Towards the total synthesis of tashironin related allo-cedrane natural products: Further exploitation of the oxidative dearomatization-IMDA-RCM triad based strategy

Article abstract of DOI:10.1016/j.tetlet.2011.01.109

Synthetic studies directed towards allo-cedrane based, tashironin sibling natural products, involving some deft functional group manipulations on a preformed tetracyclic scaffold, are delineated.

Full text of DOI:10.1016/j.tetlet.2011.01.109

Tetrahedron Letters 52 (2011) 1753–1756
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Towards the total synthesis of tashironin related allo-cedrane natural
products: further exploitation of the oxidative dearomatization-IMDA-RCM
triad based strategy
⇑
Goverdhan Mehta , Pulakesh Maity
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Synthetic studies directed towards allo-cedrane based, tashironin sibling natural products, involving
some deft functional group manipulations on a preformed tetracyclic scaffold, are delineated.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 13 January 2011
Revised 19 January 2011
Accepted 26 January 2011
Available online 1 February 2011
Keywords:
Natural products
Neurotrophic agents
Oxidative dearomatization
Intramolecular Diels–Alder reaction
Ring closing metathesis
1
In 2001, research group led by Schmidt reported the isolation
and structure determination of three closely related polycyclic ses-
quiterpenoid natural products 1–3, from North American species
of Illicium floridanum (Fig. 1). Among these novel sesquiterpenoids,
embodying hemiketal functionality on a caged tetracyclic scaffold,
structure of 3 was elucidated by X-ray crystallography and those of
dense and diverse oxygen functionalities through some subtle
functional group manoeuvers on their complex caged scaffold. In
addition, a foray towards 1–3 also provided an opportunity to
H
10
H
OH
OH
1
5
HO 11
HO
O 1
2
O
9
8
6
4
1
and 2 through detailed NMR studies on an inseparable mixture of
the two. Thus, 1–3 are more embellished siblings of previously re-
ported natural products tashironin 4 and 11-debenzoyltashironin
based on the biogenetically interesting allo-cedrane skeleton 7,
1
4
3
O
H
H
7
OH
OH
2
3
5
HO 12
13
OH
5
1: Debenzoyl 7-deoxo-7a-
2: Debenzoyl 7-deoxo-
Figure 1. Among the tashironin-type natural products, 11-O-
debenzoyltashironin 5 exhibits an interesting and unusual bioac-
tivity profile and induces neurite outgrowth in foetal rat neuron
at submicromolar concentration.3 More recently,4 tashironin 4
has been shown to exhibit anti-hepatitis B virus (HBV) activity at
submicromolar concentrations by inhibiting the HBV surface anti-
gen secretions. Interestingly, there has been no report on the bio-
logical activity of tashironin siblings 1–3.1
hydroxy-3-oxotashironin
7a-hydroxytashironin
H
OH
OH
H
OH
HO
OH
BzO
O
O
H
OH
OH
O
3: Debenzoyl 7-deoxo-1a,
7a- dihydroxytashironin
4: Tashironin
The compact, caged, highly functionalized framework of allo-
cedrane based tashironins and their bioactivity attributes have
drawn attention from synthetic chemists.5 As part of our ongoing
efforts towards the total synthesis of tashironin sesquiterpe-
H
OH
–7
RO
O
6
b
noids, we were also drawn to the more embellished 1–3 as they
posed an enhanced synthetic challenge in terms of installation of
OH
: 11-O-debenzoyltashironin, R = H
: 11-O-methyldebenzoyltashironin, R = Me
O
5
6
7
⇑
Corresponding author. Tel.: +91 40 23010785; fax: +91 40 23012460.
E-mail address: gmsc@uohyd.ernet.in (G. Mehta).
Figure 1. Natural products, isolated from Illicium species and related to tashironin.
0
040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.109

1
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G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1753–1756
amplify the general applicability of our tandem oxidative dearoma-
tization-IMDA-RCM based strategy towards tashironins and re-
lated natural products. Herein, we describe our endeavours
directed towards the synthesis of methyl ethers of natural prod-
ucts 1 and 2, through controlled modulation of functional group
alternations within the tetracyclic scaffold accessed through our
three-step strategy.
