The introduction of asymmetry into alkyl-decorated Frechet-type dendrons

Article abstract of DOI:10.1002/ejoc.200800134

A strategy for the introduction of asymmetry into Frechet-type dendrons bearing n-alkyl chains is described. Starting from a methyl 3,5-dihydroxybenzoate core, 3,5-bis(octyloxyphenyl) methoxy and 3,5-bis(alkoxyphenyl)methoxy units are introduced in a step

Full text of DOI:10.1002/ejoc.200800134

FULL PAPER
DOI: 10.1002/ejoc.200800134
The Introduction of Asymmetry into Alkyl-Decorated Fréchet-Type Dendrons
Edwin C. Constable,*[a] Stefan Graber,[a] B. A. Hermann,[b] Catherine E. Housecroft,*[a]
Michael S. Malarek,[a] and Lukas J. Scherer[a]
Keywords: Fréchet dendrons / Alkyl tails / Dendrimers / Asymmetry
A strategy for the introduction of asymmetry into Fréchet-
type dendrons bearing n-alkyl chains is described. Starting
mixed n-octyl/n-butyl, n-octyl/n-hexyl, n-octyl/n-heptyl and
n-octyl/n-dodecyl substituents. The new compounds have
from a methyl 3,5-dihydroxybenzoate core, 3,5-bis(octyloxy- been characterized by spectroscopic and mass spectrometric
phenyl)methoxy and 3,5-bis(alkoxyphenyl)methoxy units are
introduced in a stepwise manner. The method is illustrated
by the syntheses of four representative compounds having
techniques.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
monolayers. The dominant intermolecular interactions in
the monolayer arise from the interdigitation of the alkyl
chains. In efforts to control the topography of the mono-
layer, we considered the consequences of asymmetrical den-
drons with different-length alkyl chains, which are expected
to be non-commensurate and give novel structures. Fréchet-
type dendrons with different substituents in the 3- and 5-
positions are relatively rare, and in this paper, we report the
synthesis of asymmetric first- and second-generation den-
drons.
Introduction
Dendrimers and dendrons are becoming the scaffolds of
choice for multifunctional species and are finding applica-
tions in all areas of chemistry and physics.[1–5] One of the
ubiquitous core structures was introduced by Fréchet[6–8]
in which the key building blocks are 3,5-bis(alkoxybenzyl)
alcohols. Even though both convergent and divergent stra-
tegies are adopted, the critical growth steps involve reac-
tions of the nucleophilic 3,5-bis(phenoxides) with electro-
philic 3,5-bis(alkoxybenzyl) derivatives. Although prototype
Fréchet dendrimers are decorated with benzyloxy substitu-
ents, replacement by aliphatic alkoxy substituents leads to
novel hydrophobic species. Monolayers of Fréchet-type
dendrons that are rich in aromatic units may be clearly
imaged using scanning tunnelling microscopy (STM), and
octyl-decorated dendrons constructed from the 3,5-dihy-
droxybenzyl alcohol core have been central to a series of
STM studies reported to date.[6–11] Of relevance to this pa-
per are the highly resolved STM images[12–14] of 3,5-bis[3,5-
bis(octyloxyphenyl)methoxy]benzyl alcohol[12,15] and the re-
lated aldehyde[14] (Scheme 1). These long-chain octyl-decor-
ated Fréchet-type dendrons prove to be a powerful as-
sembly motif. Monolayers on highly oriented pyrolytic
graphite (HOPG) initially form with a pattern based on tri-
meric units, with a pseudo unit cell of seven molecules (one
of which remains highly mobile), and over time, the supra-
molecular ordering changes to a dimeric pattern. A combi-
nation of interdigitation of long alkyl chains, graphite–
methylene interactions, and graphite–aromatic ring π-stack-
ing interactions lead to the formation of particularly stable
Scheme 1. Octyl-decorated second-generation Fréchet-type den-
drons.[12,15]
Results and Discussion
Our strategy for the synthesis of symmetrical octyl-
decorated second-generation Fréchet-type dendrons
(Scheme 1) has been the conversion of 1-(hydroxymethyl)-
3,5-bis(octyloxy)benzene to the corresponding mesylate 1
followed by reaction with 3,5-dihydroxybenzyl alcohol. Oxi-
dation of the resultant alcohol leads to the corresponding
aldehyde. Following our STM investigations of these den-
[a] Department of Chemistry, University of Basel,
Spitalstrasse 51, 4056 Basel, Switzerland
Fax: +41-61-267-1018
E-mail: edwin.constable@unibas.ch
[b] WMI/CeNS, LMU Munich,
Walther-Meissner-Str. 8, 85748 Garching, Germany
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Introduction of Asymmetry into Alkyl-Decorated Fréchet-Type Dendrons
drons,[12] we decided to prepare the corresponding methyl metrical alkyl-decorated Fréchet-type dendrons. Our strat-
ester in order to study the effects of further altering the egy for the introduction of a second 3,5-bis(alkoxy)ben-
head group. While preparing a batch of 1, serendipitous use zyloxy substituent was the reaction of the corresponding
of non-optimal quantities of hydrochloric acid (added to 3,5-bis(alkoxy)benzyl methanesulfonate with methyl 3-[3,5-
quench excess methanesulfonyl chloride) during the workup bis(octyloxy)benzyloxy]-5-hydroxybenzoate (4). Treatment
led to crude 1 being contaminated with methanesulfonyl of 3 with LDA[18] at 0 °C in THF followed by addition of
chloride. Treatment of methyl 3,5-dihydroxybenzoate with aqueous HCl resulted in the formation of 4 in good yield
2 equiv. of the crude mesylate 1 in the presence of potas- (Scheme 3). The highest mass peak in the EI mass spectrum
sium carbonate and 18-crown-6[16,17] yielded the symmetri- of 4 corresponded to the parent ion (m/z = 514), while the
cal Fréchet-type dendron 2 as expected (Scheme 2). How- base peak (m/z = 347) confirmed fragmentation by loss of
ever, we observed that a second product, 3, was also the CH2C6H3(OC8H17)2 group. Complete NMR spectro-
formed. This product was never observed when adequate scopic assignments were made using COSY, NOESY,
HCl was added to completely remove excess methanesulfo- HMQC and HMBC techniques. The 13C NMR spectrum
nyl chloride during the workup of compound 1, and under of 4 closely resembles that of 3, except for the absence of
such conditions, compound 2 may be obtained in up to the signal for the mesylate Me group and a significant shift-
87% yield. Compounds 2 and 3 were separated by column ing of the signal for CA-5 from δ = 149.9 to 156.8 ppm. The
chromatography, with 2 being isolated as a yellow oil and 3 signals for CA-2, CA-4 and CA-6 also shift (from δ = 114.8,
as a white solid. The base peak (m/z = 861) in the EI mass 114.0 and 115.5 ppm in 3 to δ = 108.5, 107.5 and 109.6 ppm
spectrum of 2 corresponded to the parent ion with an iso- in 4, respectively). Except for the loss of the resonance for
1
1
tope pattern that matched the one simulated. The H and HSMe, the H NMR spectrum of 4 is almost identical to
13C NMR spectra indicated a symmetrical product, and the that of 3. The OH proton signal of 4 was not observed.
resonances for the mesylate methyl group, present in 1 at
The reactivity of 4 was first tested by investigating its
δ(1H) = 2.92 ppm and δ(13C) = 39 ppm, were absent. The reaction with benzyl bromide in the presence of K2CO3 and
13C and 1H NMR spectra were assigned by COSY, NOESY, 18-crown-6. Compound 5 (Scheme 3) was obtained in 85%
HMQC and HMBC techniques. The 1H and 13C NMR yield. A parent ion peak at m/z = 604 was observed in the
spectroscopic signatures of 3 confirmed the retention of a EI mass spectrum of 5, along with intense fragmentation
mesylate substituent [signals for the Me group at δ(1H) = peaks assigned to [CH2C6H3(OC8H17)2]+ (m/z = 347) and
3.15 ppm and δ(13C) = 37.8 ppm]. The asymmetry in the [M – CH2Ph]+ (m/z = 513). The 13C and H NMR spectra
1
structure of 3 is immediately apparent from the 13C NMR were fully assigned by using COSY, NOESY, DEPT,
spectrum which shows signals for carbon atoms CA-2, CA- HMQC and HMBC methods.
