Wijkens, P.; Grove, D. M.; van Koten, G. Nature
1994, 372, 659.
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Chem. 1994, 33, 5482.
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A. J . M.; Meijer, E. W. Am. Chem. Soc., Div. Polym. Mater. Sci. Eng.,
Prepr. 1995, 73, 338.
(39) Bhyrappa, P.; Young, J . K.; Moore, J . S.; Suslick, K. S. J . Am.
Chem. Soc. 1996, 118, 5708.
(44) Hanessian, S.; Gomtsyan, A.; Simard, M.; Roelens, S. J . Am.
Chem. Soc. 1994, 116, 4495.
(45) Sawamura, M.; Ito, Y. In Catalytic Asymmetric Synthesis;
Ojima, I., Ed.; VCH: New York, 1993, p 367.
(46) Devine, P. N.; Oh, T. J . Org. Chem. 1992, 57, 396.
(47) Tomioka, K.; Shindo, M.; Koga, K. J . Am. Chem. Soc. 1989, 111,
8266.
(48) Rosini, C.; Fansini, L.; Pini, D.; Salvadori, P. Tetrahedron:
Asymmetry 1990, 1, 587.
(49) Anand, R. C.; Ranjan, H. Bull. Chem. Soc. J pn. 1983, 56, 1889.
(50) Franke, I.; Binder, M. Helv. Chim. Acta 1980, 63, 2508.
(51) Lee, F. G. H.; Dickson, D. E.; Suzuki, J .; Zirnis, A.; Manian, A.
A. J . Heterocycl. Chem. 1973, 10, 649.
(40) Zeng, F.; Zimmerman, S. C. J . Am. Chem. Soc. 1996, 118, 5326.
(41) Kawaguchi, T.; Walker, K. L.; Wilkins, C. L.; Moore, J . S. J .
Am. Chem. Soc. 1995, 117, 2159.

910 J . Org. Chem., Vol. 62, No. 4, 1997
McElhanon et al.
Sch em e 1
Sch em e 3
Sch em e 2
drobenzoins 15 and 16 in 74 and 90% yields, respectively,
both in >97% ee. No attempt was made to increase the
optical purity of 15 or 16 through physical manipulation.
We found that the AD reactions were best performed in
a 3:3:5 toluene/tert-butanol/water mixture to dissolve the
substrate. Acetonide protection of the 1,2-diol moiety,
reduction of the ester group, and hydrogenolysis of the
benzyl ether protecting groups of both 15 and 16 were
all carried out under standard conditions to provide
target monomers 1 and 2 in 62 and 57% overall yields
from 8 and 10, respectively (five steps).53 1 and 2 were
crystalline solids readily soluble in acetone, ether, and
ethyl acetate. Although we anticipated catechol 2 be
susceptible to oxidation to the orthoquinone, multigram
samples of 2 have been stored over a period of months
on the benchtop with no decomposition as confirmed by
1H NMR.
Preparation of 3 and 4 from cinnamate precursors
follows a pathway analogous to that presented above
(Scheme 3). Accordingly, bis(benzyloxy)cinnamate esters
21 and 22 were prepared by a phosphonate-stabilized
Wittig coupling of aldehydes 8 and 10 to commercially
available triethyl phosphonoacetate in 84 and 76% yields,
respectively, under milder conditions than those used in
the preparation of 13 and 14. Asymmetric dihydroxyla-
tion of cinnamates 21 and 22 yielded (R,R)-diols 23 and
24 in 83 and 91% yields, respectively. The same solvent
system as above was employed (3:3:5 toluene/tert-butanol/
water), although the electronic nature of the cinnamate
substrates necessitated a higher reaction temperature (20
°C rather than 0 °C)54 for a reasonable reaction rate. The
commercially available protocatechualdehyde (9) under
identical conditions provided crystalline 10 in 95% yield
after a single recrystallization.
The phosphonate-stabilized Wittig coupling of alde-
hydes 8 and 10 to an ester-substituted benzyl phospho-
nate (11 or 12)52 provided stilbenes 13 and 14 in 95 and
80% yields, respectively (Scheme 2). Asymmetric dihy-
droxylation of stilbenes 13 and 14 yielded (R,R)-hy-
(53) The optical purity of 1 was essentially the same as that of diol
15 (>97% ee by chiral HPLC). We were not able to ascertain the optical
purity of 2 but believe it to be similarly high since no diastereomeric
products were observed in the 1H or 13C NMR of crude 18.
(54) Sharpless, K. B.; Amber, W.; Bennani, Y. L.; Crispino, G. A.;
Hartung, J .; J eong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z. M.;
Xu, D.; Zhang, X.-L. J . Org. Chem. 1992, 57, 2768.
(52) Transesterification between the phosphonate ester and the
substrate was observed to occur during this reaction resulting in a
small amount of 13 existing as the ethyl, rather than methyl, ester
(see Experimental Section). This was avoided in the preparation of 14
by employing ethyl ester 12, rather than methyl ester 11.

Chiral AB2 Monomers for Dendrimer Construction
J . Org. Chem., Vol. 62, No. 4, 1997 911
of the one A and two equivalent B rings (Figure 1c).
Similarly, 2- and 4-based zeroth-generation dendrons 20
and 28, with nonsymmetrical 1,3,4-substituted aromatic
rings, both exhibit three resonancesstwo doublets and
a doublet of doubletssin a 1:1:1 ratio (Figure 1, parts d
and e). The corresponding 2-based first-generation den-
dron 3031 (Chart 1) exhibits a more complicated pattern
in this region which is nevertheless indicative of overlap-
ping resonances for the three inequivalent C, D, and E
rings in a 1:1:1 ratio (Figure 1f).
Su m m a r y
We have prepared a series of four chiral, nonracemic
AB2 monomers for dendrimer synthesis. These mono-
mers are suitable for convergent dendrimer synthesis
since each possesses two phenolic residues and a benzylic
or aliphatic hydroxyl group.42 The monomers were
prepared in five-step sequences with the chirality in the
form of a 1,2-diol unit introduced in excellent %ee by the
Sharpless AD reaction. The 1,2-diol was protected as an
acetonide derivative which will be removed after the final
dendrimers are prepared. These interior functional
groups are intended to provide strong enthalpic contribu-
tions to guest binding. The protons on the trisubstituted
1
aromatic rings of the monomer units provide useful H
NMR spectroscopic handles for structure identification
during preparation of higher generation materials. The
details of dendrimer construction using these monomers
will be presented in due course.
Exp er im en ta l Section
Ma ter ia ls a n d Meth od s. Elemental analyses were per-
formed by Supersun Technology of Stony Brook, NY. Optical
rotations and high performance liquid chromatography (HPLC)
were performed on commercially available instrumentation.
