Synthetic studies on bafilomycin A1: Stereoselective synthesis of the C12-C17 fragment and its coupling with the C 1-C11 subunit

Article abstract of DOI:10.1016/j.tetlet.2004.04.034

Stereoselective addition of (E)-1-lithio-2-tributylstannylethylene on a chiral cyclic di-t-butylsilyleneketal C₁₄-C₁₇ aldehyde afforded the required Felkin-Anh adduct for the synthesis of the C ₁₂-C₁₇ fragment of bafilomycin A₁, the configuration of which was assigned unambiguously. After appropriate coupling with the enantiopure C₁-C₁₁ fragment, the C ₁₂-C₁₇ subunit obtained here can be used for the study of the 16-membered macrolide formation either by an acyl activation or an intramolecular Stille reaction. Intermolecular esterification of the 15-OH with an acyl activation of the carboxylic acid of the C₁-C₁₁ fragment, in modified Yamaguchi's conditions, affords here an intermediate for examining an intramolecular Stille coupling.

Full text of DOI:10.1016/j.tetlet.2004.04.034

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4533–4537
Synthetic studies on bafilomycin A1: stereoselective synthesis of the
C12–C17 fragment and its coupling with the C1–C11 subunit
*
ꢀ
Emmanuelle Queron and Robert Lett
Unitꢀe Mixte CNRS-AVENTIS Pharma (UMR 26) 102, route de Noisy, 93235 Romainville, France
Received 23 March 2004; accepted 7 April 2004
Abstract—Stereoselective addition of (E)-1-lithio-2-tributylstannylethylene on a chiral cyclic di-t-butylsilyleneketal C14–C17 alde-
hyde afforded the required Felkin–Anh adduct for the synthesis of the C12–C17 fragment of bafilomycin A1, the configuration of
which was assigned unambiguously. After appropriate coupling with the enantiopure C1–C11 fragment, the C12–C17 subunit ob-
tained here can be used for the study of the 16-membered macrolide formation either by an acyl activation or an intramolecular
Stille reaction. Intermolecular esterification of the 15-OH with an acyl activation of the carboxylic acid of the C1–C11 fragment, in
modified Yamaguchi’s conditions, affords here an intermediate for examining an intramolecular Stille coupling.
Ó 2004 Elsevier Ltd. All rights reserved.
In the preceding communication,1 we described the
synthesis of the enantiopure C1–C11 fragment 1 of
bafilomycin A1. We herein report the synthesis of the
C12–C17 subunit 2 and its structure assignment, and also
the preparation of 3 (Scheme 1), in order to examine the
formation of the 16-membered macrolactone of bafilo-
mycin A1 via an intramolecular Stille coupling, which
will be discussed in the accompanying communica-
tion.2;3
metallics) and allow to get the desired stereoisomer
stereoselectively.4 However, the addition of the E-lithio-
vinyltributylstannane 6, generated in situ from 5,5 was
found to be almost nonstereoselective in THF/hexane
(Scheme 2). The configurations of the two adducts, 7
and 8, were demonstrated unambiguously by a chemical
filiation as discussed further. Modifications of reaction
conditions (temperature, excess of 6, addition of
BF3ꢀEt2O in THF or LiClO4 in Et2O) were unsatisfac-
tory. Results were not improved with the parent OTES
aldehyde 9. Additions of TMS–CBC–Li (1.5 equiv,
THF, 0 °C, overnight) and n-BuLi (1.2 equiv, toluene,
ꢁ78 °C, 6 h) were also weakly stereoselective with 4,
affording 55/45 and 65/35 mixtures of two diastereoiso-
mers, respectively, moreover in analogous moderate
yields.3 The low stereoselectivity obtained in all those
condensations is most likely due to the fact that the two
1. Synthesis of the C12–C17 fragment
In a first approach, we prepared the enantiopure alde-
hyde 4,3 expecting that the OTBS silyl ether, a to the
aldehyde, might disfavour the formation of the Cram-
chelate adduct with lithio derivatives (or other organo-
OMe
OMe
O
I
I
CO2H
11
1
1
OTES
O
OTES
OH
nBu3Sn
nBu3Sn
ODMT
ODMT
17
12
OMe
OMe
3
2
Scheme 1.
