Linear analogues of acid- and ester-terminated polyamido dendrimers: Design, syntheses, and physical properties

Article abstract of DOI:10.1002/ejoc.200300238

The synthesis of linear, unnatural amines and carboxylic acids, based on amide connectivity and possessing identical repeat unit architecture to that of analogous dendrimers, was undertaken to assess and compare their physical characteristics. For the series, unexpected insoluble behavior was observed at low molecular weights in contrast to their branched counterparts or other known linear dendritic analogs. Molecular modeling suggests a high degree of intra- and inter-molecular H-bonding for the series. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

Full text of DOI:10.1002/ejoc.200300238

FULL PAPER
Linear Analogues of Acid- and Ester-Terminated Polyamido Dendrimers:
Design, Syntheses, and Physical Properties
[a]
[a]
[b]
George R. Newkome,* Charles N. Moorefield, and Jon D. Epperson
Keywords: Hydrogenation / Amines / Dendrimers / Peptides
The synthesis of linear, unnatural amines and carboxylic
acids, based on amide connectivity and possessing identical
repeat unit architecture to that of analogous dendrimers, was
undertaken to assess and compare their physical character-
istics. For the series, unexpected insoluble behavior was ob-
served at low molecular weights in contrast to their branched
counterparts or other known linear dendritic analogs. Mo-
lecular modeling suggests a high degree of intra- and inter-
molecular H-bonding for the series.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
on a porphyrin core was reported; their ‘‘results clearly con-
firm the anticipation that dendrimers are unique when com-
The interesting physical properties of dendrimers arise in pared to other architectures’’.
part from their three-dimensional structures.[1Ϫ18] Unlike
Recent reports of unnatural peptides
linear polymers, dendrimers possess a highly branched, ported helical γ-tetra-, hexa-, and octapeptides,
‘tree-like’’ architecture with a large number of solvent ac- with the structural relationship between the monomers used
[27Ϫ42]
and the re-
[
43]
along
‘
cessible chain-terminating groups. Following the early in our 1Ǟ3 and 1Ǟ2 branched dendritic families, have pro-
stages of dendritic growth, the termini increase in number vided the impetus for the creation of the related gem-di-
and become major factors in defining physical properties; methyl γ-amino acid derivatives. We herein report a new
in contrast, the end groups of linear polymers remain rela- class of linear analogues corresponding to our well-defined
[
44,45]
tively constant during growth and, thus, play a diminishing acid- and ester-terminated polyamido dendrimers.
An
role with increasing molecular size. These inherent struc- exponential growth strategy[46] was employed to synthesize
tural differences lead to many of the observed changes that these monodisperse linear dimers, tetramers, and octamers,
[
47]
we see in the chemical and physical properties of dendri- using standard peptide [i.e., (DCC and 1-HOBT) and 2-
[
19Ϫ21]
mers versus linear polymers. Miller and co-workers
ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline
[
48]
[49]
have demonstrated that 1,3,5-phenylene-based dendrimers (EEDQ) ] coupling conditions.
Molecular modeling
are generally more soluble (ca. 10 times) than their oligo- studies, as well as H NMR spectroscopic data, of these
6
1
p-phenylene linear analogs. Likewise, Fr e´ chet et al.[
22,23]
no- polyamides suggest that self-aggregation may contribute to
ticed a similar correlation for their dendritic poly(aryl es- the increased insolubility of the larger analogues.
ter)s. Other physical properties have been monitored such
[
24]
[25]
[25]
as: size, viscosity, crystallinity, and thermal proper-
ties.[ For example, Fr e´ chet et al. deftly synthesized an Results and Discussion
exact linear isomer of a 5th-generation polyethereal den-
26]
[25]
drimer for comparison and showed that the dendrimer’s Synthesis of Linear Analogs
hydrodynamic volume was about 30% smaller than its lin-
The controlled Michael-type addition of tert-butyl acry-
ear analogue; interestingly, the former was also more reac-
tive toward catalytic hydrogenation than its linear counter-
part. More recently, an investigation[ on the influence of
poly(benzyl ether) dendrons vs. their exact linear analogues
[50]
late
to 2-nitropropane in refluxing EtOH afforded the
desired crystalline nitro ester 1 (Scheme 1), which was sup-
27]
13
ported ( C NMR) by the single carbonyl peak at δ ϭ
4°
1
8
71.3 ppm and two peaks at δ ϭ 87.4 (O NC ) and δ ϭ
2
4°
0.7 (Me C ) ppm as well as the correct mass (ESI MS) at
m/z ϭ 240.6 [M ϩ Na] . Hydrogenation of 1 with T-1
at 25 °C afforded (95%) the amino ester
monomer 2, which was characterized by an upfield shift of
the nitro quaternary carbon ( C NMR) resonance from
δ ϭ 87.4 ppm to δ ϭ 48.7 ppm (H NC ); no other signifi-
3
[
a]
Departments of Chemistry and Polymer Science,
The University of Akron,
ϩ
[
51]
1
70 University Cr., Akron, OH 44325-4717, USA
Raney nickel
Fax: (internat.) ϩ 1-330/972-2535
E-mail: newkome@uakron.edu
13
[
b]
School of Law, George Washington University,
Washington, DC 20052, USA
4°
2
3666
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200300238
Eur. J. Org. Chem. 2003, 3666Ϫ3672

Linear Analogues of Acid- and Ester-Terminated Polyamido Dendrimers
FULL PAPER
13
which was evidenced by the notable peak ( C NMR) shift
4°
4°
from δ ϭ 48.7 (H NC ) ppm to δ ϭ 53.3 (CONHC ) ppm
2
as well as the correct mass (ESI) value m/z ϭ 331.06 [M
ϩ
ϩ H] .