4 and CA-6 at δ = 114.8, 114.0 and 115.5 ppm, compared
We next turned our attention to the synthesis of four 3,5-
to resonances for CA-2,6 and CA-4 at δ = 108.6 and bis(alkoxy)benzyl methanesulfonates for introduction into
107.4 ppm in 2. The MALDI-TOF mass spectrum of 3 ex- the Fréchet-type dendrons. Scheme 4 summarizes the reac-
hibited a base peak at m/z = 634, assigned to [M + K]+.
tion strategy. Treatment of methyl 3,5-dihydroxybenzoate
The formation of 3 in addition to 2 can readily be ex- with 2 equiv. of RBr (R = n-butyl, n-hexyl, n-heptyl or n-
plained in terms of the presence of MeSO3Cl which dodecyl) in the presence of K2CO3 and 18-crown-6, resulted
provides an electrophile that competes with 1 during the in the formation of compounds 6–9. Crude compounds 6–
reaction with 3,5-dihydroxybenzoate. The isolation of com- 8 were isolated as oils and were characterized by mass spec-
pound 3 provided a starting point for the synthesis of asym- trometry and IR and NMR spectroscopy, with the latter
Scheme 2. Formation of a symmetrical octyl-decorated Fréchet dendron and the mesylate by-product used as a building block for the
asymmetrical dendrons. Ring labels for NMR spectroscopic assignments.
Eur. J. Org. Chem. 2008, 2644–2651
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E. C. Constable, C. E. Housecroft et al.
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Scheme 3. Synthetic pathway to the asymmetrical dendron 5. Ring labels for NMR spectroscopic assignments.
spectra being fully assigned (COSY, NOESY, HMQC and 17 was the reaction of each alcohol with methanesulfonyl
HMBC). These esters were used in the next steps of the chloride. Because of the highly reactive nature of com-
syntheses without further purification. Compound 9 was pounds 14–17, each was prepared in situ, although it
isolated as an analytically pure, white, crystalline solid. A proved possible to isolate 17 as a yellow solid. NMR spec-
parent ion was observed at m/z = 504 in the MALDI-TOF troscopy may be used to confirm the conversion of the
mass spectrum of 9, and the 1H and 13C NMR spectra were CH2OH group to the mesylate group, with characteristic
in accord with the expected symmetry of the structure.
signals appearing, for example, at δ = 2.9 ppm and δ =
Reduction of esters 6–9 with LiAlH4 in diethyl ether pro- 38.8 ppm in the H and 13C NMR spectra, respectively, for
duced the corresponding alcohols 10–13 in Ͼ90% yield. A the Me group in compound 17, or monitoring the shift
parent ion was observed in the EI mass spectrum of each from δ = 4.6 ppm for the CH2OH group to δ = 5.0 ppm for
of compounds 10–12, and in the MALDI-TOF mass spec- the CH2OSO2Me group in the 1H NMR spectrum on going
trum of 13. A comparison of the 13C NMR spectra of 6– from 13 to 17.
1
10 showed the expected loss of signals assigned to the ester
Asymmetrical alkyl-decorated Fréchet dendrons were
group in 6 and the appearance of a signal in each spectrum prepared by reactions of the octyl-decorated alcohol 4 with
arising from the methylene group of CH2OH unit. Similar mesylates 14–17 in the presence of K2CO3 and 18-crown-6
changes were observed on going from 7 to 11, 8 to 12, and (Scheme 5). Each of the n-octyl/n-butyl, n-octyl/n-hexyl, n-
9 to 13. The final step in the synthesis of the mesylates 14– octyl/n-heptyl and n-octyl/n-decyl derivatives 18–21 were
Scheme 4. Reaction scheme for the formation of mesylate building blocks.
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Eur. J. Org. Chem. 2008, 2644–2651

Introduction of Asymmetry into Alkyl-Decorated Fréchet-Type Dendrons
obtained in ca. 90% yield. The highest mass peak (m/z =
Experimental Section
788) in the MALDI-TOF mass spectrum of compound 18
was assigned to [M + K]+. For 19, a parent ion (m/z = 804)
was observed in the EI mass spectrum, with fragmentation
by loss of the CH2C6H3(OC8H17)2 (m/z = 347) and
CH2C6H3(OC6H13)2 (m/z = 291) groups. Similarly, the EI
mass spectra of 20 and 21 exhibited parent ions (m/z = 832
and 973, respectively) and fragmentation by loss of the
CH2C6H3(OR)2 groups. The asymmetry of the compounds
is not apparent in either their 13C or 1H NMR spectra,
because of coincidence of the signals for pairs of related
carbon (or proton) atoms in rings B and C (Scheme 5).
General: 1H and 13C NMR spectra were recorded with Bruker
Avance DPX 400 or DRX 500 spectrometers; the numbering
scheme adopted for the compounds is shown in the Schemes.
Chemical shifts for 1H and 13C NMR spectra are referenced to
residual solvent peaks with respect to TMS (δ = 0 ppm); all spectra
were recorded at ca. 298 K. MALDI-TOF and electron impact (EI)
mass spectra were recorded with PerSeptive Biosystems Voyager
and Finnigan MAT95Q mass spectrometers, respectively. Melting
points were recorded with a Stuart Scientific SMP3 melting point
apparatus. Methyl 3,5-dihydroxybenzoate was prepared according
to a literature route.[19]
However, the relative integrals of the proton signals for the Compound 1: Compound 1 was prepared according to a method
based on that previously reported.[12]
A solution of 1-(hy-
alkyl groups are consistent with the presence of two pairs
of different alkyl chains. Attempts to grow X-ray quality
crystals of compounds 18–21 were unsuccessful.
droxymethyl)-3,5-bis(octyloxy)benzene (6.00 g, 16.4 mmol) in
CH2Cl2 (50 mL) was cooled to –10 °C, and NEt3 (10 mL, 71 mmol)
was added. Methanesulfonyl chloride (5.0 mL, 65 mmol) was
added slowly over a period of 15 min. The reaction mixture was
stirred at –10 °C for 1 h, after which time it was poured into a
mixture of concentrated HCl (5 mL, see text) and crushed ice, and
extracted with CH2Cl2. The organic layer was washed with a satu-
rated solution of NaHCO3, dried with Na2SO4, and the solvent
removed to yield a brown oil. The crude product was used in the
next step without purification.
