Asymmetric synthesis of the core structure of (-)-CP-263,114.

Article abstract of DOI:10.1021/ol000290o

The enantioselective construction of a fully functionalized core structure of (-)-CP-263,114 (1), containing most of the required functionality for total synthesis, was conducted through sequential radical fragmentation-reductive olefination.

Full text of DOI:10.1021/ol000290o

ORGANIC
LETTERS
2000
Vol. 2, No. 23
3751-3754
Asymmetric Synthesis of the Core
Structure of (−)-CP-263,114
Takehiko Yoshimitsu,* Satoshi Yanagisawa, and Hiroto Nagaoka*
Meiji Pharmaceutical UniVersity, Noshio, Kiyose, Tokyo 204-8588, Japan
takey@my-pharm.ac.jp
Received September 29, 2000
ABSTRACT
The enantioselective construction of a fully functionalized core structure of (−)-CP-263,114 (1), containing most of the required functionality
for total synthesis, was conducted through sequential radical fragmentation−reductive olefination.
CP-263,114 (1) has been found a most challenging target
compound for natural product synthesis in recent years
(Figure 1).1
complementary methods for synthesizing a bicyclic ring
model of 1, one involving Grob fragmentation and the other,
114, see: Nicolaou, K. C.; Baran, P. S.; Zhong, Y.-L.; Choi, H.-S.; Yoon,
W. H.; He, Y.; Fong, K. C. Angew. Chem., Int. Ed. 1999, 38, 1669. For
synthesis of C7 epimer of CP-263,114, see: Meng, D.; Tan, Q.; Danishefsky,
S. J. Angew. Chem., Int. Ed. 1999, 38, 3197.
(3) For other synthetic studies, see: (a) Nicolaou, K. C.; Ha¨rter, Boulton,
L.; Jandeleit, B. Angew. Chem., Int. Ed. Engl. 1997, 36, 1194. (b) Nicolaou,
K. C.; Postema, M. H. D.; Miller, N. D.; Yang, G. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2821. (c) Davies, H. M. L.; Calvo, R.; Ahmed, G.
Tetrahedron Lett. 1997, 38, 1737. (d) Sgarbi, P. W. M.; Clive, D. L. J.
Chem. Commun. 1997, 2157. (e) Armstrong, A.; Critchley, T. J.; Mortlock,
A. A. Synlett 1998, 552. (f) Kwon, O.; Su, D.-S.; Meng, D.; Deng, W.;
D’Amico, D. C.; Danishefsky, S. J. Angew. Chem., Int. Ed. 1998, 37, 1877.
(g) Kwon, O.; Su, D.-S.; Meng, D.; Deng, W.; D’Amico, D. C.; Danishefsky,
S. J. Angew. Chem., Int. Ed. 1998, 37, 1880. (h) Waizumi, N.; Itoh, T.;
Fukuyama, T. Tetrahedron Lett. 1998, 39, 6015. (i) Chen, C.; Layton, M.
E.; Shair, M. D. J. Am. Chem. Soc. 1998, 120, 10784. (j) Frontier, A. J.;
Danishefsky, S. J.; Koppel, G. A.; Meng, D. Tetrahedron 1998, 54, 12721.
(k) Bio, M. M.; Leighton, J. L. J. Am. Chem. Soc. 1999, 121, 890. (l)
Nicolaou, K. C.; Baran, P. S.; Jautelat, R.; He, Y.; Fong, K. C.; Choi, H.-
S.; Yoon, W. H.; Zhong, Y.-L. Angew. Chem., Int. Ed. 1999, 38, 549. (m)
Meng, D.; Danishefsky, S. J. Angew. Chem., Int. Ed. 1999, 38, 1485. (n)
Clive, D. L. J.; Sun, S.; He, X.; Zhang, J.; Gagliardini, V. Tetrahedron
Lett. 1999, 40, 4605. (o) Nicolaou, K. C.; He, Y.; Fong, K. C.; Yoon, W.