Keywords: Epoxides; Tin and compounds; Lithium and compounds; Aldehydes; Diastereoselection; Protecting groups; Esterification.
* Corresponding author. Tel.: +33-1-49-91-52-80; fax: +33-1-49-91-38-00; e-mail: robert.lett@aventis.com
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.034

4534
E. Quꢀeron, R. Lett / Tetrahedron Letters 45 (2004) 4533–4537
OTBS
OTBS
OTBS
a
nBu3Sn
nBu3Sn
nBu3Sn
ODMT
ODMT
29%
+
ODMT
32.5%
+
Li
O
O
OH
4
6
7
8
OH
tBu
dr = 53/47
nBuLi 2.5 M in hexane
(1 equiv.), THF, -78°C to rt
tBu
tBu
tBu
tBu
tBu
Si
nBu3Sn
nBu3Sn
Si
Si
SnBu3
O
O
O
O
O
O
5
b
nBu3Sn
nBu3Sn
+
+
Li
OH
10
6
11
40%
12
10.5%
OH
dr = 79/21
Scheme 2. Reagents and conditions: (a) 6 (1.05 equiv), addition of 4 in THF, ꢁ78 °C, 4 h, then MeOH quench at ꢁ78 °C; (b) 6 (1.05 equiv), addition
of 10 in THF, ꢁ78 °C, 7 h, then MeOH quench at ꢁ78 °C.
iPr
Si
substituents, a to the aldehyde, are large and probably
result in a dynamic equilibrium of conformers involved
in the reaction; the steric hindrance resulting from these
two substituents is also probably responsible of the
moderate reactivity of the aldehyde 4.
iPr
O
Si
OTES
iPr
iPr
O
ODMT
O
O
9
13
O
We then examined the condensations of 6 with the cyclic
di-t-butylsilyleneketal aldehyde 10 in order to still have
a nonchelating group and also to see if the cyclic ketal
might favour a conformation of the aldehyde. In fact the
best results were thus obtained with 10 (in a 95/5 ratio
with the epimerized aldehyde, see further) in THF since
the adducts 11 and 12 were isolated in 40% and 10.5%
yield, respectively, in quasi stoichiometric conditions
(Scheme 2); a mixture of two other diastereoisomers was
also isolated in 6% yield and some pure starting alde-
hyde 10 was still recovered (13.5%) after chromatogra-
phy. These results were obtained reproducibly at a 0.2–
3.5 mmole scale. The configurations of 11 and 12 were
demonstrated by a chemical filiation, as shown further.
Yields of adducts 11 and 12 were lower and stereo-
selection was not significantly improved either with
DME (ꢁ78 °C, 6 h) or THF/HMPA (9/1) (ꢁ78 °C, 4 h);
a 50/50 mixture of the two same adducts was obtained
with LiClO4 (2 equiv) in Et2O (ꢁ78 °C, 3.5 h).
The aldehyde 10 was prepared from commercially
available cis-4-benzyloxy-2-buten-1-ol 14 (Scheme 3).
