Novel chiral calix[4]arenes by direct asymmetric epoxidation reaction

Article abstract of DOI:10.1021/jo800301m

(Chemical Equation Presented) We report the first asymmetric synthesis of trans optically active (+) C₂ 1,3-bisarylepoxide of calix[4]arene in excellent chemical yield and >99% ee, and its enantiospecific conversion to the corresponding bis-dio

Full text of DOI:10.1021/jo800301m

to bind different amino acids and other biological molecules
was studied.2 Recently, carbohydrates were also introduced,3
and in such glycocalixarenes strong binding with certain proteins
was detected.4 Moreover, small molecules such as chiral
epoxides5 and, more recently, 1,2-amino alcohols6 were an-
chored to the lower rim of calix[4]arenes. A drawback of this
approach is the limited availability of the chiral fragments to
be anchored to the macrocyclic platform.
The second strategy relies on the synthesis of ”inherently”
chiral calixarenes, in which the chirality is induced by an
asymmetric substitution in the macrocycle, leading to the
nonplanarity of the molecule.7 This strategy appears more
challenging, as there are always problems on regio- and
stereoselectivity in the synthesis. Moreover, optical resolution
of the racemates usually requires the use of HPLC methods.8
In some cases, condensation with a chiral auxiliary allowed
preparative TLC or conventional column chromatographic
separation of diastereoisomers, whose cleavage afforded opti-
cally pure inherently chiral calixarenes.9
Novel Chiral Calix[4]arenes by Direct
Asymmetric Epoxidation Reaction
Carlo Bonini,*,† Lucia Chiummiento,† Maria Funicello,†
Maria Teresa Lopardo,† Paolo Lupattelli,†
Alessandro Laurita,† and Andrea Cornia‡
Dipartimento di Chimica, UniVersita` degli studi della
Basilicata, Via Nazario Sauro 85, 85100-Potenza, Italy, and
Dipartimento di Chimica, UniVersita` di Modena e Reggio
Emilia and INSTM, Via G. Campi 183, I-41100,
Modena, Italy
bonini@unibas.it
ReceiVed February 5, 2008
In principle, a third strategy for the preparation of chiral
calixarenes could be easily expected via a “direct enantiose-
lective reaction” on properly functionalized calixarenes. It is
surprising to note that in spite of the significant number of
reliable asymmetric reactions that have been developed so far,
none of these has been applied on calixarenes. Our recent
research was devoted to the synthesis of new calix[4]arenes
possessing important chiral subunits on the upper rim (such as
amino alcohols and related frameworks), which can be conve-
niently prepared by different enantioselective methods and
subsequent elaboration of the chiral compounds.10,11 In par-
ticular, we were interested in the more intriguing strategy with
the direct generation of the appropriate functional groups.
Epoxides are among the most useful moieties in organic
synthesis and, recently, 2,3-diaryloxiranes have been proved as
versatile key intermediates.12
We report the first asymmetric synthesis of trans optically
active (+) C2 1,3-bisarylepoxide of calix[4]arene in excellent
chemical yield and >99% ee, and its enantiospecific conver-
sion to the corresponding bis-dioxolane
Calixarenes have attracted much attention in recent years for
their unique structural/chemical properties, which allow their
use in the synthesis of various molecular architectures. Since
they are emerging as a new class of synthetic macrocycles
possessing extensive host-guest chemistry,1 chiral calixarenes
are of particular importance for the enantioselective recognition
and/or discrimination of chiral compounds. Chirality of calix-
arenes and, in particular, of the most studied calix[4]arenes has
been generated by two different strategies. The first and most
widely applied strategy usually requires the anchorage of the
chiral constituents (mostly natural or commercially available
compounds) at one rim of the calix[4]arenes. Among several
examples, amino acids and small peptides1c were linked to the
upper rim in the preparation of peptidocalixarenes, whose ability
Most of the successful and widely applied asymmetric
methods for their synthesis involve a transition metal-catalyzed
(3) (a) Meunier, S. J.; Roy, R. Tetrahedron Lett. 1996, 37, 5469. (b) Dondoni,
A.; Marra, A.; Scherrmann, M.-C.; Casnati, A.; Sansone, F.; Ungaro, R. Chem.
Eur. J. 1997, 3, 1774. (c) Budka, J.; Tkadlecova´, M.; Lhota´k, P.; Stibor, I.
Tetrahedron 2000, 56, 1883.
