Tandem α-aminoxylation-allylation reaction based approach for the synthesis of goniothalesdiol A, leiocarpin A and (+)-goniodiol

Article abstract of DOI:10.1016/j.tetlet.2011.09.105

A short and efficient syntheses of goniothalesdiol A, leiocarpin A, and (+)-goniodiol are reported by a convergent strategy using tandem aminoxylation-allylation reaction as a key step starting from benzaldehyde.

Full text of DOI:10.1016/j.tetlet.2011.09.105

Tetrahedron Letters 52 (2011) 6550–6553
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Tandem
a
-aminoxylation–allylation reaction based approach
for the synthesis of goniothalesdiol A, leiocarpin A and (+)-goniodiol
Gowravaram Sabitha a, , T. Rammohan Reddy a, J.S. Yadav a,b
⇑
a Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 607, India
b Bee Research Chair, College of Food and Agriculture Science, King Saud University, Riyadh, Saudi Arabia
a r t i c l e i n f o
a b s t r a c t
Article history:
A short and efficient syntheses of goniothalesdiol A, leiocarpin A, and (+)-goniodiol are reported by a con-
vergent strategy using tandem aminoxylation–allylation reaction as a key step starting from benzaldehyde.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 25 August 2011
Revised 21 September 2011
Accepted 22 September 2011
Available online 2 October 2011
Keywords:
Styryl lactones
Tandem aminoxylation–allylation
Oxa-Michael
Still–Gennari
Goniothalamus
Tandem aminoxylation–allylation reaction catalyzed by
enantiopure proline was first reported by Zhong1 in 2004 has pro-
ven as an important transformation to the enantioselective synthe-
sis of non-terminal 1,2-diol units (both syn and anti). The
application of this strategy2 was not much explored in natural prod-
uct synthesis. In continuation of our efforts3 toward the use of
spectroscopy. Owing to the challenges posed by the substitution
pattern and also due to the interesting biological properties, the
synthesis of this compound has attracted attention. So far, four syn-
theses10 have appeared for this compound. Leiocarpin A 2 belongs
to a group of styryl lactones recently isolated from ethanolic extract
of the stem bark of Goniothalamus leiocarpus, (Annonaceae), a
tropical plant found in the South of Yunnan province in China,11
which is found to possess cytotoxic activities against several tumor
cell lines.12 So far two syntheses13 are known for leiocarpin A. (+)-
Goniodiol 3 was isolated from the leaves and twigs of Goniothala-
mus sesquipedalis (Annonaceae)14a and the stem bark of Thai
Goniothalamus giganteus.14b Goniodiol exhibited potent selective
cytotoxicity against human lung carcinoma cell lines A-549,15 HL-
60 cells,16 and P-388 murine leukemia cells.17 Consequently, a large
number of reports have appeared on the total synthesis of (+)-
Goniodiol.18
proline-catalyzed asymmetric a-aminoxylation of aldehydes using
nitrosobenzene as the oxygen source and followed by Horner–
Wadsworth Emmons olefination,4 we became interested in the
use of proline catalyzed
a-aminoxylation of aldehydes followed
by in situ indium-promoted allylation for the synthesis of natural
products, such as goniothalesdiol A 1, leiocarpin A 2, and (+)-gonio-
diol 3 (Fig. 1). The genus Goniothalumus (Annonaceae) comprises
several species of shrubs and trees growing in Asia and has long
been recognized as a potential source of chemotherapeutic agents.5
Studies on natural products isolated from Asian trees of the genus
Goniothalamus have led to the discovery of several classes of com-
pounds including acetogenins, alkaloids, styryllactones, and flavo-
noids with interesting biological properties,6 such as cytotoxic,
pesticidal, and teratogenic. (+)-Goniothalesdiol A 1,7 a new type
styryl derivative, 2,6-disubstituted tetrahydropyran, was isolated
recently from the stem of the Taiwan tree Goniothalumus amuyon.