Sharpless asymmetric epoxidation6 afforded the epoxy-
alcohol 15 in 76% yield with an ee of 80%, determined
1
by H NMR (400 MHz) of the corresponding MTPA
esters.7 We then preferred to open directly the epoxide
by Me2CuLi in Et2O, even if the reaction afforded a 70/
30 mixture of the two regioisomers as in previous related
examples,8 rather than to develop a more lengthy
sequence to solve that problem. As the two isomers 16
and 17 were not separable, the most efficient solution
was to use the crude mixture for converting them into
the corresponding di-t-butylsilyleneketals since those
corresponding to 1,2-diols are known to be very labile.9
Thus after aqueous work-up and chromatography over
silicagel, the desired ketal 18 was isolated in 58% yield
over the two steps from 15. After hydrogenolysis of the
benzyl ether (84% yield), Swern oxidation10 of the
alcohol 19, using i-Pr2NEt to minimize the epimeriza-
tion of this sensitive aldehyde, afforded 10 in 90% yield
as a 95/5 mixture of epimers at C15, which could not be
On the other hand, the aldehyde 13 gave with 6, at
ꢁ78 °C, a 50/50 mixture of the corresponding adducts in
THF or with LiClO4 (2 equiv) in Pr2O.3
OH
a
b
PhCH2O
OH
PhCH2O
OH
OH
OH
+
PhCH2O
PhCH2O
76%
O
14
15
16
17
OH
e
tBu
tBu
tBu
tBu
ee = 80%
tBu
tBu
Si
Si
O
Si
O
O
O
O
O
d
c
PhCH2O
HO
15
18
58% (over 2 steps)
19
10
O
90% (5% epimer at C15)
84%
Scheme 3. Reagents and conditions: (a) Ti(O-i-Pr)4 (1.0 equiv), (ꢁ)-DET (1.2 equiv), anhyd CH2Cl2, ꢁ30 °C, 30 min, then 14, ꢁ30 °C, 1 h, followed
by t-BuOOH (2.6 M in anhyd CH2Cl2, 5 equiv, ꢁ30 °C, 4 days); (b) CuI (5 equiv), MeLi 1.6 M in Et2O (9 equiv) at 0 °C, then ꢁ40 °C, 15, 5 h; (c) crude
mixture of 16 and 17 (70/30), 2,6-lutidine (10 equiv), t-Bu2Si(OTf)2 (3.2 equiv), CH2Cl2, rt, 3 h; (d) 10% Pd/C (40% in weight), H2, 95% EtOH, rt, 4 h;
(e) oxalyl chloride (1.2 equiv), DMSO (2.4 equiv), CH2Cl2, ꢁ78 °C, 15 min, then 19, 30 min, followed by i-Pr2NEt (5.0 equiv), ꢁ78 °C to rt, 1 h.

E. Quꢀeron, R. Lett / Tetrahedron Letters 45 (2004) 4533–4537
4535
separated. It is worthy to point out that epimerization
was observed only on upscaling, after chromatography
(heptane/AcOEt 95/5). The configuration of the alde-
perature, with no destannylation, 20 thus affording the
diol 21 in 88% yield. The diols 21 and 24 were then
converted into the corresponding acetonides 22 and 25
with 2-methoxypropene and PPTS as a catalyst, condi-
tions which were mild enough to avoid protodestanny-
lation. The chemical filiations of 11 with 7, and of 12
with 8, were achieved via 2 and 26, respectively.3
hyde 10 was clearly demonstrated by NMR (3J15;16
¼
3
4.5 Hz, compared to J15;16 ¼ 11 Hz for the minor
diastereoisomer). The aldehyde 10 is thus obtained in
33% overall yield from 14 (five steps).
The configurations of the adducts 7, 8, 11 and 12, were
determined unambiguously by the chemical filiation
between them and 22, which was an intermediate of the
synthesis of bafilomycin A1 achieved by Toshima et al.
(Scheme 4).11 The NMR spectra of the acetonides 22
and 25 are clearly different in CDCl3 (1H at 300 MHz,
13C at 50 MHz), and comparison with the data pub-
lished by Toshima for 22 allows an unambiguous
assignment of the structures.12
For the synthesis of bafilomycin A1, the required C12–
C17 fragment 2 is thus obtained with a 10% overall yield
from 14 (ee ¼ 80%, nine steps).