enones 15 and 16 in 1:3 ratio with complete relocation of the ori-
ginal C2–C3 double bond. Although the minor enone 15 retained
the requisite stereogenic centre at C1, it was compromised in the
6
9
case of the major enone 16 , Scheme 2. Nonetheless, we chose to
forge ahead with the major enone 16 with the intent to regenerate
the C1 b-methyl stereochemistry at an appropriate stage. At this
stage, it was considered crucial to chemo-differentiate the C3 and
C7 carbonyl groups in 16 and its reduction with sodium borohy-
dride was chemoselective as well as stereoselective (10:1) to fur-
nish hydroxy-enone 17 although C7 stereochemistry was not
clear at this juncture, Scheme 2. Unmindful of this stereochemical
ambiguity, we proceeded further and hoped to resolve it along the
way. Catalytic hydrogenation of hydroxyl-enone 17 on 10% Pd–C
was again stereoselective and predictable in view of the folded
topology of 17 and additional steric shielding on the ‘top face’
engendered by the C10 TES-protecting group to furnish 18 as a sin-
gle diastereomer, Scheme 2. At this stage, it was considered pru-
dent to protect C7 hydroxyl group in 18 as p-nitrobenzoate ester
In our recent studies leading to the synthesis of 11-debenzoyl-
tashironin methyl ether 6 we have reported6 a short and efficient
access to the tetracyclic intermediate 8 through hypervalent iodine
mediated oxidative dearomatization of 9 in the presence of E,Z-die-
nol 10 to furnish 11, followed by intramolecular Diels–Alder cyclo-
addition to 12 and RCM to deliver 13 as a mixture (1:1) of C1
diastereomers, Scheme 1. Stereoselective reduction of C10 car-
bonyl group in 13 and TES protection led smoothly to the isolation
of 8 as the C1 b-methyl diastereomer.6 This tetracyclic intermedi-
ate 8 was to serve as the starting point in our quest for the natural
products 1 and 2.
b
b
Evaluation of the projected functional group modifications in 8
enroute 1 and 2 pointed to the necessity of establishing a vinyl bro-
mide–carbonyl equivalence in order to install the C7 carbonyl
group. Towards this end, the vinyl bromide 8 was subjected to me-
19. The key task now was to install the crucial tertiary
a-hydroxy
group at C4 stereoselectively and for this purpose we opted for the
1
1
Rubottom oxidation protocol. Consequently, 19 was exposed to
TESOTf/Et N in Et O to afford the desired silyl-enol ether 20 regio-
selectively and in near quantitative yield. TES-enol ether 20 was
treated with mCPBA to furnish the intermediate -face selective
epoxide 21 and subsequent treatment with TBAF afforded the de-
3
2
t
tal-halogen exchange with BuLi in TMEDA and subsequently
i
8
quenched with B(O Pr)
3
to generate a borate intermediate which
afforded the re-
a
on concomitant treatment with alkaline H
2 2
O
9
quired ketone 14 along with the reductive debromination product
of 8 in 2:1 ratio, Scheme 2.9 Attempted allylic oxidation in 14
with PDC/TBHP in benzene led to two regio-isomeric transposed
sired 4
a-hydroxy ketone 22 in very good yield, Scheme 2.
10
Arrival at crystalline 22 brought mixed satisfaction as its single
1
2
crystal X-ray structure determination (Fig. 2) revealed that C1
methyl and C4 hydroxyl groups had the requisite stereochemistry
and routine disengagement of the protective groups was expected
to deliver our objective. However, the hydroxyl functionality at C7
Me
Z
OH
O
4
(installed during the NaBH reduction of 16) had the opposite un-
OMe
Me
HO
Br
BTIB
required disposition with respect to that present in the natural
product 1. To circumvent the unexpected problem of C7 hydroxy
group stereochemistry, which appeared to result from the steric
shielding by the –OMe group and consequent attack of the hydride
from the more accessible ‘bottom face’, we decided to change track
and gambled on altering the reaction sequence followed in
Scheme 3.
Consequently, enone double bond of 16 was reduced over 10%
Pd–C under hydrogen atmosphere to furnish diketone 23 as a sin-
3
gle diastereomer, Scheme 3. Treatment of 23 with TESOTf/Et N
+
OMe
O
Br
9
10
11
Δ
O
O
H
OTES
MeO
MeO
NaBH4
MeO
O
O
O
RCM
TESOTf
Br
afforded the desired silyl-enol ether regioselectively and in quanti-
tative yield. Oxidation of the resulting silyl-enol ether with mCPBA
led to the intermediate epoxide which on desilylation with TBAF
H
Br
Br
8
13
12
Scheme 1. BTIB: bis(trifluoroacetoxy)iodobenzene.