Compounds 2 and 3: K2CO3 (3.73 g, 27.0 mmol), methyl 3,5-dihy-
droxybenzoate (1.14 g, 6.79 mmol) and 18-crown-6 (53 mg,
0.20 mmol) were added to a solution of crude 1 (5.98 g, 13.5 mmol,
see text) in acetone (150 mL). The reaction mixture was heated un-
der reflux for 48 h, and then H2O (300 mL) was added. The organic
layer was extracted three times with CH2Cl2, and the combined
organic layers were dried with MgSO4. The solvent was then re-
moved. Column chromatography (SiO2; ethyl acetate/hexane, 1:3)
yielded 2 as a pale yellow oil (Rf = 0.71; 2.20 g, 2.56 mmol, 38%)
and 3 as a white solid (Rf = 0.29; 1.8 g, 3.0 mmol, 45%). 2: 1H
NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 12 H, Me), 1.23–
1.38 [m, 32 H, (CH2)4Me], 1.44 (m, 8 H, OCH2CH2CH2), 1.77 (m,
8 H, OCH2CH2), 3.90 (s, 3 H, OMe), 3.94 (t, J = 6.5 Hz, 8 H,
OCH2CH2), 4.98 [s, 4 H, CH2O(ringA)], 6.41 (t, J = 2.2 Hz, 2 H,
4-HB), 6.55 (d, J = 2.0 Hz, 4 H, 2-HB), 6.79 (t, J = 2.2 Hz, 1 H, 4-
HA), 7.28 (d, J = 2.2 Hz, 2 H, 2-HA) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.3 (Me), 22.9 (CH2), 26.3 (CH2), 29.5 (2CH2), 29.6
(CH2), 32.0 (CH2), 52.5 (OMe), 68.3 (OCH2CH2), 70.5 [CH2O-
(ringA)], 101.1 (CB-4), 105.9 (CB-2), 107.4 (CA-4), 108.6 (CA-2),
132.2 (CA-1), 138.8 (CB-1), 160.0 (CA-3), 160.7 (CB-3), 167.0 (C=O)
Scheme 5. Formation of asymmetrical alkyl-decorated Fréchet den-
drons. Ring labels for NMR spectroscopic assignments.
ppm. IR (neat): ν = 2950 (w), 2925 (s), 2870 (w), 2855 (m), 1725
˜
(m), 1596 (s), 1455 (m), 1446 (w), 1378 (w), 1347 (w), 1324 (m),
1299 (m), 1233 (w), 1168 (s), 1054 (m), 1006 (w), 849 (w), 832 (w),
767 (w), 680 (w), 634 (w) cm–1. EI-MS: m/z = 861 [M]+. C54H84O8
(861.2): calcd. C 75.31, H 9.83; found C 75.48, H 9.78. 3: M.p. 60–
Conclusions
1
We have detailed a strategy to introduce asymmetry into
61 °C. H NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H,
Fréchet-type dendrons bearing n-alkyl chains. Starting from Me), 1.23–1.38 [m, 16 H, (CH2)4Me], 1.44 (m,
4
H,
OCH2CH2CH2), 1.77 (m, 4 H, OCH2CH2), 3.15 (s, 3 H, SMe),
3.92 (s, 3 H, OMe), 3.94 (t, J = 7.0 Hz, 4 H, OCH2CH2), 5.03 [s,
2 H, CH2O(ringA)], 6.42 (t, J = 2.0 Hz, 1 H, 4-HB), 6.54 (d, J =
2.0 Hz, 2 H, 2-HB), 7.11 (t, J = 2.0 Hz, 1 H, 4-HA), 7.53 (m, 1 H,
6-HA), 7.63 (m, 1 H, 2-HA) ppm. 13C NMR (125 MHz, CDCl3): δ
= 14.3 (Me), 22.8 (CH2), 26.2 (OCH2CH2CH2), 29.4 (CH2), 29.5
(CH2), 32.0 (CH2), 37.8 (SMe), 52.7 (OMe), 68.3 (OCH2CH2), 70.8
[CH2O(ringA)], 101.2 (CB-4), 105.9 (CB-2), 114.0 (CA-4), 114.8
(CA-2), 115.5 (CA-6), 132.9 (CA-1), 137.9 (CB-1), 149.9 (CA-5),
a methyl 3,5-dihydroxybenzoate core, 3,5-bis(octyloxy-
phenyl)methoxy and 3,5-bis(alkoxyphenyl)methoxy units
are introduced in a stepwise manner. The method has been
illustrated by the syntheses and characterizations of four
representative compounds having mixed n-octyl/n-butyl, n-
octyl/n-hexyl, n-octyl/n-heptyl and n-octyl/n-dodecyl sub-
stituents. In a future paper, we shall report the results of
STM studies of monolayers of esters 18–21 which self-orga-
nize on HOPG surfaces and compare the two-dimensional
motifs with those formed by the symmetrical 2.[12]
159.9 (CA-3), 160.8 (CB-3), 165.7 (C=O) ppm. IR (neat): ν = 2922
˜
(m), 2867 (w), 2854 (m), 1738 (m), 1587 (m), 1472 (w), 1455 (m),
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E. C. Constable, C. E. Housecroft et al.
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1435 (m), 1362 (s), 1345 (m), 1329 (m), 1319 (w), 1292 (s), 1266
(w), 1220 (m), 1171 (s), 1131 (s), 1096 (m), 1067 (w), 1043 (m),
1004 (m), 963 (s), 947 (w), 876 (s), 827 (m), 812 (s), 766 (m), 732
(m), 682 (m), 638 (m), 623 (m) cm–1. MALDI-TOF MS: m/z = 634
[M + K]+. C32H48O8S (592.8): calcd. C 64.84, H 8.16; found C
64.98, H 8.26.
(1.0 g, 6.0 mmol). The reaction mixture was heated under reflux for
3 d, after which time all the solid material was removed by fil-
tration. The fitrate was collected and the solvent removed. After
the addition of water and CH2Cl2, the organic layer was collected,
dried with Na2SO4, and the solvent was removed; 6 was isolated
as a yellow oil and used in the next step without further purifica-
tion. 1H NMR (500 MHz, CDCl3): δ = 0.96 (t, J = 7.5 Hz, 6 H,
Me), 1.48 (m, 4 H, CH2Me), 1.75 (m, 4 H, OCH2CH2), 3.89 (s, 3
H, OMe), 3.97 (t, J = 6.5 Hz, 4 H, OCH2), 6.63 (t, J = 2.5 Hz, 1 H,
4-HAr), 7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.2 (Me), 19.6 (CH2Me), 31.5 (OCH2CH2), 52.4
(OMe), 67.8 (OCH2), 106.6 (CAr-4), 108.1 (CAr-2), 132.5 (CAr-1),
Compound 4: Compound 3 (1.00 g, 1.69 mmol) was dissolved in
THF (15 mL), and the solution was cooled to 0 °C. Freshly pre-
pared LDA (5.1 mmol in 10 mL THF) was added by syringe, and
the reaction mixture was stirred at 0 °C for 30 min, after which
time HCl (4 mL, 5% aqueous) was added. The product was ex-
tracted with ethyl acetate and then the solvent removed. Column
chromatography (SiO2; ethyl acetate/hexane, 1:2) yielded 4 as a
white solid (700 mg, 1.36 mmol, 80%). M.p. 49–52 °C. 1H NMR
(500 MHz, CDCl3): δ = 0.88 (t, J = 7.0 Hz, 6 H, Me), 1.25–1.32
[m, 16 H, (CH2)4Me], 1.42 (m, 4 H, OCH2CH2CH2), 1.76 (m, 4 H,
OCH2CH2), 3.90 (s, 3 H, OMe), 3.93 (t, J = 7.0 Hz, 4 H,
160.5 (CAr-3), 167.3 (C=O) ppm. IR (neat): ν = 2962 (m), 2878
˜
(m), 2852 (m), 1705 (s), 1597 (s), 1450 (m), 1358 (m), 1327 (m),
1304 (m), 1234 (m), 1165 (s), 1049 (m), 1003 (w), 949 (w), 910 (w),
849 (w), 764 (m), 741 (w), 679 (w), 617 (w) cm–1. EI-MS: m/z =
280 [M]+.