Extracts of seeds of G. amuyon have been used to treat edema, rheu-
matism8 as a painkiller and mosquito repellent.9 The structure and
relative stereochemistry of 1 were assigned on the basis of 1H NMR
Because of the antitumor activities of styryl lactones, much
effort has been centered on the development of methodologies
H
O
H
Ph
O
O
CO2Me
OH
O
O
7
HO
3
O
4
6
OH
HO
H
OH
(+)-goniodiol 3
Figure 1. Substituted pyran and styryl lactone natural products.
leiocarpin A 2
goniothalesdiol A 1
⇑
Corresponding author. Tel.: +91 40 27191629; fax: +91 40 27160512.
E-mail address: gowravaramsr@yahoo.com (G. Sabitha).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.105

G. Sabitha et al. / Tetrahedron Letters 52 (2011) 6550–6553
6551
H
H
Ph
O
OBn
MOMO
Ph
CO2Me
H
O
O
HO
7
3
4
O
OBn
6
OH
4a
HO
goniothalesdiol A 1
+
leiocarpin A 2
O
MOMO
Ph
OBn
OH
OH
O
PhCHO
Ph
OH
OBn
5
4b
(+)-goniodiol 3
Scheme 1. Retrosynthetic analysis.
for the synthesis of these lactones. As part of our program on the
total synthesis of bioactive lactones,19 herein, we report a total
synthesis of goniothalesdiol A 1, leiocarpin A 2, and (+)-goniodiol
3 using a tandem aminoxylation–allylation reaction as a key step.
The retrosynthetic plan for goniothalesdiol A, leiocarpin A, and
(+)-goniodiol is outlined in Scheme 1. We envisioned that goniot-
halesdiol A and leiocarpin A could be obtained from the anti diol
4a and goniodiol from syn diol 4b. The key syn and anti diols can
be synthesized through a proline-catalyzed tandem aminoxyla-
tion–allylation of aldehyde derived from homoallylic alcohol 5,
which in turn was obtained from benzaldehyde.
The synthesis of these molecules started from the commercially
available benzaldehyde (Scheme 2), which was converted to
homoallylic alcohol 5 with excellent enantioselectivity of 98% ee
(determined by chiral HPLC) by subjecting it to Keck allylation20
using (S)-BINOL. After protection of the secondary hydroxy group
as MOM ether 6 using MOMCl and DIPEA, the terminal double
bond was subjected to dihydroxylation with OsO4 to give vicinal
diol, which on oxidative cleavage with NaIO4 provided aldehyde
this stage we could not define which isomer, syn or anti, was the
major product, but it was assumed that the syn-isomer was the
major product according to the literature2 and was also found at
the final stage the major product is the syn- isomer 4b.
The minor anti-isomer 4a was subjected to the cross-metathesis
reaction with methyl acrylate in the presence of second-generation
Grubbs’ catalyst at room temperature for 2 h to provide
a,b-
unsaturated ester 9 in 94% yield (Scheme 3). Next, acid-catalyzed
(PTSA) deprotection of MOM group followed by concomitant oxa-
Michael reaction yielded cyclized compound 10 (85%). Finally, deb-
enzylation with TiCl4 led to goniothalesdiol A 1 in 84% yield, which
proceeded in only nine steps from readily available benzaldehyde.
The structure of 1 was confirmed by comparing its spectral and
physical data with previous synthetic report. The optical purity
and other spectral data were in full accordance with those reported
for the natural product. Since, the anti configuration of two hydro-
xyl groups in goniothalesdiol A at C3 and C4 is already known, thus
the synthesis unambiguously confirms that the starting isomer 4a
has anti configuration.
