Incorporation of substituents at the methylene linkages of the calix[5]arene skeleton

Article abstract of DOI:10.1021/jo901450x

(Chemical Equation Presented) Under S_N1 reaction conditions, the bromine atoms of the pentabromo p-tert-butylcalix[5]arene 6 were replaced by alkoxy, electron-rich aryl, and acetylacetonate groups.

Full text of DOI:10.1021/jo901450x

pubs.acs.org/joc
bridges (3a,b and 4a, respectively).8,9 We have recently
Incorporation of Substituents at the Methylene
Linkages of the Calix[5]arene Skeleton
reported that the bromocalixarene derivatives 3a,b and 4a
react with O-, N-, and even some C-nucleophiles under SN1
reaction conditions, yielding fully monosubstituted methy-
lene-functionalized calix[4]- and calix[6]arenes.9,10 Attrac-
tive features of this facile reaction are (i) Lewis acid or dry
solvents are not required and (ii) purification of the product
is typically conducted by simple recrystallization. In most
cases, the all-cis isomer product was isolated, while a mixture
Katerina Kogan and Silvio E. Biali*
Institute of Chemistry, The Hebrew University of Jerusalem,
Jerusalem 91904, Israel
silvio@vms.huji.ac.il
Received July 7, 2009
of isomers was obtained in the reaction of 3a with the reactive
- 9b
and sterically unhindered nucleophiles SCN- or N3
.
Incorporation of substituents at the bridges of the calix
scaffold is of interest since these groups may be involved in
stabilizing interactions with a putative guest, thus affecting
the binding properties of the macrocycle. The substituents at
the bridge may affect the binding properties of the calixarene
in an indirect fashion by modifying the intrinsic conforma-
tional preferences of the calixarene scaffold. For example,
whereas tetramethoxycalix[4]arene 1 exists in CDCl3 solu-
tion as a conformational mixture where the partial cone form
is the major conformer,11 NMR data of the rccc form of the
methylene-functionalized calix[4]arene 3c are consistent with
a pinched cone conformation. Additionally, the presence of
substituents at the bridges may affect the rigidity of the
system. In contrast to the parent 2, NMR data indicate that
the pinched cone conformation of hexamesityl calix[6]arene
4b is conformationally rigid.
Under SN1 reaction conditions, the bromine atoms of the
pentabromo p-tert-butylcalix[5]arene 6 were replaced by
alkoxy, electron-rich aryl, and acetylacetonate groups.
Although numerous synthetic routes have been developed
for the functionalization of the aromatic rings of the calix-
arenes,1 only a handful of methods are available for the
chemical modification of the methylene bridges.2-7Radical
bromination of the calixarene methyl ethers 1a,b and 2
affords derivatives incorporating bromine groups at the
€
(1) For reviews on calixarenes see: (a) Bohmer, V. Angew. Chem., Int. Ed.
Engl. 1995, 34, 713. (b) Gutsche, C. D. Calixarenes Revisited; Royal Society of
€
Chemistry: Cambridge, UK, 1998. (c) Bohmer, V. In The Chemistry of Phenols;
Rappoport, Z., Ed.; Wiley: Chichester, UK, 2003; Chapter 19. (d) Gutsche, C. D.
Calixarenes. An Introduction, 2nd ed.; Royal Society of Chemistry: Cambridge,
UK, 2008.
€
(2) Fragment condensation: (a) Tabatabai, M.; Vogt, W.; Bohmer, V.
Tetrahedron Lett. 1990, 31, 3295. (b) Sartori, G.; Maggi, R.; Bigi, F.; Arduini,
A.; Pastorio, A.; Porta, C. J. Chem. Soc., Perkin Trans. 1 1994, 1657. (c) Biali,
€
€
S. E.; Bohmer, V.; Cohen, S.; Ferguson, G.; Gruttner, C.; Grynszpan, F.;
Paulus, E. F.; Thondorf, I.; Vogt, W. J. Am. Chem. Soc. 1996, 118, 2261.