Melting points were measured on a Thomas-Hoover capillary
melting point apparatus which was calibrated with commercial
standards. Anhydrous ether was purchased from J . T. Baker
and used as received. Tetrahydrofuran (THF) was distilled
from sodium benzophenone ketyl under nitrogen (N2). Toluene
and methylene chloride (CH2Cl2) were distilled from sodium
and calcium hydride, respectively, under N2. Dimethyl form-
amide (DMF) was distilled at reduced pressure under N2 and
stored in the dark. Potassium carbonate (granular) was dried
at 150 °C at reduced pressure for at least 12 h and stored in
a desiccator. Methyl 3,5-dihydroxybenzoate (5), 3,4-dihydroxy-
benzaldehyde (9), (DHQD)2PHAL (dihydroquinidine 1,4-
phthalazinediyl diether), and methyl 4-(bromomethyl)benzoate
(11) were purchased from Aldrich or Acros and used as
received. Ethyl 4-(bromomethyl)benzoate (12) was prepared
from p-toluic acid (Aldrich) by published procedures.56 Triethyl
phosphonoacetate was prepared from ethyl bromoacetate and
triethyl phosphite. Pyridinium chlorochromate (PCC) was
prepared according to the literature.57 Flash chromatography
was performed by the method of Still et al.58 using silica gel
(32-63 µm, Scientific Adsorbants, Inc.). Thin-layer chroma-
tography (TLC) was performed on precoated TLC plates (Silica
Gel HLO, F-254, Scientific Adsorbants, Inc.).
1
F igu r e 1. Selected regions of the H NMR spectra of (a) 19,
(b) 27, (c) 29, (d) 20, (e) 28, and (f) 30 exhibiting the resonances
for the oxygen-substituted aryl rings.
enantiomeric excesses of 23 and 24, both >99%, did not
suffer as a result. Acetonide protection of the 1,2-diol
moiety, reduction of the ester group, and hydrogenolysis
of the benzyl ether protecting groups of both 23 and 24
were again carried out under standard conditions to
provide target monomers 3 and 4 in 64 and 67% overall
yields from 8 and 10, respectively (five steps).55 3 and 4
were both crystalline solids which were readily soluble
in acetone, ether, and ethyl acetate.
Ch a r a cter iza tion . All compounds have been thor-
oughly characterized by H and 13C NMR and, with the
1
exception of compounds 13 and 15, which were obtained
as mixtures of methyl and ethyl esters, give satisfactory
combustion analyses. While constructing dendrimers
from monomers 1-4, we find the characteristic reso-
nances appearing in the 6.6-7.0 ppm region for the three
protons on the diphenolic aryl rings useful in identifying
new structures. For example, consider dendrons built
from monomers 1-4. In the 1- and 3-based zeroth-
generation dendrons 19 and 27 the three protons on the
symmetrical 1,3,5-substituted aromatic ring appear as
a doublet and a triplet in a 2:1 ratio by integration
(Figure 1, parts a and b). The corresponding 1-based
first-generation dendron 2931 (Chart 1) gives rise to two
sets of doublet/triplet patterns in a 1:2 ratio, indicative
Meth yl 3,5-Bis(ben zyloxy)ben zoa te (6). A slurry of
methyl 3,5-dihydroxybenzoate (5) (50.0 g, 0.30 mol), anhydrous
potassium carbonate (164.5 g, 1.19 mol), benzyl chloride (69
mL, 0.60 mol), and DMF (400 mL) was stirred at 80 °C for 24
h under N2. The reaction mixture was allowed to cool to
ambient temperature, and the DMF was removed in vacuo.
(56) Tietze, L.-F.; Eicher, T. Reactions and Syntheses in the Organic
Chemistry Laboratory; University Science Books: Mill Valley, Cali-
fornia, 1989.
(55) The optical purities of both 3 and 4 were essentially the same
as that of diols 21 and 22 (>99% ee by chiral HPLC).
(57) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647.
(58) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.

912 J . Org. Chem., Vol. 62, No. 4, 1997
McElhanon et al.
solved in triethyl phosphite (5.2 mL, 30 mmol), and the
solution was heated to 120 °C under a reflux condenser. After
24 h, at which time the reaction was complete by TLC (SiO2,
4:1 petroleum ether-ethyl acetate), the reaction was cooled
to room temperature, and excess triethyl phosphite was
removed in vacuo. A slurry of the resulting phosphonate ester,
8 (6.85 g, 21.5 mmol), and sodium hydride (1.26 g, 50%
dispersion in mineral oil, 26.3 mmol) in dry THF (250 mL)
was stirred at rt until analysis by TLC (SiO2, 3:1 petroleum
ether-ethyl acetate) indicated consumption of starting materi-
als (approximately 36 h). The reaction was quenched with H2O
(40 mL) and acidified with 1 N HCl (60 mL). The organic layer
was separated, and the aqueous layer was further extracted
with ether (3 × 50 mL). The combined organic fractions were
washed with saturated NaHCO3 (50 mL), dried (MgSO4), and
concentrated to yield crude 13 (9.21 g, 95%) as a pale tan solid
which was used without further purification. Spectroscopic
characterization indicated that a 4:1 mixture of methyl and
ethyl ester was present: 1H NMR (400 MHz, CDCl3) δ 8.01
(d, J ) 8.4 Hz, 2H), 7.53 (d, J ) 8.4 Hz, 2H), 7.45-7.32 (m,
10H), 7.13 and 7.04 (AB pattern, J ) 15.8 Hz, 2H), 6.77 (d, J
) 2.2 Hz, 2H), 6.57 (t, J ) 2.2 Hz, 1H), 5.06 (s, 4H), 4.37 (q, J
) 7.1 Hz, 0.4H), 3.91 (s, 2.4H), 1.39 (t, J ) 7.1 Hz, 0.6H); 13C
NMR (100 MHz, CDCl3) δ 166.8, 160.2, 141.6, 138.8, 136.8,
131.1, 130.0, 129.0, 128.6, 128.2, 128.0, 127.5, 126.4, 106.1,
102.2, 70.2, 60.9 (Et), 52.1 (Me), 14.3 (Et).
4-Ca r beth oxy-3′,4′-bis(ben zyloxy)-tr a n s-stilben e (14).