7.
and
a
-Aminoxylation of aldehyde 7 with nitrosobenzene (1 equiv
For the synthesis of leiocarpin A 2, the terminal double bond of
the anti-isomer 4a was subjected to dihydroxylation with OsO4 to
give vicinal diol, which on oxidative cleavage with NaIO4 provided
aldehyde 11 (Scheme 4). The aldehyde on chain elongation with a
Wittig ylide (Horner–Wodsworth–Emmons) provided the corre-
L-proline (20 mol %) as the catalyst in CHCl3 followed by
in situ indium mediated allylation with allyl bromide in the pres-
ence of NaI at room temperature provided a mixture of products
8a and 8b. The crude reaction mixture 8 obtained was directly sub-
jected to the cleavage of the N–O bond proceeded uneventfully
using Cu(OAc)2 in ethanol to give the corresponding 8a diol after
filter column chromatography, as a mixture of anti/syn in 4:6 ratio
(chiral HPLC) in a total yield of 65%. This diastereomeric mixture
was separated as syn and anti isomers after protecting the hydroxyl
groups. Thus treatment of 8a with benzyl bromide produced the
diols 4a and 4b, respectively. The anti 4a and syn 4b isomers21
were separated by column chromatography. Excellent optical puri-
ties were found for both syn-4b and anti-4a with over 98% ee’s. At
sponding
a,b-unsaturated ester 12 ((F3CCH2O)2POCH2COOMe,
NaH, THF, ꢀ78 °C, 87%) as the (Z)-isomer, that could be purified
by flash column chromatography.
Debenzylation of 12 with TiCl4 led to the formation of triol 13
by deprotecting MOM group also as expected, which under acidic
conditions using HCl in THF/H2O (8:2) at room temperature for
12 h brought about spontaneous ring closure to provide leiocarpin
A in 86% yield. The spectral and physical properties of synthetic
leiocarpin A 2 were identical to those reported in the literature.
MOMO
Ph
OH
MOMO
Ph
OMOM
OH
OR
a
d
c
+
CHO
PhCHO
Ph
Ph
OH
8a
ONHPh
8b
7
5; R = H
b
f
R = MOM
6;
e
4b
4a
+
dr = 4:6 (anti:syn)
Scheme 2. Reagents and conditions: (a) S-BINOL, Ti(OiPr)4, DCM, reflux, 2 h, benzaldehyde, rt, 10 min, then allyltributyltin, ꢀ78 °C, 24 h, 91%; (b) iPr2NEt, MOMCl, DCM, 0 °C–
rt, 15 h, 92%; (c) (i) OsO4 (cat), NMO, acetone/H2O (2:1), rt, 24 h; (ii) NaIO4, THF/H2O (2:1), 85% for two steps; (d) PhNO, -Proline, CHCl3, 0 °C, 4 h, allylbromide, NaI, In, DMSO,
L
rt, 90 min, 65% (diastereomers with ratio syn:anti, 6:4); (e) Cu(OAc)2, EtOH, 12 h, rt; (f) NaH, BnBr, TBAI, THF, 0 °C–rt, 12 h, 90%.

6552
G. Sabitha et al. / Tetrahedron Letters 52 (2011) 6550–6553
OBn
MOMO
Ph
Ph
O
a
b
CO2Me
c
CO2Me
4a
10; R1 = Bn
1; R1 = H
R1O
OBn
9
OR1
Scheme 3. Reagents and conditions: (a) methyl acrylate, G-II, rt, 2 h, 94%; (b) PTSA, MeOH, reflux, 3 h, 85%; (c) TiCl4, DCM, 0 °C–rt, 4 h, 84%.
OR
OR1
OBn
MOMO
Ph
b
H
a
O
d
OMe
CHO
4a
O
Ph
O
OR1
O
6
7
OBn
11
HO
12; R = MOM, R1 = Bn
13; R = R1 = H
leiocarpin A 2
c
Scheme 4. Reagents and conditions: (a) (i) OsO4 (cat), NMO, acetone/H2O (2:1), rt, 24 h; (ii) NaIO4, THF/H2O (2:1), 85% two steps; (b) MeOOCCH2P(O)(OCH2CF3)2, NaH, THF,
ꢀ78 °C, 1 h, 87%; (c) TiCl4, DCM, 0 °C–rt, 15 h, 82%; (d) concd HCl, THF/H2O (8:2) rt, 12 h, 86%.