(d) Tsue, H.; Enyo, K.; Hirao, K. Org. Lett. 2000, 2, 3071. (e) For a review on
the synthesis of calixarenes via the stepwise and fragment condensation
The present study was conducted to examine whether this
synthetic methodology can also be applied to the functiona-
lization of the methylene bridges of the calix[5]arene skele-
ton. Calix[5]arenes are attractive potential hosts since their
cavity is larger than that of calix[4]arenes, but in contrast to
the larger calixarenes, they still may adopt nearly symmetric
cone conformations.
€
methods see: Bohmer, V. Liebigs Ann./Recl. 1997, 2019.
(3) Spirodienone route: Agbaria, K.; Biali, S. E. J. Am. Chem. Soc. 2001,
123, 12495.
(4) Homologous anionic ortho Fries rearrangement: Middel, O.; Greff,
Z.; Taylor, N. J.; Verboom, W.; Reinhoudt, D. N.; Snieckus, V. J. Org.
Chem. 2000, 65, 667.
(5) Lithiation/alkylation: Scully, P. A.; Hamilton, T. M.; Bennett, J. L.
Org. Lett. 2001, 3, 2741.
(6) Addition of organolithium reagents to ketocalixarenes: Kuno, L.;
Seri, N.; Biali, S. E. Org. Lett. 2007, 9, 1577.
Bromination of Pentamethoxy p-tert-Butylcalix[5]arene.
The pentrabromo p-tert-butylcalix[5]arene derivative 6 was
€
(7) Oxidation of the methylene bridges: (a) Gormar, G.; Seiffarth, K.;
Schultz, M.; Zimmerman, J.; Flamig, G. Macromol. Chem. 1990, 191, 81.
(b) Matsuda, K.; Nakamura, N.; Takahashi, K.; Inoue, K.; Koga, N.;
Iwamura, H. J. Am. Chem. Soc. 1995, 117, 5550. (c) Seri, N.; Simaan, S.;
Botoshansky, M.; Kaftory, M.; Biali, S. E. J. Org. Chem. 2003, 68, 7140. (d)
Kogan, K.; Biali, S. E. Org. Lett. 2007, 9, 2393.
€
(9) (a) Columbus, I.; Biali, S. E. Org. Lett. 2007, 9, 2927. (b) Columbus, I.;
Biali, S. E. J. Org. Chem. 2008, 73, 2598. (c) Kogan, K.; Columbus, I.; Biali,
S. E. J. Org. Chem. 2008, 73, 7327.
(10) For examples of silver-mediated substitutions in bromodienone
calix-arene derivatives see: Troisi, F.; Pierro, T.; Gaeta, C.; Neri, P. Org.
Lett. 2009, 11, 697.
€
(8) Bromination of the methylene bridges: (a) Klenke, B.; Nather, C.;
Friedrichsen, W. Tetrahedron Lett. 1998, 39, 8967. (b) Kumar, S. K.; Chawla,
H. M.; Varadarajan, R. Tetrahedron Lett. 2002, 43, 7073.
(11) Harada, T.; Rudzinski, J. M.; Shinkai, S. J. Chem. Soc., Perkin
Trans. 2 1992, 2109.
7172 J. Org. Chem. 2009, 74, 7172–7175
Published on Web 08/25/2009
DOI: 10.1021/jo901450x
r
2009 American Chemical Society

Kogan and Biali
JOCNote
prepared via photochemical bromination of pentamethoxy
p-tert-butylcalix[5]arene 512 (eq 1).
Whereas the bromine atoms of 4a can be replaced by primary
and secondary alkoxy groups simply by refluxing the calix-
arene in the appropriate alcohol, the less reactive 3a requires
the presence of an ionizing solvent (e.g., 2,2,2-trifluoroetha-
nol (TFE)).