2. Precursor of the macrolide formation (Scheme 5)
The prepared subunits 1 and 2 now allowed us to study
the formation of the macrolide either via an acyl acti-
vation of their coupling product obtained after an
intermolecular Stille coupling, or via an intramolecular
Stille reaction of the corresponding ester 3. For bafilo-
mycin A1 synthesis, the 16-membered macrolide for-
mation has always been achieved via an acyl
activation.11;13–15 Therefore, instead of an acyl activation
and in order to find an alternate solution, we decided to
examine the formation of the macrocycle via an intra-
molecular Stille coupling.16 Thus, the required enantio-
pure precursor 3 was obtained in 89% yield by an
intermolecular esterification of the enantiopure C1–C11
acid 1 with the chiral C12–C17 alcohol 2 (ee ¼ 80%)
(1.08 equiv), in the presence of Yamaguchi’s chloride,17
NEt3 and DMAP, at room temperature, and 11% of the
Formation of the methyl ether at C14 was quite a diffi-
cult problem for avoiding silyl migration, desilylation or
destannylation for the adducts 7 and 11, and showed to
be even more difficult for 8 and 12. The corresponding
methyl ethers could however be obtained by reaction of
the derived lithium alkoxide, generated in situ, with a
large excess of methyl iodide, in THF/HMPA at room
temperature. Fortunately, yields were higher with the
diastereoisomer required further for the synthesis. Evans
and Calter already pointed out the difficulty of the for-
mation of the methyl ether for a related compound with
the (S) configuration at C14, and gave an other solution
to this problem.13 The di-t-butylsilylene ketal could be
cleaved with an excess TBAF in THF, at room tem-
tBu
tBu
tBu
tBu
Si
Si
O
O
O
O
OH
c
OH
a
b
nBu3Sn
nBu3Sn
nBu3Sn
89 %
88 %
11
20
OH
MeO
MeO
21
d
97 %
e (74 %)
f (71 %)
OTBS
OH
O
O
nBu3Sn
nBu3Sn
nBu3Sn
nBu3Sn
nBu3Sn
ODMT
ODMT
88 %
7
2
22
OH
MeO
MeO
tBu
tBu
tBu
O
tBu
Si
Si
a
O
O
O
OH
c
OH
b
nBu3Sn
56 %
64 %
12
23
OH
MeO
MeO
24
d
57 %
e (22 %)
f (34 %)
OTBS
OH
O
O
nBu3Sn
nBu3Sn
nBu3Sn
ODMT
ODMT
87 %
8
26
25
OH
MeO
MeO
Scheme 4. Reagents and conditions: (a) n-BuLi 1.6 M in hexane (1.2 equiv), MeI (20 equiv), THF, ꢁ78 °C to rt, 1 h, then HMPA to get THF/HMPA
(10/1), rt, 16 h; (b) TBAF 1 M in THF (5 equiv), rt, 3 days; (c) CH2@CMe(OMe) (3 equiv), PPTS (0.01 equiv), CH2Cl2, rt, 20 h; (d) DMTBF4
(1.8 equiv for 21, 1.1 equiv for 24), 2,6-di-t-butyl-4-methylpyridine (2.5 equiv for 21, 1.5 equiv for 24), MeCN, rt, 4 h; (e) n-BuLi 1.6 M in hexane
(1.2 equiv), MeI (100 equiv), THF, ꢁ78 °C to rt, 1 h, then HMPA to get THF/HMPA (5/1), rt, 16 h; (f) TBAF 1 M in THF (10 equiv), rt, 5 days for 2,
6 days for 26.

4536
E. Quꢀeron, R. Lett / Tetrahedron Letters 45 (2004) 4533–4537
OMe
O
OH
I
O
nBu3Sn
OMe
ODMT
OTES
2
I
MeO
CO2H
nBu3Sn
ODMT
(0.1 M)
OTES
OMe
1
3
89%
Scheme 5. Reagents and conditions: 1, toluene, DMAP (2 equiv), rt, then addition of NEt3 (4 equiv), followed by 2,4,6-trichlorobenzoyl chloride
(2 equiv) and addition of 2 in toluene (1.08 equiv), then rt, 24 h.