O
OR
OR1
OBn
MOMO
Ph
OH
O
a
b
d
OMe
CHO
4b
Ph
OH
(+)-goniodiol 3
OR1
O
OBn
14
15; R = MOM, R1 = Bn
16; R = R1 = H
c
Scheme 5. Reagents and conditions: (a) (i) OsO4 (cat), NMO, acetone/H2O (2:1), rt, 24 h; (ii) NaIO4, THF/H2O (2:1), 85% for two steps; (b) MeOOCCH2P(O)(OCH2CF3)2, NaH,
THF, ꢀ78 °C, 1 h, 87%; (c) TiCl4, DCM, 0 °C–rt, 15 h, 82%; (d) concd HCl, THF/H2O (8:2) rt, 48 h, 91%.
3. (a) Sabitha, G.; Chandrashekhar, G.; Yadagiri, K.; Yadav, J. S. Tetrahedron Lett.
For the preparation of goniodiol 3, terminal double bond of the
syn-isomer 4b was subjected to dihydroxylation with OsO4 to give
vicinal diol, which on oxidative cleavage with NaIO4 provided alde-
2010, 51, 3824; (b) Sabitha, G.; Reddy, D. V.; Rao, A. S.; Yadav, J. S. Tetrahedron
Lett. 2010, 51, 4195.
4. Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247.
5. (a) Blázquez, M. A.; Bermejo, A.; Zafra-Polo, M. C.; Cortés, D. Phytochem. Anal.
1999, 10, 161; (b) Surivet, J. P.; Vatéle, J. M. Tetrahedron 1999, 55, 13011.
6. (a) Zeng, L.; Ye, Q.; Oberlies, N. H.; Shi, G.; Gu, Z. M.; He, K.; Mc Laughlin, J. L.
Nat. Prod. Rep. 1996, 13, 275; (b) Din, L. B.; Colegate, S. M.; Razak, D. A.
Phytochemistry 1990, 29, 346; (c) Omar, S.; Chee, C. L.; Ahmad, F.; Ni, J. X.; Jaber,
H.; Huang, J.; Nakatsu, T. Phytochemistry 1992, 31, 4395; (d) Sam, T. W.; Chew,
S. Y.; Matsjeh, S.; Gan, E. K.; Razak, D.; Mohamed, A. L. Tetrahedron Lett. 1987,
28, 2541; (e) Fang, X.-P.; Anderson, J. E.; Chang, C. J.; McLauglin, J. L. Tetrahedron
1991, 4, 9751.
hyde 14. The aldehyde on chain elongation with a Wittig ylide
(Horner–Wodsworth–Emmons) provided the corresponding
a,b-
unsaturated ester 15 ((F3CCH2O)2 POCH2COOMe, NaH, THF,
ꢀ78 °C, 87%) as the (Z)-isomer, that could be purified by flash col-
umn chromatography. Debenzylation with TiCl4 led to the forma-
tion of triol 16, which under acidic conditions using HCl in THF/
H2O (8:2) at rt for 2 days provided (+)-goniodiol 3 in 91% yield
(Scheme 5).
Highlights of the synthetic venture included the successful uti-
lization of tandem aminoxylation–allylation to introduce the stere-
ogenic centers.
7. Talapatra, S. K. Indian J. Chem., Sect. B 1985, 24, 561.
8. Lan, Y. H.; Chang, F.-R.; Yang, Y.-L.; Wu, Y.-C. Chem. Pharm. Bull. 2006, 54, 1040.
9. Wu, Y. C.; Duh, C. Y.; Chang, F. R.; Chang, G. Y.; Wang, S. K.; Chang, J. S.; Mc
Phail, D. R.; Mc Phail, A. T.; Lee, K. H. J. Nat. Prod. 1991, 54, 1077.
