Synthesis of a water-soluble 1,3-Bis(diphenylene)-2-phenylallyl Radical

Article abstract of DOI:10.1021/jo100577g

The design and synthesis of a water-soluble 1,3-bis(diphenylene)-2- phenylallyl (BDPA) radical via the conjugate addition of a derivatized fluorene nucelophile is described. The compound is designed for use in dynamic nuclear polarization NMR. Its 9 GHz EPR spectrum in glycerol/water is reported.

Full text of DOI:10.1021/jo100577g

pubs.acs.org/joc
SCHEME 1
Synthesis of a Water-Soluble 1,3-Bis(diphenylene)-
2-phenylallyl Radical
Eric L. Dane and Timothy M. Swager*
Massachusetts Institute of Technology, 77 Massachusetts
Avenue, Cambridge, Massachusetts 02139
tswager@mit.edu
Received March 26, 2010
spectra by transferring the polarization of electrons to
nuclei.5 Electrons are inherently easier to polarize because
of their larger magnetic moment. Unfortunately, BDPA can-
not be used in experiments that require an aqueous cosol-
vent, such as studies with DNP to improve NMR protein
structure determination, because of its hydrophobicity.5b
We report the synthesis of a water-soluble BDPA
(WS-BDPA) radical. Previous syntheses of BDPA deriva-
tives have not focused on imparting water solubility.1b,3a,6
However, there are several reports of water-soluble deriva-
tives of the triarylmethyl (trityl) radical.7 In addition to their
use in DNP-NMR, some water-soluble trityl derivatives
have been used as EPR probes for oxygen concentration
and pH, which is a possible application of water-soluble
BDPA derivatives.8
Building on our previously reported synthesis of a BDPA-
TEMPO biradical9 (Scheme 1), the conjugate addition of a
fluorene anion to compound 1 became the crucial transfor-
mation in our route to WS-BDPA. Compound 1 contains a
carboxylic acid at the para-position of its phenyl ring that
can aid in aqueous solubility. We reasoned that the addition
of two additional carboxylic acids, masked as esters, at the
2- and 7-positions of the fluorene nucleophile would greatly
improve the solubility of the resulting BDPA radical in
polar solvents. However, we observed that adding electron-
withdrawing groups to fluorene slows the conjugate addi-
tion. For example, when 2,7-dibromofluorene (pKa=17.9 in
DMSO) is used as the nucleophile instead of fluorene (pKa=
22.6 in DMSO)10 the required reaction time increases from
1 to 24 h. The stabilization of the fluorene carbanion results
The design and synthesis of a water-soluble 1,3-bis-
(diphenylene)-2-phenylallyl (BDPA) radical via the con-
jugate addition of a derivatized fluorene nucelophile is
described. The compound is designed for use in dynamic
nuclear polarization NMR. Its 9 GHz EPR spectrum in
glycerol/water is reported.
The 1,3-bis(diphenylene)-2-phenylallyl (BDPA) radical1
(Scheme 1, green) is an air-stable, carbon-centered radical
that is unique among organic radicals in the extent of
delocalization of its unpaired electron. The unpaired elec-
tron is predominantly located at the 1- and 3-positions of
the compound’s allyl core, but is further stabilized by
delocalization into the two biphenyl ring systems attached
at those positions.2 In addition, the propeller-like geometry
of the compound has been suggested to sterically shield
and further protect the radical from potential reaction
partners.3
The BDPA radical’s resonance has a narrow line width in
high-field EPR, presumably because it is highly delocalized,
which makes it attractive for use in certain NMR experi-
ments utilizing dynamic nuclear polarization (DNP).4 DNP
can be used to increase the signal-to-noise ratio in NMR
€
(5) (a) Barnes, A. B.; Paepe, G. D.; Wel, P. C. A. v. d.; Hu, K.-N.; Joo,
C.-G.; Bajaj, V. S.; Mak-Jurkauskas, M. L.; Sirigiri, J. R.; Herzfeld, J.;
Temkin, R. J.; Griffin, R. G. Appl. Magn. Reson. 2008, 34, 237. (b) Maly, T.;
Debelouchina, G. T.; Bajaj, V. S.; Hu, K.-N.; Joo, C.-G.; Mak-Jurkauskas,
M. L.; Sigirhi, J. R.; van der Wel, P. C. A.; Herzfeld, J.; Temkin, R. J.; Griffin,
R. G. J. Chem. Phys. 2008, 128, 052211.
(6) (a) Plater, M. J.; Kemp, S.; Lattmann, E. J. Chem. Soc., Perkin Trans.