OCH2CH2), 4.99 [s, 2 H, CH2O(ringA)], 6.41 (t, J = 2.3 Hz, 1 H, Compound 7: 18-Crown-6 (350 mg, 1.3 mmol), K2CO3 (2.00 g,
4-HB), 6.55 (d, J = 2.3 Hz, 2 H, 2-HB), 6.66 (t, J = 2.0 Hz, 1 H, 4-
14.5 mmol) and 1-bromohexane (2.3 mL, 16 mmol) were added to
HA), 7.13 (m, 1 H, 6-HA), 7.24 (m, 1 H, 2-HA) ppm. 13C NMR an acetone (50 mL) solution of methyl 3,5-dihydroxybenzoate
(125 MHz, CDCl3): 14.3 (Me), 22.9 (CH2), 26.3 (1.0 g, 6.0 mmol). The reaction procedure and workup were as for
δ
=
(OCH2CH2CH2), 29.5 (2CH2), 29.6 (CH2), 32.0 (CH2), 52.5 6. Compound 7 was isolated as a yellow oil and used in the next
1
(OMe), 68.3 (OCH2CH2), 70.5 [CH2O(ringA)], 101.1 (CB-4), 105.9 step without further purification. H NMR (500 MHz, CDCl3): δ
(CB-2), 107.5 (CA-4), 108.5 (CA-2), 109.6 (CA-6), 132.4 (CA-1), = 0.90 (m, 6 H, Me), 1.30 (m, 8 H, CH2CH2Me), 1.44 (m, 4 H,
138.8 (CB-1), 156.8 (CA-5), 160.2 (CA-3), 160.8 (CB-3), 166.9 (C=O) OCH2CH2CH2), 1.76 (m, 4 H, OCH2CH2), 3.89 (s, 3 H, OMe),
ppm. IR (neat): ν = 3361 (br.), 2954 (w), 2942 (m), 2921 (m), 2849
(m), 1694 (m), 1607 (m), 1592 (s), 1470 (m), 1447 (m), 1392 (w),
3.96 (t, J = 6.5 Hz, 4 H, OCH2), 6.62 (t, J = 2.5 Hz, 1 H, 4-HAr),
7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C NMR (125 MHz,
˜
1372 (w), 1334 (m), 1321 (m), 1256 (m), 1244 (m), 1156 (s), 1141 CDCl3): δ = 14.2 (Me), 22.8 [(CH2)2Me], 25.9 (OCH2CH2CH2),
(s), 1117 (w), 1050 (s), 1026 (w), 1013 (w), 1009 (w), 999 (w), 990
(w), 957 (w), 861 (m), 852 (m), 823 (m), 766 (s), 728 (w), 712 (w),
675 (s), 640 (m) cm–1. EI-MS: m/z = 514 [M]+. C31H46O6 (514.7):
calcd. C 72.34, H 9.01; found C 71.86, H 9.22.
29.3 (OCH2CH2), 31.7 [(CH2)2Me], 52.4 (OMe), 68.5 (OCH2),
106.7 (CAr-4), 107.8 (CAr-4), 132.0 (CAr-1), 160.3 (CAr-3), 167.2
(C=O) ppm. IR (neat): ν = 2932 (m), 2862 (m), 1921 (w), 1852 (w),
˜
1720 (s), 1597 (s), 1512 (m), 1443 (s), 1350 (m), 1327 (m), 1304 (m),
1234 (m), 1165 (s), 1080 (w), 1049 (m), 1026 (w), 980 (w), 918 (m),
848 (m), 771 (s), 752 (w), 687 (w), 656 (w), 625 (m) cm–1. EI-MS:
m/z = 336 [M]+.
Compound 5: 18-Crown-6 (20.6 mg, 0.78 mmol), K2CO3 (161 mg,
1.17 mmol) and benzyl bromide (100 mg, 0.58 mmol) were added
to a solution of 4 (200 mg, 0.39 mmol) in acetone (15 mL). The
reaction mixture was heated at reflux for 48 h, after which time
water was added. The organic layer was extracted with CH2Cl2,
dried with MgSO4, and the solvent was removed. Column
chromatography (SiO2; ethyl acetate/hexane, 1:3) yielded 5 as a
Compound 8: 18-Crown-6 (500 mg, 1.86 mmol), K2CO3 (3.0 g,
21.8 mmol) and 1-bromoheptane (3.6 mL, 23 mmol) were added to
an acetone (80 mL) solution of methyl 3,5-dihydroxybenzoate
(1.5 g, 9.0 mmol). The reaction procedure and workup were as for
white solid (200 mg, 0.33 mmol, 85%). M.p. 38 °C. 1H NMR 6, and 8 was isolated as a yellow oil and used in the next step
1
(500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H, Me), 1.25–1.36
[m, 16 H, (CH2)4Me], 1.44 (m, 4 H, OCH2CH2CH2), 1.77 (m, 4 H,
OCH2CH2), 3.91 (s, 3 H, OMe), 3.94 (t, J = 6.5 Hz, 4 H,
OCH2CH2), 4.99 [s, 2 H, (ringB)CH2O], 5.07 [s, 2 H, (ringC)-
CH2O], 6.41 (t, J = 2.0 Hz, 1 H, 4-HB), 6.55 (d, J = 2.0 Hz, 2 H,
of the synthesis without further purification. H NMR (500 MHz,
CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H, Me), 1.26–1.35 (m, 12 H,
CH2), 1.44 (m, 4 H, OCH2CH2CH2), 1.76 (m, 4 H, OCH2CH2),
3.89 (s, 3 H, OMe), 3.93 (t, J = 6.5 Hz, 4 H, OCH2), 6.63 (t, J =
2.5 Hz, 1 H, 4-HAr), 7.15 (d, J = 2.5 Hz, 2 H, 2-HAr) ppm. 13C
2-HB), 6.80 (t, J = 2.0 Hz, 1 H, 4-HA), 7.29 (m, 2 H, 2,6-HA), 7.31– NMR (125 MHz, CDCl3): δ = 14.3 (Me), 22.8 (CH2), 26.2
7.45 (m, 5 H, HC) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.3
(OCH2CH2CH2), 29.3 (CH2), 29.4 (OCH2CH2), 32.0 (CH2), 52.4
(Me), 22.8 (CH2), 26.2 (OCH2CH2CH2), 29.4 (2CH2), 29.5 (CH2), (OMe), 68.5 (OCH2), 106.7 (CAr-4), 107.8 (CAr-2), 132.0 (CAr-1),
32.0 (CH2), 52.4 (OMe), 68.2 (OCH2CH2), 70.4 [(ringB)- 160.3 (CAr-3), 167.2 (C=O) ppm. IR (neat): ν = 2924 (s), 2854 (m),
˜
CH2O+(ringC)CH2O], 101.0 (CB-4), 105.8 (CB-2), 107.4 (CA-4),
1720 (s), 1597 (s), 1450 (m), 1381 (w), 1350 (w), 1327 (w), 1304 (w),
1234 (m), 1165 (s), 1057 (w), 849 (w), 771 (w), 679 (w), 633 (w)
108.5 (CA-2,6), 108.6 (CA-2,6), 127.7 (CC-2,3), 128.3 (CC-4), 128.8
(CC-2,3), 132.2 (CA-1), 136.6 (CC-1), 138.7 (CB-1), 159.9 (CA-3), cm–1. EI-MS: m/z = 364 [M]+.