(4) Casnati, A.; Sansone, F.; Ungaro, R. Acc. Chem. Res. 2003, 36, 246.
(5) Neri, P.; Bottino, A.; Geraci, C.; Piattelli, M. Tetrahedron: Asymmetry
1996, 7, 17.
(6) Zheng, Y. S.; Zhang, C. Org. Lett. 2004, 6, 1189.
(7) For reviews on inherently chiral calixarenes, see: (a) Bo¨hmer, V.; Kraft,
D.; Tabatabai, M. J. Incl. Phenom. Mol. Recogn. 1994, 19, 17. (b) Otsuka, H.;
Shinkai, S. Supramol. Sci. 1996, 3, 189. (c) Vysotsky, M.; Schmidt, C.; Bo¨hmer,
V. AdV. Spramol. Chem. 2000, 7, 139.
(8) (a) Caccamese, S.; Bottino, A.; Cunsolo, F.; Parlato, S.; Neri, P.
Tetrahedron: Asymmetry 2000, 11, 3103. (b) Hesek, D.; Inoue, Y.; Drew,
M. G. B.; Beer, P. D.; Hembury, G. A.; Ishida, H.; Aoki, F. Org. Lett. 2000, 2,
2237.
† Universita` degli studi della Basilicata.
‡ Universita` di Modena e Reggio Emilia and INSTM.
(1) (a) Asfari, Z.; Bo¨hmer, V.; Harrowfield J.; Vicens, J. Calixarene 2001;
Kluwer Academic: Dortrecht, The Netherlands, 2001. (b) Mandolini L.; Ungaro,
R. Calixarenes in Action; Imperial College Press: London, UK, 2000. (c) Gutsche,
C. D. Calixarenes ReVisited; The Royal Society of Chemistry: Cambridge, UK,
1998. (d) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry:
Cambridge, UK, 1989.
(2) (a) Brewster, R. E.; Caran, K. L.; Sasine, J. S.; Shuker, S. B. Curr. Org.
Chem. 2004, 8, 867. (b) Sansone, F.; Baldini, L.; Casnati, A.; Chierici, E.;
Faimani, G.; Ugozzoli, F.; Ungaro, R. J. Am. Chem. Soc. 2004, 126, 6204. (c)
Francese, S.; Cozzolino, A.; Caputo, I.; Esposito, C.; Martino, M.; Gaeta, C.;
Troisi, F.; Neri, P. Tetrahedron Lett. 2005, 46, 1611.
(9) Luo, J.; Zheng, Q.-Y.; Chen, C.-F.; Huang, Z.-T. Chem. Eur. J. 2005,
11, 5917.
(10) For recent reviews see:(a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem.
ReV. 1996, 96, 835. (b) Bergmeir, S. C. Tetrahedron 2000, 56, 2561. (c) Bonini,
C.; Righi, G. Tetrahedron 2002, 58, 4981.
(11) On this subject we are also working on the preparation of suitable 1,3
calix[4]arenes, bearing commercially available and synthetic 1,2 amino alcohol
subunits on the upper rim: Bonini, C.; Chiummiento, L.; Funicello, M.; Lopardo,
M. T.; Lupattelli, P.; Velluzzi, E.; Viggiani, L. FIMOC IV Annecy (France)
2004, P14.
(12) Bonini, C.; Lupattelli, P. ARKIVOC 2008, Part (viii), p 150.
10.1021/jo800301m CCC: $40.75
Published on Web 04/24/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 4233–4236 4233

SCHEME 1. Synthesis of Calix[4]arene Bis-Epoxide in
Achiral Conditions
SCHEME 2. Synthesis of (R,R,)-(R,R)-Calix[4]arene
Bis-Epoxide 3
monitoring), which were obtained in 1:1 ratio and 87% overall
yield, after chromatographic purification.
1H and 13C NMR analyses revealed the presence of two biaryl
epoxides in both compounds. The coupling constant for the AB
system of the oxiranyl protons appeared very small (JAB ) 2.0
Hz for one compound and JAB ) 1.5 Hz for the other one),
confirming the expected trans,trans stereochemistry of the
epoxides. Therefore, the two trans,trans stereoisomers were
identified as the chiral C2 compound 3 and the meso compound
4, although we were unable, at that moment, to assign the correct
structure of the two products. The complete stereoselectivity
toward the trans,trans epoxides was delightfully unexpected,
since the trans/cis ratio in model diarylepoxides bearing electron
releasing groups on one aryl ring usually ranges between 2/1
and 4/1.15b,18 This good preliminary result prompted us to
attempt the asymmetric version of the reaction using the chiral
sulfonium salt 5 derived from Eliel’s oxathiane. After some
attempts with different bases and conditions, the ylide was
properly prepared with the phosphazene base EtP2 in dichlo-
romethane at -78 °C under argon atmosphere and reacted
immediately with the 1,3-diformyl calix[4]arene 1. In this case
a single product was detected and the reaction was completed
in 6 h. After the usual workup and chromatographic purification,
a single product was obtained in a gratifying 71% chemical yield
(Scheme 2).