1 2000, 971. (b) Nishide, H.; Yoshioka, N.; Saitoh, Y.; Gotoh, R.; Miyakawa,
T.; Tsuchida, E. J. Macromol. Sci., Part A: Pure Appl. Chem. 1992, A29, 775.
(c) Solar, S. L. J. Org. Chem. 1963, 28, 2911.
(1) (a) Koelsch, C. F. J. Am. Chem. Soc. 1957, 79, 4439. (b) Kuhn, R.;
Neugebauer, F. A. Monatsh. Chem. 1964, 95, 3.
(2) Azuma, N.; Ozawa, T.; Yamauchi, J. Bull. Chem. Soc. Jpn. 1994,
67, 31.
(3) (a) Breslin, D. T.; Fox, M. A. J. Phys. Chem. 1993, 97, 13341.
(b) Griller, D.; Ingold, K. U. Acc. Chem. Res. 1976, 9, 13.
(4) (a) Wind, R. A.; Duijvestijn, M. J.; van der Luat, C.; Manenschijn, A.;
Vriend, J. Prog. Nucl. Magn. Reson. Spectrosc. 1985, 17, 33. (b) Afeworki,
M.; Schaefer, J. Macromolecules 1992, 25, 4092. (c) Becerra, L. R.; Gerfen,
G. J.; Temkin, R. J.; Singel, D. J.; Griffin, R. G. Phys. Rev. Lett. 1993, 71,
3561. (d) Weis, V.; Bennati, M.; Rosay, M.; Griffin, R. G. J. Chem. Phys.
2000, 113, 6795.
(7) (a) Reddy, T. J.; Iwama, T.; Halpern, H. J.; Rawal, V. H. J. Org.
Chem. 2002, 67, 4635. (b) Bowman, M. K.; Mailer, C.; Halpern, H. J.
J. Magn. Reson. 2005, 172, 254. (c) Roques, N.; Maspoch, D.; Wurst, K.;
Ruiz-Molina, D.; Rovira, C.; Veciana, J. Chem.;Eur. J. 2007, 12, 9238.
(d) Liu, Y.; Villamena, F. A.; Sun, J.; Xu, Y.; Dhimitruka, I.; Zweier, J. L.
J. Org. Chem. 2008, 73, 1490. (e) Anderson, S.; Golman, K.; Rise, F.; Wikstrom,
H.; Wistrand, L.-G., U.S. Patent No. 5,530,140, 1996.
(8) Bobko, A. A.; Dhimitruka, I.; Zweier, J. L.; Khramtsov, V. V. J. Am.
Chem. Soc. 2007, 129, 7240.
(9) Dane, E. L.; Maly, T.; Debelouchina, G. T.; Griffin, R. G.; Swager,
T. M. Org. Lett. 2009, 11, 1871.
(10) Bordwell, F. G.; McCollum, G. J. J. Org. Chem. 1976, 41, 2391.
DOI: 10.1021/jo100577g
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Published on Web 04/26/2010
J. Org. Chem. 2010, 75, 3533–3536 3533
2010 American Chemical Society

Dane and Swager
JOCNote
SCHEME 2
in decreased nucleophilicity and less driving force to form the
more stabilized BDPA carbanion (pKa=14).11 As a result, a
fluorene with esters directly attached would likely not be a
good reaction partner with 1. A fluorene derivative with a
saturated carbon between the aromatic ring system and the
ester would likely have the desired nucleophilicity at the
9-position, but its benzylic protons located R to an ester
could be deprotonated under the reaction conditions. The
simplest route to separate the esters from the conjugated
system and still maintain selectivity for deprotonation at the
9-position of the fluorene ring system was to introduce an
ethylene linker, as in 2 (protons R to the ester in 2 have a
pKa ≈ 30 in DMSO12).
Diester 2 was synthesized in moderate yield from 2,7-
dibromofluorene and tert-butyl acrylate via a Heck reac-
tion13 followed by hydrogenation (Scheme 2). The reaction
conditions for the addition of 2 to 1 required adjustment
from those of the previous procedure.9 We found that the
slow addition of 2 to a stirring solution of 1 and excess
sodium tert-butoxide in dimethylacetamide (DMA) impro-
ved yields, as compared to the previous procedure in which 1
was added to a solution of the fluorene anion. Maintaining a
low concentration of fluorene anion inhibits side reactions.