H.; Choi, H.-S.; Zhong, Y.-L.; Baran, P. S. Org. Lett. 1999, 1, 63. (p)
Baldwin, J. E.; Beyeler, A.; Cox, R. J.; Keats, C.; Pritchard, G. J.; Adlington,
R. M.; Watkin, D. J. Tetrahedron 1999, 55, 7363. (q) Clive, D. L. J.; Zhang,
J. Tetrahedron 1999, 55, 12059. (r) Nicolaou, K. C.; Baran, P. S.; Zhong,
Y.-L.; Choi, H.-S.; Fong, K. C.; He, Y.; Yoon, W. H. Org. Lett. 1999, 1,
883. (s) Sulikowski, G. A.; Agnelli, F.; Corbett, R. M. J. Org. Chem. 2000,
65, 337. (t) Clive, D. L. J.; Sun, S.; Gagliardini, V.; Sano, M. K. Tetrahedron
Lett. 2000, 41, 6259. (u) Bio, M. M.; Leighton, J. L. Org. Lett. 2000, 2,
2905. (v) For biosynthetic studies, see: Spencer, P.; Agnelli, F.; Williams,
H. J.; Keller, N. P.; Sulikowski, G. A. J. Am. Chem. Soc. 2000, 122, 420.
(w) For reviews, see: Diederichsen, U. Nachr. Chem., Tech. Lab. 1999,
47, 1423., Carreira, E. M. Angew. Chem., Int. Ed. 2000, 39, 1415. Hepworth,
D. Chem. Ind. (London) 2000, 2, 59.
Figure 1.
The highly functionalized molecular architecture and
biological significance of the CP molecule have stimulated
considerable effort toward establishing routes for the total
synthesis of this natural product.2,3 We have developed two
(1) (a) Dabrah, T. T.; Kaneko, T.; Massefski, W., Jr.; Whipple, E. B. J.
Am. Chem. Soc. 1997, 119, 1594. (b) Dabrah, T. T.; Harwood, H. J., Jr.;
Huang, L. H.; Jankovich, N. D.; Kaneko, T.; Li, J.-C.; Lindsey, S.; Moshier,
P. M.; Subashi, T. A.; Therrien, M.; Watts, P. C. J. Antibiot. 1997, 50, 1.
(2) For asymmetric total syntheses and determination of the absolute
configuration of CP-263,114, see: (a) Nicolaou, K. C.; Jung, J.-K.; Yoon,
W. H.; He, Y.; Zhong, Y.-L,; Baran, P. S. Angew. Chem., Int. Ed. 2000,
39, 1829. (b) Chen, C.; Layton, M. E.; Sheehan, S. M.; Shair, M. D. J. Am.
Chem. Soc. 2000, 122, 7424. (c) Waizumi, N.; Itoh, T.; Fukuyama, T. J.
Am. Chem. Soc. 2000, 122, 7825. For total synthesis of racemic CP-263,-
10.1021/ol000290o CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/25/2000

sequential radical fragmentation-reductive olefination.4,5 The
latter, using radical ring cleavage followed by reductive
olefination to obtain the keto olefin, has been found an
effective alternative to ionic fragmentation reaction usually
requiring harsh conditions. The method has the following
features: (1) applicability to base- or acid-sensitive substrates
and (2) no requirement for conversion of alcohol intermedi-
ates to activated ones with leaving groups such as methane-
sulfonates and halides.
Scheme 2a
In the present study, the enantioselective construction of
the fully functionalized core structure of natural (-)-1 was
accomplished by this method and is thus shown an effective
means for the synthesis of CP-263,114 (1) (Scheme 1).
Scheme 1. Key Reaction for Constructing Core Structure of 1
a Reagents: (a) LDA, (E)-methyl 4-benzyloxycrotonate, THF,
-78 °C to rt, 65%; (b) Ca(OCl)2, aq CH2Cl2, rt, 74%; (c) SmI2,
HMPA, THF, -78 °C; (d) TMSOTf, Et3N, CH2Cl2, -78 °C, 66%,
two steps; (e) LAH, THF, rt; (f) O3, CH2Cl2, then Ph3P, -78 °C to
rt, 93%, two steps; (g) mCPBA, Na2HPO4, CH2Cl2, rt, 90%; (h)
hν (150 W tungsten lamp), I2, PhI(OAc)2, CH2Cl2, 0 °C; (i)
MOMCl, i-Pr2NEt, CH2Cl2, rt, 85%; (j) O3, CH2Cl2, then Ph3P,
-78 °C to rt, 89%; (k) Zn(BH4)2, Et2O, 0 °C; (l) TBAF, THF, 0
°C, 78%, twp steps; (m) 2,2-DMP, PPTS, acetone, rt, 93%.