(m, 1H, H14), 4.10 (dd, 1H, H15, J15;16 ¼ 2.5, J15;14 ¼ 8), 4.34
alcohol 2 (ee not determined) were reisolated after
chromatography (Scheme 5).18
(dd, 1H, H17a, J17a;17b ¼ 11, J17a;16 ¼ 3), 3.92 (dd, 1H, H17b
,
J17a;17b ¼ 11, J17b;16 ¼ 2), 1.81 (d, 1H, OH, JOH;14 ¼ 4), 2.01
(m, 1H, H16), 1.48 (m, 6H, CH3CH2CH2CH2Sn), 1.30 (m,
6H, CH3CH2CH2CH2Sn), 1.22 (d, 3H, CH3, J16;CH ¼ 7),
3
1.07 (s, 9H, t-BuSi), 1.05 (s, 9H, t-BuSi), 0.90 (t, 6H,
CH3CH2CH2CH2Sn, JCH CH Sn ¼ 7), 0.88 (t, 9H,
Acknowledgements
2
2
CH3CH2CH2CH2Sn, JCH CH ¼ 7); 13C NMR (50.3 MHz,
3
2
We thank the staff of the Analytical Department of the
Research Center at Romainville and also Roussel Uclaf,
Hoechst Marion Roussel and the CNRS for a Ph.D.
grant to E. Queron, the Direction des Recherches
Chimiques of Roussel Uclaf and HMR for support of
this work.
CDCl3): 149.0 (C13), 127.5 (C12), 78.8 (C15), 74.9 (C14),
71.4 (C17), 34.2 (C16), 29.2 and 27.4 (CH3CH2CH2CH2Sn),
28.7 and 27.6 (t-BuSi), 23.5 and 20.7 (CqSi), 13.8
(CH3CH2CH2CH2Sn), 11.4 (CH3), 9.5 (CH3CH2CH2
CH2Sn); C27H56O3SiSn ¼ 575.53; MS (EI, m=z): 575
(Mþ), 518, 461.
ꢀ
Compound 12: pale yellow oil; ½aꢂ þ2:0 (c 0.4, CHCl3);
D
1H NMR (300 MHz, CDCl3): d/TMS 6.41 (d, 1H, H12,
J13;12 ¼ 19), 5.88 (dd, 1H, H13, J13;12 ¼ 19, J13;14 ¼ 7), 4.00
(m, 1H, H14), 4.05 (dd, 1H, H15, J15;16 ¼ 2.5, J15;14 ¼ 8), 4.33
References and notes
(dd, 1H, H17a, J17a;17b ¼ 11, J17a;16 ¼ 3), 3.89 (dd, 1H, H17b
,
J17a;17b ¼ 11, J17b;16 ¼ 2), 2.98 (d, 1H, OH, JOH;14 ¼ 1), 1.78
(m, 1H, H16), 1.47 (m, 6H, CH3CH2CH2CH2Sn), 1.29 (m,
ꢀ
1. Queron, E.; Lett, R. Tetrahedron Lett. 2004, 45, preceding
paper, doi:10.1016/j.tetlet.2004.04.033.
2. Queron, E.; Lett, R. Tetrahedron Lett. 2004, 45, following
paper, doi:10.1016/j.tetlet.2004.04.035.