160.7 (CB-3), 166.9 (C=O) ppm. IR (neat): ν = 2950 (w), 2919 (m),
˜
Compound 9: 18-Crown-6 (6.26 g, 23.7 mmol), K2CO3 (40.9 g,
2855 (m), 1717 (m), 1597 (s), 1468 (m), 1455 (m), 1445 (m), 1431
(m), 1386 (m), 1378 (m), 1348 (s), 1299 (s), 1256 (m), 1231 (m),
1171 (s), 1154 (m), 1128 (w), 1056 (s), 1027 (s), 998 (w), 867 (w),
847 (m), 826 (m), 776 (w), 765 (m), 745 (w), 695 (m), 689 (w), 674
(w), 640 (w) cm–1. EI-MS: m/z = 604 [M]+. C38H52O6 (604.8): calcd.
C 75.46, H 8.67; found C 75.21, H 8.63.
296 mmol) and 1-bromododecane (70.9 mL, 296 mmol) were added
to an acetone (190 mL) solution of methyl 3,5-dihydroxybenzoate
(9.95 g, 59.2 mmol). The reaction mixture was heated at reflux for
39 h, after which it was cooled to room temperature. White needles
of 9 formed and were removed by filtration and washed with Et2O.
Ethyl acetate (100 mL), Et2O (200 mL) and water (300 mL) were
added to the filtrate, and the organic layer was collected and dried
Compound 6: 18-Crown-6 (350 mg, 1.3 mmol), K2CO3 (2.00 g,
14.5 mmol) and 1-bromobutane (2.0 mL, 19 mmol) were added to with Na2SO4. The solvent was then removed to yield 9 as a while
an acetone (50 mL) solution of methyl 3,5-dihydroxybenzoate solid. The combined products were recrystallized twice from acte-
2648
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 2644–2651

Introduction of Asymmetry into Alkyl-Decorated Fréchet-Type Dendrons
tone to give 9 as a white solid (26.6 g, 52.7 mmol, 89.0%). M.p.
4 H, OCH2CH2), 3.93 (t, J = 6.5 Hz, 4 H, OCH2), 4.62 (s, 2 H,
CH2OH), 6.37 (t, J = 2.0 Hz, 1 H, 4-HAr), 6.50 (d, J = 2.0 Hz, 2
1
61 °C. H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.9 Hz, 6 H,
Me), 1.19–1.38 (m, 32 H, CH2), 1.39–1.49 (m, 4 H, CH2), 1.77 H, 2-HAr) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.3 (Me), 22.8
(quint, J = 7.0 Hz, 4 H, OCH2CH2), 3.89 (s, 3 H, OMe), 3.96 (t, J
[(CH2)3Me], 26.2 (OCH2CH2CH2), 29.3 [(CH2)3Me], 29.5
(OCH2CH2), 32.0 [(CH2)3Me], 65.7 (CH2OH), 68.2 (OCH2), 100.7
= 6.6 Hz, 4 H, OCH2), 6.63 (t, J = 2.3 Hz, 1 H, 4-HAr), 7.15 (d, J
= 2.4 Hz, 2 H, 2-HAr) ppm. 13C NMR (100 MHz, CDCl3): δ = 14.5 (CAr-4), 105.2 (CAr-2), 143.4 (CAr-1), 160.7 (CAr-3) ppm. IR (neat):
(Me), 23.1 (CH2), 26.4 (CH2), 29.6 (CH2), 29.8 (2CH2), 30.0
ν = 2924 (s), 2854 (s), 1597 (s), 1458 (s), 1381 (m), 1342 (w), 1327
˜
(3CH2), 30.1 (CH2), 32.3 (CH2), 52.6 (OMe), 68.7 (OCH2), 107.0 (w), 1296 (w), 1165 (s), 1057 (m), 903 (w), 833 (w), 679 (w), 640
(CAr-4), 108.0 (CAr-2), 132.2 (CAr-1), 160.5 (CAr-3), 167.4 (C=O)
(w), 594 (w) cm–1. EI-MS: m/z = 336 [M]+. C21H36O3 (336.5) calcd.
ppm. IR (neat): ν = 2919 (s), 2846 (m), 1720 (m), 1597 (m), 1466
C 74.95, H 10.78; found C 75.20, H 10.58.
˜
(m), 1443 (m), 1389 (w), 1319 (s), 1234 (s), 1119 (w), 1049 (m), 995
(m), 856 (w), 764 (w), 717 (w) cm–1. MALDI-MS: m/z = 504
[M]+. C32H56O4 (504.8): calcd. C 76.14, H 11.18; found C 76.27, H
10.92.
Compound 13: LiAlH4 (1.71 g, 45.0 mmol) in Et2O (500 mL) was
cooled to 0 °C, and 9 (18.0 g, 35.7 mmol) was added slowly over a
period of 1 h. The reaction mixture was heated under reflux for 5 h
and then stirred at room temperature overnight. NaOH (11 mL,
1 ) was added until a white precipitate formed. The solid was
filtered through Celite and washed thoroughly with Et2O and
water. Purification was as for 10, and compound 13 was isolated
as a white solid (16.0 g, 33.5 mmol, 94%). M.p. 41 °C. 1H NMR
(400 MHz, CDCl3): δ = 0.88 (t, J = 6.9 Hz, 6 H, Me), 1.20–1.38
(m, 32 H, CH2), 1.39–1.48 (m, 4 H, CH2), 1.62 (br. s, 1 H, OH),
1.76 (quint, J = 7.0 Hz, 4 H, OCH2CH2), 3.93 (t, J = 6.6 Hz, 4 H,
OCH2), 4.61 (s, 2 H, CH2OH), 6.37 (t, J = 2.3 Hz, 1 H, 4-HAr), 6.50
(d, J = 2.3 Hz, 2 H, 2-HAr) ppm. 13C NMR (100 MHz, CDCl3): δ
= 14.5 (Me), 23.1 (CH2), 26.5 (CH2), 29.7 (CH2), 29.8 (2CH2), 30.0
(3CH2), 30.1 (CH2), 32.3 (CH2), 65.9 (CH2OH), 68.5 (OCH2),
100.9 (CAr-4), 105.4 (CAr-2), 143.6 (CAr-1), 160.9 (CAr-3) ppm. IR
Compound 10: LiAlH4 (388 mg, 10.2 mmol) in Et2O (40 mL) was
cooled to 0 °C, and 6 (2.01 g, 7.17 mmol) was added slowly over a
period of 1 h. The reaction mixture was heated at reflux for 3 h
and then stirred at room temperature overnight. NaOH (6 mL, 1 )
was added until a white precipitate formed. The mixture was fil-
tered through Celite and the solid washed thoroughly with Et2O
and water. The organic layer was washed with water, and the aque-
ous layers were combined and extracted with Et2O. The organic
layers were combined and dried with MgSO4, and the solvent was
then removed; 10 was isolated as a yellow oil (1.72 g, 6.81 mmol,
1
95%). H NMR (500 MHz, CDCl3): δ = 0.97 (t, J = 7.5 Hz, 6 H,
Me), 1.48 (m, 4 H, CH2Me), 1.75 (m, 4 H, OCH2CH2), 1.82 (br. s,
1 H, OH), 3.94 (t, J = 6.5 Hz, 4 H, OCH2), 4.62 (s, 2 H, CH2OH),
(neat): ν = 3510 (br. w), 2916 (s), 2854 (m), 1589 (m), 1466 (m),
˜
1396 (w), 1312 (m), 1165 (m), 1011 (m), 833 (m), 710 (m) cm–1.