As the first step in the synthesis, bicyclic compound 6
was prepared by sequential Michael addition reaction of (R)-
(-)-carvone (5) with R,â-unsaturated ester (Scheme 2). The
allylic chlorination of 6 with Ca(OCl)2 afforded 7, which
was cyclized with SmI2 in the presence of HMPA to give
tricyclic alcohol 8. The silylation of 8 with TMSOTf and
Et3N gave 9, which was then reduced with LAH to provide
alcohol 10. Following oxidative manipulation involving
ozonolysis and Baeyer-Villiger oxidation with mCPBA,
lactone 11 was obtained in 90% yield.
Photolytic olefination reaction of alcohol 11, previously
developed in our laboratory, led to the desired olefin 12,
iodo ether 13, and cyclic ether 14 in moderate yields (Scheme
3).6 The reduction of iodo ether 13 with Zn in the presence
of acetic acid provided olefin 12, thereby producing olefin
12 in 49% combined yield from 11. Subsequent protection
of the hydroxy group of 12 with methoxymethyl chloride
and ozonolysis of 15 afforded ketone 16 in good overall
yield.
The reduction of ketone 16 with Zn(BH4)2 proceeded
stereoselectively from its concave site to give a single
diastereomer of alcohol 17. Desilylation with TBAF provided
the diol, whose subsequent protection with 2,2-dimethoxy-
propane and PPTS furnished acetonide 18 in 93% yield.
Scheme 3. Photolytic Olefination of 11
(4) (a) Yoshimitsu, T.; Yanagiya, M.; Nagaoka, H. Tetrahedron Lett.
1999, 40, 5215. (b) For other fragmentation strategy for the construction
of the core of CP-263,114, see: Crimmins, M. T.; Hauser, E. B. Org. Lett.
2000, 2, 281.
(5) For precedents of efficient synthesis of bridgehead olefins, see: (a)
Holton, R. A. J. Am. Chem. Soc. 1984, 106, 5731. (b) Kraus, G. A.; Zheng,
D. Synlett 1993, 71. (c) Lee, J.; Oh, J.; Jin, S.-J.; Choi, J.-R.; Atwood, J.
L.; Cha, J. K. J. Org. Chem. 1994, 59, 6955. (d) Sheehan, S. M.; Lalic, G.;
Chen, J. S.; Shair, M. D. Angew. Chem., Int. Ed. 2000, 39, 2714.
(6) For reviews of the remote free radical functionalization, see: (a)
Kalvoda, J.; Heusler, K. Synthesis 1971, 501. (b) Majetich, G.; Wheless,
K. Tetrahedron 1995, 51, 7095. (c) For other remote olefination, see: Jung,
M. E.; Johnson, T. W. J. Am. Chem. Soc. 1997, 119, 12412 and references
therein.
3752
Org. Lett., Vol. 2, No. 23, 2000

The allylation of 18 followed by one-carbon degradation
through ozonolysis and reduction with NaBH4 afforded
alcohol 20 (Scheme 4). The olefination of 20 was conducted
1,1′-carbonyldiimidazole gave cyclic carbonate 26. The
TBAF-mediated desilylation of 26 and Dess-Martin oxida-
tion of 27 resulted in â-elimination to provide R,â-unsatur-
ated aldehyde 28. Aldehyde 28 was reduced with NaBH4 in
the presence of CeCl3 to afford allylic alcohol 29 in 89%
yield. The efficient construction of the quaternary stereogenic
center at C14 of the CP molecule was achieved by Stork
radical cyclization.8 Alcohol 29 was treated with ethyl vinyl
ether and NBS to give an inseparable diastereomixture of
bromo ether 30, which by radical cyclization with Bu3SnH
and AIBN gave 4a and 4b as separable diastereomers,
respectively.
Scheme 4a
Using these pivotal intermediates, sequential radical
fragmentation-reductive olefination for synthesis of the core
motif of 1 was carried out. The original method4a using zinc-
acetic acid for reductive olefination, however, provided only
moderate yield of bridgehead olefin 2 as a result of
competitive cyclization (Table 1). This situation required a
more appropriate reagent, and n-BuLi was found effective
for the reduction.9
Table 1. Reductive Olefination of â-Iodo Ether 3a and 3b
entry substratea
conditions
yields (%)
1
2
3
3a
3a
3b
Zn, AcOH/MeOH, rt
2a (14%)
4a (49%)
2a (63%)
3a (21%)
3.6 equiv n-BuLi/THF, -78 °C
1.2 equiv n-BuLi/THF, -78 °C 2b (49%)
3b (28%)
a 3a (Rf ) 0.5), 3b (Rf ) 0.4); AcOEt/Hex 2:3.