ꢀ
3. Queron, E. Ph.D. thesis, Paris VI University, 2000.
4. (a) Keck, G. E.; Boden, E. P. Tetrahedron Lett. 1984, 25,
6H, CH3CH2CH2CH2Sn), 1.16 (d, 3H, CH3, J16;CH ¼ 7),
3
ꢀ
1.10 (s, 9H, t-BuSi), 1.06 (s, 9H, t-BuSi), 0.89 (t, 6H,
CH3CH2CH2CH2Sn, JCH CH Sn ¼ 7), 0.87 (t, 9H,
2
2
CH3CH2CH2CH2Sn, JCH CH ¼ 7); 13C NMR (50.3 MHz,
3
2
CDCl3): 144.9 (C13), 133.4 (C12), 79.3 (C15), 77.2 (C14),
71.0 (C17), 34.1 (C16), 29.0 and 27.1 (CH3CH2CH2CH2Sn),
28.5 and 27.4 (t-BuSi), 23.3 and 20.6 (CqSi), 13.6
(CH3CH2CH2CH2Sn), 11.5 (CH3), 9.3 (CH3CH2-
CH2CH2Sn); C27H56O3SiSn ¼ 575.53; MS (EI, m=z): 575
(Mþ), 518.
€
265–268; (b) Reetz, M. T.; Hullmann, M. J. Chem. Soc.,
Chem. Commun. 1986, 1600–1602; (c) Chen, X.; Horte-
lano, E. R.; Eliel, E. L.; Frye, S. V. J. Am. Chem. Soc.
1992, 114, 1778–1784.
5. (a) Corey, E. J.; Wollenberg, R. H. J. Am. Chem. Soc.
1974, 96, 5581–5583; (b) Seyferth, D.; Vick, S. C.
J. Organomet. Chem. 1978, 144, 1–12.
6. (a) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc. 1980,
102, 5974–5976; (b) Johnson, R. A.; Sharpless, K. B. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon: 1991; Vol. 6, pp 389–436; (c) Katsuki,
T.; Martin, V. S. Org. React. 1996, 48, pp 1–299.
7. Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969,
34, 2543–2549.
8. (a) Roush, W. R.; Adam, M. A.; Peseckis, S. M.
Tetrahedron Lett. 1983, 24, 1377–1380; (b) Tius, M. A.;
Fauq, A. H. J. Org. Chem. 1983, 48, 4131–4132; (c)
Chakraborty, T. K.; Joshi, S. P. Tetrahedron Lett. 1990,
31, 2043–2046.
9. Corey, E. J.; Hopkins, P. B. Tetrahedron Lett. 1982, 23,
4871–4874.
10. (a) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651–
1660; (b) Huang, S. L.; Omura, K.; Swern, D. Synthesis
1978, 297–299.
11. Toshima, K.; Jyojima, T.; Yamaguchi, H.; Noguchi, Y.;
Yoshida, T.; Murase, H.; Nakata, M.; Matsumura, S.
J. Org. Chem. 1997, 62, 3271–3284.
Compound 22: pale yellow oil; IR (cmꢁ1, CHCl3): 1600
(C@C); 1H NMR (300 MHz, CDCl3): d/TMS 6.21 (d, 1H,
H12, J12;13 ¼ 19), 5.79 (dd, 1H, H13, J12;13 ¼ 19, J13;14 ¼ 6),
4.08 (dd, 1H, H17a, J17a;17b ¼ 11.5, J17a;16 ¼ 3), 3.82 (dd, 1H,
H15, J15;14 ¼ 9, J15;16 ¼ 2), 3.60 (dd, 1H, H17b, J17a;17b ¼ 11.5,
J17b;16 ¼ 2), 3.40 (dd, 1H, H14, J14;15 ¼ 9, J14;13 ¼ 6), 3.28 (s,
3H, OCH3), 1.77 (m, 1H, H16), 1.37 (s, 3H, CH3gem), 1.35
(s, 3H, CH3gem), 1.48 (m, 6H, CH3CH2CH2CH2Sn), 1.30
(m, 6H, CH3CH2CH2CH2Sn), 1.10 (d, 3H, CH3, J16;CH
¼
3
7), 0.89 (t, 6H, CH3CH2CH2CH2Sn, JCH CH Sn ¼ 7), 0.88 (t,
2
2
9H, CH3CH2CH2CH2Sn, JCH CH ¼ 7); 13C NMR
3 2
(50.3 MHz, CDCl3): 146.2 (C13), 132.7 (C12), 98.7 (Cq),
83.6 (C14), 73.8 (C15), 67.1 (C17), 56.4 (OCH3), 30.4 and
29.7 (CH3gem), 29.6 and 27.3 (CH3CH2CH2CH2Sn), 19.0
(C16), 13.8 (CH3CH2CH2CH2Sn), 11.2 (CH3), 9.6
(CH3CH2CH2CH2Sn); C23H46O3Sn ¼ 489.32; MS (EI,
m=z): 490 (Mþ).