led to the desired 4
a
-hydroxy ketone 24 in excellent yield,
H
OTES
H
H
H
H
OTES
OTES
OTES
OTES
MeO
MeO
MeO
MeO
MeO
a
O
b
O
O
O
c
O
d
O
8
+
O
HO
O
HO
O
O
O
O
H
H
1
4
15
16
17
18
e
H
H
H
H
OTES
OTES
OTES
OTES
MeO
MeO
MeO
MeO
g
f
O
O
O
O
OTES
PNBO
PNBO
O
PNBO
PNBO
O
OTES
OH
O
H
H
H
H
2
2
21
20
19
t
i
Scheme 2. Reagents and conditions: (a) (i) BuLi, TMEDA, B(O Pr)
3
, THF, À78 °C, 2 h; (ii) NaOH, H
(1 atm.), EtOAc, rt, 3 h, 94%; (e) p-nitrobenzoyl chloride, Et
O, rt, 2 h, 97%; (g) (i) mCPBA, DCM, À10 °C, 1 h; (ii) TBAF, DCM, rt, 2 h, 87% (over two steps).
2
O
2
, 65%; (b) PDC, TBHP (70% aqueous), Celite, benzene, rt, 5 h, 68%
(
15:16 = 1:3); (c) NaBH
4
, DCM/MeOH (1:3), À15 °C, 4.5 h, 84%; (d) 10% Pd/C, H
2
3
N, DMAP, DCM, rt, 2 h, 89%; (f)
TESOTf, Et N, Et
3
2

G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1753–1756
1755
H
H
OTES
OTES
MeO
a, b
MeO
O
O
OH
c
24
O
OH
AcO
AcO
27
28
d
H
H
OH
OH
MeO
MeO
O
O
e
2
H
O
OH
AcO
OH
Figure 2. ORTEP diagram of the compound 22 with 30% ellipsoidal probability.
3
3
0a, α OH
0b, β OH
2
9
Scheme 4. Reagents and conditions: (a) DIBAL-H, DCM, À78 °C, 1 h; (b) Ac
2
O,
H
H
pyridine, DMAP, DCM, 0 °C, 2 h, 82% (over two steps); (c) MsCl, Et N, DMAP, DCM,
OTES
OTES
3
0
°C to rt, 3 h, 90%; (d) HF (40% aqueous), THF, rt, 5 h, 89%; (e) DIBAL-H, DCM, 0 °C to
MeO
O
MeO
b,c
O
O
rt, 6 h, 85%.
a
1
6
O
O
OH
O
Scheme 4. However, it was obvious that the C3 carbonyl reduction
was stereoselective with hydride approaching from the less hin-
dered ‘bottom face’, further assisted by the adjacent hydroxy
group. Therefore, the diastereomeric mixture emanated from the
non-stereoselective reduction of the C7 carbonyl group. The C7-
hydroxy epimers were regioselectively protected as the acetate
derivative 27. The C3 hydroxy group was then activated as its mes-
2
3
24
d
H
H
OH
OTES
MeO
MeO
O
O
e
1
1
5
H
O
H
O
3
ylate (MsCl/Et N/DMAP) which underwent in situ cyclization to
OH
OH
provide the -epoxide 28. TES deprotection in 28 unravelled a free
a
OH
OH
hydroxyl group at C10 in 29. DIBAL-H reduction of the epoxide in
2
2
5a, α OH
5b, β OH
29 was smooth to deliver an easily separable epimeric mixture of
alcohols 30a and 30b after concomitant reduction of the acetate.
26
9
As planned, 30a was the methyl ether derivative of the natural
Scheme 3. Reagents and conditions: (a) 10% Pd/C, H
b) TESOTf, Et N, Et
2
(1 atm.), EtOAc, rt, 3 h, 85%;
O, rt, 2 h, quant.; (c) (i) mCPBA, DCM, À10 °C, 1.5 h; (ii) TBAF,
product 2. In view of the earlier encountered difficulty6 in depro-
(
3
2
tecting the methyl ether moiety in this system, the present endeav-
our was terminated with the acquisition of 30a, Scheme 4. Once
again, the spectral characteristics of 30a were reminiscent of natu-
ral product 2 and were in conformity with its putative formulation.
In summary, we have considerably amplified the scope of our
oxidative dearomatization-IMDA-RCM triad based strategy for
accessing tashironin sibling natural products by orchestrating a
series of functional group manipulations on the allo-cedrane based
tetracyclic framework.