In addition, we found that freshly prepared sodium tert-
butoxide14 was superior to the commercially available ma-
terial, likely because it contained less sodium hydroxide and
therefore caused less unwanted ester cleavage. In this regard,
the use of dry DMA was also important. After protonation
and purification, the product was isolated as a 2:1 mixture of
tautomers.
FIGURE 1. Molecular models of 3 and 30 (tert-butyl groups have
been omitted for clarity) and the aromatic region of the 1H NMR
spectrum.
specifically those above 8.0 ppm and below 6.0 ppm.9 The
0
upfield shift in signals HC and HC is caused by an interaction
with the magnetic field of the nearby phenyl ring. The
0
downfield signals (HB, HB ) result from a steric interaction
with HA and HA .15 An NOE of 20% was measured between
0
the analogous protons in 3a.9
To prepare triacid 4, removal of the tert-butyl groups is
achieved with trifluoroacetic acid in dichloromethane with
the addition of triethylsilane as a carbocation trap.16 The
acidic conditions do not cause a change in the ratio of
tautomers in 4 as compared to 3.
To generate the radical by one-electron oxidation, compound
4 was deprotonated to form the tetra-anion (see Figure 2,
blue solution). We found that a large excess (20 equiv) of
potassium tert-butoxide in a 4:1 solution of DMSO/tert-
butanol provided the best results. Because excess base can
cause reduction of the radical back to the carbanion, the
amount of oxidant had to be increased to ensure complete
The tautomers have distinct 1H NMR spectra, as shown in
Figure 1. Previously, we reported NMR experiments and an
X-ray crystal structure of 3a, which revealed the origin of
the signals outside the normal range of aromatic protons,
(11) Kuhn, R.; Rewicki, D. Liebigs Ann. Chem. 1967, 706, 250.
(12) Zhang, X.-M.; Bordwell, F. G.; Van Der Puy, M.; Fried, H. E.
J. Org. Chem. 1993, 58, 3060.
(13) Patel, B. A.; Ziegler, C. B.; Cortese, N. A.; Plevyak, J. E.; Zebovitz,
T. C.; Terpko, M.; Heck, R. F. J. Org. Chem. 1977, 42, 3903.
(14) Sodium tert-butoxide was prepared by refluxing sodium with excess
freshly distilled tert-butanol followed by evaporation of excess solvent under
high vacuum. The material was stored and weighed in a nitrogen glovebox.
(15) Cheney, B. V. J. Am. Chem. Soc. 1968, 90, 5386.
(16) Mehta, A.; Jaouhari, R.; Benson, T. J.; Douglas, K. T. Tetrahedron
Lett. 1992, 33, 5441.
3534 J. Org. Chem. Vol. 75, No. 10, 2010

Dane and Swager
JOCNote
FIGURE 2. Absorption spectra of carbanion 4 in dimethyl sulf-
oxide and WS-BDPA in 3:2 glycerol and water.
FIGURE 3. The 9 GHz EPR of BDPA (0.1 mM, 4 mm diameter
tube) in toluene and WS-BDPA (10.0 mM, 150 μL flat cell) in
glycerol/water. Experimental parameters: rt, 2 mW, modulation
amplitude 10 mT.
oxidation. Addition of the oxidant was quickly followed by a
dilution of the reaction mixture with acidic water (pH 2), and
subsequent extraction of the triacid into diethyl ether. The
isolated red-brown powder showed no 1H NMR signals at a
concentration of 20 mM in d4-methanol beyond those of the
solvent and water, as would be expected for a paramagnetic
compound. HRMS and FT-IR agreed with the proposed
structure. As shown in Figure 2, in a glycerol and water
solution (3:2) the radical has a strong absorption in the
visible region (λmax = 496 nm) and a weak absorption in
the near-infrared region (λmax=867 nm). BDPA in dichlor-
omethane has similar absorbance maxima, which are 485
and 859 nm, respectively.1b,3a
The solubility of the radical in aqueous solution (PBS
buffer, pH 8.0) was approximately 1.0 mM. Because the
material was designed for use in DNP-NMR experiments
dealing with biomolecules, we also tested the solubility of the
radical in a 3:2 solution of glycerol and water, a solvent
mixture favored for those experiments.5b The radical was
soluble at 1 mM at pH 7, but required the addition of sodium
bicarbonate to be soluble at 10 mM (pH 8). Figure 3 shows
the 9 GHz EPR spectrum of WS-BDPA in glycerol/water
beneath the spectrum of BDPA in toluene. The radicals
have the same g-value (g = 2.003) and a similar coupling
pattern (see the Supporting Information for a simulated
spectrum).1b,2,17 In addition, the radical was persistent at
room temperature both in the solid state and in solution, but
detailed studies of its stability as compared to BDPA have
not yet been performed.