Compound 25: pale yellow oil; IR (cmꢁ1, CHCl3): 1601
(C@C); 1H NMR (300 MHz, CDCl3): d/TMS 6.33 (d, 1H,
H12, J12;13 ¼ 19), 5.66 (dd, 1H, H13, J12;13 ¼ 19, J13;14 ¼ 8.5),
4.11 (dd, 1H, H17a, J17a;17b ¼ 11.5, J17a;16 ¼ 2.5), 3.91 (dd,
1H, H15, J15;14 ¼ 8.5, J15;16 ¼ 2.5), 3.55 (dd, 1H, H17b
,
12. Compound 11: pale yellow oil; ½aꢂ ꢁ190 (c 0.05, CHCl3);
J17a;17b ¼ 11.5, J17b;16 ¼ 2), 3.49 (dd, 1H, H14, J14;15 ¼ 1,
J14;13 ¼ 8.5), 3.29 (s, 3H, OCH3), 1.48 (s, 3H, CH3gem), 1.47
(m, 6H, CH3CH2CH2CH2Sn), 1.46 (s, 3H, CH3gem), 1.43
D
IR (cmꢁ1, CHCl3): 3598 (OH), 1598 (C@C); 1H NMR
(300 MHz, CDCl3): d/TMS 6.29 (m, 2H, H12, H13), 4.05

E. Quꢀeron, R. Lett / Tetrahedron Letters 45 (2004) 4533–4537
4537
(m, 1H, H16), 1.32 (m, 6H, CH3CH2CH2CH2Sn), 1.07 (d,
3H, CH3, J16;CH ¼ 7), 0.92 (t, 6H, CH3CH2CH2CH2Sn,
J5;6 ¼ 10, JCH ;5 ¼ 1), 5.83 (s, 1H, H11), 5.83 (dd, 1H, H13,
3
J13;12 ¼ 19, J13;14 ¼ 6), 5.38 (dd, 1H, H15, J15;14 ¼ 6,
J15;16 ¼ 6), 3.77 (s, 6H, OCH3), 3.50 (m, 1H, H14), 3.49 (s,
3H, CH3, C2OCH3), 3.39 (dd, 1H, H7, J6;7 ¼ 3.5,
J7;8 ¼ 5.5), 3.21 (s, 3H, CH3, HC14OCH3), 3.03 (dd, 1H,
3
JCH CH Sn ¼ 7), 0.88 (t, 9H, CH3CH2CH2CH2Sn,
2
2
JCH CH ¼ 7); 13C NMR (50.3 MHz, CDCl3): 143.1 (C13),
3
2
136.0 (C12), 99.0 (Cq), 86.8 (C14), 74.0 (C15), 67.2 (C17),
56.4 (OCH3), 30.4 and 29.9 (CH3gem), 29.2 and 27.2
(CH3CH2CH2CH2Sn), 19.0 (C16), 13.8 (CH3CH2-
H
17a, J17a;17b ¼ 9, J17a;16 ¼ 6), 2.92 (dd, 1H, H17b, J17a;17b ¼ 9,
J17b;16 ¼ 6), 2.68 (m, 1H, H6), 2.44 (dd, 1H, H9a, J9a;9b ¼ 13,
CH2CH2Sn),
10.9
(CH3),
9.6
(CH3CH2CH2-
J9a;8 ¼ 3), 2.20 (m, 1H, H16), 1.94 (d, 3H, CH3, JCH ;5 ¼ 1),
3
CH2Sn); C23H46O3Sn ¼ 489.32; MS (EI, m=z): 490 (Mþ).