DCM, rt, 2 h, 96% (over two steps); (d) NaBH
aqueous), MeCN, rt, 6 h, 91%.
4
, MeOH, À10 °C, 6 h, 92%; (e) HF (40%
Scheme 3. Having installed the C4-hydroxyl group in an efficient
manner, the stage was now set for the C7 carbonyl group reduc-
tion. Controlled and careful carbonyl reduction of 24 with NaBH
4
at low temperature was regio-selective and yielded an easily sep-
arable mixture of epimeric alcohols 25a and 25b in 2:1 ratio and
in good yield. The gratifying alteration in the stereoselectivity
during the reduction of 24 could be attributed to the long range
stereoelectronic effect, the precise nature of which remains ob-
Acknowledgements
1
3
P.M. and G.M. thank CSIR, Government of India for the award of
a research and Bhatnagar fellowships, respectively. G.M. acknowl-
edges the support from the Eli Lilly and Jubilant—Bhartia Founda-
tion at the University of Hyderabad. We thank Dr. Saikat Sen for
determining the X-ray crystal structure. We also thank Professor
T. J. Schmidt for helpful correspondence and exchange of spectra.
scure. After considerable efforts to optimize the conditions for
1
4
the desilylation of C10-TES group, aqueous HF in acetonitrile
was found to offer best option for deprotection leading to the
methyl ether 26, Scheme 3.9
The final act in accomplishing the total synthesis of natural
product 1 was the deprotection of the C11 methyl ether moiety.
However, several efforts to accomplish this seemingly straightfor-
ward manoeuvre proved unsuccessful and we were content to set-
tle for the synthesis of the methyl ether derivative 26 of the natural
product 1. As expected, the spectral data for 26 bore close resem-
blance to those of the natural product 1, although the reported data
for the latter had some contamination of 2.1
References and notes
1. Schmidt, T. J.; Muller, E.; Fronzek, F. R. J. Nat. Prod. 2001, 64, 411–414.
2.
(a) Fukuyama, Y.; Shida, N.; Kodama, M. Tetrahedron Lett. 1995, 36, 583–
586; (b) Huang, J.-M.; Yang, C.-S.; Tanaka, M.; Fukuyama, Y. Tetrahedron
2001, 57, 4691–4698; (c) Song, W.-Y.; Ma, W.-B.; Bai, X.; Zhang, X.-M.; Gu,
We next turned our attention to the synthesis of natural prod-
uct 2 and recognised that diketone 24 had the attributes to serve
as an advanced precursor. Exhaustive DIBAL-H reduction of 24 fur-
nished an inseparable mixture of diastereomeric triols in 3:1 ratio,
Q.; Zheng, Y.-T.; Zhou, J.; Chen, J.-J. Planta Med. 2007, 73, 372–375.
Huang, J.-M.; Yokoyama, R.; Yang, C.-S.; Fukuyama, Y. J. Nat. Prod. 2001, 64,
3
.
.
428–431.
4
Liu, J. F.; Jiang, J. Y.; Zhang, Q.; Shi, Y.; Ma, Y. B.; Xie, M. J.; Zhang, Y. M.; Chen, J. J.
Planta Med. 2010, 76, 152–158.

1
756
G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1753–1756
5
.
Cook, S. P.; Polara, A.; Danishefsky, S. J. J. Am. Chem. Soc. 2006, 128, 16440– (s, 3H), 3.15 (d, J = 3.0 Hz, 1H), 2.73 (s, 1H), 3.59 (dd, J = 7.6, 16.8 Hz, 1H), 2.36–
1
5
6441; (b) Polara, A.; Cook, S. P.; Danishefsky, S. J. Tetrahedron Lett. 2008, 49,
906–5908.
2.50 (m, 2H), 2.26 (d, J = 8.2 Hz, 1H), 1.98 (dd, J = 9.2, 15.0 Hz, 1H), 1.74 (dd,
J = 1.2, 14.7 Hz, 1H), 1.31 (s, 3H), 1.23 (d, J = 6.7 Hz, 3H), 1.15 (s, 3H); 13C NMR
6
.
.
(a) Mehta, G.; Maity, P. Tetrahedron Lett. 2007, 48, 8865–8868; (b) Mehta, G.;
Maity, P. Tetrahedron Lett., accompanying communication.
For related contributions from our group, see: (a) Mehta, G.; Singh, R.