reaction. However, the use of such metals appears, in principle,
not to be compatible with substrates prone to coordination and/
or complexation, like calixarenes. This can be, indeed, the main
reason for the apparent lack of studies on direct asymmetric
reactions on such macrocycles.
In this paper we report the first example of an efficient
enantioselective preparation of a chiral calix[4]arene bis-epoxide
via a direct asymmetric reaction on the parent 1,3-diformyl
calix[4]arene.
Our attention turned to the construction of a chiral epoxide
fragment on the upper rim of the calix[4]arene with metal free
methodologies.
Among the most successful ones, the Solladie´-Cavallo
preparation method of chiral trans biarylepoxides, which are
usually obtained in high chemical yield and ee higher than 99%,
seemed to be particularly appropriate.13 In fact, this is a reaction
between an appropriate aryl aldehyde and a chiral benzyliden
sulfur ylide, which is derived from Eliel’s oxathiane14 and is
generated in situ by deprotonation of the parent sulfonium salt
with a strong base. Such an approach has proved to be general,
allowing us to prepare, recently, new optically pure biarylep-
oxides, which were used as starting materials for the synthesis
of functionalized 1,2-diarylethanols and acetonides.15
To test the reactivity of 1,3-diformyl calix[4]arene 1 toward
sulfur ylides, the reaction was first performed with the achiral
dimethyl benzyliden sulfur ylide (Scheme 1).
The bis-aldehyde 1 was easily prepared from commercial
calix[4]arene by a slightly modified procedure16 of the well-
known approach,17 in three steps by selective alkylation,
formylation, and final exhaustive alkylation. The reaction on 1
was performed in homogeneous conditions, using benzyldim-
ethylsulfonium triflate 2 as a soluble ylide precursor. The ylide
was preformed in situ by deprotonation with NaH and after 15 h
the reaction was complete toward two products (by TLC
1H and 13C NMR analyses revealed the product as identical
with one of the two (3 or 4) previously obtained via the achiral
method (see Scheme 1). Moreover, the product appeared
optically active, having a significant [R]25 value of +79.5 (c
D
1, CHCl3). This strongly supported the formation of the chiral
C2 bis-epoxide 3, which could be assigned to the structure
previously described.
The ultimate determination of the optical purity of compound
3 was not trivial and was achieved after numerous attempts by
using different chiral stationary phases in the HPLC analysis.
Nevertheless, the final result with CHIRALPAK IA was quite
satisfactory, not only in terms of separation conditions (Figure
1) but also for the ee value for compound 3, which was higher
than 99%.
(13) (a) Solladie´-Cavallo, A.; Roje, M.; Isarno, T.; Sunijc, V.; Vinkovic, V.
Eur. J. Org. Chem. 2000, 1077. (b) Solladie´-Cavallo, A.; Diep-Vohuule, A.;
Sunijc, V.; Vinkovic, V. Tetrahedron: Asymmetry 1996, 7, 1783.
(14) Eliel, E. L.; Lynch, J. E.; Kurne, F.; Frye, S. V. Org. Synth. 1987, 65,
215.
To unambigously determine the absolute configuration of (+)-
3, the bis-epoxide was crystallized from n-hexane and its
(15) (a) Solladie´-Cavallo, A.; Lupattelli, P.; Bonini, C.; Ostuni, V.; Di Blasio,
N. J. Org. Chem. 2006, 71, 9891. (b) Solladie´-Cavallo, A.; Lupattelli, P.; Bonini,
J. Org. Chem. 2005, 70, 1605. (c) Lupattelli, P.; Bonini, C.; Gambacorta, C.;
Caruso, L. J. Org. Chem. 2003, 68, 3360. (d) Solladie´-Cavallo, A.; Lupattelli,
P.; Marsol, C.; Isarno, T.; Bonini, C.; Caruso, L.; Maiorella, A. Eur. J. Org.