Ethyl 4-(bromomethyl)benzoate (15.6 g, 68.1 mmol) was dis-
solved in triethyl phosphite (11.7 mL, 68.1 mmol), and the
solution was heated to 120 °C under a reflux condenser. After
72 h, at which time the reaction was complete by TLC (SiO2,
4:1 petroleum ether-ethyl acetate), the reaction was cooled
to room temperature, and excess triethyl phosphite was
removed in vacuo to give diethyl (4-carbethoxybenzyl)phos-
phonate as a clear liquid which was used without further
purification: 1H NMR (270 MHz, CDCl3) δ 7.96 (d, J ) 8.1
Hz, 2H), 7.35 (dd, J ) 2.3, 8.1 Hz, 2H), 3.94-4.13 (m, 6H),
3.88 (s, 3H), 3.18 (d, J ) 22.1 Hz, 2H), 1.07-1.37 (m, 9H).
The phosphonate ester (22.8 g, 75.9 mmol) was dissolved in
dry THF (500 mL) over 3 Å molecular sieves stirred at room
temperature. After 20 min, NaH (7.28 g, 50% dispersion in
mineral oil, 152 mmol) was added and stirring was continued
for another 30 min. Aldehyde 10 (24.2 g, 76.0 mmol) was
added, and the reaction was monitored by TLC (SiO2, 7:3
petroleum ether-ethyl acetate) until completion (approxi-
mately 48 h). The reaction was quenched with H2O (150 mL)
and 1 N HCl (150 mL), the organic layer was separated, and
the aqueous layer was extracted with ether (2 × 200 mL). The
combined organic layers were washed with concentrated
NaHCO3 (200 mL) and brine (200 mL), dried (MgSO4), and
concentrated. Recrystallization from hot ethanol gave pale
yellow crystals (27.4 g, 78%): 1H NMR (400 MHz, CDCl3) δ
7.99 (d, J ) 8.4 Hz, 2H), 7.25-7.51 (m, 12H), 7.14 (d, J ) 2.0
Hz, 1H), 7.08 (d, J ) 15.8 Hz, 1H), 7.04 (dd, J ) 2.0, 8.4 Hz,
1H), 6.91 (d, J ) 8.5 Hz, 1H), 6.90 (d, J ) 15.8 Hz, 1H), 5.20
(s, 2H), 5.17 (s, 2H), 4.36 (q, J ) 7.1 Hz, 2H), 1.38 (t, J ) 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 150.3, 150.0, 142.8,
138.0, 131.6, 131.5, 130.8, 129.8, 129.40, 129.38, 128.76,
128.73, 128.2, 128.1, 126.9, 121.8, 115.8, 114.0, 72.4, 72.1, 61.7,
15.2. A sample for combustion analysis was prepared by
recrystallization from Et2O (colorless needles). Anal. Calcd
for C31H28O4: C, 80.15; H, 6.08. Found: C, 79.87; H, 6.34.
(R,R)-1-(4′-Ca r b om et h oxyp h en yl)-2-[3′,5′-b is(b en zyl-
oxy)p h en yl]-1,2-eth a n ed iol (15). To a cold (0 °C) slurry of
K3Fe(CN)6 (39.5 g, 0.12 mol), K2CO3 (16.6 g, 0.12 mol),
potassium osmate(VI) dihydrate (K2[OsO2(OH)4]) (148 mg, 0.40
mmol, 1.0 mol %), (DHQD)2PHAL (312 mg, 0.40 mmol, 1.0 mol
%), and methanesulfonamide (3.80 g, 40.0 mmol) in tert-butyl
alcohol (120 mL), water (200 mL), and toluene (120 mL) was
added 13 (18.0 g, 40.0 mmol). Stirring was continued at 0 °C
until TLC (SiO2, 1:1 petroleum ether-ethyl acetate) indicated
consumption of starting material (48 h). Na2SO3 (60 g, 0.48
mol) was added, and the reaction mixture was allowed to warm
to rt over the course of 5 h. The resulting green emulsion was
extracted with ethyl acetate (4 × 50 mL). The combined
organic layers were washed with 5% NaOH, dried (MgSO4),
Ch a r t 1
The residue was extracted with ethyl acetate and filtered
through Celite. Concentration of the resulting solution gave
crude product as a yellow solid. Recrystallization from metha-
nol/water yielded pure 6 as colorless crystals (97.4 g, 94%):
1
mp 69-71 °C (lit.50 68-70 °C); H NMR (270 MHz, CDCl3) δ
7.24-7.41 (m, 10 H), 6.79 (s, 3H), 5.05 (s, 4H), 3.90 (s, 3H).
3,5-Bis(ben zyloxy)ben zyl a lcoh ol (7). A literature pro-
cedure59 was used with modification as follows. To a cold (0
°C) suspension of LiAlH4 (3.04 g, 80 mmol) in anhydrous ether
(300 mL) was added with stirring 6 (15.0 g, 43 mmol). The
reaction was allowed to warm to rt under N2 while stirring (1
h) and then quenched by slow addition of water (150 mL)
followed by 5% H2SO4 (150 mL). After the mixture was
allowed to stir at ambient temperature (1 h), the organic layer
was separated, the aqueous phase was further extracted with
ether (3 × 100 mL), and the combined organic phase was dried
over Na2SO4. Concentration in vacuo yielded 7 as a colorless
solid (12.0 g, 87%) which was used without further purifica-
tion: mp 78-80 °C (lit.50 79-81 °C); 1H NMR (270 MHz,
CDCl3) δ 7.33-7.42 (m, 10 H), 6.60 (d, J ) 2.2 Hz, 2H), 6.54
(t, J ) 2.2 Hz, 1H) , 5.02 (s, 4H), 4.61 (d, J ) 8.8 Hz, 2H), 1.64
(t, J ) 8.8 Hz, 1H).
3,5-Bis(b en zyloxy)b en za ld eh yd e (8). A solution of 7
(15.2 g, 47.6 mmol) in dry CH2Cl2 was added to a slurry of
PCC (15.5 g, 71.4 mmol), Celite (15.0 g), and 3 Å molecular
sieves (10 g) in dry CH2Cl2 (125 mL) . The reaction was left
to stir at rt until complete by TLC (SiO2, 3:1 petroleum ether-
ethyl acetate) at which time the solvent was removed in vacuo.
The remaining dark brown solids were then extracted with
ether which was filtered through florisil. Concentration of the
pale yellow filtrate resulted in the precipitation of 8 (14.3 g,
94%) as colorless crystals: mp 80.5-81 °C (lit.50 79-81); H
1
NMR (400 MHz, CDCl3) δ 9.88 (s, 1H), 7.33-7.43 (m, 10 H),
7.10 (d, J ) 2.2 Hz, 2H), 6.86 (t, J ) 2.2 Hz, 1H), 5.08 (s, 4H);
13C NMR (100 MHz, CDCl3) δ 190.5, 160.3, 138.4, 136.2, 128.6,
128.2, 127.5, 108.6, 108.3, 70.3.