MALDI MS: m/z = 476 [M]+. C31H56O3 (476.8): calcd. C 78.09, H
11.84; found C 78.02, H 11.65.
6.38 (t, J = 2.5 Hz, 1 H, 4-HAr), 6.50 (d, J = 2.5 Hz, 2 H, 2-HAr
)
ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1 (Me), 19.5 (CH2Me),
31.5 (OCH2CH2), 65.7 (CH2OH), 67.9 (OCH2), 100.7 (CAr-4),
105.2 (CAr-2), 143.4 (CAr-1), 160.7 (CAr-3) ppm. IR (neat): ν = 2955
˜
Compound 18: A solution of 10 (230 mg, 0.91 mmol) in CH2Cl2
(10 mL) was cooled to –10 °C, and NEt3 (1.0 mL, 7.1 mmol) was
added. Methanesulfonyl chloride (0.40 mL, 5.2 mmol) was added
slowly over a period of 15 min. The reaction mixture was stirred at
–10 °C for 1 h, after which it was poured into a mixture of concen-
trated HCl (3 mL) and crushed ice and extracted with CH2Cl2. The
organic layer was washed with a saturated solution of NaHCO3,
dried with Na2SO4, and the solvent removed to yield a brown oil.
Crude 14 was used immediately without purification. Compound
14 (289 mg), 18-crown-6 (25.7 mg, 0.0972 mmol) and K2CO3
(269 mg, 1.94 mmol) were added to a solution of 4 (250 mg,
0.49 mmol) in acetone (15 mL). The reaction mixture was heated
under reflux for 48 h, after which time water was added. The or-
ganic layer was extracted with CH2Cl2, dried with MgSO4, and
solvent removed. Column chromatography (SiO2; ethyl acetate/hex-
(m), 2932 (m), 2870 (m), 1597 (s), 1458 (s), 1381 (m), 1342 (w),
1319 (w), 1296 (m), 1165 (s), 1041 (m), 833 (w), 671 (w), 640 (w),
594 (w) cm–1. EI-MS: m/z = 252 [M]+. C15H24O3 (252.3): calcd. C
71.39, H 9.59; found C 71.53, H 9.55.
Compound 11: LiAlH4 (358 mg, 9.42 mmol) in Et2O (40 mL) was
cooled to 0 °C, and 7 (1.98 g, 5.88 mmol) was added slowly over a
period of 1 h. The reaction mixture was heated under reflux for
3 h. and then stirred at room temperature overnight. NaOH (6 mL,
1 ) was added until a white precipitate formed. Purification was
as for 10. Compound 11 was isolated as a yellow oil (1.69 g,
5.47 mmol, 93%). 1H NMR (500 MHz, CDCl3): δ = 0.90 (t, J =
7.0 Hz, 6 H, Me), 1.33 [m, 8 H, (CH2)2Me], 1.45 (m, 4 H,
OCH2CH2CH2), 1.76 (m, 4 H, OCH2CH2), 3.93 (t, J = 6.5 Hz, 4
H, OCH2), 4.61 (s, 2 H, CH2OH), 6.38 (t, J = 2.0 Hz, 1 H, 4-HAr),
6.50 (d, J = 2.0 Hz, 2 H, 2-HAr) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.3 (Me), 22.8 [(CH2)2Me], 25.9 (OCH2CH2CH2),
29.4 (OCH2CH2), 31.8 [(CH2)2Me], 65.7 (CH2OH), 68.2 (OCH2),
100.7 (CAr-4), 105.2 (CAr-2), 143.4 (CAr-1), 160.7 (CAr-3) ppm. IR
1
ane, 1:3) yielded 18 as a yellow oil (300 mg, 0.40 mmol, 82%). H
NMR (500 MHz, CDCl3): δ = 0.88 (t, J = 6.5 Hz, 6 H, Me), 0.97
(t, J = 7.0 Hz, 6 H, Me), 1.23–1.39 [m, 16 H, (CH2)4Me(octyl)],
1.40–1.54 [m, 8 H, OCH2CH2CH2(octyl + butyl)], 1.76 [m, 8 H,
OCH2CH2(octyl + butyl)], 3.90 (s, 3 H, OMe), 3.94 [m, 8 H, OCH2-
(octyl + butyl)], 4.98 [s, 4 H, CH2O(ringA)], 6.40 (t, J = 2.0 Hz, 2
H, 4-HB+C), 6.55 (d, J = 2.0 Hz, 4 H, 2-HB+C), 6.79 (t, J = 2.5 Hz,
1 H, 4-HA), 7.27 (d, J = 2.5 Hz, 2 H, 2,6-HA) ppm. 13C NMR
(125 MHz, CDCl3): δ = 13.9 (Me), 14.2 (Me), 19.3 (CH2), 22.7
(neat): ν = 2924 (s), 2862 (m), 1597 (s), 1458 (s), 1381 (m), 1342
˜
(w), 1319 (w), 1296 (m), 1165 (s), 1057 (m), 833 (w), 679 (w), 586
(m) cm–1. EI-MS: m/z = 308 [M]+. C19H32O3 (308.5): calcd. C
73.98, H 10.46; found C 73.82, H 10.35.
Compound 12: LiAlH4 (250 mg, 6.58 mmol) in Et2O (30 mL) was (CH2), 26.1 (CH2), 29.3 (CH2), 29.4 (CH2), 31.0 (CH2), 31.3 (CH2),
cooled to 0 °C, and 8 (1.49 g, 4.09 mmol) was added slowly over a
period of 1 h. The reaction mixture was heated at reflux for 10 h,
after which time NaOH (4 mL, 1 ) was added until a white pre-
cipitate formed. The solid was filtered through Celite and washed
thoroughly with Et2O and water. Purification was as for 10. Com-
pound 12 was isolated as a yellow oil (1.29 g, 3.85 mmol, 94%). 1H
NMR (500 MHz, CDCl3): δ = 0.89 (t, J = 7.0 Hz, 6 H, Me), 1.25–
31.9 (CH2), 52.5 (OMe), 67.8 (OCH2CH2), 68.1 (OCH2CH2), 70.5
[CH2O(ringA)], 100.9 (CB+C-4), 105.7 (CB+C-2), 107.2 (CA-4), 108.3
(CA-2,6), 132.2 (CA-1), 138.8 (CB+C-1), 159.9 (CA-3), 160.7 (CB+C
-
3), 167.0 (C=O) ppm. IR (neat): ν = 2932 (m), 2878 (m), 1728 (m),
˜
1597 (s), 1450 (s), 1373 (m), 1342 (m), 1319 (m), 1296 (m), 1234
(w), 1165 (s), 949 (w), 833 (w), 771 (w), 679 (w), 640 (w), 617 (w)
cm–1. MALDI-MS: m/z = 788 [M + K]+. C46H68O8 (749.0): calcd.
1.38 [m, 12 H, (CH2)3Me], 1.44 (m, 4 H, OCH2CH2CH2), 1.76 (m, C 73.65, H 9.15; found C 73.70, H 9.17.