Compounds 4a and 4b were thus separately irradiated with
visible light under Sua´rez conditions10,11 to give keto iodides
3a and 3b as single diastereomers, respectively.
The reductive removal of â-halo ether functionalities
through metal-halogen exchange was achieved by treating
3a and 3b with n-BuLi in THF at -78 °C to provide the
core motifs of the CP molecule, 2a and 2b, in good yields.12
The structures of these motifs were unambiguously deter-
mined by NOE measurement of acetates 31a and 31b derived
from 2a and 2b (Figure 2).13
a Reagents: (a) LHMDS, AllylBr, HMPA, THF, -78 °C, 86%;
(b) O3, CH2Cl2, then Ph3P, -78 °C to rt; (c) NaBH4, MeOH, rt;
(d) o-O2NC6H4SeCN, Bu3P, THF, -78 to -40 °C to rt, then H2O2,
rt; (e) LAH, 1,4-dioxane, reflux, 71%, five steps; (f) TBSCl, Et3N,
CH2Cl2, rt, 90%; (g) TPAP, NMO, MeCN, rt, 94%; (h) O3, CH2Cl2,
then Ph3P, -78 °C to rt; (i) SmI2, HMPA, THF, -40 °C, 91%,
two steps; (j) CDI, DMAP, THF, rt; (k) TBAF, THF, rt, 95%, two
steps; (l) Dess-Martin periodinane, CH2Cl2, rt, 98%; (m) NaBH4,
CeCl3, MeOH, rt, 89%; (n) ethyl vinyl ether, NBS, Et2O, 0 °C,
61% (ds ) 1.5/1); (o) Bu3SnH, AIBN, benzene, reflux, 4a (42%)
and 4b (35%); (p) hν, I2, PhI(OAc)2, CH2Cl2, 0 °C, 3a (80% from
4a), 3b (80% from 4b); (q) n-BuLi, THF, -78 °C; (r) Ac2O, Et3N,
DMAP, CH2Cl2, rt, quant.
(8) Stork, G.; Mook, R., Jr.; Biller, S. A.; Rychnovsky, S. D. J. Am.
Chem. Soc. 1983, 105, 3741.
(9) For the use of n-BuLi or t-BuLi for this type of olefination reaction,
see: (a) Maeda, K.; Shinokubo, H.; Oshima, K.; Utimoto, K. J. Org. Chem.
1996, 61, 2262. (b) Ireland, R. E.; Habich, D.; Norbeck, D. W. J. Am. Chem.
Soc. 1985, 107, 3271. (c) Wender, P. A.; Keenan, R. M.; Lee, H. Y. J. Am.
Chem. Soc. 1987, 109, 4390.
by the Grieco method7 to provide vinyl lactone 21, which
was reduced with LAH to furnish diol 22 in 71% overall
yield from 18. Diol 22 was selectively protected as monosilyl
ether 23, whose secondary hydroxy group was oxidized in
the presence of catalytic TPAP and 4-methylmorpholine
N-oxide to provide ketone 24 in 94% yield. Ozonolysis
followed by stereoselective intramolecular pinacol coupling
of keto aldehyde 25 afforded the diol, whose treatment with
(10) Arencibia, R. N.; Salazar, J. A.; Sua´rez, E. Tetrahedron Lett. 1994,
35, 7463 and references therein.
(11) For a recent application of alkoxyradical fragmentation in natural
product synthesis, see: (a) Nowakowski, M.; Hoffmann, H. M. R.
Tetrahedron 1997, 53, 4331. (b) Shultz, A. G.; Zhang, X. Chem. Commun.
2000, 399. For pertinent reviews, see: (c) Ramaiah, M. Tetrahedron 1987,
43, 3541. (d) Jasperse, C. P.; Curran, D. P.; Fevig, T. L. Chem. ReV. 1991,
91, 1237. (e) Dowd, P.; Zhang, W. Chem. ReV. 1993, 93, 2091.
(12) The stereochemistry of iodine atom at C16 of 3a/3b was assigned
to be cis to the adjacent oxygen at C15 on the basis of the coupling constants
(JH16-17 ) 12.2 Hz for 3a, JH16-17 ) 12.5 Hz for 3b) and the NOE
experiments. This result indicates that the olefination may proceed through
syn-elimination mechanism.