Tetrahedron Lett. 2005, 46, 2079–2082; (b) Mehta, G.; Singh, R. Angew. Chem.,
Int. Ed. 2006, 45, 953–955; (c) Mehta, G.; Shinde, H. M. Tetrahedron Lett. 2007,
(75 MHz, CDCl
3
) d 213.8, 107.6, 81.7, 74.2, 72.2, 70.8, 51.1, 50.3, 48.8, 47.1, 44.7,
35.6, 34.9, 16.8, 13.1, 12.8; HRMS(ES) m/z calcd for C16
H
24
O
6
Na (M+Na):
À1
7
335.1471; found: 335.1471; 30a IR (neat) 3465, 3416, 2927, 2853, 1014 cm
;
1
3
H NMR (400 MHz, CDCl ) d 3.85 (d, J = 9.4 Hz, 1H), 3.75 (d, J = 9.5 Hz, 1H), 3.69
(br s, 1H), 3.60 (d, J = 4.9 Hz, 1H), 3.36 (s, 3H), 3.20 (d, J = 5.0 Hz, 1H), 2.44 (d,
J = 5.1 Hz, 1H), 2.32 (s, 1H), 2.01–2.22 (m, 4H), 1.85 (dd, J = 9.4, 14.8 Hz, 1H),
48, 8297–8300.
8
.
.
(a) Tietze, L. F.; Wiegand, J. M.; Vock, C. A. Eur. J. Org. Chem. 2004, 4107–4112;
1.65 (d, J = 15.1 Hz, 1H), 1.16 (s, 3H), 1.15 (s, 3H), 1.14 (d, J = 10.7 Hz, 3H); 13
C
(
b) Organ, M. G.; Bratovanov, S. Tetrahedron Lett. 2000, 41, 6945–6949.
3
NMR (100 MHz, CDCl ) d 108.3, 86.7, 74.6, 73.7, 71.4, 51.3 (2C), 50.3, 49.6, 39.2,
37.9, 32.8, 31.3, 16.5, 14.1, 13.7; HRMS(ES) m/z calcd for C16
All new compounds were fully characterized on the basis of IR, H NMR, 13C
1
9
26 5
H O Na (M+Na):
NMR and HRMS spectral data. Spectral data of selected compounds: 14 IR
321.1678; found: 321.1664.
À1
1
(
neat) 2952, 2877, 1716, 1156 cm
;
H NMR (400 MHz, CDCl
3
) d 5.70–5.72 (m,
10. Chidambaram, N.; Chandrasekaran, S. J. Org. Chem. 1987, 52, 5048–5051.
11. (a) Hassner, A.; Reuss, R. H.; Pinnick, H. W. J. Org. Chem. 1975, 40, 3427–3429;
(b) Rubottom, G. M.; Vazquez, M. A.; Pelegrina, D. A. Tetrahedron Lett. 1974, 15,
4319–4320; (c) Patin, A.; Kanazawa, A.; Philouze, C.; Greene, A. E. J. Org. Chem.
2003, 68, 3831–3837.
1
3
2
0
1
1
4
2
H), 5.59 (br s, 1H), 3.98 (d, J = 7.9 Hz, 1H), 3.95 (s, 1H), 3.54 (d, J = 7.9 Hz, 1H),
.33 (s, 3H), 2.59–2.60 (m, 1H), 2.47 (br s, 1H), 2.28 (1/2ABq, J = 18.5 Hz, 1H),
.17 (1/2ABq, J = 18.4 Hz, 1H), 1.24 (d, J = 7.4 Hz, 3H), 1.14 (s, 3H), 1.01 (s, 3H),
1
3
.93 (t, J = 7.9 Hz, 9H), 0.57–0.69 (m, 6H); C NMR (100 MHz, CDCl
39.2, 125.8, 108.7, 79.7, 70.9, 62.3, 60.9, 52.0, 50.7, 49.3, 47.3, 46.7, 21.8, 12.0,
0.2, 7.1 (3C), 5.3 (3C); HRMS(ES) m/z calcd for SiNa (M+Na):
15.2281; found: 415.2278; 22 mp 179.3–180.0 °C; IR (neat) 3473, 2926,
3
) d 213.2,
12. X-ray data on 22 was collected at 291 K on
a
a
Bruker Kappa APEX II
radiation (k = 0.7107 Å).