10. (a) Yadav, J. S.; Reddy, N. R.; Harikrishna, V.; Reddy, B. V. S. Tetrahedron Lett.
2009, 50, 1318; (b) Li, J.; Zheng, H.; Su, Y.; Xie, X.; She, X. Synlett 2010, 2283; (c)
Venkataiah, M.; Somaiah, P.; Gowrisankar, R.; Fadnavis, N. W. Tetrahedron:
Asymmetry 2009, 20, 2230; (d) Yadav, J. S.; Nageshwar Rao, R.; Somaiah, R.;
Harikrishna, V.; Subba Reddy, B. V. Helv. Chim. Acta 2010, 93, 1362.
11. Mu, Q.; Tang, W.; Li, C.; Lu, Y.; Sun, H.; Zheng, X.; Wu, N.; Lou, B.; Xu, B.
Heterocycles 1999, 12, 2969.
12. Mu, Q.; Li, C. M.; He, Y. N.; Sun, H. D.; Zheng, H. L.; Lu, Y.; Zheng, Q. T.; Jiang, W.
Chin. Chem. Lett. 1999, 10, 135.
13. (a) Chen, J.; Lin, G.-Q.; Liu, H.-Q. Tetrahedron Lett. 2004, 45, 8111–8113; (b)
Nagaiah, K.; Sreenu, D.; Purnima, K. V.; Rao, R. S.; Yadav, J. S. Synthesis 2009,
1386–1392.
In summary, a facile synthesis of 1, 2, and 322 was accomplished
starting from benzaldehyde in a total of 8–9 steps, compared to the
known syntheses which required more than 10 steps. This syn-
thetic sequence provides an easy access to the preparation of styryl
lactones of biological importance. Further investigations on the
utility of this methodology for other bioactive natural products
are currently underway in our laboratory and will be reported in
due course.
14. (a) Talapatra, S. K.; Basu, D.; Goaswami, S.; Talapatra, B. Indian J. Chem., Sect. B
1985, 24, 29; (b) Fang, X. P.; Anderson, J. E.; Chang, C. J.; Mclaughlin, J. L.;
Fanwick, P. E. J. Nat. Prod. 1991, 54, 1034.
Acknowledgements
15. Nakashima, K.; Kikuchi, N.; Shirayama, D.; Miki, T.; Ando, K.; Sono, M.; Suzuki,
S.; Kawasw, M.; Kondoh, M.; Sato, M.; Kanai, K.; Nagase, H.; Honda, T. Bull.
Chem. Soc. Jpn. 2007, 80, 387.
16. Tsubuki, M.; Kanai, K.; Nagase, H.; Honda, T. Tetrahedron 1999, 55, 2493.
17. (a) Prasad, K. R.; Gholap, S. L. Tetrahedron Lett. 2007, 28, 4679; (b) Tate, E. W.;
Dixon, D. J.; Ley, S. V. Org. Biomol. Chem. 2006, 4, 1698; (c) Deligny, M.;
Carreaux, M.; Carboni, B. Synlett 2005, 1462.
18. (a) Tsubiki, M.; Kanai, K.; Honda, T. J. Chem. Soc., Chem. Commun. 1992, 1640;
(b) Annaick, F.; Francois, C.; Michael, D.; Bertrand, C. Eur. J. Org. Chem. 2008, 29,
4900; (c) Mukai, C.; Hirai, S.; Hanaoka, M. J. Org. 1997, 62, 6619; (d) Surivet, J.