In principle, four isomeric forms are possible for a derivative
of 5 in which the five bridges are monosubstituted by a single
substituent (Figure 1). 1H NMR analysis of the crude
mixture indicated that the major product displays a simple
signal pattern (one singlet each for the t-Bu, methoxy,
methine, and aromatic protons), consistent with an rc4 (all-
cis) disposition of stereocenters.13
Heating of 6 in TFE, 2-propanol, or cyclopentanol at
reflux afforded the corresponding pentaalkoxy derivatives
7a-c (eq 2).14 In each case, the NMR spectra of the major
products indicated 5-fold symmetry under the NMR time
scale, and on this basis the all-cis configuration is assigned to
these products. X-ray diffraction of the pentaisopropoxy
derivative 7b corroborated this configurational assignment
(Figure 3). Similar to 6, the macrocycle adopts a distorted
cone conformation with a single methoxy group oriented “in”.
FIGURE 1. Four possible patterns of stereocenters for a derivative
of 5 in which the five bridges are monosubstituted by a given
substituent.
The pentabromo derivative 6 was crystallized from a
CHCl3/MeOH mixture and submitted to X-ray crystallo-
graphy. The crystal structure (Figure 2) shows that the
product obtained is the all-cis isomer, which adopts in the
crystal a distorted cone conformation. All the bromine
atoms are located at the sterically unencumbered equatorial
positions. A single methoxy group (O1-C36) is oriented “in”
(toward the cavity center) while the rest of the methoxy
groups are oriented “out”.
FIGURE 3. Crystal structure of the pentaisopropoxy derivative 7b.
The reaction of 6 with propargyl alcohol is of interest,
since after reaction of the alcohol functionality, additional
reactions can be conducted at the triple bond, allowing
further modification of the substituents at the bridges. The
reaction with propargyl alcohol was conducted with HFIP
(1,1,1,3,3,3-hexafluoroisopropanol) as the ionizing solvent
and afforded 7d in 23% yield.
Reaction with C-Nucleophiles. a. Friedel-Crafts Reac-
tions. We have previously shown that solvolytic Friedel-
Crafts alkylation reactions (in the absence of a Lewis acid)15
can be conducted for the derivatives 3a,b and 4a. The
reaction involves a competition between reaction of the
carbocation generated by heterolytic cleavage of the C-Br
bonds with the ionizing solvent and with the aromatic
substrate. For electron-rich, aromatic substrates (e.g.,
2-methylfuran) the reaction was conducted in TFE, while
the less nucleophilic HFIP was used for less activated sub-
strates such as m-xylene.
FIGURE 2. Crystal structure of the pentabromocalix[5]arene 6.
Reactions of the Pentabromo Derivative 6. The reactivity of
3a and 4a differs toward solvolysis under SN1 conditions.
The solvolytic Friedel-Crafts reaction of
6 was
examined with benzene derivatives substituted by electron-
donating groups. Under solvolytic conditions in HFIP,
6 reacted with m-xylene, p-xylene, tert-butylphenol, and
(12) Stewart, D. R.; Krawiec, M.; Kashyap, R. P.; Watson, W. H.;
Gutsche, C. D. J. Am. Chem. Soc. 1995, 117, 586.
(13) The configuration of the stereocenters is designated by describing the
cis (c) or trans (t) disposition of the substituents relative to the reference (r)
substituent. For example, a calix[5]arene derivative possessing all bridges
monofunctionalized, in which all substituents are in a cis disposition relative
to the reference substituent is designated as rc4.
(14) The reaction with MeOH or EtOH displayed poor stereoselectivity
affording a complex stereoisomeric mixture.
(15) Hofmann, M.; Hampel, N.; Kanzian, T.; Mayr, H. Angew. Chem.,
Int. Ed. 2004, 43, 5402.
J. Org. Chem. Vol. 74, No. 18, 2009 7173

Kogan and Biali
JOCNote
1
the H NMR of 9a and 9b in CDCl3, indicating that the
compound exists almost exclusively in its keto form.
thymol affording the corresponding pentaarylated derivatives
8a-d (eq 3). In contrast to the reaction of 3b under similar
conditions, no cleavage of ArO-Me bonds was observed
under the reaction conditions. No Friedel-Crafts product
was obtained when the reaction was conducted with the
crowded mesitylene.
Acetylacetonyl groups undergo fragmentation in the pre-
sence of base affording a β-ketoalkyl chain.17 Reflux of 9a
with NaOH in MeOH resulted in a 5-fold cleavage of the
acetylacetonyl, and yielded the pentakis(2-propanonyl)
derivative 10. Reaction of 9a with hydrazine hydrate/ethanol
afforded 11 (Scheme 2).