Eur. J. Org. Chem. 2008, 2644–2651
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2649

E. C. Constable, C. E. Housecroft et al.
FULL PAPER
Compound 19: NEt3 (1.0 mL, 7.1 mmol) was added to a solution
of 11 (280 mg, 0.908 mmol) in CH2Cl2 (10 mL) previously cooled
to –10 °C. Methanesulfonyl chloride (0.40 mL, 5.2 mmol) was
added slowly over a period of 15 min. The reaction mixture was
stirred at –10 °C for 1 h, after which time it was poured into a
mixture of concentrated HCl (3 mL) and crushed ice and extracted
with CH2Cl2. The organic layer was washed with a saturated solu-
tion of NaHCO3, dried with Na2SO4, and the solvent removed to
yield 15 as a brown oil. This crude product was used immediately
without further purification. Compound 15 (352 mg), 18-crown-6
(25.7 mg, 0.0972 mmol), and K2CO3 (269 mg, 1.94 mmol) were
added to a solution of 4 (250 mg, 0.486 mmol) in acetone (15 mL).
The reaction mixture was heated at reflux for 48 h, after which time
water was added. The organic layer was extracted with CH2Cl2,
dried with MgSO4, and the solvent removed. Column chromatog-
raphy (SiO2; ethyl acetate/hexane, 1:3) yielded 19 as a yellow oil
(360 mg, 0.447 mmol, 92%) 1H NMR (500 MHz, CDCl3): δ = 0.89
[m, 12 H, Me(octyl + hexyl)], 1.23–1.35 [m, 24 H, (CH2)(octyl +
hexyl)], 1.44 [m, 8 H, OCH2CH2CH2(octyl + hexyl)], 1.76 [m, 8
H, OCH2CH2(octyl + hexyl)], 3.89 (s, 3 H, OMe), 3.96 [m, 4 H,
OCH2(octyl/hexyl)], 3.93 [m, 4 H, OCH2(octyl/hexyl)], 4.98 [s, 4 H,
CH2O(ringA)], 6.40 (t, J = 2.0 Hz, 2 H, 4-HB+C), 6.55 (d, J =
2.0 Hz, 4 H, 2-HB+C), 6.79 (t, J = 2.5 Hz, 1 H, 4-HA), 7.28 (d, J =
2.5 Hz, 2 H, 2,6-HA) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.25
(Me), 14.3 (Me), 22.8 (CH2), 22.9 (CH2), 25.9 (OCH2CH2CH2),
26.3 (OCH2CH2CH2), 29.4 (CH2), 29.5 (2CH2), 29.6 (CH2), 31.8
(CH2), 32.0 (CH2), 52.5 (OMe), 68.3 [OCH2(octyl + hexyl)], 70.5
[CH2O(ringA)], 101.1 (CB+C-4), 105.9 (CB+C-2), 107.4 (CA-4), 108.5
ppm. IR (neat): ν = 2923 (m), 2854 (m), 1720 (m), 1597 (s), 1450
˜
(m), 1373 (w), 1342 (w), 1319 (w), 1296 (m), 1234 (w), 1165 (s),
1049 (m), 833 (m), 771 (w), 717 (w), 679 (w), 633 (w), 548 (w) cm–1.
EI-MS: m/z = 832 [M]+. C52H80O8 (833.2): calcd. C 74.96, H 9.68;
found C 74.61, H 9.58.
Compound 21: NEt3 (22 mL, 0.16 mol) was added to a solution of
13 (15.0 g, 0.314 mol) in CH2Cl2 (100 mL), previously cooled to
–10 °C. Methanesulfonyl chloride (9.7 mL, 0.13 mol) was added
slowly over a period of 20 min, and then the reaction mixture was
stirred at –10 °C for 1 h. The mixture was filtered, the filtrate
poured into a mixture of concentrated HCl (20 mL) and crushed
ice, and extracted with CH2Cl2. The organic layer was washed with
a saturated solution of NaHCO3, dried with Na2SO4, and the sol-
vent removed. Compound 17 was isolated as a yellow solid which
was pure by NMR spectroscopy. 17: 1H NMR (400 MHz, CDCl3):
δ = 0.88 (t, J = 6.9 Hz, 6 H, Me), 1.18–1.38 [m, 32 H, (CH2)8],
1.39–1.49 (m, 4 H, OCH2CH2CH2), 1.76 (quint, J = 7.0 Hz, 4 H,
OCH2CH2), 2.92 (s, 3 H, SMe), 3.92 (t, J = 6.6 Hz, 4 H,
OCH2CH2), 5.15 (s, 2 H, CH2OS), 6.45 (t, J = 2.2 Hz, 1 H, 4-HAr),
6.52 (d, J = 2.2 Hz, 2 H, 2-HAr) ppm. 13C NMR (100 MHz,
CDCl3): δ = 14.5 (Me), 23.1 (CH2), 26.4 (CH2), 29.6 (CH2), 29.8
(2CH2), 30.0 (3CH2), 30.1 (CH2), 32.3 (CH2), 38.8 (SO2CH3), 68.6
(OCH2), 72.0 (CH2OS), 102.5 (CAr-4), 107.3 (CAr-2), 135.6 (CAr
-
1), 161.1 (CAr-3) ppm. IR (neat): ν = 2916 (s), 2847 (w), 2600 (s),
˜
2492 (s), 1605 (w), 1474 (s), 1396 (m), 1342 (m), 1173 (s), 1034 (s),
972 (w), 926 (w), 849 (m), 810 (m), 648 (m) cm–1. Compound 17
(404 mg), 18-crown-6 (25.7 mg, 0.0972 mmol), K2CO3 (269 mg,
1.94 mmol) were added to a solution of 4 (250 mg, 0.486 mmol) in
acetone (15 mL) cm–1. The reaction mixture was heated at reflux
for 48 h. Water was then added and the organic layer extracted
with CH2Cl2, dried with MgSO4, and the solvent removed. Column
chromatography (SiO2; ethyl acetate/hexane, 1:3) gave 21 as a
white/yellow sticky solid (420 mg, 0.431 mmol, 89%). 1H NMR
(500 MHz, CDCl3): δ = 0.88 [m, 12 H, Me(octyl + dodecyl)], 1.22–
1.38 [m, 48 H, (CH2)(octyl + dodecyl)], 1.44 [m, 8 H, OCH2CH2-
CH2(octyl + dodecyl)], 1.77 [m, 8 H, OCH2CH2(octyl + dodecyl)],
3.90 (s, 3 H, OMe), 3.93 [t, J = 6.0 Hz, 8 H, OCH2(octyl + dode-
cyl)], 4.98 [s, 4 H, CH2O(ringA)], 6.41 (t, J = 2.2 Hz, 2 H, 4-HB+C),
6.55 (d, J = 2.0 Hz, 4 H, 2-HB+C), 6.79 (t, J = 2.2 Hz, 1 H, 4-HA),
7.28 (d, J = 2.0 Hz, 2 H, 2,6-HA) ppm. 13C NMR (125 MHz,
CDCl3): δ = 14.37 (Me), 14.39 (Me), 22.94 (CH2), 22.90 (CH2),
26.3 [OCH2CH2CH2(octyl + dodecyl)], 29.47 [OCH2CH2(octyl +
dodecyl)], 29.48 (CH2), 29.60 (2CH2), 29.64 (CH2), 29.82 (CH2),
29.85 (CH2), 29.88 (CH2), 29.91 (CH2), 32.0 (CH2), 32.1 (CH2),
52.5 (OMe), 68.3 [OCH2(octyl + dodecyl)], 70.5 [CH2O(ringA)],
101.0 (CB+C-4), 105.9 (CB+C-2), 107.3 (CA-4), 108.5 (CA-2,6), 132.1
(CA-1), 138.7 (CB+C-1), 159.9 (CA-3), 160.7 (CB+C-3), 167.0 (C=O)
(CA-2,6), 132.2 (CA1), 138.8 (CB+C-1), 159.9 (CA-3), 160.7 (CB+C
-
3), 167.0 (C=O) ppm. IR (neat): ν = 2955 (m), 2929 (s), 2871 (w),
˜
2857 (m), 1726 (m), 1597 (s), 1464 (m), 1455 (m), 1447 (m), 1435
(w), 1386 (w), 1349 (w), 1325 (w), 1300 (m), 1231 (w), 1166 (s),
1056 (w), 630 (w) cm–1. EI-MS: m/z = 804 [M]+. C50H76O8 (805.1):
calcd. C 74.59, H 9.51; found C 74.58, H 9.62.