P.; Goré, J.; Vatèle, J. M. Tetrahedron 1996, 37, 14877; (e) Prasad, K. R.; Gholap,
S. L. Tetrahedron Lett. 2007, 48, 4679; (f) Surivet, J. P.; Vetele, J. M. Tetrahedron
T.R.R. thanks UGC, New Delhi for the award of fellowship. J.S.Y.
acknowledges the partial support by King Saud University for Glo-
bal Research Network for Organic Synthesis (GRNOS).
References and notes
1. Zhong, G. Chem. Commun. 2004, 606.
2. (a) Kim, S.-G.; Park, T.-H.; Kim, B. J. Tetrahedron Lett. 2006, 47, 6369; (b) Kim, S.-
G. Synthesis 2009, 2418.

G. Sabitha et al. / Tetrahedron Letters 52 (2011) 6550–6553
6553
Lett. 1998, 39, 7299; (g) Ramachandran, P. V.; Subash, C. J.; Reddy, M. V. J. Org.
22. Data for compound 1: ½a D27
ꢁ
ꢀ23.4 (c 1, CHCl3). IR (KBr): 700, 1046, 1078, 1170,
Chem. 2002, 67, 7547; (h) Yadav, J. S.; Krishna, V. H.; Srilatha, A.; Somaiah, R.;
Reddy, B. V. Synthesis 2010, 3004; (i) Sabitha, G.; Bhikshapathi, M.; Ranjith, N.;
Ashwini, N.; Yadav, J. S. Synthesis 2011, 821–825.
1439, 1732, 2919, 3032, 3440. 1H NMR (300 MHz, CDCl3): d = 1.52 (br s, 1H),
1.68–1.80 (m, 1H), 2.07 (dq, J = 2.26, 14.3 Hz, 1H), 2.44 (dd, J = 6.0, 15.1 Hz, 1H),
2.60 (dd, J = 7.5, 15.1 Hz, 1H), 3.49 (dd, J = 3.0, 9.8 Hz, 1H), 3.65 (s, 3H), 4.20 (q,
J = 3.0, 6.0 Hz, 1H), 4.33–4.44 (m, 1H), 4.53 (d, J = 9.8 Hz, 1H), 7.28–7.41 (m,
5H). 13C NMR (75 MHz, CDCl3): d = 37.1, 40.3, 51.7, 67.1, 68.5, 72.5, 77.7, 127.4,
128.3, 128.9, 139.2, 171.4. ESI: m/z = 289 [M+Na]+. HRMS (ESI): m/z [M+Na]+
calcd for C14H18O5Na: 289.1051: found: 289.1054.
19. (a) Sabitha, G.; Sudhakar, K.; Yadav, J. S. Tetrahedron Lett. 2006, 47, 8599; (b)
Sabitha, G.; Siva Sankara Reddy, S.; Vasudeva Reddy, D.; Bhaskar, V.; Yadav, J. S.
Synthesis 2010, 3453; (c) Sabitha, G.; Siva Sankara Reddy, S.; Yadav, J. S.
Tetrahedron Lett. 2010, 51, 6259.
20. Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467.
Data for compound 2: ½a D27
ꢀ99.1 (c 1, CHCl3). IR (KBr): 702, 756, 975, 1084,
ꢁ
21. Data for compound 4a: ½a D27
ꢁ
ꢀ64.98 (c 8, CHCl3). IR (KBr): 699, 915, 1028, 1101,
1203, 1270, 1387, 1724, 2855, 2925, 3416. 1H NMR (500 MHz, CDCl3): d = 2.20
(br s, 2H), 2.75 (br s, 1H), 2.83 (dd, J = 4.9, 19.7 Hz, 1H), 2.95 (d, J = 18.7 Hz, 1H),
3.49 (d, J = 9.8 Hz, 1H), 4.39–4.44 (m, 1H), 4.41 (d, J = 9.8 Hz, 1H), 4.87 (br s,
1H), 7.26–7.41 (m, 5H). 13C NMR (75 MHz, CDCl3): d = 29.6, 29.8, 36.5, 65.8,
72.6, 74.3, 76.7, 126.5, 127.3, 128.6, 128.7, 169.0. ESI: m/z = 257 [M+Na]+.