SCHEME 2
Since HFIP is substantially more expensive than TFE,
we also examined the reaction of 6 in a TFE/m-xylene
mixture containing an acid (HBr). Since TFE is more
nucleophilic than m-xylene and is present in excess, it was
expected that the carbocation would initially react with a
TFE molecule. However, if the reaction is reversible under
the acidic reaction conditions and the reaction with the
aromatic ring is irreversible, we anticipated that the ary-
lated product should eventually be formed (Scheme 1).
Indeed, the only product obtained was the Friedel-Crafts
product 8b.
Conclusions
Reaction of the pentabromocalix[5]arene 6 under SN1
conditions with the appropriate nucleophile affords calix-
[5]arene derivatives monosubstituted at all bridges. In all
cases a single major product was formed (assigned to the
all-cis rc4 form) that could be purified by simple recrystalli-
zation.
SCHEME 1
Experimental Section
5,11,17,23,29-Penta-tert-butyl-31,32,33,34,35-pentamethoxy-
2,8,14,20,26-pentabromocalix[5]arene (6). A mixture of 512
(2.96 g, 3.36 mmol), NBS (3.11 g, 17.47 mmol) and 150 mL of
CCl4 was refluxed overnight while being irradiated with a spot-
light (100 W). The organic phase was washed with aq Na2S2O5
and water, dried (MgSO4), and evaporated. The crude product
was recrystallized from CHCl3/MeOH giving 3.03 g of 6 (71%).
Mp 302-304 °C; 1H NMR (CDCl3, 400 MHz) δ 7.54 (s, 10H),
6.90 (s, 5H), 3.72 (s, 15H), 1.16 (s, 45H) ppm; 13C NMR (CDCl3,
125 MHz) δ 150.3, 147.0, 134.2, 127.2, 61.2, 41.8, 34.6, 31.2 ppm;
HRMS (ESI) m/z 1275.1563 [(M þ H)þ, calcd for C60H76Br5O5,
1275.1569]. Anal. Calcd for C60H75Br5O5: C, 56.49; H, 5.93.
Found: C, 56.41; H, 5.92.
b. Reaction with β-Diketones. The Lewis acid-catalyzed
alkylation of benzhydryl cations with compounds possessing
active methylenes has been reported in the literature.16 The
introduction of the acetylacetonyl group at the bridges of the
calixarene skeleton is of interest, since this group can bind
metal cations and can be further transformed into a wide
array of groups. We have shown that the carbocation derived
from the heterolytic cleavage of the C-Br bonds of 4a reacts
with the enol form of 1,3-pentanedienone, yielding the
acetylacetonate derivative 4c.9c
Heating of 6 in a 1,3-pentadienone/TFE mixture at reflux
afforded the derivative 9a. Reaction with dibenzoylmethane
required reaction conditions similar to those used in the
reaction with m-xylene (i.e., TFE /HBr) to yield 9b. As
observed previously for 4c, no enolic form was detected in
General Procedure for the Preparation of the Hexaalkoxy
Calix[5]arene Derivatives. A mixture of 6 (0.10 g, 0.078 mmol)
and 10 mL of the appropriate alcohol was refluxed overnight.
After evaporation of the solvent, the residue was recrystallized
from CHCl3/MeOH.
7a: yield 30%, mp 289-291 °C; 1H NMR (CDCl3, 400 MHz)
δ 7.29 (s, 10H), 6.20 (s, 5H), 3.88 (q, J = 8.5 Hz, 10H), 3.56 (s,
15H), 1.09 (s, 45H) ppm; 13C NMR (CDCl3, 125 MHz) δ 153.8,
146.9, 132.6, 124.5, 124.0 (q, JC-F = 277.4 Hz), 72.7, 66.4 (q,
JC-C-F = 34.5 Hz), 62.2, 34.4, 31.2 ppm; HRMS (ESI) m/z
1393.5795 [(M þ Na)þ, calcd for C70H85F15NaO10, 1393.5801].