3,4-Bis(ben zyloxy)ben za ld eh yd e (10). A literature pro-
cedure60 was used with modification as follows: A mixture of
9 (32.7 g, 236 mmol), dry K2CO3 (163 g, 1.18 mol), and dry
DMF (ca. 150 mL) was stirred at room temperature for 1 h
under N2. Benzyl chloride (54.4 mL, 473 mmol) was then
added, and the mixture was refluxed for 24 h. The dark brown
slurry was allowed to cool to ambient temperature and was
then filtered through Celite. The filtrate was concentrated to
a brown solid. Recrystallization from ethanol yielded tan
crystals (71.6 g, 95%): mp 90-91 °C (lit.60 90-92 °C); 1H NMR
(270 MHz, CDCl3) δ 9.79 (s, 1H), 7.30-7.47 (m, 12H), 7.00 (d,
J ) 8.2 Hz, 1H), 5.24 (s, 2H), 5.20 (s, 2H); 13C NMR (67.5 MHz,
CDCl3) δ 191.0, 154.4, 149.4, 136.7, 136.4, 130.5, 128.7, 128.6,
128.2, 128.1, 127.5, 127.2, 126.7, 113.4, 112.7, 71.1, 71.0. Anal.
Calcd for C21H18O3: C, 79.23; H, 5.70. Found: C, 79.05; H,
5.73.
4-Car bom eth oxy-3′,5′-Bis(ben zyloxy)-tr a n s-stilben e (13).
Methyl 4-(bromomethyl)benzoate (5.04 g, 22 mmol) was dis-
(59) Reimann, E. Chem. Ber. 1969, 102, 2881.
(60) Ramage, R.; Griffiths, G. J .; Shutt, F. E.; Sweeney, J . N. A. J .
Chem. Soc., Perkin Trans. 1 1984, 1539.

Chiral AB2 Monomers for Dendrimer Construction
J . Org. Chem., Vol. 62, No. 4, 1997 913
and concentrated to yield crude diol. Purification by flash
chromatography (SiO2 1:1 ethyl acetate-hexane) afforded diol
15 (14.3 g, 74%, >97% ee) as a pale yellow solid. The
enantiomeric excess was determined by HPLC analysis of the
diol on a Chiralcel OD column. Spectroscopic characterization
indicated a 15:1 mixture of methyl and ethyl ester was
present: 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J ) 8.3 Hz,
2H), 7.25-7.40 (m, 10H), 7.14 (d, J ) 8.3 Hz, 2H), 6.47 (t, J )
2.2 Hz, 1H), 6.33 (d, J ) 2.2 Hz, 2H), 4.91 and 4.87 (AB
pattern, J ) 11.7 Hz, 4H), 4.68 (dd, J ) 2.5, 7.0 Hz, 1H), 4.52
(dd, J ) 3.0, 7.0 Hz, 1H), 4.35 (q, J ) 7.1 Hz, 0.13H), 3.86 (s,
2.8H), 2.99 (d, J ) 2.5 Hz, 1H), 2.80 (d, J ) 3.0 Hz, 1H), 1.35
(t, J ) 7.1 Hz, 0.19H); 13C NMR (400 MHz, CDCl3) δ 166.9,
159.7, 145.0, 141.9, 136.7, 129.5, 129.3, 128.5, 128.0, 127.4,
126.9, 106.1, 102.0, 79.0, 78.5, 70.0, 52.0; [R]D ) +120.8 (c )
1.00, CH2Cl2).
(R,R)-1-(4′-Ca r beth oxyp h en yl)-2-[3′,4′-bis(ben zyloxy)-
p h en yl]-1,2-eth a n ed iol (16). Following the procedure for 15,
K3Fe(CN)6 (52.6 g, 160 mmol), K2CO3 (22.0 g, 160 mmol), K2-
[OsO2(OH)4] (196 mg, 0.53 mmol, 1 mol %), (DHQD)2-PHAL
(414 mg, 0.53 mmol, 1.0 mol %), methanesulfonamide (5.06 g,
53.2mmol), tert-butyl alcohol (160 mL), water (266 mL),
toluene (160 mL), and 14 (24.0 g, 53.2 mmol) yielded 16 as a
pale tan oil (23.3 g, 90%, >97% ee) which was used without
further purification. The enantiomeric excess was determined
(R,R)-4-[4′-(H yd r oxym et h yl)p h en yl]-5-[3′,5′-b is(b en z-
yloxy)p h en yl]-2,2-d im eth yl-1,3-d ioxola n e (19). To a cold
(0 °C) solution of LiAlH4 (2.46 g, 65 mmol) and anhydrous ether
(300 mL) was added a solution of 17 (19.4 g, 37 mmol) and
anhydrous ether (300 mL) dropwise over 30 min. Stirring was
continued for 1 h at 0 °C, after which time the reaction was
allowed to warm to ambient temperature. The reaction was
quenched with H2O (2 mL), 15% NaOH (2 mL), and H2O (6
mL), stirred at rt for 2 h, filtered through a pad of Celite, and
concentrated to yield 19 (17.9 g, 97%) as a colorless oil which
solidified on standing: 1H NMR (400 MHz, CDCl3) δ 7.2-7.4
(m, 14H), 6.54 (t, J ) 2.3 Hz, 1H), 6.45 (d, J ) 2.3 Hz, 2H),
4.96 (s, 4H), 4.69 (d, J ) 8.5 Hz, 1H), 4.67 (d, J ) 5.3 Hz, 1H),
4.63 (d, J ) 8.5 Hz, 1H), 1.66 (br t, J ) 5.3 Hz, 1H), 1.64 (s,
3H), 1.62 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 140.9,
139.3, 136.7, 136.3, 128.5, 128.0, 127.5, 126.97, 126.95, 109.4,
105.9, 101.8, 85.2, 84.9, 70.08, 65.0, 27.16, 27.10; [R]D ) +94.2
(c ) 2.05, CH2Cl2). Anal. Calcd for C32H32O5: C, 77.40; H,
6.49. Found: C, 77.67; H, 6.62.
(R,R)-4-[4′-(H yd r oxym et h yl)p h en yl]-5-[3′,4′-b is(b en z-
yloxy)p h en yl]-2,2-d im eth yl-1,3-d ioxola n e (20). Ester 18
(21.8 g, 40.5 mmol) was dissolved in diethyl ether (20 mL) and
cooled to 0 °C, and solid LiAlH4
(1.69 g, 44.6 mmol) was added
portionwise. After 20 min, the reaction mixture was allowed
to warm to room temperature and stirred for 24 h. The
reaction was quenched with H2O (1.5 mL), 15% NaOH (1.5
mL), and H2O (4.5 mL), stirred at rt for 2 h, filtered through
a pad of Celite, and concentrated to yield benzyl alcohol 20
by HPLC analysis of the diol on a Chiralcel OD column.