Catalytic (T-1 Raney nickel) hydrogenation of the nitro
moiety in dimer 4 gave rise to the terminal amine 6, struc-
13
turally characterized ( C NMR) by the shift of the signal
4
°
4°
at δ ϭ 87.8 (O NC ) ppm to δ ϭ 49.4 (H NC ) ppm, the
2
2
1
upfield ( H NMR) proton shifts at
δ
ϭ
1.49
4°
4°
[
O NC (CH ) ] ppm to δ ϭ 1.0 [NH C (CH ) ] ppm, and
2
3 2
2
3 2
4
°
4°
δ ϭ 2.15 (O NC CH ) ppm to δ ϭ 1.57 (H NC CH )
2
2
2
2
ppm, as well as the correct mass (ESI) at m/z ϭ 301.56 [M
ϩ
ϩ H] . Deprotection of the ester end group of dimer 4 with
formic acid provided (90%) the terminal acid 5, confirmed
by the typical loss of the 13C NMR resonances correspond-
ing to the tert-butyl group at δ ϭ 170.8 (CO R), 80.6
2
4°
4°
(
C Me ), and 28.0 [C (CH ) ] ppm along with the forma-
3 3 3
tion of a new signal at δ ϭ 178.2 (CO H) ppm.
2
Combination of amine 6 with acid 5 according to the
same coupling conditions (DCC and 1-HOBT) afforded
(
44%) the desired tetramer 7, as evidenced by the appropri-
13
ate C NMR shifts caused by amidation: δ ϭ 49.4
4°
4°
(H NC ) ppm to δ ϭ 53.15 (CONHC ) ppm. This new
2
4°
tetramer 7 possesses three slightly different CONHC
peaks at δ ϭ 53.2, 53.15, and 53.1 ppm and exhibits the
ϩ
correct mass (ESI) at m/z ϭ 557.3 [M ϩ H] . Two peaks
were also detected at m/z ϭ 501.3 and 454.5 corresponding
to the loss of the tert-butyl and nitro groups, respectively,
which was demonstrated in a related series of building
[
53,54]
blocks.
Catalytic hydrogenation (T-1 Raney nickel) of
the nitro terminus of tetramer of 7 generated (95%) the ter-
minal amine 9, whose structural conformation was sup-
13
ported by the shift of the C NMR resonance at δ ϭ 87.8
4
°
4°
(
(
O NC ) ppm to δ ϭ 53.9 (H NC ) ppm, the upfield shift
2
2
Scheme 1. Synthesis of the linear, amide-based unnatural peptides
cant changes were observed indicating that the rest of the
1
4°
H NMR) for peaks at δ ϭ 1.49 [O NC (CH ) ] ppm to
δ ϭ 1.15 [H NC (CH ) ] ppm and δ ϭ 2.15 (O NC CH )
ppm to δ ϭ 1.71 (H NC CH ) ppm, as well as the ob-
served correct mass (ESI) at m/z ϭ 527.8 [M ϩ H] . Depro-
2
3 2
4°
4°
2
3 2
2
2
4°
2
2
ϩ
tection of tetramer 7 with formic acid provided (92%) the
acid-terminated tetramer 8, as denoted by the loss ( C
NMR) of peaks corresponding to the tert-butyl ester at δ ϭ
13
1
molecule was intact. Its H NMR signals corresponding to
the methyl and methylene groups adjacent to the nitro qua-
1
70.8 (CO R), 80.6 (CMe ), and 28.0 [C(CH ) ] ppm
2 3 3 3
along with the appearance of a resonance at δ ϭ 177.8 ppm
CO H); the amide groups are stable towards these reac-
ternary carbon atom also shifted upfield from δ ϭ 1.49
(
2
4
°
4°
[
O NC (CH ) ] ppm to δ ϭ 1.21 [H NC (CH ) ] ppm and
2 3 2 2 3 2
tion conditions.
4
°
4°
from δ ϭ 2.13 (O NC CH ) ppm to δ ϭ 1.8 (H NC CH )
2
2
2
2
Using diverse variations of the DCC and 1-HOBT coup-
ling procedures, reagents 8 and 9 were recovered in toto, in
part because these monomers were not readily soluble in
DMF. To circumvent this problem, 2-ethoxy-N-(ethoxycar-
bonyl)-1,2-dihydroquinoline (EEDQ) was used to effect the
coupling in EtOH affording (74%) the nitro-terminated oc-
tamer 10; no purification was required, since the product
cleanly precipitated. This octamer 10 was generally insol-
uble in most organic solvents but readily dissolved in 95%
formic acid, from which the 13C and 1H NMR spectra
ppm, respectively, upon reduction. Care must be taken to
keep 2 below 40 °C to prevent the facile lactam formation
that occurs for γ-amino esters;[
52]
ester 2 was typically
stored at 0 °C to minimize cyclization. Treatment of ester 1
with 95% formic acid provided (91%) the monomer 3, as
1
3
shown ( C NMR) by the loss of resonances corresponding
4
°
to the tert-butyl group at δ ϭ 171.3 (CO R), 80.7 (C Me ),
2
3
4
°
and 27.8 [C (CH ) ] ppm and the appearance of a new acid
3
3
carbonyl peak at δ ϭ 178.6 (CO H) ppm.
2
The two key monomers (amine 2 and acid 3) were sub- could be acquired. As expected, acquisition of the NMR
jected to amidation by standard peptide coupling con- spectroscopic data had to be accomplished rapidly to avoid
ditions (DCC and 1-HOBT)[ to generate (40%) dimer 4, significant tert-butyl ester hydrolysis. Pertinent H NMR
47]
1
Eur. J. Org. Chem. 2003, 3666Ϫ3672
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3667

G. R. Newkome, C. N. Moorefield, J. D. Epperson
FULL PAPER
peaks for 10 include two broad signals at δ ϭ 2.05 and
1
.85 ppm corresponding to the linear chain methylene pro-
4
°
tons (C CH CH ), and three distinct methyl proton ab-
sorptions at δ ϭ 1.28 [O NC(CH ) ], 1.14 [C (CH ) ],
and 1.04 [HNC (CH ) ] ppm in a 2:3:12 ratio. The ESI
2
2
4
°
2
3 2
3 3
4
°
3
2
mass spectrum of octamer 10 exhibited the correct mass at
ϩ
m/z ϭ 1,009.8 [M ϩ H] .