Chem. 2002, 1439.
(16) One equivalent of base (K2CO3) was used in the first dipropylation step,
and the last exhaustive propylation was performed directly on the bis-aldehyde,
obtaining the desired bis-aldehyde 1 in 60% overall yield from commercial
calix[4]arene.
(17) (a) Van Loon, J. D.; Arduini, A.; Coppi, L.; Verboom, W.; Pochini, A.;
Ungaro, R.; Harkema, S.; Reinhoudt, D. N. J. Org. Chem. 1990, 55, 5639–
5646. (b) Sansone, S.; Barboso, S.; Casnati, A.; Fabbi, N.; Pochini, A.; Ugozzoli,
F.; Ungaro, R. Eur. J. Org. Chem. 1998, 905.
FIGURE 1. HPLC analysis using the chiral stationary phase: (a) racemic
bis-epoxide (+/-)-3 and (b) optically pure bis-epoxide (+)-3.
4234 J. Org. Chem. Vol. 73, No. 11, 2008

Experimental Section
trans,trans-5,17-Bis(3′-phenyl-2′-oxiranyl)-25,26,27,28-
tetrapropyloxycalix[4]arenes, 3 and 4. To a suspension of NaH
97% (9.36 mg, 0.38 mmol) in CH2Cl2 (1.2 mL) a solution of 0.5
M benzyldimethylsulfonium triflate (2) in CH2Cl2 (0.64 mL) was
added at 0 °C. After 1 h a solution of 5,17-diformyl 25,26,27,28-
tetrapropyloxycalix[4]arene (1) (100 mg, 0.15 mmol) in CH2Cl2
(0.32 mL) was added and the mixture was stirred for 15 h at 0 °C.
Once it reached room temperature, the mixture was quenched with
2 mL of H2O and extracted with CH2Cl2 (3 × 5 mL). The organic
layers were dried over Na2SO4 and evaporated giving a residue
that was purified on a silica gel column with hexane/diethyl ether
(9:1) as eluent to afford 3 (55 mg, 44%) and 4 (53 mg, 43%).
FIGURE 2. ORTEP plot of (+)-3 with thermal ellipsoids drawn at
50% probability. Color code: red ) O, black ) C. Hydrogen atoms
have been omitted for clarity.
1
(+/-)-3 and (+)-3: H NMR (500 MHz, CDCl3) δ (ppm) 0.90
SCHEME 3. Enantiospecific Conversion of Bis-Epoxide
(R,R),(R,R)-3 to Bis-Acetonide (R,R),(R,R)-6
(m, 12H), 1.93 (m, 8H), 3.17 (d, 2H, J ) 13 Hz), 3.21 (d, 2H, J
)13 Hz), 3.68 (d, 1H, J ) 1.5 Hz), 3.79 (d, 1H, J ) 1.5 Hz), 3.87
(m, 8H), 4.48 (d, 2H, J ) 13 Hz), 4.50 (d, 2H, J ) 13 Hz), 6.55
(s, 2H), 6.59 (s, 2H), 6.62 (m, 6H), 7.31 (m, 10H); 13C NMR (125
MHz, CDCl3) δ (ppm) 10.2, 10.4, 23.2, 23.3, 29.7, 30.9, 31.1, 62.7,
62.9, 122.1, 123.4, 125.7, 127.9, 128.3, 128.4, 130.4, 134.8, 134.9,
135.1, 135.4, 137.6, 156.6, 156.7; mp 165-167 °C; MS ES+ (828)
851 (M + Na)+. Anal. Calcd for C56H60O6: C, 81.13; H, 7.29.
Found: C, 80.0; H, 7.4.
1
4: H NMR (500 MHz, CDCl3) δ (ppm) 0.99 (t, 6H, J ) 7.5
Hz), 1.04 (t, 6H, J ) 7.5 Hz), 1.94 (m, 8H), 3.17 (d, 2H, J ) 13
Hz), 3.20 (d, 2H, J ) 13 Hz), 3.77 (t, 4H, J ) 7 Hz), 3.79 (d, 1H,
J ) 2 Hz), 3.90 (d, 1H, J ) 2 Hz), 3.99 (t, 4H, J ) 7 Hz), 4.48 (d,
4H, J ) 13 Hz), 6.34-6.40 (m, 6H), 6.95 (s, 2H), 6.96 (s, 2H),
7.37(m, 10H); 13C NMR (125 MHz, CDCl3) δ (ppm) 10.0, 10.6,
23.1, 30.9, 31.0, 62.5, 63.1, 76.7, 76.8, 122.2, 125.5, 126.6, 127.9,
128.1, 128.5, 130.1, 133.4, 133.6, 136.3, 136.7, 137.5, 155.6, 157.8;
mp 194-199 °C; MS ES+ (828) 851 (M + Na)+. Anal. Calcd for
C56H60O6: C, 81.13; H, 7.29. Found: C, 80.2; H, 7.2.