2,7-dibromofluorene, 0.087 g (0.390 mmol, 2.5 mol %) of
palladium acetate, 0.470 g (0.780 mmol, 5 mol %) of tri(o-tol)-
phosphine, 5 mL of dicyclohexylmethylamine, and 100 mL of
anhydrous dimethylformamide. The solution was degassed with
bubbling argon and 7.00 mL (6.13 g, 47.8 mmol, 3.1 equiv) of
tert-butyl acrylate was added. After heating to 80 °C for 4 h and
cooling overnight, excess water was added and the resulting
solid was filtered, washed with water, and dried on the filter pad.
The material was suspended in 150 mL of methanol and 1.00 g of
5% Pd/C was added. Hydrogenation was performed overnight
in a Parr Hydrogenator at 40 PSI with shaking. After removal of
the methanol, the crude material was chromatographed with
silica gel and eluted with increasingly polar mixtures of hexane
1
and ethyl acetate to yield 3.25 g (50%) of a white powder. H
NMR (500 MHz, CD2Cl2, δ) (all coupling constants (J) in Hz)
7.64 (d, J=7.5, 2H), 7.36 (s, 2H), 7.18 (d, J=8.0, 2H), 3.82
(s, 2H), 2.94 (t, J=7.5, 4H), 2.54 (t, J=7.5, 4H), 1.39 (s, 18 H);
13C NMR (126 MHz, CD2Cl2, δ) 172.6, 144.1, 140.2, 140.0,
127.4, 125.6, 119.9, 80.6, 37.8, 37.2, 31.8, 28.4; HRMS (ESI)
calcd for C27H34O4Na [M þ Na]þ 445.2349, found 445.2329.
FT-IR (KBr, thin film) νmax (cm-1) 2978, 1729 (s), 1454, 1365,
1257, 1133, 1009, 956, 817, 741. Mp 99-101 °C (methanol).
4-((2,7-Bis(3-(tert-butoxy)-3-oxopropyl)-9H-fluoren-9-ylidene)-
(9H-fluoren-9-yl)methyl)benzoic Acid (3) and 4-((2,7-Bis(3-(tert-
butoxy)-3-oxopropyl)-9H-fluoren-9-yl)(9H-fluoren-9-ylidene)-
methyl)benzoic Acid (30). To a 100 mL flask were added 0.100 g
(0.265 mmol, 1.0 equiv) of bromide 2, 0.255 g (2.65 mmol, 10
equiv) of sodium tert-butoxide, and 6.0 mL of degassed, anhy-
drous dimethylacetamide (DMA). The solution was cooled to
0 °C. In a separate flask, 0.168 g (0.398 mmol, 1.5 equiv) of ester
1 was dissolved in 10 mL of DMA and this solution was slowly
added to the first flask over a period of 20 min. The reaction
became deep blue. After stirring at room temperature for 2 h,
excess (3 mL) of acetic acid was added, turning the reaction from
deep blue to light yellow. Additional water was added and the
solution was extracted with diethyl ether (3ꢀ30 mL). The ether
was washed twice with water and once with brine and dried over
sodium sulfate. After removal of the solvent, the crude material
was purified by silica gel column chromatography, using in-
creasingly polar mixtures of ethyl acetate in dichloromethane,
after which 0.163 g (85%) of a light yellow powder was isolated.
In conclusion, the design and synthesis of a water-soluble
derivative of the BDPA radical is reported. We characterize
the pair of tautomers that are a consequence of constructing
the BDPA skeleton with nonidentical fluorene rings. Finally,
the generation of the stable radical and its characterization
by EPR spectroscopy in aqueous solution are reported.