Catalytic hydrogenation (T-1 Raney nickel) of the nitro
terminus in octamer 10 afforded (48%; presumably, increas-
ing chain length might necessitate the use of higher pres-
sures and longer reaction times) the desired terminal amine
1
2, whose structural conformation was supported by the
1
3
4°
C NMR shift of the peak at δ ϭ 87.8 (O NC ) ppm to
2
4
°
1
δ ϭ 53.9 (H NC ) ppm and by the observation of the H
2
NMR upfield shifts for the signals at
δ
ϭ
1.28
4
°
4°
[
O NC (CH ) ] ppm to δ ϭ 1.05 [H NC (CH ) ] ppm and
2
3 2
2
3 2
4
°
4°
δ ϭ 2.05 (O NC CH ) ppm to δ ϭ 1.61 (H NC CH )
2
2
2
2
ppm. The correct mass (ESI) for the amino ester 12 at
ϩ
m/z ϭ 980.2 [M ϩ H] was also obtained. Treatment of
octamer 10 with formic acid provided (90%) acid-termin-
1
ated octamer 11, as confirmed by the loss ( H NMR) of
the signals corresponding to the tert-butyl group, as noted
above, and the correct parent ion (ESI) at m/z ϭ 953.6 [M
ϩ
ϩ H] .
In general, these linear analogs of the acid- and ester-
terminated polyamidoamine dendrimers[
44,45]
are less sol-
uble and more crystalline than their dendritic counterparts.
This is in good agreement with the previous studies pre-
[
22]
[19Ϫ21]
sented by Fr e´ chet
and Miller
in aryl, convergently
generated dendrimers; however, the physical properties of
these linear analogs presented here are quite dramatic. For
example, the linear octamer 10, possessing only 8 repeat
units (1,009 Da) corresponding to an intermediate size be-
tween a first (4 repeats) and second (12 repeats) generation
polyamido dendrimer (Figure 1), was insoluble in all non-
polar organic solvents and formed a thermally reversible gel
in polar solvents such as DMF and nitrobenzene.
Figure 1. Idealized representations of 1st- and 2nd-generation poly-
In contrast, the physical properties of the polyethereal peptide dendrimers for comparison to the linear analogs
[
25]
linear analogs
do not change significantly until they are
as large as a 5th-generation polyethereal dendrimer (31 re- to δ ϭ 6.05 ppm) for amino ester 6 when progressing from
peats) with a molecular weight of 6,680 Da. This confirms a dilute to a concentrated sample; this fits with literature
[
55]
that the physical behavior of acid- and ester-terminated po- precedence.
lyamidoamine dendrimers is quite different from their re- The diminished solubility of the octamer 12 prevented its
spective linear analogs. Figure 2 shows elongated ball-and- addition to the acid-terminated dendrimers; however, the
stick models, with exaggerated methyl groups, of the nitro tetramer 9 was covalently linked to members of the acid-
acid tetramer 8 (Figure 2, a) and the nitro acid octamer 11 terminated dendrimers as demonstrated by the coupling of
[
56]
(
5
Figure 2, b) with measured extended lengths of 27.3 and the known tetraacid chloride
13 with a slight excess of
˚
3.5 A, respectively. Figure 2 (c) represents two octamers amine 9 in THF in the presence of Et N to afford (62%)
3
(
i.e., 11; they are shaded differently to aid in visualizing the 1st-generation dendritic core 14 (Scheme 2). The pres-
13
the intertwined chains) minimized together starting from ence ( C NMR) of two carbonyl peaks at δ ϭ 173.2
an elongated and perpendicular overlapping conformation. (CONH) and 170.9 ppm (CO R); three quaternary carbon
2
4
°
Notably, much of the exterior is occupied by the lipophilic peaks at δ ϭ 80.1 (Me C), 52.8 (four overlapped HNC ),
methyl groups; whereas, the heteroatom connectivity is ori- and 45.2 ppm (C CH ); seven distinct methylene peaks at
ented inward. This suggests that the unexpected insolubility δ ϭ 68.9 (C CH O), 67.4 (OCH CH ), 37.0 (OCH CH ),
at even these low molecular weights might be due to extens- 36.1 and 34.7 (C CH CH ), 31.8 and 30.5 (C CH CH )
ive intra- and intermolecular H-bonding. Other data sup- ppm; and three methyl peaks at δ ϭ 27.9 [C (CH ) ], 26.5
porting this conclusion includes the downfield shift and and 26.4 [C (CH ) ] ppm as well as ESI MS possessing m/
3
4
°
2
4
°
2
4
2
2
2
2
°
4°
2
2
2
2
4°
3
3
4°
3
2
broadening of the amide proton absorption (δ ϭ 5.85 ppm z ϭ 1230.7 corresponding to the doubly charged parent ion
3668
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org Eur. J. Org. Chem. 2003, 3666Ϫ3672

Linear Analogues of Acid- and Ester-Terminated Polyamido Dendrimers
(
FULL PAPER
CO H). The tetraacid 15 also showed (ESI) the parent ion
2
2ϩ
peak at m/z ϭ 1117.7 [M ϩ 2 H]
.
Conclusion
These simple, linear polyamides are but new members of
a growing family of extended, unnatural polypeptides,
which are physically interesting as related to either their
highly branched or natural, well-known counterparts. Even
at low molecular weights and low repeat unit number, these
materials show unexpectedly poor solubility in nonpolar
solvents due to H-bonding interactions, an attribute of
structural self-assembly. The complementary amine and es-
ter functionalities make these materials ideal for use as
spacer moieties in dendritic constructs.
Figure 2. Ball-and-stick representations of the nitro acids 8 (a) and
˚
1
1 (b) with measured lengths of 27.3 and 53.5 A, respectively, and
Experimental Section
two octamers 11 (c) minimized together resulting in aggregation
modeling, minimization, and dynamics were performed with
(
Cerius2 version 4.6 software by Accelrys, Inc.)
General Remarks: Melting point data were obtained in capillary
tubes with an Electrothermal 9100 melting point apparatus and are
1
13
3
uncorrected. H and C NMR spectra were obtained in CDCl ,
1
except where noted, and are recorded at 250.13 MHz. The H and
C NMR spectra of samples dissolved in formic acid were ob-
1
3
tained without a lock signal and were shimmed on the FID. Infra-
red spectra (IR) were obtained (KBr pellet, unless otherwise noted)
and recorded with an ATI Mattson Genesis Series FTIR spec-
trometer. Mass spectrometric data were obtained using an Esquire
electron ionization mass spectrometer (ESI) and are reported as:
(
relative intensity) [assignment]. ESI samples were typically pre-
pared in MeOH/H O/TFA (70:30:01) for positive ion mode or Me2-
CHOH/H O/NH (70:30:1) for negative ion mode. The 8-mer nitro/
ester, nitro/acid, and amino/ester samples were all first dissolved in
5% formic acid and then diluted 1:10 in MeOH/H O (4:1) before
loading into the ESI.