13. Calter, M. A. Ph.D. thesis, Harvard University, 1993.
14. (a) Scheidt, K. A.; Tasaka, A.; Bannister, T. D.; Wendt,
M. D.; Roush, W. R. Angew. Chem., Int. Ed. 1999, 38,
1652–1655; (b) Scheidt, K. A.; Bannister, T. D.; Tasaka,
A.; Wendt, M. D.; Savall, B. M.; Fegley, G. J.; Roush,
W. R. J. Am. Chem. Soc. 2002, 124, 6981–6990.
1.92 (m, 1H, H9b), 1.78 (s, 3H, CH3), 1.72 (m, 1H, H8),
1.45 (m, 6H, CH3CH2CH2CH2Sn), 1.27 (m, 6H,
CH3CH2CH2CH2Sn), 1.04 (d, 3H, CH3, J16;CH ¼ 7), 0.96
3
(d, 3H, CH3, J6;CH ¼ 7), 0.96 (t, 9H, CH3CH2Si,
3
JCH ;CH Si ¼ 8), 0.86 (t, 9H, CH3CH2CH2CH2Sn,
3
2
JCH CH ¼ 7; t, 6H, CH3CH2CH2CH2Sn, JCH CH Sn ¼ 7),
3
2
2
2
0.73 (d, 3H, CH3, J8;CH ¼ 7), 0.66 (q, 6H, CH3CH2Si,
3
15. Hanessian, S.; Ma, J.; Wang, W.; Gai, Y. J. Am. Chem.
Soc. 2001, 123, 10200–10206.
16. Duncton, M. A. J.; Pattenden, G. J. Chem. Soc., Perkin
Trans. 1 1999, 1235–1246.
17. Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yama-
guchi, M. Bull. Chem. Soc. Jpn. 1979, 52, 1989–1993.
JCH ;CH Si ¼ 8); 13C NMR (50.3 MHz, CDCl3): 164.2 (C1),
3
2
158.1 (C@COCH3), 146.9 (C10), 144.7 (C13), 144.4 and
136.2 (Cq Ar), 142.9 and 135.2 (C2, C4), 140.9 (C5), 130.2
(C3), 129.3(C12), 129.9, 128.1, 127.5 and 126.4 (CH Ar),
112.8 (C@COCH3), 85.4 (C15), 85.2 (CqO), 80.4 (C7), 75.4
(C11), 75.0 (C14), 65.7 (C17), 60.0 (C2OCH3), 56.1
(HC14OCH3), 54.9 (OCH3), 42.9 (C9), 35.8 and 34.7 (C6,
C8), 28.9 and 27.0 (CH3CH2CH2CH2Sn), 24.5, 18.2, 15.6,
14.5 and 13.5 (CH3), 13.9 (CH3CH2CH2CH2Sn), 12.6
18. Compound 3: pale yellow oil; ½aꢂ þ27 (c 0.7, CHCl3); IR
D
1
(cmꢁ1, CHCl3): 1710 (C@O), 1607 (C@C), 1509 (Ar); H
NMR (300 MHz, CDCl3): d/TMS 7.43 (d, 2H, Ha,
JHa;Hb ¼ 9), 7.31 (d, 4H, Hd, JHd;He ¼ 9), 7.26 (m, 2H,
Hb), 7.17 (m, 1H, Hc), 6.81 (d, 4H, He, JHd;He ¼ 9), 6.51 (s,
1H, H3), 5.98 (d, 1H, H12, J13;12 ¼ 19), 5.89 (dq, 1H, H5,
(CH3CH2CH2CH2Sn),
6.9
(CH3),
5.3
(CH2Si);
C63H97IO8SiSn ¼ 1256.15; MS (FD, m=z): 1256 (Mþ),
1199, 1128.