Experimental Section
Di-tert-butyl 3,30-(9H-Fluorene-2,7-diyl)dipropanoate (2). To
a 250 mL flask were added 5.00 g (15.4 mmol, 1.0 equiv) of
(17) Watanabe, K.; Yamauchi, J.; Ohya-Nishiguchi, H.; Deguchi, Y.;
Ishizu, K. Bull. Inst. Chem. Res., Kyoto Univ. 1975, 53, 161.
J. Org. Chem. Vol. 75, No. 10, 2010 3535

Dane and Swager
JOCNote
1H NMR (500 MHz, CD2Cl2, δ) (all coupling constants (J) in
Hz) for 3: 8.25 (s,1H), 7.75 (d, J=8.0, 1H), 7.71 (d, J=8.0, 2H),
7.69 (d, J=8.0, 2H), 7.60 (ddd, J=8.0, 1.0, 0.5, 2H), 7.59 (d, J=
8.0, 1H), 7.36 (td, J=8.0, 1.0, 2H), 7.32 (dd, J=8.0, 1.0, 1H), 7.29
(td, J=8.0, 1.0, 2H), 7.05 (dd, J=8.0, 1.0, 1H), 6.78 (d, J=8.0,
2H), 6.49 (s, 1H), 5.62 (s, 1H), 2.95 (t, J=7.5, 2H), 2.54 (t, J=7.5,
2H), 2.45 (t, J=7.5, 2H), 2.07 (t, J=7.5, 2H), 1.35 (s, 9H), 1.30 (s,
9H). 1H NMR (500 MHz, CD2Cl2, δ) (all coupling constants (J)
in Hz) for 30: 8.44 (ddd, J=8.0, 1.0, 0.5, 1H), 7.89 (ddd, J=8.0,
1.0, 0.5, 1H), 7.75 (ddd, J=8.0, 1.0, 0.5, 1H), 7.69 (d, J=8.0, 2H),
7.52 (d, J=8.0, 2H), 7.49 (td, J=8.0, 1.0, 1H), 7.44 (s, 2H), 7.38
(td, J=8.0, 1.0, 1H), 7.23 (td, J=8.0, 1.0, 1H), 7.18 (d, J=8.0,
2H), 6.79 (td, J=8.0, 1.0, 1H), 6.78 (d, J=8.0, 2H), 6.47 (s, 1H),
5.85 (d, J=8.0, 1H), 2.90 (t, J=7.5, 4H), 2.49 (t, J=7.5, 4H), 1.35
(s, 18H). 13C NMR (126 MHz, CD2Cl2, δ) 172.5, 172.4, 172.3,
171.6, 171.5, 145.2, 144.9, 144.6, 144.4, 144.0, 143.5, 142.5,
141.8, 140.7, 140.6, 140.5, 140.4, 139.4 (2), 139.3, 139.0, 138.5,
136.7, 136.6, 130.0, 129.5, 129.2, 129.0, 128.6, 128.5 (3), 128.3,
128.2, 128.0, 127.7, 127.1, 126.5, 126.3, 125.9, 125.8 (2), 125.7,
120.6, 120.5, 120.2, 119.7, 119.3, 80.7 (2), 80.4, 52.8, 52.7, 37.8
(2), 36.7, 32.1, 31.7, 31.6, 28.3, 28.2. HRMS (ESI) calcd for
C48H45O6 [M - H]- 717.3222, found 717.3206. FT-IR (KBr,
thin film) νmax (cm-1) 2977, 2930, 1727 (s), 1694 (s), 1607, 1447,
1419, 1367, 1260, 1148, 1018, 846, 822, 736.