2
2
3
9
2
tert-Butyl 4,4-Dimethyl-4-nitropentanoate (1): A total of 1.2 equiv.
0.2 equiv. excess) of tert-butyl acrylate (172.6 g, 1.35 mol) was ad-
(
ded portionwise over 10 min to a refluxing solution of 2-nitropro-
pane (100 g, 1.12 mol) and Triton B (2.2 mL, 40% in MeOH) in
refluxing abs. EtOH (500 mL). After the tert-butyl acrylate was ad-
ded, additional Triton B (2.2 mL) was added and the mixture was
refluxed for 14 h. The solvent was removed in vacuo to afford a
2
crude light-yellow solid, which was recrystallized with EtOH/H O
1
3
to give (60%) the desired ester: 146 g; m.p. 63.7Ϫ65.1 °C.
C
4
°
NMR: δ ϭ 171.3 (CϭO), 87.4 (O
2
NC ), 80.7 (CMe
3
), 35.3
4
°
4°
4°
1
(
C CH
2
), 30.3 (C CH
2
CH
2
), 27.8 [C(CH
CH
] ppm. IR (KBr): ν˜ ϭ 1730 (ester CϭO), 1540
3
)
3
], 25.6 [C (CH
3
)
2
]. H
4
°
NMR: δ ϭ 2.13 (br., 4 H, CH
2
2
), 1.49 [s, 6 H, C (CH
3
)
2
], 1.34
4
°
[
(
s, 9 H, C (CH
3
)
3
Ϫ1
NO ), 1373 (NO ) cm . MS (ESI): m/z (%) ϭ 240.6 (100) [M
2
2
ϩ
ϩ Na] .
tert-Butyl 4,4-Dimethyl-4-aminopentanoate (2): A solution of nitro
ester 1 (40 g, 184 mmol) in abs. EtOH (300 mL) with T-1 Raney Ni
5
(
30 g, 50:50% Al/Ni) was hydrogenated (3.79 ϫ 10 Pa) at 25 °C
Scheme 2. Facile attachment of the tetramer 9 to a poly(acid chlo-
for 12 h. The solution was filtered through Celite to remove the
catalyst, using care to not let the filter pad become dry due to the
pyrophoric nature of the catalyst, and the solvent was removed in
vacuo to give (95%) the amino ester 2, as a clear liquid: 32.7 g.
ride)
ϩ
M ϩ 2 H]2 supported the transformation. Ester 14 was
[
subsequently hydrolyzed with formic acid to give (92%) the
tetraacid 15, as suggested by the loss of the signature ab-
sorptions corresponding to the tert-butyl groups along with NMR: δ ϭ 2.35 (t, J ϭ 8.3 Hz, 2 H, C CH CH ), 1.8 (t, J ϭ
the formation of a new acid peak at δ ϭ 177.5 ppm 8.3 Hz, 2 H, C CH
13
4°
C NMR: δ ϭ 173.1 (CϭO), 79.6 (CMe
3
), 48.7 (H
2
NC ), 39.1
4°
4°
4°
1
(
C CH
2
), 30.8 (C CH
2
CH
2
), 30.0 [C (CH
3
)
2
], 27.7 [C(CH ) ]. H
3 3
4
°
2
2
4
°
2
CH
2
), 1.55 [s, 9 H, C(CH
3
)
3
], 1.44 (s, 2 H,
Eur. J. Org. Chem. 2003, 3666Ϫ3672
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 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3669

G. R. Newkome, C. N. Moorefield, J. D. Epperson
FULL PAPER
4°
ϩ
ϩ
NH
287 (NH
41.2) [M ϩ H] , 132.3 (100) [M ϩ H Ϫ CMe
2
), 1.21 [s, 6 H, C (CH
3
)
2
] ppm. IR (neat): ν˜ ϭ 3355 (NH
2
),
(ESI): m/z (%) ϭ 323.28 (6.1) [M ϩ Na] , 301.56 (100) [M ϩ H] .
Ϫ1
3
(
2
), 1729 (ester CϭO) cm . MS (ESI): m/z (%) ϭ 188.2
ϩ
ϩ
4-mer 7: A stirred mixture of acid 5 (6.35 g, 23 mmol), 1-HOBT
3.13 g, 23 mmol), and DCC (4.8 g, 23 mmol) in DMF (100 mL)
3
] .
(
4
,4-Dimethyl-4-nitropentanoic Acid (3): Ester 1 (40 g, 184 mmol)
was maintained at 25 °C for 30 min, then amine 6 (6.95 g, 23 mmol)
was added. The mixture was stirred for an additional 18 h. The
solution was subsequently filtered through Celite and concentrated
was dissolved in formic acid (95%, 200 mL) and stirred at 25 °C
for 12 h. The excess formic acid was removed in vacuo, water was
added (200 mL), and the solution was again concentrated in vacuo
to ensure the absence of any residual formic acid affording (91%)
the acid 3, as a white solid: 27 g; m.p. 150Ϫ151 °C. C NMR: δ ϭ (5%, 200 mL). The solvent was removed in vacuo to afford the
1
2
in vacuo to give the crude product, which was dissolved in CH
2 2
Cl
(100 mL) and washed with 5% HCl (3 ϫ 200 mL), then aq. NaOH
13
4
°
4°
4°
78.6 (CO
5.7 [C (CH
2
H), 87.2 (O
2
1
NC ), 34.8 (C CH
2
), 29.1 (C CH
2 2
CH ), tetramer 7, which was recrystallized (EtOAc) to give (44%) the de-
4°
13
3
)
2
] ppm. H NMR: δ ϭ 11.2 (br., 1 H, CO
2
H), 2.29 sired product: 5.6 g; m.p. 189.3Ϫ190.3 °C. C NMR: δ ϭ 173.5,
4°
4°
4°
(
m, 2 H, C CH
2
), 2.16 (m, 2 H, C CH
] ppm. IR (KBr): ν˜ ϭ 3500Ϫ3000 (CO
), 1367 (NO
) cmϪ1. MS (ESI): m/z (%) ϭ 160.8 (100)
2
CH
2
), 1.47 [s, 6 H,
173.4, 173.3 (CONH), 170.8 (CO
2
R), 87.8 (O
2
NC ), 80.6 (CMe
3
),
4°
4°
4°
C (CH
1
3
)
2
2
H), 1674 (CϭO), 53.2, 53.15, 53.1 (HNC ), 35.9, 35.1 (C CH
2
), 31.8, 30.6
4°
4°
1
563 (NO
2
ϩ
2
(C CH
2
CH
2
), 28.0 [C(CH
3
)
3
], 26.5, 25.7 [C (CH
3
)
2
] ppm.