(7) Grieco, P. A.; Gilman, S.; Nishizawa, M. J. Org. Chem. 1976, 41,
1485.
Org. Lett., Vol. 2, No. 23, 2000
3753

Our reported enantioselective construction of the fully
functionalized core motif of (-)-CP-263,114 demonstrates
(13) 2a: Rf ) 0.39 (AcOEt/Hex 3:1); [R]28 +49.0 (c 0.102, CHCl3);
D
1
IR (neat) 3429, 2926, 1699, 1454, 1151, 1111, 1042 cm-1; H NMR (400
MHz, CDCl3) δ 7.38-7.27 (m, 5H), 5.69 (dd, J ) 2.44, 2.20 Hz, 1H),
5.19 (dd, J ) 5.37, 1.95 Hz, 1H), 4.66 (s, 2H), 4.55 (d, J ) 12.5 Hz, 1H),
4.52 (d, J ) 12.2 Hz, 1H), 4.37 (bds, 1H), 4.11 (d, J ) 8.30 Hz, 1H), 3.98
(d, J ) 8.30 Hz, 1H), 3.73 (dq, J ) 9.52, 7.08 Hz, 1H), 3.71 (dd, J ) 9.03,
3.66 Hz, 1H), 3.59-3.53 (m, 3H), 3.45 (dd, J ) 9.03, 6.10 Hz, 1H), 3.44
(dq, J ) 9.52, 7.08 Hz, 1H), 3.35 (s, 3H), 2.86 (d, J ) 11.7 Hz, 1H), 2.82-
2.76 (m, 1H), 2.73 (dd, J ) 11.7, 1.22 Hz, 1H), 2.68 (dd, J ) 11.5, 8.05
Hz, 1H), 2.60-2.58 (m, 1H), 2.40 (dd, J ) 13.2, 5.62 Hz, 1H), 2.12-2.08
(m, 1H), 1.95 (dd, J ) 13.4, 1.95 Hz, 1H), 1.59-1.54 (m, 1H), 1.19 (t, J
) 7.08 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 209.0, 145.6, 138.3, 128.4,
128.2, 127.7, 127.5, 104.4, 96.6, 76.1, 73.2, 72.8, 69.9, 69.4, 63.4, 55.8,
55.1, 51.7, 47.7, 43.0, 42.0, 41.4, 35.2, 15.4; HRMS m/z calcd for C26H36O7
Figure 2. Key NOESY interactions in 31a/31b.
(M+) 460.2462, found 460.2467. 2b: Rf ) 0.36 (AcOEt/hex 3:1); [R]28
D
-81.2 (c 0.079, CHCl3); IR (neat) 3441, 2926, 1699, 1454, 1151, 1113,
1
1042 cm-1; H NMR (400 MHz, CDCl3) δ 7.38-7.27 (m, 5H), 5.71 (dd,
the successful utilization of sequential radical fragmentation-
reductive olefination. The present method provides routes
to both enantiomers of the CP-molecule simply by switching
the chirality of readily available starting material and thus
should constitute an effective means for the asymmetric total
synthesis of natural and unnatural CP-263,114.
J ) 2.93, 1.71 Hz, 1H), 5.26 (dd, J ) 5.37, 4.64 Hz, 1H), 4.66 (s, 2H),
4.53 (s, 2H), 4.38 (bds, 1H), 3.98 (d, J ) 8.30 Hz, 1H), 3.93 (dd, J ) 8.30,
1.00 Hz, 1H), 3.78 (dq, J ) 9.52, 7.08 Hz, 1H), 3.72 (dd, J ) 9.28, 3.90
Hz, 1H), 3.60-3.42 (m, 5H), 3.35 (s, 3H), 2.82-2.74 (m, 1H), 2.77 (d, J )
11.5 Hz, 1H), 2.71 (dd, J ) 11.7, 8.06 Hz, 1H), 2.62-2.56 (m, 1H), 2.34
(dd, J ) 11.5, 1.23 Hz, 1H), 2.27 (ddd, J ) 13.4, 5.62, 1.00 Hz, 1H),
2.14-2.07 (m, 2H), 1.58-1.54 (m, 1H), 1.20 (t, J ) 7.08 Hz, 3H); 13C
NMR (100 MHz, CDCl3) δ 208.9, 144.1, 138.3, 130.2, 128.4, 127.6, 127.5,
104.2, 96.6, 74.9, 73.2, 72.8, 69.6, 69.4, 63.8, 55.9, 55.4, 51.7, 49.5, 43.4,
42.0, 41.9, 35.2, 15.4; HRMS m/z calcd for C26H36O7 (M+) 460.2462, found
Acknowledgment. Financial support from the Japan
Society for the Promotion of Science (Grant-in-Aid for
Encouragement of Young Scientists 12771369) is gratefully
acknowledged.