Anal. Calcd for C70H85F15O10: C, 61.31; H, 6.25. Found: C,
61.51; H, 6.24.
7b: yield 27%, mp 279 °C; 1H NMR (CDCl3, 500 MHz) δ 7.24
(s, 10H), 6.20 (s, 5H), 3.66 (h, J = 6.0 Hz, 5H), 3.57 (s, 15H), 1.22
(16) (a) Bisaro, F.; Prestat, G.; Vitale, M.; Poli, G. Synlett 2002, 1823. (b)
Jana, U.; Biswas, S.; Maiti, S. Tetrahedron Lett. 2007, 48, 4065. (c) Sanz, R.;
Miguel, D.; Martinez, A.; Alvarez-Gutierrez, J. M.; Rodriguez, F. Org. Lett.
2007, 9, 727.
(17) Bray, D. J.; Jolliffe, K. A.; Lindoy, L. F.; McMurtrie, J. C. Tetra-
hedron 2007, 63, 1953.
7174 J. Org. Chem. Vol. 74, No. 18, 2009

Kogan and Biali
JOCNote
(d, J = 6.0 Hz, 30H), 1.07 (s, 45H) ppm; 13C NMR (CDCl3, 125
MHz) δ 153.6, 145.6, 134.5, 124.4, 68.9, 68.4, 62.1, 34.3, 31.3,
22.4 ppm; HRMS (ESI) m/z 1193.7987 [(M þ Na)þ, calcd for
C75H110NaO10, 1193.7997]. Anal. Calcd for C75H110O10: C,
76.88; H, 9.46. Found: C, 76.45; H, 9.34.
125.2, 117.5, 60.9, 40.0, 34.1, 31.4, 26.4, 23.1, 20.1 ppm; HRMS
(ESI) m/z 1645.0372 [(M þ Na)þ, calcd for C110H140NaO10,
1645.0378].
9a: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of TFE, and
1 mL of 2,4-pentanedione was refluxed overnight. After eva-
poration of the solvent, the residue was recrystallized from
CHCl3/MeOH to afford 25 mg (23%) of 9a, mp 293-295 °C;
1H NMR (CDCl3, 500 MHz) δ 6.99 (s, 10H), 5.43 (d, J = 11.9
Hz, 5H), 4.52 (d, J = 11.9 Hz, 5H), 3.87 (s, 15H), 2.01 (s, 30H),
1.06 (s, 45H) ppm; 13C NMR (CDCl3, 125 MHz) δ 203.2, 153.0,
146.2, 134.4, 124.0, 74.7, 61.6, 37.3, 34.3, 31.2, 30.2 ppm; MS
(MALDI) m/z 1393.4331 [(M þ Na)þ, calcd for C85H110NaO15,
1393.7742]. Anal. Calcd for C85H110O15: C, 74.42; H, 8.08.
Found: C, 74.24; H, 8.08.
7c: yield 32%, mp 325-327 °C; 1H NMR (CDCl3, 400 MHz)
δ 7.24 (s, 10H), 6.11 (s, 5H), 4.00 (m, 5H), 3.58 (s, 15H), 1.61 (m,
40H), 1.07 (s, 45H) ppm; 13C NMR (CDCl3, 125 MHz) δ 153.6,
145.5, 134.5, 124.4, 79.4, 69.7, 62.1, 34.3, 32.5, 31.3, 23.6 ppm;
HRMS (ESI) m/z 1323.8804 [(M þ Na)þ, calcd for C85H120
-
NaO10, 1323.8779].
7d: A mixture of 6 (0.10 g, 0.078 mmol), 8 mL of chloroform,
2 mL of HFIP, and 1 mL of propargyl alcohol was refluxed
overnight. After evaporation of the solvents, the residue was
recrystallized from CHCl3/MeOH affording 21 mg (23%) of 7d,
mp 195-197 °C; 1H NMR (CDCl3, 500 MHz) δ 7.26 (s, 10H),
6.40 (s, 5H), 4.22 (d, J = 2.5 Hz, 10H), 3.66 (s, 15H), 2.46 (t, J =
2.5 Hz, 5H), 1.09 (s, 45H) ppm; 13C NMR (CDCl3, 125 MHz)
δ 154.1, 146.2, 133.2, 124.2, 80.2, 74.6, 70.3, 62.5, 56.0, 34.3,
31.3 ppm; HRMS (ESI) m/z 1173.6426 [(M þ Na)þ, calcd for
C75H90NaO10, 1173.6432].