H
[M Ϫ H] .
NMR: δ ϭ 7.00, 6.92 (br., NH), 2.14 (m, 8 H, CH
2
CH
2
), 2.05 (m,
4
°
4°
2
1
H, O
2
NC CH
2
), 1.85Ϫ1.75 (m, J ϭ 7.4 Hz, 6 H, HNC CH
2
)
2-mer 4: A stirred mixture of nitro acid 3 (10.95 g, 68 mmol), 1-
4°
.48 [s, 6 H, O
2
NC (CH
3
)
2
], 1.35 [s, 9 H, C(CH
3
)
3
], 1.22 [br, 18 H,
HOBT (9.18 g, 68 mmol), and DCC (14.0 g, 68 mmol) in DMF
4°
HNC (CH
1
3
)
2
] ppm. IR (KBr): ν˜ ϭ 3284 (NH), 1729 (ester CϭO),
(100 mL) was maintained at 25 °C for 30 min, before amine 2
Ϫ1
2 2
642 (amide CϭO), 1546 (NO ), 1369 (NO ) cm . MS (ESI): m/
(12.71 g, 68 mmol) was added. The mixture was stirred for 18 h,
ϩ
ϩ
z (%) ϭ 557.3 (45.6) [M ϩ H] , 501.3 (100) [M ϩ H Ϫ CMe
3
] .
then filtered through Celite to remove the dicyclohexylurea. The
solvent was removed in vacuo to give the crude product, which was
4-mer Acid 8: Tetramer 7 (5 g, 90 mmol) was dissolved in formic
dissolved in CH
00 mL). After concentration in vacuo, the residue was recrys-
tallized (cyclohexane) to give (40%) the desired amide 4, as color-
2
Cl
2
(100 mL) and washed with water (3 ϫ, acid (95%, 200 mL) and stirred at 25 °C for 14 h. The workup was
2
similar to that of 3, and afforded (92%) acid 8, as a pure white
1
3
solid: 4.1 g; m.p. 176.3Ϫ177.7 °C. C NMR (CD
3
OD): δ ϭ 177.8
13
4°
less crystals: 8.9 g; m.p. 83Ϫ84.5 °C. C NMR: δ ϭ 173.5 (CO
2
H), 175.8, 173.8 (CONH), 89.0 (O
2
NC ), 54.3, 54.2, 54.0
), 33.1, 33.0, 32.6, 30.5
4
°
4°
4°
(
(
(
CONH), 170.8 (CO
2
R), 87.8 (O
2
NC ), 80.6 (CMe
3
), 53.3 (HNC ), 37.5, 37.3, 37.2, 35.7 (C CH
2
4°
4°
4°
4°
4°
1
HNC ), 35.9 (O
CH
2
NC CH
2
), 35.1 (HNC CH
R), 28.0 [C(CH
2
), 31.8
(C CH
2
CH
2
), 27.2, 27.1, 26.1 [C (CH
3
)
2
]
ppm.
H NMR
2
CONH), 30.6 (CH
2
4°
CO
2
3
)
3
], 26.5 (CD
3
OD): δ ϭ 11.0 (br., 1 H, CO
2
H), 6.15 (br., 3 H, CONH) 2.2
4°
] ppm. 1H NMR: δ ϭ 5.84 (m, 12 H), 1.9 (m, 4 H), 1.58 [s, 6 H, O
4°
[NHC (CH
3
)
2
], 25.7 [O
2
NC (CH
3
)
2
2
NC (CH
3
)
2
], 1.28 [s, 18
H), 3279
4
°
4°
(NH), 2.15 (m, 4 H, O
2
NC CH
2
, CH
2
CO
2
4°
R), 2.01 (m, 2 H,
H, HNC (CH
3
)
2
] ppm. IR (KBr): ν˜ ϭ 3500Ϫ3300 (CO
2
4°
Ϫ1
HNC CH
O
HNC (CH
amide CϭO), 1538 (NO
2
), 1.84 (t, J ϭ 7.4 Hz, 2 H, HNC CH
2
), 1.49 [s, 6 H, (NH), 1711 (acid CϭO), 1642 (amide CϭO), 1544 (NO ) cm .
2
4
°
4°
ϩ
2
NC (CH
3
)
2
], 1.35 [s,
9
H, C (CH
3
)
3
], 1.22 [s,
6
H, MS (ESI): m/z (%) ϭ 501.2 (100) [M ϩ H] .
4°
3 2
)
] ppm. IR (KBr): ν˜ ϭ 3333 (NH), 1689, 1667 (ester/
Ϫ1
4-mer Amine 9: A solution of nitro ester 7 (5 g, 90 mmol) in abs.
2
ϩ
2
), 1366 (NO ) cm . MS (ESI): m/z (%) ϭ
ϩ
EtOH (300 mL) with T-1 Raney Ni [10 g, Al/Ni (1:1)] was hydro-
3
53.19 (10.3) [M ϩ Na] , 275.13 (100) [M ϩ H Ϫ CMe
3
] .