5,17-Bis((2′R,3′R)-3′-phenyl-2′-oxiranyl)-25,26,27,28-
tetrapropyloxycalix[4]arene, (+)-3. To a solution of benzylic
sulfonium salt 5 (190 mg, 0.43 mmol) in CH2Cl2 (2.5 mL) at -78
°C was added phosphazene base EtP2 (0.16 mL, 0.48 mmol)
dropwise. After 10 min, a solution of 5,17-diformyl-25,26,27,28
tetrapropyloxy calix[4]arene (1) (127 mg, 0.19 mmol) in CH2Cl2
(0.35 mL) was added and the reaction was stirred for 6 h. The
mixture was then warmed to rt, the reaction was quenched with
H2O (2 mL), and the organic phase extracted with CH2Cl2 (3 × 5
mL). The organic phases were collected, dried over anhydrous
Na2SO4, and evaporated under vacuum. The crude residue was
purified on silica gel column with n-hexane/CH2Cl2 (1:1) as eluent,
to afford (+)-3 (115 mg) as a white solid, in 71% yield. Mp
195-197 °C; [R]25D +79.5 (c 1 in CHCl3); ee 99% (CHIRALPAK
IA, hexane/2-propanol 95:5, flow rate 1 mL min-1). Anal. Calcd
for C56H60O6: C, 81.13; H, 7.29. Found: C, 80.3; H, 7.1.
(+)-3: X-ray Crystallography. Single-crystal data were col-
lected at 100(2) K with a single-crystal diffractometer (Cu KR
radiation, λ ) 1.54184 Å). The SIR92 program was used for
structure solution by direct method.20 The SHELXL97 program
package was used for full-matrix least-squares structure refine-
ment.21 ORTEP3 was used for molecular graphics.22 All non-
hydrogen atoms were refined anisotropically. The hydrogen atoms
were included in the refinement at calculated positions by using a
riding model included in the SHELXL program. Absolute config-
uration was determined by anomalous-dispersion effects in diffrac-
tion measurements. Data: monoclinic, C2, a ) 25.7719(3) Å, b )
9.74588(16) Å, c ) 18.1938(2) Å, ꢀ ) 95.8354(12)°; Z ) 4; F(000)
) 1.776; V ) 4546.05(10); 1.211 Mg/m3; ϑ-range 4.02-72.15°;
data/restraints/parameters: 7299/1/570; GOOF 1.094; R1 0.0422;
structure was determined by single-crystal X-ray analysis.
Compound (+)-3 crystallizes in monoclinic space group C2 and
the crystal lattice comprises two inequivalent molecules with
crystallographic C2 symmetry and identical absolute configu-
ration. As shown in the representation, the calix[4]arene
diepoxide adopts a “pinched cone” conformation and the
oxiranyl carbon atoms have the (R,R)-(R,R) absolute configu-
ration (Figure 2). This is the first direct confirmation of the
general mechanistic model proposed for such reaction.13a
With these results in hand, we tried to stereoselectively
transform such a diepoxide, in order to test its synthetic
versatility as a chiral building block. Among our recent results
on regio- and stereoselective ring-opening reactions of diaryl
epoxides,15 the direct conversion into 2,2-dimethyl-1,3-
dioxolanes by the mild acetone/Amberlyst 15 system ap-
peared very promising, on the way to the synthesis of diaryl
glycols.19 Thus, we submitted 3 to our conditions, and the
corresponding trans,trans bis-acetonide 6 was obtained in
excellent chemical yield (79%), with no loss of stereochem-
ical integrity (Scheme 3).
1H NMR analysis confirmed the trans,trans stereochemistry
and HPLC analysis with the chiral stationary phase gave an ee
value of 99%, which is identical with that of diepoxide 3. The
absolute configuration was assigned to be (R,R)-(R,R) by
chemical correlation. On the basis of these data, the unprec-
edented diastereo- and enantioselective reaction on 1,3-
diformylcalix[4]arene 1 to the corresponding 1,3-diepoxide (+)-
3, coupled with the subsequent stereo- and enantiospecific
conversion into 1,3-bisdioxolane 6 opens the way, currently
under investigation in our laboratory, for further chiral func-
tionalization of this important class of macrocycles via direct
asymmetric reactions.