9b: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of TFE, 2
drops of HBr, and 0.1 g of dibenzoylmethane was refluxed
overnight. After evaporation of the solvent, the residue was
chromatographed on silica gel first with petroleum ether (40-
60 °C)/ethyl acetate (2:1 v/v) and finally with ethyl acetate neat
to give a crude product. Recrystallization from CHCl3/MeOH
1
afforded 15 mg (10%) of 9b, mp 225 °C; H NMR (CDCl3,
8a: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of HFIP, and
1 mL of p-xylene was refluxed overnight. After evaporation of
the solvent, the residue was recrystallized from CHCl3/MeOH
to afford 43 mg (39%) of 8a, mp 248 °C dec; 1H NMR (CDCl3,
500 MHz) δ 6.96 (d, J = 7.6 Hz, 5 H), 6.90 (s, 5H), 6.87 (d, J =
7.8 Hz, 5H), 6.77 (s, 10H), 6.32 (s, 5H), 3.37 (s, 15H), 2.19 (s,
15H), 2.14 (s, 15H), 1.00 (s, 45H); 13C NMR (CDCl3, 125 MHz)
δ 154.1, 144.5, 142.2, 135.7, 134.2, 133.7, 130.2, 130.0, 126.3,
125.3, 60.9, 40.5, 34.1, 31.2. 21.2, 20.2 ppm; MS (MALDI) m/z
1424.4006 [(M þ Na)þ, calcd for C100H120NaO5, 1424.9067].
8b: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of TFE,
2 drops of HBr, and 1 mL of m-xylene was refluxed overnight.
After evaporation of the solvent, the residue was recrystallized
from CHCl3/MeOH to afford 66 mg (60%) of 8b, mp 268 °C dec;
1H NMR (CDCl3, 400 MHz) δ 6.98 (d, J = 7.8 Hz, 5H), 6.89 (s,
5H), 6.87 (d, J = 7.9 Hz, 5H), 6.78 (s, 10H), 6.31 (s, 5H), 3.30 (s,
15H), 2.25 (s, 15H), 2.14 (s, 15H), 0.99 (s, 45H) ppm; 13C NMR
(CDCl3, 125 MHz) δ 154.2, 144.6, 139.5, 136.6 135.8, 135.0,
131.3, 128.9, 125.9, 125.3, 60.9, 40.2, 34.1, 31.3, 20.8, 20.6 ppm;
500 MHz) δ 7.57 (d, J = 8.3 Hz, 20H), 7.31 (t, J = 7.3 Hz, 10H),
7.16 (t, J = 7.9 Hz, 20H), 6.95 (s, 10H), 6.16 (d, J = 10.2 Hz,
5H), 5.77 (d, J = 10.1 Hz, 5H), 3.74 (s, 15H), 0.79 (s, 45H) ppm;
13C NMR (CDCl3, 125 MHz) δ 194.3, 154.1, 144.4, 138.0, 134.7,
132.5, 128.5, 128.4, 124.5, 62.6, 61.8, 39.0, 34.1, 31.1 ppm;
HRMS (ESI) m/z 2014.9338 [(M þ Na)þ, calcd for C135H130
-
NaO15, 2014.9341].
10: A mixture of 9a (0.068 g, 0.05 mmol), 10 mL of methanol,
and 10 mL of 0.5 M NaOH was refluxed for 6 h. During this
period the mixture was stirred vigorously. After vacuum
filtration, the white solid was recrystallized from CHCl3/MeOH
to afford 33 mg (57%) of 10, mp 283 °C; 1H NMR (CDCl3, 500
MHz) δ 6.87 (s, 10H), 5.30 (t, J = 8.1 Hz, 5H), 3.73 (s, 15H), 3.03
(d, J = 8.2 Hz, 5H), 2.07 (s, 15H), 1.00 (s, 45H) ppm; 13C NMR
(CDCl3, 125 MHz) δ 207.2, 153.5, 145.9, 136.3, 122.7, 61.6, 50.0,
34.2, 32.7, 31.3, 30.1 ppm; HRMS (ESI) m/z 1183.7261 [(M þ
Na)þ, calcd for C75H100NaO10, 1183.7214].