5
genated (3.79 ϫ 10 Pa) at 25 °C for 14 h. The solution was filtered,
2
-mer Acid 5: Amide 4 (4 g, 12 mmol) was dissolved in formic acid
as in the procedure for compound 2, through Celite and the solvent
was removed in vacuo to give (95%) the amino ester 9, as a white
(95%, 200 mL) and stirred at 25 °C for 12 h. The workup was as
1
3
for 3 above to give (90%) 5, as a pure white solid: 3.0 g; m.p. solid: 4.5 g; m.p. 209.7Ϫ210.7 °C. C NMR (CD
1
3
OD): δ ϭ 175.8,
), 54.1, 53.9 (NHC ), 41.4, 37.3,
1
3
4°
20Ϫ122 °C. C NMR: δ ϭ 178.2 (CO
2
H), 171.7 (CONH), 87.9 175.7, 174.9 (CONH), 81.4 (CMe
3
4°
4°
4°
4°
4°
(O
2
NC ), 53.4 (HNC ), 36.0, 34.7 (C CH
2
), 31.7, 29.2
37.2, 35.7 (C CH
2
), 33.5, 33.1, 31.8 (C CH
2
CH
2
), 29.8, 28.7, 28.5,
OD): δ ϭ
CO), 1.95 (m, 6 H,
4°
4°
1
4°
1
(
C CH
H, CO
CH CO ), 2.05 (m, 2 H, O
.88 (t, J ϭ 7.4 Hz, 2 H, HNC CH
2
CH
2
), 26.5, 25.6 [C (CH
3
)
2
] ppm. H NMR: δ ϭ 11.0 (br.,
27.3 [C (CH
3
)
2
], 27.1 [C(CH
3
)
3
] ppm. H NMR (CD
3
1
2
H), 6.15 (br., 1 H, CONH) 2.21 (t, J ϭ 7.2 Hz, 2 H, 7.6, 7.5, 7.4 (CONH), 2.15 (m, 8 H, CH
2
4°
4°
4°
2
2
2
NC CH
2
), 1.95 (m, 2 H, CH
2
NH), HNC CH
2
), 1.71 (m, 2 H, H
2
NC CH
2
), 1.48 [s, 9 H, C(CH
3
)
3
],
]
4°
4°
4°
4°
1
1
3
2
), 1.43 [s, 6 H, O
2
NC (CH
3
)
2
], 1.33, 1.32 [s, 18 H, HNC (CH
3
)
2
], 1.15 [s, 6 H, H
2
NC (CH
3
)
2
4
°
.17 [s, 6 H, HNC (CH
3 2
)
] ppm. IR (KBr): ν˜ ϭ 3384 (NH), ppm. IR (KBr): ν˜ ϭ 3274 (NH), 1726 (ester CϭO), 1642 (amide
Ϫ1
Ϫ1
200Ϫ2900 (CO H), 1738 (acid CϭO), 1538 (NO
2
2
) cm . MS
2
CϭO), 1566 (NO ) cm . MS (ESI): m/z (%) ϭ 527.8 (100) [M
ϩ
ϩ
ϩ
(ESI): m/z (%) ϭ 297.1 (55.7) [M ϩ Na] , 275.2 (100) [M ϩ H] .
ϩ H] .
2
-mer Amine 6: A solution of the ester 4 (4 g, 12 mmol) in abs.
8-mer 10: Nitro acid 8 (100 mg, 2 mmol) and amine 9 (105 mg,
2 mmol) were dissolved in EtOH (ca. 5 mL) and refluxed, then
cooled and 2-ethoxy-N-(ethoxycarbonyl)-1,2-dihydroquinoline
(EEDQ; 54 mg, 22 mmol) was added; the mixture was stirred at 50
°C for 14 h. The mixture was subsequently cooled to 25 °C and the
resultant white precipitate was filtered and washed with EtOH (3
EtOH (300 mL) with T-1 Raney Ni [10 g, Al/Ni (1:1)] was hydro-
genated (3.79 ϫ 10 Pa) at 25 °C for 12 h. The solution was care-
5
fully filtered, as in the procedure for compound 2, through Celite,
then concentrated in vacuo to give (92%) the amino ester 6: 3.4 g;
m.p. 68.5Ϫ70 °C. 13C NMR: δ ϭ 173.6 (CONH), 172.9 (CO
R),
NC CH
CO R), 30.4
] ppm.
), 1.84 (t, J ϭ
), 1.57 (t, J ϭ 7.9 Hz,
2
4
°
4°
4°
8
3
0.6 (CMe
3
4
), 53.1 (CONHC ), 49.4 (H
2
NC ), 39.9 (H
2
2
), ϫ 5 mL) to yield (74%) the desired 8-mer 10: 150 mg; m.p.
°
13
5.2 (NHC CH
2
CH
], 28.1 [C(CH
NMR: δ ϭ 5.88 (CONH), 2.1 (m, 4 H, C CH
2
), 33.0 (CH
2
CONH), 30.7 (CH
2
2
250Ϫ251.5 °C. C NMR (HCO
2
H): δ ϭ 176.9 (CONH), 173.6
4
°
4°
1
4°
4°
[H
2
NC (CH
3
)
2
3
)
3
], 26.7 [NHC (CH
3
)
2
H
(CO
2
R), 87.8 (O
2
NC ), 82.5 (CMe
3
), 54.6 (HNC ), 35.8, 35.0
4
°
4°
4°
2
CH
2
(C CH
2
), 31.2, 30.3 (C CH
] ppm. H NMR (HCO
2
CH
2
), 26.8 [C(CH
3 3
) ], 25.4, 24.4, 19.7
4°
4°
1
7
2
.8 Hz, 2 H, HNC CH
2
), 1.61 (s, 2 H, NH
2
[C (CH
3
)
2
2
H): δ ϭ 7.18, 7.16, 7.1, 6.95
4°
4°
H, H
2
NC CH
2
), 1.33 [s, 9 H, C (CH
3
)
3
], 1.21 [s, 6 H, (br., 7 H, NH), 2.05, 1.85 (br., 32 H, CH
2
CH
], 1.04 [s, 42 H,
] ppm. IR (KBr): ν˜ ϭ 3280 (NH), 1730 (ester CϭO),
2
), 1.28 [s, 6 H,
4
°
4°
4°
HNC (CH
3
3
)
2
], 1.0 [s, 6 H, H
2
NC (CH
3
)
2
] ppm. IR (neat): ν˜ ϭ
O
2
NC (CH
3
)
2
], 1.14 [s,
9
H, C(CH
3
)
3
Ϫ1
4°
313 (NH
2
), 1726 (ester CϭO), 1646 (amide CϭO) cm . MS HNC (CH
3
)
2
3670
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2003, 3666Ϫ3672

Linear Analogues of Acid- and Ester-Terminated Polyamido Dendrimers
FULL PAPER
1
641 (amide CϭO), 1552 (NO
2
) cmϪ1. MS (ESI): m/z (%) ϭ 1047.7
Acknowledgments
We gratefully thank the National Science Foundation (DMR-
ϩ
ϩ
(100) [M ϩ K] , 1009.8 (34.1) [M ϩ H] .