A
small quantity of crude product was purified by flash chro-
matography to give the diol as colorless oil: 1H NMR (400
MHz, CDCl3) δ 7.84 (d, J ) 8.2 Hz, 2H), 7.27-7.40 (m, 10H),
7.01 (d, J ) 8.2 Hz, 2H), 6.72 (d, J ) 8.2 Hz, 1H), 6.71 (d, J )
2.0 Hz, 1H), 6.50 (dd, J ) 2.0, 8.2 Hz, 1H), 5.09 (s, 2H), 5.03
and 5.01 (AB pattern, J ) 12.2 Hz, 2H), 4.61 (d, J ) 7.7 Hz,
1H), 4.51 (d, J ) 7.7 Hz, 1H), 4.33 (q, J ) 7.1 Hz, 2H), 2.90
(br s, 1H), 2.65 (br s, 1H), 1.36 (t, J ) 7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3) 164.6, 146.5, 146.4, 143.4, 135.12, 135.10,
131.0, 127.6, 127.1, 126.5, 125.9, 125.4, 125.1, 118.4, 112.5,
112.0, 76.8, 69.18, 69.15, 59.1, 12.3; [R]D ) +144.0 (c ) 2.63,
CH2Cl2). Anal. Calcd for C31H30O6: C, 74.68; H, 6.06.
Found: C, 74.84; H, 6.42.
(20.1 g, 100%):
1H NMR (400 MHz, CDCl3) δ 7.43 (m, 14H),
7.13 (d, J ) 8.1 Hz, 2H), 6.88 (d, J ) 2.0 Hz, 1H), 6.86 (d, J )
8.3 Hz, 1H), 6.69 (dd, J ) 2.0, 8.3 Hz, 1H), 5.15 (s, 2H), 5.14
and 5.09 (AB pattern, J ) 12.1 Hz, 2H), 4.69 (s, 2H), 4.64 (d,
J ) 8.5 Hz, 1H), 4.59 (d, J ) 8.5 Hz, 1H), 1.64 (s, 3H), 1.62 (s,
3H); 13
C NMR (100 MHz, CDCl3) δ 148.8, 148.6, 140.8, 137.0,
136.9, 135.8, 129.5, 128.3, 127.6, 127.19, 127.15, 126.7, 126.5,
120.1, 114.5, 113.5, 109.0, 84.9, 84.8, 71.2, 71.0, 64.4, 27.03,
26.98; [R]D
) +118.6o (c ) 2.05, CH2Cl2). Anal. Calcd for
C32H32O5: C, 77.40; H, 6.49. Found: C, 77.32; H, 6.58.
(R ,R )-4-[4′-(H y d r o x y m e t h y l)p h e n y l]-5-(3′,5′-d ih y -
d r oxyp h en yl)-2,2-d im eth yl-1,3-d ioxola n e (1). A solution
of benzyl alcohol 19 (7.09 g, 14.3 mmol) in ethyl acetate (150
mL) was charged with 10% Pd/C (280 mg) and stirred under
1 atm H2 at rt. After completion by TLC (SiO2, 1:1 petroleum
ether-ethyl acetate), the reaction mixture was filtered through
a Celite column and concentrated to yield 1 (4.52 g, 100%,
>97% ee) as a colorless solid which may be recrystallized from
petroleum ether/ethyl acetate. The enantiomeric excess was
determined by HPLC analysis on a Chiralcel OD column. 1H
NMR (400 MHz, acetone-d6) δ 8.18 (s, 2H), 7.32 (d, J ) 8.2
Hz, 2H), 7.24 (d, J ) 8.2 Hz, 2H), 6.28 (t, J ) 2.2 Hz, 1H),
6.23 (d, J ) 2.2 Hz, 2H), 4.68 (d, J ) 8.5 Hz, 1H), 4.63 (d, J )
5.8 Hz, 2H), 4.59 (d, J ) 8.5 Hz, 2H), 4.23 (t, J ) 5.8 Hz, 1H);
13C NMR (100 MHz, acetone-d6) δ 159.3, 143.3, 140.7, 136.8,
127.8, 127.3, 109.6, 106.0, 103.1, 86.1, 86.0, 64.4, 27.5, 27.4;
[R]D ) +112.2 (c ) 1.58, EtOH); Anal. Calcd for C18H20O5: C,
68.34; H, 6.37; Found: C, 68.63; H, 6.61.
(R,R)-4-(4′-Ca r b om et h oxyp h en yl)-5-[3′,5′-b is(b en zyl-
oxy)p h en yl]-2,2-d im eth yl-1,3-d ioxola n e (17). A solution
of 15 (22.7 g, 47 mmol), 2,2-dimethoxypropane (280 mL),
p-toluenesulfonic acid monohydrate (372 mg, 2.0 mmol), and
DMF (95 mL) was heated at reflux (100 °C bath) for 2 h. The
reaction mixture was cooled to rt, poured into 0.5% NaHCO3
(150 mL), and extracted with CH2Cl2 (3 × 100 mL). The
combined organic extracts were dried (Na2SO4) and concen-
trated. Recrystallization from hot hexane yielded acetal 17
(22.3 g, 91%) as colorless needles in two crops: 1H NMR (400
MHz, CDCl3) δ 7.96 (dd, J ) 1.7, 6.6 Hz, 2H), 7.25-7.34 (m,
12H), 6.56 (t, J ) 2.2 Hz, 1H), 6.43 (d, J ) 2.2 Hz, 2H), 4.96
(s, 4H), 4.73 (d, J ) 8.4 Hz, 1H), 4.59 (d, J ) 8.4 Hz, 1H), 3.90
(s, 3H), 1.64 (s, 3H), 1.63 (s, 3H); 13C NMR (100 MHz, CDCl3)
166.8, 160.0, 142.1, 138.9, 136.7, 130.1, 129.7, 128.6, 128.0,
127.5, 126.6, 109.8, 105.9, 102.1, 85.3, 84.7, 70.1, 52.1, 27.12,
27.07; [R]D ) +113.0 (c ) 2.05, CH2Cl2). Anal. Calcd for
C33H32O6: C, 75.55; H, 6.15. Found: C, 75.65; H, 6.27.