3,30-(9-((4-Carboxyphenyl)(9H-fluoren-9-yl)methylene)-9H-
fluorene-2,7-diyl)dipropanoic Acid (4) and 3,30-(9-((4-carboxy-
phenyl)(9H-fluoren-9-ylidene)methyl)-9H-fluorene-2,7-diyl)-
dipropanoic Acid (40). To a 50 mL flask were added 0.150 g (0.209
mmol, 1.0 equiv) of 3, 9.0 mL of anhyd CH2Cl2, 1 drop of tri-
ethylsilane, and 4.5 mL of TFA. The reaction mixture was
stirred under an argon atmosphere for 30 min, after which
excess sodium bicarbonate solution was added. The aqueous
layer was washed with diethyl ether (2ꢀ10 mL) and acidified
with 2 M HCl to a pH of 1. The aqueous layer was extracted with
diethyl ether (3ꢀ10 mL). The combined ether layers were washed
with brine and dried over sodium sulfate. Removal of the sol-
vent followed by drying under high vacuum yielded 0.0960 g
(0.158 mmol, 76%) of an off-white powder. 1H NMR (500
MHz, d4-methanol, δ) (all coupling constants(J) in Hz) of 4: 8.25
(s, 2H), 7.73 (d, J=8.0, 1H), 7.64 (d, J=8.0, 2H), 7.63 (d, J=8.0
Hz, 2H), 7.58 (d, J=8.0, 4H), 7.32 (m, 3H), 7.25 (t, J=8.0, 2H),
7.04 (d, J=16.0, 1H), 6.71 (d, J=8.5, 2H), 6.45 (s, 1H), 5.64 (s,
1H), 2.98 (t, J=8.0, 2H), 2.62 (t, J=8.0, 2H), 2.48 (t, J=8.0, 2H),
2.17 (t, J=8.0, 2H). 1H NMR (500 MHz, d4-methanol, δ) (all
coupling constants(J) in Hz) of 40: 8.41 (d, J=8.0 Hz, 1H), 7.87
(d, J=7.5, 1H), 7.72 (d, J=7.5, 1H), 7.64 (d, J=8.0, 2H), 7.48 (d,
J=8.0, 2H), 7.46 (t, J=8.0, 1H), 7.43 (s, 2H), 7.36 (t, J=8.0, 1H),
7.19 (t, J=8.0, 1H), 7.16 (d, J=8.0, 2H), 6.74 (t, J=8.0, 1H), 6.71
(d, J=8.0, 2H), 6.42 (s, 1H), 5.85 (d, J=8.0, 1H), 2.92 (t, J=8.0,
4H), 2.57 (t, J=8.0, 4H). 13C NMR (126 MHz, d4-methanol and
CDCl3, δ) 176.3, 176.1, 175.8, 169.7, 144.9, 144.6, 144.3, 144.2,
144.0, 142.8, 142.1, 140.9, 140.4 (2), 139.7, 139.4, 139.2, 138.9,
136.8, 136.7, 129.8 (2), 129.6, 129.5, 129.3, 129.2, 128.4, 127.8,
127.2, 126.5, 126.0, 125.9, 125.7, 120.7 (2), 120.5, 119.9, 119.6,
53.1, 53.0, 36.9, 36.8, 35.8, 32.2, 31.8, 31.6. HRMS (ESI) calcd
for C40H29O6 [M - H]- 605.1970, found 605.1968. FT-IR (KBr,
thin film) νmax (cm-1) 3600-2800 (br), 1700 (s), 1606, 1446,
1417, 1274, 1178, 1017, 824, 734.
WS-BDPA Radical. To a 200 mL flask were added 0.040 g
(0.066 mmol, 1.0 equiv) of compound 4, 0.150 g (1.34 mmol,
20 equiv) of sublimed potassium tert-butoxide, and 50 mL of a
4:1 mixture of DMSO/t-BuOH. After 30 min, 0.180 g (1.06 mmol,
16.0 equiv) of silver nitrate was added. The solution immedi-
ately became brown and was diluted after 1 min with 400 mL of
0.01 M HCl and extracted with diethyl ether (3ꢀ10 mL). The
combined organic layers were washed with water (3ꢀ25 mL)
and brine. After drying with sodium sulfate, the solvent was
removed. The resulting solid was washed with hexane, and
0.023 g (58%) of a dark red-brown powder was isolated. HRMS
(ESI) calcd for C40H29O6 M - 605.1970, found 605.1968. FT-IR
(KBr, thin film) νmax (cm-1) 3600-2800 (br), 1708 (s), 1604,
1446, 1417, 1282, 1177, 1018, 824, 730. EPR (9 GHz) [WS-
BDPA] 10 mM in 3:2 glycerol/H2O, quartz flat cell, g-value=
2.003.
Acknowledgment. We thank Dr. Thorsten Maly, Galia
Debelouchina, and Professor Robert G. Griffin for helpful
discussions. Funding for this project was provided by the
National Science Foundation and the National Institute of
Biomedical Imaging and Bioengineering (EB-002804).
Supporting Information Available: Additional experimental
details, and copies of 1H, gCOSY, and 13C NMR spectra for 2, 3,
and 4. This material is available free of charge via the Internet at
http://pubs.acs.org.
3536 J. Org. Chem. Vol. 75, No. 10, 2010