8-mer Acid 11: A stirred mixture of ester 8 (120 mg, 12 mmol) in
9
0
901393 & 0196231), the Office of Naval Research (N00013-99-1-
082), and the Ohio Board of Regents for financial support.
formic acid (95%, 10 mL) was maintained at 25 °C for 14 h, then
worked up as for 3 affording (90%) the desired acid 11, as a pure
white solid: 100 mg; m.p. 246Ϫ248 °C. 13C NMR (HCO
H): δ ϭ
NC ), 54.6, 54.3 (HNC ),
2
[1]
4°
4°
G. R. Newkome, C. N. Moorefield, F. Vögtle, Dendrimers and
Dendrons: Concepts, Syntheses, Applications, Wiley-VCH,
Weinheim, Germany 2001.
[2]
1
79.1 (CO
2
H), 176.9 (CONH), 87.8 (O
2
4°
4°
3
5.8, 35.0, 33.3 (C CH
2
), 31.1, 28.6 (C CH
] ppm. H NMR (HCO H): δ ϭ 7.18, 7.20, 6.95 (br., 7
H, NH), 2.07, 1.85 (br., 32 H, CH CH ), 1.28 [s, 6 H,
] ppm. IR (KBr): ν˜ ϭ
H), 3280 (NH), 1717 (acid CϭO), 1641 (amide
2 2
CH ), 25.4, 24.4, 19.7
4°
1
[C (CH
3
)
2
2
Dendrimers and Other Dendritic Polymers (Eds.: J. M. J. Fr e´ -
chet, D. A. Tomalia), John Wiley & Sons, West Sussex, UK,
2
2
4°
4°
O
2
NC (CH
500Ϫ3300 (CO
CϭO), 1552 (NO
3 2 3 2
) ], 1.04 [s, 42 H, HNC (CH )
2
001.
[
3]
3
2
A. W. Bosman, H. M. Janssen, E. W. Meijer, Chem. Rev. 1999,
99, 1665Ϫ1688.
Ϫ1
2
) cm . MS (ESI): m/z (%) ϭ 975.4 (5.3) [M ϩ
[4]
ϩ
ϩ
I. P. Beletskaya, A. V. Chuchurjukin, Russ. Chem. Rev. 2000,
Na] , 953.6 (100) [M ϩ H] .
6
9, 639Ϫ660.
8-mer Amine 12: A stirred solution of ester 10 (150 mg, 15 mmol)
[5]
[6]
A.-M. Caminade, R. Laurent, B. Chaudret, J.-P. Majoral, Co-
ord. Chem. Rev. 1998, 178Ϫ180, 793Ϫ821.
in abs. EtOH (100 mL) with T-1 Raney Ni [2 g, Al/Ni (50:50)] was
hydrogenated (1.38 ϫ 10 Pa) at 115 °C for 14 h in a metal bomb.
6
J. M. J. Fr e´ chet, C. J. Hawker, in Comprehensive Polymer Chem-
istry, 2nd suppl. (Eds.: S. L. Aggarwal, S. Russo), Elsevier, Ox-
ford, UK, 1996, pp. 71Ϫ132.
The solution was filtered, as in the procedure for compound 2,
through Celite and the solvent was removed in vacuo to give (48%)
the amino ester 12, as a white solid: 70 mg; m.p. 245Ϫ246.5 °C.
[7]
C. J. Hawker, W. Devonport, in Step-Growth Polymers for High-
Performance Materials New Synthetic Methods (Eds.: J. L.
Hedrick, J. W. Labadie), American Chemical Society, Wash-
ington, D. C., 1996, pp. 186Ϫ196.
13
4°
C NMR (HCO
2
H): δ ϭ (CONH), 81.4 (C Me
3
), 54.1, 53.9
4°
4°
(HNC ), 41.4, 37.3, 37.2, 35.7 (C CH
2
), 33.5, 33.1, 31.8
], 27.1 [C(CH
H): δ ϭ 7.5, 7.4, 7.3 (CONH), 2.05 (m, 8
4°
4°
(C CH
2
CH
2
), 29.8, 28.7, 28.5, 27.3 [C (CH
3
)
2
3
)
3
]
[8]
[9]
B. Klajnert, M. Bryszewska, Acta Biochim. Pol. 2001, 48,
1
ppm. H NMR (HCO
H, CH CO), 1.85 (m,
H
HNC (CH
3
2
1
99Ϫ208.
4
°
2
6
H, HNC CH
2
), 1.61 (m,
], 1.23, 1.22 [s, 18 H,
] ppm. IR (KBr): ν˜ ϭ
2
H,
L. J. Twyman, A. S. H. King, I. K. Martin, Chem. Soc. Rev.
2002, 31, 69Ϫ82.
4
°
2
NC CH
2
), 1.38 [s, 9 H, C(CH
], 1.05 [s, 6 H, H
3
)
3
4
°
4°
[10]
)
2
2
NC (CH
3
)
2
M. Seiler, Chem. Eng. Technol. 2002, 25, 237Ϫ253.
I. Gitsov, in Advances in Dendritic Macromolecules (Ed.: G.
R. Newkome), Elsevier Science Ltd., Kidlington, Oxford, UK,
2002, pp. 45Ϫ87.
S. M. Grayson, J. M. J. Fr e´ chet, Chem. Rev. 2001, 101,
3819Ϫ3867.
D. Astruc, F. Chardac, Chem. Rev. 2001, 101, 2991Ϫ3023.
A. M. Muzafarov, E. A. Rebrov, Vysokomol. Soedin., Ser. A
2000, 42, 2015Ϫ2040.
3
[11]
2
279 (NH), 1731 (ester CϭO), 1641 (amide CϭO), 1553 (NO )
Ϫ1
ϩ
cm . MS (ESI): m/z (%) ϭ 1008.0 (77.0) [M ϩ Na] , 980.2 (100)
ϩ
[M ϩ H] .
[12]
4
؋ 4 Ester 14: To a refluxing solution of amine 9 (1.53 g,
[
[
13]
14]
2.9 mmol) and Et N (300 mg, 2.9 mmol) in dry THF (50 mL) was
3
added dropwise, the tetraacid chloride 13 (320 mg, 646 mol), pre-
pared from the corresponding tetracarboxylic acid,[
57]
in THF
[
[
15]
16]
K. Inoue, Prog. Polym. Sci. 2000, 25, 453Ϫ571.
F. Vögtle, S. Gestermann, R. Hesse, H. Schwierz, B. Windisch,
Prog. Polym. Sci. 2000, 25, 987Ϫ1041.