460.2465. 3a: Rf ) 0.50 (AcOEt/Hex 2:3); [R]28 -11.4 (c 0.333, CHCl3);
D
IR (neat) 2928, 1697, 1107, 1061 cm-1
;
1H NMR (400 MHz, CDCl3) δ
7.39-7.28 (m, 5H), 5.12 (d, J ) 5.86 Hz 1H), 5.00 (d, J ) 12.2 Hz, 1H),
4.62 (d, J ) 12.0 Hz, 1H), 4.55 (s, 2H), 4.49 (d, J ) 12.0 Hz, 1H), 4.03
(dd, J ) 8.06, 1.22 Hz, 1H), 3.97 (dd, J ) 10.0, 2.44 Hz, 1H), 3.93 (d, J
) 8.05 Hz, 1H), 3.75 (dq, J ) 9.52, 7.08 Hz, 1H), 3.68 (dd, J ) 10.0, 1.95
Hz, 1H), 3.61 (d, J ) 2.44 Hz, 1H), 3.55-3.53 (m, 2H), 3.39 (dq, J )
9.52, 7.08 Hz, 1H), 3.30 (s, 3H), 3.23 (dd, J ) 13.4, 0.73 Hz, 1H), 2.94
(dd, J ) 13.4, 6.10 Hz, 1H), 2.78-2.72 (m, 2H), 2.60-2.55 (m, 1H), 2.49
(dd, J ) 14.9, 3.42 Hz, 1H), 2.38-2.31 (m, 1H), 2.10-2.03 (m, 1H), 1.81
(d, J ) 13.4 Hz, 1H), 1.64 (s, 3H), 1.36 (s, 3H), 1.18 (t, J ) 7.08 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 209.1, 138.2, 128.4, 127.8, 127.7, 108.7,
104.5, 96.7, 82.3, 80.4, 73.6, 71.8, 71.3, 70.8, 63.2, 55.5, 50.8, 50.3, 48.1,
43.4, 42.7, 41.2, 41.1, 29.9, 27.6, 26.3, 15.4; HRMS m/z calcd. for C29H41O8I
OL000290O
2H), 4.49 (d, J ) 12.0 Hz, 1H), 4.08 (dd, J ) 8.05, 1.46 Hz, 1H), 3.96 (dd,
J ) 10.0, 2.44 Hz, 1H), 3.77 (dq, J ) 9.76, 7.08 Hz, 1H), 3.73 (d, J )
2.44 Hz, 1H), 3.69-3.64 (m, 2H), 3.54 (d, J ) 5.61 Hz, 2H), 3.48 (dq, J
) 9.76 7.08 Hz, 1H), 3.30 (s, 3H), 2.77 (dd, J ) 14.7, 8.55 Hz, 1H), 2.68
(dd, J ) 13.7, 5.37 Hz, 1H), 2.64-2.56 (m, 3H), 2.51 (dd, J ) 14.7, 3.66
Hz, 1H), 2.33-2.27 (m, 1H), 2.10-1.98 (m, 2H), 1.62 (s, 3H), 1.34 (s,
3H), 1.22 (t, J ) 7.08 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 208.5,
138.3, 128.4, 127.8, 127.7, 108.7, 104.3, 96.7, 81.4, 79.9, 73.5, 72.1, 71.0,
68.9, 64.0, 55.5, 52.2, 49.7, 48.1, 43.1, 42.9, 41.1, 40.9, 30.3, 27.5, 26.0,
15.4; HRMS m/z calcd for C29H41O8I (M+) 644.1847, found 644.1845.
(M+): 644.1847, found: 644.1858.; 3b: Rf ) 0.40 (AcOEt/Hex 2:3); [R]28
D
-85.7 (c 0.369, CHCl3); IR (neat) 2899, 1693, 1150, 1105, 1055 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.38-7.28 (m, 5H), 5.15 (dd, J ) 5.61, 5.37
Hz, 1H), 4.89 (d, J ) 12.5 Hz, 1H), 4.63 (d, J ) 12.0 Hz, 1H), 4.55 (s,
3754
Org. Lett., Vol. 2, No. 23, 2000