(20) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi, A. J. Appl.
Crystallogr. 1993, 26, 343.
(18) Solladie´-Cavallo, A.; Boue´rat, L.; Roje, M. Tetrahedron Lett. 2000, 41,
7309.
(21) Sheldrick. G. M. SHELXL97, Programs for Crystal Structure Analysis
(Release 97-2); University of Go¨ttingen: Go¨ttingen, Germany, 1997.
(22) Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
(19) Solladie´-Cavallo, A.; Choucair, E.; Balaz, M.; Lupattelli, P.; Bonini,
C.; Di Blasio, N. Eur. J. Org. Chem. 2006, 3007.
J. Org. Chem. Vol. 73, No. 11, 2008 4235

wR2 0.1022 on all data. Flack parameter 0.04(15). The crystal
structure has been deposited at the Cambridge Crystallographic Data
Centre; Dep. no. CCDC 649979.
CDCl3) δ (ppm) 8.7, 9.9, 10.7, 23.0, 23.4, 27.1, 27.3, 29.7, 30.8,
30.9, 45.8, 76.5, 76.9, 85.4, 85.6, 109.1, 121.9, 126.4, 126.9, 127.4,
127.4, 128.0, 128.2, 129.4, 133.2, 133.3, 136.4, 136.9, 137.1, 155.3,
157.5. Anal. Calcd for C62H72O8: C, 78.78; H, 7.68. Found: C, 78.5;
H, 7.8.
5,17-Bis((4′R,5′R)-2′,2′-dimethyl-5′-phenyl-1′,3′-dioxolyl)-
25,26,27,28-tetrapropyloxycalix[4]arene, 6. To a solution of bis-
epoxide 3 (34.5 mg, 0.04 mmol) in a 2:1 mixture of CH2Cl2/acetone
(3 mL) at room temperature was added Amberlyst 15 (9 mg, 220
mg/mmol). After 1 h of stirring, the reaction was quenched by
adding solid NaHCO3, the solid residue was removed by filtration,
and the solvent was evaporated. The crude product was purified
on a silica gel column with petroleum ether:EtOAc 95:5 as eluent,
to give pure compound 6 (30 mg) in 79% yield.
Acknowledgment. We thank MUR (Ministry of University
and Research-Rome) (Project PRIN 2005) and the University
of Basilicata for financial support. We acknowledge Dr. Samuele
Ciattini (Centro di Cristallografia Strutturale, Università degli
Studi di Firenze) for X-ray data collection.
6: [R]20 +123 (c 0.63, CH2Cl2); ee 99% (CHIRALPAK IA;
D
1
Supporting Information Available: Experimental proce-
dures for compound 1; 1H and 13C NMR of compounds 1, 3, 4,
and 6; chiral HPLC spectra of compounds (+/-)-3 and (+)-3;
X-ray structure of (+)-3 in CIF format, structure refinement
details. This material is available free of charge via the Internet
at http://pubs.acs.org.
n-hexane/2-propanol 95:5; flow rate: 0.8 mL/min); H NMR (500
MHz, CDCl3) δ (ppm) 0.83 (t, 6H, J ) 7 Hz), 0.99 (t, 3H, J ) 7
Hz), 1.35 (t, 3H, J ) 7 Hz), 1.59 (s, 6H), 1.62 (s, 6H), 3.06 (d, 2H,
J ) 13 Hz), 3.14 (d, 2H, J ) 13 Hz), 3.69 (t, 4H, J ) 7 Hz), 3.98
(t, 4H, J ) 7 Hz), 4.43 (2d, 4H, J ) 13 Hz), 4.63 (d, 1H, J ) 8.5
Hz), 4.79 (d, 1H, J ) 8.5 Hz), 6.09 (d, 2H, J ) 7.5 Hz), 6.22 (d,
2H, J ) 7.5 Hz), 6.32 (t, 2H, J ) 7.5 Hz), 6.83 (s, 2H), 7.03 (s,
2H), 7.20 (d, 4H, J ) 8 Hz), 7.32 (m, 6H); 13C NMR (125 MHz,
JO800301M
4236 J. Org. Chem. Vol. 73, No. 11, 2008