(10 mL) over 30 min. The solution was then refluxed for 14 h then
the solvent was removed in vacuo to give the crude product, which
was dissolved in MeOH (5 mL) and dialyzed against MeOH (3 ϫ
1
[17]
S. Hecht, J. M. J. Fr e´ chet, Angew. Chem. Int. Ed. 2001, 40,
000 mL) using a 1000 MWCO dialysis membrane (regenerated
7
5Ϫ91.
[18]
cellulose) to afford (62%) the ester 14: 980 mg; m.p. 177Ϫ179 °C.
M. W. P. L. Baars, E. W. Meijer, Top. Curr. Chem. 2000, 210,
131Ϫ227.
13
C NMR: δ ϭ 173.2 (CONH), 170.9 (CO
2
4°
R), 80.1 (CMe
3
), 68.9
), 37.0
CH ),
2 2
[
[
19]
20]
4°
4°
T. M. Miller, T. X. Neenan, Chem. Mater. 1990, 2, 346Ϫ349.
T. M. Miller, T. X. Neenan, R. Zayas, H. E. Bair, J. Am. Chem.
Soc. 1992, 114, 1018Ϫ1025.
(
(
2
6
C CH
OCH CH
7.9 [C(CH
.97, 6.32 (br., 12 H, CONH), 3.52 (br., 8 H, OCH
2
O), 67.4 (OCH
2
CH
2
), 52.8 (HNC ), 45.2 (C CH
2
4°
4°
2
2
), 36.1, 34.7 (C CH
2
CH ), 31.8, 30.5 (C CH
] ppm. 1H NMR: δ ϭ 7.0,
3 2
], 26.5, 26.4 [C (CH )
2
4°
3
)
3
[21]
T. M. Miller, E. W. Kwock, T. X. Neenan, Macromolecules
2
CH ), 3.22
), 2.1 (m, 32 H,
), 1.32 [s, 36 H,
2
1
992, 25, 3143Ϫ3148.
4°
(br., 8 H, C CH
2
O), 2.23 (br., 8 H, OCH
2
CH
2
[22]
[23]
K. L. Wooley, J. M. J. Fr e´ chet, C. J. Hawker, Polymer 1994,
5, 4489Ϫ4495.
4
°
4°
C CH
C (CH
2
CH
2
), 1.85 (m, 32 H, C CH
2
CH
2
3
4°
4°
)
3
], 1.20 [s, 96 H, C (CH
3
)
2
] ppm. IR (KBr): ν˜ ϭ 3307
´
3
C. J. Hawker, J. M. J. Frechet, in Step-Growth Polymers for
High-Performance Materials New Synthetic Methods (Eds.: J.
L. Hedrick, J. W. Labadie), American Chemical Society, Wash-
ington, D. C., 1996, pp. 132Ϫ144.
Ϫ1
(NH), 1732 (ester CϭO), 1647 (amide CϭO), 1547 cm . MS
2ϩ
(ESI): m/z (%) ϭ 1230.7 (100) [M ϩ 2 H]
.
4
؋ 4 Acid 15: A stirred mixture of ester 14 (880 mg, 36 mmol) in
[24]
C. J. Hawker, E. E. Malmström, C. W. Frank, J. P. Kampf, J.
Am. Chem. Soc. 1997, 119, 9903Ϫ9904.
T. H. Mourey, S. R. Turner, M. Rubinstein, J. M. J. Fr e´ chet,
C. J. Hawker, K. L. Wooley, Macromolecules 1992, 25,
2401Ϫ2406.
K. L. Wooley, C. J. Hawker, J. M. Pochan, J. M. J. Fr e´ chet,
Macromolecules 1993, 26, 1514Ϫ1519.
E. M. Harth, S. Hecht, B. Helms, E. E. Malmström, J. M. J.
Fr e´ chet, C. J. Hawker, J. Am. Chem. Soc. 2002, 124,
formic acid (95%, 10 mL) was maintained at 25 °C for 15 h, then
worked up as described above for 3, to yield (92%) the desired acid
1
[25]
5, as a pure white solid: 730 mg; m.p. 159Ϫ161 °C. 13C NMR
(
(
(
3 2
CD OD): δ ϭ 177.5 (CO H), 175.6, 173.4 (CONH), 70.6
C CH
OCH CH
[
[
26]
27]
4°
4°
4°
2
O), 68.9 (OCH
2
), 54.2, 54.1 (HNC ), 46.6 (C CH
2
), 38.5
), 27.2,
3
OD): δ ϭ 7.58 (br., 16 H, CONH),
4°
4°
2
2
), 37.2, 35.6 (C CH ), 33.1, 30.4 (C CH CH
2 2 2
4
°
1
27.1 [C (CH
3
)
2
]. H NMR (CD
CH ), 3.4 (br., 8 H, C CH
4°
3.65 (br., 8 H, OCH
2
2
2
O), 2.4 (br., 8 H,
), 2.05 (br., 32 H,
3
926Ϫ3938.
4°
OCH
C CH CH
2
CH
2
), 2.2 (br., 32 H, C CH
2
CH
2
[28]
[29]
S. Abele, K. Vögtli, D. Seebach, Helv. Chim. Acta 1999, 82,
4°
4°
), 1.30 [s, 96 H, C (CH
3
)
2
]. IR (KBr): ν˜ ϭ 3315 (NH),
2
2
1539Ϫ1558.
Ϫ1
3
(
082, 1715 (acid CϭO), 1651 (amide CϭO) cm . MS (ESI): m/z
S. Abele, P. Seiler, D. Seebach, Helv. Chim. Acta 1999, 82,
1559Ϫ1571.
%) ϭ 1117.7 (100) [M ϩ 2 H]2
ϩ
.
Eur. J. Org. Chem. 2003, 3666Ϫ3672
www.eurjoc.org
 2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3671

G. R. Newkome, C. N. Moorefield, J. D. Epperson
FULL PAPER
[
[
[
30]
31]
32]
[42]
A. Boeijen, R. M. J. Liskamp, Eur. J. Org. Chem. 1999,
127Ϫ2135.
B. T. Burlingham, T. S. Widlanski, J. Am. Chem. Soc. 2001,
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