HRMS (ESI): m/z [M+Na]+ calcd for C13H14O4Na: 257.0789: found: 257.0799.
1151, 1454, 1637, 2890, 3030. 1H NMR (300 MHz, CDCl3): d = 2.44–2.54 (m,
2H), 3.30 (s, 3H), 3.61–3.69 (m, 1H), 3.82 (dd, J = 3.0, 6.8 Hz, 1H), 4.37–4.56 (m,
6H), 4.70 (d, J = 6.8 Hz, 1H), 4.99–5.14 (m, 2H), 5.82–5.98 (m, 1H), 6.93–7.01
(m, 2H), 7.13–7.19 (m, 2H), 7.22–7.34 (m, 11H). 13C NMR (75 MHz, CDCl3):
d = 33.9, 55.9, 71.3, 74.1, 77.8, 79.2, 82.0, 94.1, 116.6, 127.2, 127.4, 127.7, 127.8,
128.0, 128.2, 128.4, 135.7, 138.4, 138.5, 138.9. ESI: m/z = 455 [M+Na]+. HRMS
(ESI): m/z [M+Na]+ calcd for C28H32O4Na: 455.2198: found: 455.2186.
Data for compound 3: ½a D27
ꢁ
+76.1 (c 1, CHCl3). IR (KBr): 1035, 1260, 1387, 1705,
2855, 2924, 3413. 1H NMR (500 MHz, CDCl3): d = 2.11 (dq, J = 3.9, 18.8 Hz, 1H),
2.44 (br s, 1H), 2.72–2.80 (m, 1H), 2.83 (br s, 1H), 3.65 (d, J = 5.9 Hz, 1H), 4.73
(dt, J = 2.96, 12.8 Hz, 1H), 4.91 (d, J = 6.9 Hz, 1H), 5.95 (dd, J = 2.9, 9.8 Hz, 1H),
6.86–6.90 (m, 1H), 7.26–7.41 (m, 5H). 13C NMR (75 MHz, CDCl3): d = 29.8, 73.4,
75.2, 96.2, 120.8, 126.6, 128.3, 128.8, 140.2, 145.9, 163.3. ESI: m/z = 257
[M+Na]+. HRMS (ESI): m/z [M+Na]+ calcd for C13H14O4Na: 257.0789: found:
257.0786.
Data for compound 4b: ½a D27
ꢀ32.1 (c 3.4, CHCl3). IR (KBr): 1030, 1217, 1453,
ꢁ
1640, 2924 cmꢀ1 1H NMR (300 MHz, CDCl3): d = 2.37–2.56 (m, 2H), 3.27 (s,
.
3H), 3.61 (dd, J = 3.3, 7.5 Hz, 1H), 3.80–3.88 (m, 1H), 3.91 (d, J = 11.1 Hz, 1H),
4.15 (d, J = 10.76 Hz, 1H), 4.49 (s, 2H), 4.65 (q, J = 11.52, 22.85 Hz, 2H), 4.83 (d,
J = 7.5, 1H), 5.02–5.11 (m, 2H), 5.72–5.88 (m, 1H), 7.01–7.06 (m, 2H), 7.19–7.40
(m, 11H), 7.44–7.49 (m, 2H). 13C NMR (75 MHz, CDCl3): d = 35.2, 56.0, 72.1,
74.4, 77.5, 78.5, 83.4, 94.7, 117.2, 127.4, 127.8, 127.9, 128.0, 128.1, 128.2,
128.4, 135.1, 138.2, 138.9, 139.7. ESI: m/z = 455 [M+Na]+. HRMS (ESI): m/z
[M+Na]+ calcd for C28H32O4Na: 455.2198: found: 455.2181.