Compound 20: A solution of 12 (330 mg, 0.98 mmol) in CH2Cl2
(10 mL) was cooled to –10 °C, and NEt3 (1.0 mL, 7.1 mmol) was
added. Methanesulfonyl chloride (0.40 mL, 5.2 mmol) was added
slowly over a period of 15 min, and the reaction mixture was then
stirred at –10 °C for 1 h. The mixture was then poured into a mix-
ture of concentrated HCl (3 mL) and crushed ice and extracted
with CH2Cl2. The organic layer was washed with a saturated solu-
tion of NaHCO3, dried with Na2SO4, and the solvent removed to
yield 16 as a brown oil. The crude product was used immediately
without further purification. Compound 16 (362 mg), 18-crown-6
(25.7 mg, 0.0972 mmol) and K2CO3 (269 mg, 1.94 mmol) were
added to a solution of 4 (250 mg, 0.49 mmol) in acetone (15 mL).
The reaction mixture was heated at reflux for 72 h, after which time
water was added. The organic layer was extracted with CH2Cl2,
dried with MgSO4, and the solvent removed. Column chromatog-
raphy (SiO2; ethyl acetate/hexane, 1:3) yielded 20 as a yellow oil
(350 mg, 0.420 mmol, 86%). 1H NMR (500 MHz, CDCl3): δ = 0.88
[m, 12 H, Me(octyl + heptyl)], 1.23–1.36 [m, 28 H, (CH2)(octyl +
heptyl)], 1.44 [m, 8 H, OCH2CH2CH2(octyl + heptyl)], 1.76 [m, 8
H, OCH2CH2(octyl + heptyl)], 3.90 (s, 3 H, OMe), 3.93 [m, 8 H,
OCH2(octyl + heptyl)], 4.98 [s, 4 H, CH2O(ringA)], 6.41 (t, J =
2.0 Hz, 2 H, 4-HB+C), 6.55 (d, J = 2.0 Hz, 4 H, 2-HB+C), 6.79 (t, J
= 2.0 Hz, 1 H, 4-HA), 7.28 (d, J = 2 Hz, 2 H, 2,6-HA) ppm. 13C
NMR (125 MHz, CDCl3): δ = 14.16 (Me), 14.17 (Me), 22.65
(CH2), 22.7 (CH2), 26.05 (OCH2CH2CH2), 26.1 (OCH2CH2CH2),
ppm. IR (neat): ν = 2956 (m), 2919 (s), 2871 (m), 2852 (m), 1719
˜
(m), 1595 (s), 1464 (m), 1438 (m), 1392 (w), 1369 (m), 1349 (m),
1337 (w), 1301 (m), 1239 (w), 1172 (s), 1146 (m), 1103 (w), 1056
(m), 836 (w), 829 (w), 761 (w), 683 (w), 668 (w) cm–1. EI-MS: m/z
= 973 [M]+. C62H100O8 (973.5): calcd. C 76.50, H 10.35; found C
76.41, H 10.29.
Acknowledgments
We thank the Swiss National Science Foundation, in part under
29.1 (CH2), 29.3 (3CH2), 29.4 (CH2), 31.83 (CH2), 31.86 (CH2), program NRP 47, the Swiss National Center of Competence in
52.5 (OMe), 68.3 [OCH2(octyl + heptyl)], 70.5 [CH2O(ringA)],
Research in Nanoscale Science, and the University of Basel for
financial support. We also thank Marc Häusler for helpful dis-
101.1 (CB+C-4), 105.9 (CB+C-2), 107.4 (CA-4), 108.5 (CA-2,6), 132.2
(CA-1), 138.8 (CB+C-1), 160.0 (CA-3), 160.7 (CB+C-3), 167.0 (C=O) cussion.
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Eur. J. Org. Chem. 2008, 2644–2651

Introduction of Asymmetry into Alkyl-Decorated Fréchet-Type Dendrons
[11]
L. J. Scherer, L. Merz, E. C. Constable, C. E. Housecroft, M.
Neuburger, B. A. Hermann, J. Am. Chem. Soc. 2005, 127,
4033–4041.
[1] Topics in Current Chemistry (Dendrimers) (Ed.: F. Vögtle),
Springer-Verlag, Berlin, 1998, vol. 197.
[2] Topics in Current Chemistry (Dendrimers II) (Ed.: F. Vögtle),
Springer-Verlag, Berlin, 2000, vol. 210.
[12]
L. Merz, H.-J. Güntherodt, L. J. Scherer, E. C. Constable, C. E.
Housecroft, M. Neuburger, B. A. Hermann, Chem. Eur. J.
2005, 11, 2307–2318.
B. A. Hermann, L. J. Scherer, E. C. Constable, C. E. Housec-
roft, Adv. Funct. Mater. 2006, 16, 221–235.
E. C. Constable, M. Häusler, B. A. Hermann, C. E. Housec-
roft, M. Neuburger, S. Schaffner, L. J. Scherer, CrystEngComm
2007, 9, 176–180.
[3] Topics in Current Chemistry (Dendrimers III) (Ed.: F. Vögtle),
Springer-Verlag, Berlin, 2001, vol. 212.
[4] Topics in Current Chemistry (Dendrimers IV) (Ed.: F. Vögtle),
Springer-Verlag, Berlin, 2001, vol. 217.
[5] Topics in Current Chemistry (Dendrimers V) (Eds.: C. A. Schal-
ley, F. Vögtle), Springer-Verlag, Berlin, 2003, vol. 228.
[6] C. J. Hawker, J. M. J. Fréchet, J. Am. Chem. Soc. 1990, 112,
7638–7647.
[13]
[14]
[15]
P. B. Rheiner, D. Seebach, Chem. Eur. J. 1999, 5, 3221–3226.
[16] G. W. Gokel, H. D. Durst, Synthesis 1976, 168–184.
[17] S. A. DiBiase, G. W. Gokel, J. Org. Chem. 1978, 43, 447–452.
[18] T. Ritter, K. Stanek, I. Larrosa, E. M. Carreira, Org. Lett.
2004, 6, 1513–1514.
[7] C. J. Hawker, J. M. J. Fréchet, J. Chem. Soc., Chem. Commun.
1990, 1010–1013.
[8] S. K. Grayson, J. M. J. Fréchet, Chem. Rev. 2001, 101, 3819–
3867.
[19] J. Zhu, R. Beugelmans, S. Bourdet, J. Chastanet, G. Roussi, J.
Org. Chem. 1995, 60, 6389–6396.
[9] I. Widmer, U. Hubler, M. Stöhr, L. Merz, H.-J. Güntherodt,
B. A. Hermann, P. Samorí, J. P. Rabe, P. B. Rheiner, G. Greiv-
eldinger, P. Murer, Helv. Chim. Acta 2002, 85, 4255–4263.
[10] E. C. Constable, B. A. Hermann, C. E. Housecroft, L. Merz,
L. J. Scherer, Chem. Commun. 2004, 928–929.
Received: February 4, 2008
Published Online: April 4, 2008
Eur. J. Org. Chem. 2008, 2644–2651
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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