(R,R)-4-(4′-Ca r beth oxyp h en yl)-5-[3′,4′-bis(ben zyloxy)-
p h en yl]-2,2-d im eth yl-1,3-d ioxola n e (18). Following the
procedure for 17, diol 16 (22.5 g, 46.0 mmol), 2,2-dimethox-
ypropane (340 mL), p-toluenesulfonic acid monohydrate (880
mg, 4.6 mmol), and anhydrous DMF (135 mL) yielded acetal
18 as a brown oil (2.24 g, 89%) which was carried directly to
the next step. A small quantity of crude product was purified
by flash chromatography to give the acetal as a yellow oil: 1H
NMR (400 MHz, CDCl3) δ 7.94 (d, J ) 8.3 Hz, 2H), 7.43-7.24
(m, 10H), 7.17 (d, J ) 8.3 Hz, 2H), 6.84 (d, J ) 8.3 Hz, 1H),
6.82 (d, J ) 2.0 Hz, 1H), 6.67 (dd, J ) 2.0, 8.3 Hz, 1H), 5.14
(s, 2H), 5.12 and 5.09 (AB pattern, J ) 12.3 Hz, 2H), 4.65 (d,
J ) 8.5 Hz, 1H), 4.53 (d, J ) 8.5 Hz, 1H), 4.36 (q, J ) 7.1 Hz,
2H), 1.62 (s, 3H), 1.61 (s, 3H), 1.38 (t, J ) 7.1 Hz, 3H); 13C
NMR (67.5 MHz, CDCl3) δ 166.3, 149.2, 148.9, 142.0, 137.1,
130.3, 129.6, 129.3, 128.4, 127.8, 127.3, 126.2, 120.3, 114.9,
113.9, 109.5, 85.1, 84.7, 71.4, 71.3, 60.9, 27.2, 27.0, 14.3; [R]D
) +103.6 (c ) 4.22, CH2Cl2). Anal. Calcd for C34H34O6: C,
75.82; H, 6.36. Found: C, 75.82; H, 5.96.
(R ,R )-4 -[4 ′-(H y d r o x y m e t h y l )p h e n y l ]-5 -(3′,4 ′-d i -
h yd r oxyp h en yl)-2,2-d im eth yl-1,3-d ioxola n e (2). Follow-
ing the procedure for 1, benzyl alcohol 20 (5.00 g, 10.1 mmol),
ethyl acetate (100 mL), and 10% Pd/C (645 mg) stirred under
1 atm H2 at room temperature yielded 2 (2.83 g, 89%) as a
colorless solid after purification by flash chromatography (SiO2,
1:1 petroleum ether-ethyl acetate): 1H NMR (270 MHz,
CDCl3) δ 7.23 (d, J ) 8.1 Hz, 4H), 7.13 (d, J ) 8.1 Hz, 4H),
6.51-6.68 (m, 3H), 6.07 (s, 2H), 4.65 (d, J ) 8.5 Hz, 1H), 4.58
(s, 2H), 4.51 (d, J ) 8.6 Hz, 1H), 1.62 (s, 6H); 13C NMR (67.5
MHz, acetone-d6) δ 145.2, 145.0, 142.2, 136.2, 128.8, 126.8,
126.6, 118.9, 115.1, 114.1, 108.6, 85.4, 85.2, 63.7, 26.84, 26.78;
[R]D ) +124.0 (c ) 2.30, CH3CN). Anal. Calcd for C18H20O5:
C, 68.34; H, 6.37. Found: C, 68.10; H, 6.52.
Eth yl 3,5-Bis(ben zyloxy)cin n a m a te (21). Sodium metal
(0.11 g, 4.7 mmol) was dissolved in anhydrous EtOH (50 mL).
Triethyl phosphonoacetate (0.70 g, 3.1 mmol) was added at
once followed by 8 (1.0 g, 3.1 mmol) after 20 min. The reaction
was stirred at rt under N2 and monitored by TLC (SiO2, 4:1
petroleum ether-ethyl acetate). The reaction was quenched

914 J . Org. Chem., Vol. 62, No. 4, 1997
McElhanon et al.
with water (100 mL) and extracted with ether (3 × 100 mL).
The combined organic extracts were dried (MgSO4) and
concentrated to yield crude product. Recrystallization from
hexane yielded 21 as a pale yellow solid (1.03 g, 84%): 1H NMR
(270 MHz, CDCl3) δ 7.57 (d, J ) 15.9 Hz, 1H), 7.34-7.42 (m,
10H), 6.74 (d, J ) 2.2 Hz, 2H), 6.63 (t, J ) 2.2 Hz, 1H), 6.36
(d, J ) 15.9 Hz, 1H), 4.24 (q, J ) 7.3 Hz, 2H), 1.32 (t, J ) 7.3
Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ 167.0, 160.2, 144.4,
136.6, 136.4, 128.6, 128.1, 127.5, 118.9, 107.2, 104.2, 70.2, 60.5,
14.3. Anal. Calcd for C25H24O4: C, 77.30; H, 6.23; Found: C,
77.22; H, 6.23.
Eth yl 3,4-Bis(ben zyloxy)cin n a m a te (22). Following the
procedure for 21, sodium metal (3.13 g, 0.136 mmol), EtOH
(750 mL), triethyl phosphonacetate (15.0 g, 66.7 mmol), and
10 (17.4 g, 54.5 mmol) yielded 22 as a pale yellow solid from
hexane (16.0 g, 76%): 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J
) 15.9 Hz, 1H), 7.27-7.45 (m, 10H), 7.10 (d, J ) 2.0 Hz, 1H),
7.04 (dd, J ) 2.0, 8.3 Hz, 1H), 6.89 (d, J ) 8.3 Hz, 1H), 6.22
(d, J ) 15.9 Hz, 1H), 5.24 (s, 2H), 5.23 (s, 2H), 4.22 (q, J ) 7.1
Hz, 2H), 1.30 (t, J ) 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3)
δ 167.2, 149.0, 144.3, 136.9, 136.8, 128.7, 128.6, 127.97, 127.95,
127.3, 127.2, 122.8, 116.2, 114.3, 113.8, 71.4, 71.0. 60.4, 14.3.
Anal. Calcd for C25H24O4: C, 77.30; H, 6.23; Found: C, 77.30;
H, 6.42.
(R,R)-1-[3′,5′-Bis(b en zyloxy)p h en yl]-2-(ca r b et h oxy)-
1,2-eth a n ed iol (23). To a slurry of K3Fe(CN)6 (988 mg, 3.0
mmol), K2CO3 (415 mg, 3.0 mmol), K2[OsO2(OH)4] (3.7 mg, 0.01
mmol, 1 mol %), (DHQD)2PHAL (7.8 mg, 0.01 mmol, 1.0 mol
%), and methanesulfonamide (95 mg, 1.0 mmol) in tert-butyl
alcohol (3 mL), water (5 mL), and toluene (3 mL) was added
21 (388 mg, 1.0 mmol). Stirring was continued at room
temperature until TLC (SiO2, 7:3 petroleum ether-ethyl
acetate) indicated comsumption of starting material (72 h).