C
22
H
36
O
4
diffractometer with graphite monochromated Mo K
The crystal structure was solved by direct methods (SIR92) and refined by full-
matrix least-squares method on F2 using SHELXL-97. Crystallographic data have
been deposited with the Cambridge Crystallographic Data Centre, CCDC-
À1
1
877, 1726, 1530, 1122 cm
3
; H NMR (300 MHz, CDCl ) d 8.32 (1/2ABq,
J = 8.7 Hz, 2H), 8.24 (1/2ABq, J = 8.4 Hz, 2H), 5.39 (dd, J = 5.7, 9.9 Hz, 1H), 4.10
(
(
(
6
1
1
5
1
3
d, J = 9.3 Hz, 1H), 3.98 (s, 1H), 3.69 (d, J = 9.6 Hz, 1H), 3.58 (s, 3H), 2.36–2.57
m, 3H), 2.25–2.33 (m, 1H), 2.03 (s, 1H), 1.39 (dd, J = 5.7, 13.5 Hz, 1H), 1.21
s, 3H), 1.13 (d, J = 6.6 Hz, 3H), 1.09 (s, 3H), 0.97 (t, J = 7.8 Hz, 9H), 0.66–0.75 (m,
798242. Compound 22:
monoclinic, space group: C2/c, cell parameters: a = 31.4711(11) Å,
29 9
C H41NO Si, MW = 575.72, crystal system:
3
b = 8.2373(3) Å, c = 22.6847(8) Å, b = 91.999(2)°, V = 5877.1(4) Å , Z = 8,
1
3
À3
À1
H); C NMR (75 MHz, CDCl
23.6, 108.2, 81.5, 81.2, 72.8, 70.3, 52.5, 50.9, 48.9, 46.3, 44.2, 35.2, 33.8, 14.5,
3.3, 12.3, 7.0 (3C), 5.2 (3C); HRMS(ES) m/z calcd for C29 41NO SiNa (M+Na):
98.2448; found: 598.2477; 24 IR (neat) 3460, 2918, 2850, 1736, 1722,
3
) d 212.8, 164.2, 150.6, 135.9 (2C), 130.7 (2C),
q
calcd = 1.301 g cm
,
F(0 0 0) = 2464,
= 0.0655 for 3582 reflections with I > 2
= 0.2018, GOF = 1.133 for all data.
l
= 0.134 mm
,
number of l. s.
parameters = 406, R
1
r(I) and 0.1048
H
9
for all 5427 data. wR
2
13. (a) Mehta, G.; Chandrasekhar, J. Chem. Rev. 1999, 99, 1437–1467; (b) Mehta, G.;
Uma, R. Acc. Chem. Res. 2000, 33, 278–286.
14. (a) Mascarenas, J. L.; Mourino, A.; Castedo, L. J. Org. Chem. 1986, 51, 1269–1272;
(b) Boschelli, D.; Takemasa, T.; Nishitani, Y.; Masamune, S. Tetrahedron Lett.
1985, 26, 5239–5242.
15. (a) Jones, M. F.; Myers, P. L.; Robertson, C. A.; Storer, R.; Williamson, C. J. Chem.
Soc., Perkin Trans. 1 1991, 2479–2484; (b) Sabila, P. S.; Howell, A. R. Tetrahedron
Lett. 1997, 48, 8353–8355.
À1
1
138 cm
3
; H NMR (300 MHz, CDCl ) d 4.22 (d, J = 9.6 Hz, 1H), 4.09 (s, 1H),
.68 (d, J = 9.3 Hz, 1H), 3.39 (s, 3H), 2.45–2.62 (m, 3H), 2.31–2.44 (m, 1H), 2.10
(
(
1
d, J = 18.6 Hz, 1H), 1.92 (s, 1H), 1.21 (d, J = 6.6 Hz, 3H), 1.12 (s, 6H), 0.97
13
t, J = 7.5 Hz, 9H), 0.66–0.75 (m, 6H); C NMR (75 MHz, CDCl
08.4, 80.8, 79.8, 71.4, 61.6, 52.4, 51.4, 49.8, 44.2, 41.6, 34.8, 15.4, 12.4, 10.3, 7.0
3C), 5.1 (3C); HRMS(ES) m/z calcd for C22 SiNa (M+Na): 447.2179; found:
3
) d 212.4, 211.1,
(
36 6
H O
À1
1
4
47.2181; 26 IR (neat) 3401, 2925, 2876, 1738, 1017 cm
; H NMR (400 MHz,
3
CDCl ) d 3.99 (d, J = 9.8 Hz, 1H), 3.73 (d, J = 3.1 Hz, 1H), 3.68–3.72 (m, 2H), 3.34