11: A mixture of 9a (0.05 g, 0.04 mmol), 10 mL of ethanol, and
1 mL of hydrazine monohydrate was refluxed overnight. The
white solid was vacuum filtered and washed several times with
water to afford 19 mg (39%) of 11, mp 310-312 °C; 1H NMR
(DMSO-d6, 400 MHz) δ 6.87 (s, 10H), 5.96 (s, 5H), 3.24 (s, 15H),
1.80 (s, 30H), 0.96 (s, 45H) ppm; 13C NMR (DMSO-d6, 125
MHz, 343 K) δ 153.1, 143.7, 141.1, 135.5, 124.8, 115.8, 78.9,
60.2, 33.5, 30.7, 11.6 ppm; HRMS (ESI) m/z 1351.8733 [(M þ
H)þ, calcd for C85H111N10O5, 1351.8739].
HRMS (ESI) m/z 1424.9059 [(M þ Na)þ, calcd for C100H120
-
NaO5, 1424.9067].
8c: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of HFIP, and
0.10 g of p-tert-butylphenol was refluxed overnight. After
evaporation of the solvent, the residue was recrystallized from
CHCl3/MeOH to afford 9.1 mg (7%) of 8c, mp 310-312 °C; 1H
NMR (CDCl3, 500 MHz) δ 7.12 (d, Jm = 2.5 Hz, 5H), 7.07 (d,
Jo = 8.2 Hz, Jm = 2.5 Hz, 5H), 6.93 (s, 10H), 6.69 (d, Jo =
8.2 Hz, 5H), 6.48 (s, 5H), 5.00 (br s, 5H), 3.40 (s, 15H), 1.15 (s,
45H), 1.02 (s, 45H) ppm; 13C NMR (CDCl3, 125 MHz) δ 154.0,
151.4, 145.3, 142.6, 135.4, 129.2, 127.2, 125.5, 123.8, 115.5, 61.4,
37.3, 34.2, 34.0, 31.6, 31.3 ppm; HRMS (ESI) m/z 1645.0372 [(M
þ Na)þ, calcd for C110H140NaO10, 1645.0378].
Acknowledgment. We thank Dr. Shmuel Cohen (Hebrew
University, Jerusalem) for the crystal structure determina-
tions and Dr. Norbert Itzhak (Hebrew University, Jerusalem)
and Dr. Ishay Columbus (Institute for Biological
Research, Ness Ziona) for helpful discussions. This research
was supported by the Israel Science Foundation (grant no.
257/07).
8d: A mixture of 6 (0.10 g, 0.078 mmol), 10 mL of HFIP, and
0.10 g of thymol was refluxed for 2.5 h. After evaporation of the
solvent, the residue was recrystallized from CHCl3/MeOH to
afford 25 mg (20%) of 8d, mp 210 °C dec; 1H NMR (CDCl3, 500
MHz) δ 7.01 (s, 5H), 6.79 (s, 10H), 6.50 (s, 5H), 6.28 (s, 5H), 4.60
(br s, 5H), 3.28 (s, 15H), 3.09 (h, J = 6.9 Hz, 5H), 2.06 (s, 15H),
1.05 (d, J = 6.9 Hz, 30H), 1.00 (s, 45H) ppm; 13C NMR (CDCl3,
125 MHz) δ 154.0, 150.2, 144.5, 136.1, 135.2, 134.9, 130.5, 127.4,
Supporting Information Available: 1H and 13C NMR spec-
tra of 6-11 and crystal structures of 6 and 7b (CIF files). This
material is available free of charge via the Internet at http://
pubs.acs.org.
J. Org. Chem. Vol. 74, No. 18, 2009 7175