Na2SO3 (1.5 g, 12 mmol) was added, and the reaction mixture
was allowed to stir for an additional 2.5 h. The resulting green
emulsion was extracted with ethyl acetate (3 × 5 mL). The
combined organic layers were washed with 5% NaOH, dried
(MgSO4), and concentrated to yield crude diol. Purification
by flash chromatography (SiO2, 3:2 petroleum ether-ethyl
acetate) yielded 23 as a colorless solid (350 mg, 83%, >99%
ee). The enantiomeric excess was determined by HPLC
analysis of the diol on a Chiralcel OD column. 1H NMR (270
MHz, CDCl3) δ 7.30-7.42 (m, 10H), 6.65 (d, J ) 2.2 Hz, 2H),
6.55 (t, J ) 2.2 Hz, 1H), 5.02 (s, 4H), 4.93 (dd, J ) 2.8, 5.7 Hz,
1H), 4.32 (dd, J ) 2.8, 7.4 Hz, 1H), 4.25 (q, J ) 7.2 Hz, 2H),
3.03 (d, J ) 5.7 Hz, 1H), 2.65 (d, J ) 7.4 Hz, 1H), 1.27 (t, J )
7.2 Hz, 3H); 13C NMR (67.5 MHz, CDCl3) δ 172.6, 160.1, 142.5,
136.8, 128.6, 128.0, 127.6, 105.5, 101.6,74.5, 74.3, 70.2, 62.2,
14.1; H, 6.48; [R]D ) -6.64 (c ) 1.96, CH2Cl2). Anal. Calcd
for C25H26O6: C, 71.07; H, 6.20. Found: C, 70.99; H, 6.48.
(R,R)-1-[3′,4′-Bis(ben zyloxy)p h en yl]-2-Ca r beth oxy-1,2-
eth a n ed iol (24). Following the procedure for 23, K3Fe(CN)6
(43.0 g, 0.13 mol), K2CO3 (18.1 g, 0.13 mol), K2[OsO2(OH)4]
(0.16 g, 0.44 mmol, 1 mol %), (DHQD)2PHAL (343 mg, 0.44
mmol, 1 mol %), methanesulfonamide (4.1 g, 43 mmol), tert-
butyl alcohol (130 mL), water (220 mL), toluene (130 mL), and
22 (16.9 g, 43.4 mmol) yielded 24 (16.7 g, 91%, >99% ee) as a
colorless solid after flash chromatography (SiO2, 3:2 petroleum
ether-ethyl acetate). The enantiomeric excess was deter-
mined by HPLC analysis of the diol on a Chiralcel OD column.
1H NMR (400 MHz, CDCl3) δ 7.24-7.44 (m, 10H), 7.04 (s, 1H),
6.91 and 6.89 (AB pattern, J ) 8.2 Hz, 2H), 5.15 (s, 2H), 5.14
(s, 2H), 4.86 (dd, J ) 3.2, 6.7 Hz, 1H), 4.26 (dd, J ) 3.2, 5.9
Hz, 1H), 4.21 (q, J ) 7.1 Hz, 1H), 4.19 (q, J ) 7.1 Hz, 1H),
3.02 (d, J ) 5.9 Hz, 1H), 2.59 (d, J ) 6.7 Hz, 1H), 1.22 (t, J )
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 172.6, 149.0, 148.8,
137.22, 137.16, 133.3, 128.4, 127.80, 127.76, 127.4, 127.2,
96%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.31-
7.42 (m, 10H), 6.67 (d, J ) 2.2 Hz, 2H), 6.56 (t, J ) 2.2 Hz,
1H), 5.09 (d, J ) 7.4 Hz, 1H), 5.02 (s, 4H), 4.30 (d, J ) 7.4 Hz,
1H), 4.23 (q, J ) 7.1 Hz, 2H), 1.56 (s, 3H), 1.52 (s, 3H), 1.27 (t,
J ) 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 170.5, 160.2,
140.6, 136.9, 128.7, 128.1, 127.6, 111.8, 105.7, 102.0, 81.3, 80.6,
70.3, 61.6, 27.0, 25.9, 14.3; [R]D ) +28.7 (c ) 3.41, CH2Cl2).
Anal. Calcd for C28H30O6: C, 72.71; H, 6.54. Found: C, 72.82;
H, 6.69.
(R,R)-4-(Ca r b et h oxy)-5-[3′,4′-Bis(b en zyloxy)p h en yl]-
2,2-d im eth yl-1,3-d ioxola n e (26). Following the procedure
for 17, diol 24 (15.6 g, 36.9 mmol), 2,2-dimethoxypropane (550
mL), p-toluenesulfonic acid monohydrate (740 mg, 3.9 mmol),
and anhydrous DMF (185 mL) yielded 26 (17.0 g, 100%) as a
colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.28-7.44 (m, 10H),
7.01 (s, 1H), 6.89 and 6.92 (AB pattern, J ) 8.2 Hz, 2H), 5.17
and 5.12 (AB pattern, J ) 11.4 Hz, 2H), 5.03 (d, J ) 7.6 Hz,
1H), 4.22 (d, J ) 7.6 Hz, 1H), 4.19 (q, J ) 7.1 Hz, 2H), 1.54 (s,
3H), 1.51 (s, 3H), 1.23 (t, J ) 7.1 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 170.3, 149.2, 149.1, 137.2, 130.9, 128.5, 127.83,
127.80, 127.4, 127.3, 119.9, 114.9, 113.4, 111.4, 81.2, 80.5, 71.4,
71.3, 61.4, 26.9, 25.8, 14.2; [R]D ) +34.67 (c ) 2.32, CH2Cl2).
A small amount was purified by flash chromatography (SiO2,
4:1 petroleum ether-ethyl acetate) for analysis. Anal. Calcd
for C28H30O6: C, 72.71; H, 6.54. Found: C, 72.54; H, 6.65.
(R,R)-4-(Hydr oxym eth yl)-5-[3′,5′-bis(ben zyloxy)ph en yl]-
2,2-d im eth yl-1,3-d ioxola n e (27). To a cold (0 °C) solution
of LiAlH4 (1.10 g, 28.9 mmol) and anhydrous ether (200 mL)
was added a solution of 25 (7.20 g, 15.6 mmol) and anhydrous
ether (200 mL) dropwise over 30 min. The reaction was then
allowed to warm to rt under N2 and left to stir until TLC (SiO2
7:3 petroleum ether-ethyl acetate) indicated consumption of
starting material (45 min). The reaction was quenched with
water (80 mL), acidified with 5% H2SO4 (80 mL), and allowed
to stir at rt (1 h). The mixture was then extracted with ether
(3 × 100 mL), dried (Na2SO4), and concentrated to yield 27 as
1
a colorless solid (6.29 g, 96%): H NMR (400 MHz, CDCl3) δ
7.29-7.41 (m, 10H), 6.62 (d, J ) 2.1 Hz, 2H), 6.55 (t, J ) 2.1
Hz), 5.02 (s, 4H), 4.82 (d, J ) 8.5 Hz, 1H), 3.77-3.84 (m, 2H),
3.59 (m, 1H), 1.87 (m, 1H), 1.52 (s, 3H), 1.50 (s, 3H); 13C NMR
(67.5 MHz, CDCl3) δ 160.2, 140.4, 136.7, 128.6, 128.0, 127.5,
109.3, 105.5, 101.8, 83.3, 78.4, 70.2, 60.4, 27.1; [R]D ) -4.05
(c ) 2.05, CH2Cl2). Anal. Calcd for C26H28O5: C, 74.26; H,
6.71. Found: C, 74.41; H, 6.90.
(R,R)-4-(Hydr oxym eth yl)-5-[3′,4′-bis(ben zyloxy)ph en yl]-
2,2-d im eth yl-1,3-d ioxola n e (28). Following the procedure
for 27, LiAlH4 (2.45 g, 63.9 mmol), anhydrous ether (400 mL),
and 26 (16.4 g, 35.5 mmol) yielded 28 as a white solid (14.5 g,
1
97%): H NMR (400 MHz, CDCl3) δ 7.43-7.28 (m, 10H), 6.95
(d, J ) 1.8 Hz, 1H), 6.89 (d, J ) 8.2 Hz, 1H), 6.86 (dd, J ) 1.8,
8.2 Hz, 1H), 5.17 and 5.14 (AB pattern, J ) 12.4 Hz, 2H), 5.14
(s, 2H), 4.77 (d, J ) 8.5 Hz, 1H), 3.74 (m, 2H), 3.52 (m, 1H),
1.85 (dd, J ) 4.0, 8.4 Hz, 1H), 1.50 (s, 3H), 1.48 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 149.0, 137.2, 130.8, 128.5, 127.82,
127.79, 127.4, 127.3, 119.8, 115.0, 113.8, 109.1, 83.3, 78.3, 71.4,
71.3, 60.3, 27.1, 27.0; [R]D ) -8.31 (c ) 3.02, CH2Cl2). Anal.
Calcd for C26H28O5: C, 74.26; H, 6.71. Found: C, 74.16; H,
6.71.
(R,R)-4-(H yd r oxym et h yl)-5-[3′,5′-d ih yd r oxyp h en yl]-
2,2-d im eth yl-1,3-d ioxola n e (3). Following the procedure for
1, benzyl alcohol 27 (2.90 g, 6.90 mmol), ethyl acetate (50 mL),
and 10% Pd/C (250 mg) stirred under 1 atm H2 at room
temperature yielded 8 (1.67 g, 100%, >99% ee) as a colorless
solid (mp 147-148 °C). The enantiomeric excess was deter-
mined by HPLC analysis on a Chiralcel OD column. 1H NMR
(400 MHz, acetone-d6) δ 8.21 (s, 2H), 6.41 (d, J ) 2.2 Hz, 2H),
6.27 (t, J ) 2.2 Hz, 1H), 4.70 (d, J ) 8.1 Hz, 1H), 3.57-3.83
(m, 4H), 1.44 (s, 3H), 1.40 (s, 3H); 13C NMR (67.5 MHz,
acetone-d6) δ 159.4, 142.5, 109.4, 105.6, 102.9, 85.2, 79.6, 61.6,
27.4, 27.3; [R]D ) -7.08 (c ) 1.56, EtOH). Anal. Calcd for
C12H16O5: C, 59.99; H, 6.71. Found: C, 60.36; H, 7.04.
(R,R)-4-(H yd r oxym et h yl)-5-[3′,4′-d ih yd r oxyp h en yl]-
2,2-d im eth yl-1,3-d ioxola n e (4). Following the procedure for
1, 28 (4.15 g, 9.87 mmol), ethyl acetate (150 mL), and 10%
Pd/C (370 mg) yielded 4 (1.67 g, 100%) as a colorless, sticky
solid. Evaporation of a CH2Cl2 solution yielded a colorless
119.5, 114.9, 113.5, 74.6, 74.2, 71.4, 71.3, 62.1, 14.5; [R]D
)
-2.70 (c ) 2.33, CH2Cl2). A small amount was recrystallized
from ethyl acetate-petroleum ether for analysis. Anal. Calcd
for C25H26O6: C, 71.07; H, 6.20. Found: C, 71.14; H, 6.24.
(R,R)-4-(Ca r b et h oxy)-5-[3′,5′-Bis(b en zyloxy)p h en yl]-
2,2-d im eth yl-1,3-d ioxola n e (25). Following the procedure
for 17, diol 23 (296 mg, 0.70 mmol), 2,2-dimethoxypropane
(10.5 mL), p-toluenesulfonic acid monohydrate (14 mg, 0.074
mmol), and anhydrous DMF (3.5 mL) yielded 25 (310.5 mg,

Chiral AB2 Monomers for Dendrimer Construction
J . Org. Chem., Vol. 62, No. 4, 1997 915
powder (mp 112-113 °C). The enantiomeric excess was
determined by HPLC analysis on a Chiralcel OD column. 1H
NMR (400 MHz, acetone-d6) δ 7.89 (s, 1H), 7.88 (s, 1H), 6.92
(d, J ) 1.9 Hz, 1H), 6.80 (d, J ) 8.1 Hz, 1H), 6.74 (dd, J ) 2.0,
8.1 Hz, 1H), 4.71 (d, J ) 8.5 Hz, 1H), 3.8 (m, 1H), 3.7 (m, 1H),
3.55 (m, 1H), 1.46 (s, 3H), 1.40 (s, 3H); 13C NMR (100 MHz,
acetone-d6) d 145.9, 145.7, 131.4, 119.2, 115.9, 114.5, 109.1,
85.3, 79.8, 61.5, 27.47, 27.43; [R]D ) +18.0 (c ) 1.91, EtOH).
Anal. Calcd for C12H16O5: C, 59.99; H, 6.71. Found: C, 59.85;
H, 6.95.
the preparation of this manuscript. Acknowledgment
is made to the donors of The Petroleum Research Fund,
administered by the American Chemical Society, for
partial support of this research. This research is also
supported in part by the University of Connecticut
Research Foundation. M.E. was the recipient of a Pfizer
Summer Undergraduate Research Fellowship, for which
she is grateful.
Ack n ow led gm en t. We are grateful to Amy Howell
for helpful discussions and Bill Price for assistance with
J O961587W