A total synthesis of 11-O-methyldebenzoyltashironin

Article abstract of DOI:10.1016/j.tetlet.2011.02.012

A concise total synthesis of 11-O-methyldebenzoyltashironin is reported in which oxidative dearomatization-IMDA-RCM triad constitutes the key ring forming steps, while an unorthodox DIBAL-H mediated stereo- and regioselective reductive epoxide openings an

Full text of DOI:10.1016/j.tetlet.2011.02.012

Tetrahedron Letters 52 (2011) 1749–1752
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A total synthesis of 11-O-methyldebenzoyltashironin
⇑
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:
A concise total synthesis of 11-O-methyldebenzoyltashironin is reported in which oxidative dearomati-
zation-IMDA-RCM triad constitutes the key ring forming steps, while an unorthodox DIBAL-H mediated
stereo- and regioselective reductive epoxide openings and implementation of the vinyl bromide–car-
bonyl equivalency concept were pivotal to the success of this endeavor.
Received 13 January 2011
Revised 29 January 2011
Accepted 1 February 2011
Available online 24 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Natural products
Neurotrophic agents
Oxidative dearomatization
Intramolecular Diels–Alder reaction
Ring closing metathesis
Tetracyclic and densely oxygenated neurotrophic agent 11-O-
debenzoyltashironin 1,1a,b isolated from the pericaps of North
American species Illicium merrillianum exhibits impressive neuro-
trophic activity in cultured fetal rat cortical neurons at sub-micro-
molar concentration.1a This neurotrophic activity has implications
in the maintenance of cognitive functions and neuronal repair that
are relevant to several neurodegenerative disorders like Alzhei-
mer’s, Parkinson’s, and Huntington’s diseases, etc.2 This uncom-
mon but impressive biological activity profile and the intriguing
structural intricacy of its tetracyclic framework, laced with oxygen
functionalities and seven contiguous stereogenic centers, have
stimulated interest in the total synthesis of 11-O-debenzoyltashi-
ronin 1 with the added intent of creating diversity around its bio-
active scaffold.3,4 As a part of our ongoing interest in the synthesis
of neurotrophically active natural products,5 we disclose here a
be constructed in a very short sequence. A retreosynthetic perspec-
tive that would lead to the total synthesis of 1 is unveiled in
Scheme 1 which identified 3 as an advanced precursor with its vi-
nyl bromide moiety as the masked equivalent of the C7 carbonyl
group and a strategically positioned hydroxyl group at C10 to di-
rect the regio- and stereoselective openings of the epoxide ring
to deliver the C4 tertiary hydroxy functionality. The access to the
advanced intermediate 3 was envisaged through functional group
amplification/adjustment in the precursor 4 whose tetracyclic core
could be assembled from an embellished aromatic precursor 5 via
10
H
H
OH
1
OTES
11
RO
8
MeO
O
O
concise total synthesis of 11-O-methyldebenzoyltashironin
2
9
4
wherein the tetracyclic core present in the natural product was
assembled in just three steps from an appropriately crafted aro-
matic precursor.
As the target for a total synthesis endeavors, the natural product
1 presents quite a few significant challenges. Apart from its com-
pact tetracyclic cage-like architecture, it also embodies tertiary
7
O
OH
5
Br
O
3
1: 11-O-debenzoyltashironin, R = H
2: 11-O-methyldebenzoyltashironin, R = Me
a
-hydroxyl and secondary hydroxy groups at C4 and C10, respec-
O
OH
tively, a b-methyl group at C1 and a carbonyl functionality at C7
position whose installation requires special attention. In order to
conceptualize a viable roadmap toward 1, we recognized the
importance and centrality of a scalable and flexible strategy
through which the tetracyclic core of the natural product could
MeO
OMe
Me
O
Br
Br
5
4
⇑
Corresponding author. Tel.: +91 40 23010785; fax: +91 40 23012460.
E-mail address: gmsc@uohyd.ernet.in (G. Mehta).
Scheme 1. Retrosynthetic analysis of 1.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.02.012

1750
G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1749–1752
the Still–Gennari olefination protocol.4,7 The choice of diene 8 to
OH
OH
O
set-up the contemplated IMDA reaction was important to ensure
the regio- and steroselectivities and to obtain the requisite orienta-
tion of the two alkene arms for the following RCM reaction.
Oxidative dearomatization of penta-substituted aromatic com-
pound 5 with bis(trifluoroacetoxy)iodobenzene (BTIB)8 in the pres-
ence of (2Z,4E)-2-methyl-2,4-hexadien-1-ol 8 led to the masked
o-benzoquinone based pentaene 9, which could be isolated and
spectroscopically recognized. As predicted, when the crude pent-
aene 9 was refluxed in toluene, a single tricyclic [4+2]-adduct 10
was obtained in a decent yield, through the preferred endo-
transition state (see 9). The exclusive participation of the Z-double
bond of 8 in the IMDA reaction ensured that the two alkenyl side
arms in 10 were syn-disposed and well poised for effecting the
RCM reaction. Initial attempts toward RCM reaction on 10 using
Grubbs’ catalyst I proved problematic and deployment of Grubbs’
catalyst II, though encouraging, was plagued by low yields. It was
reasonable to surmise that the presence of the additional methyl
substituents on the alkene arms of 10 may be primarily responsible
for its refractoriness toward the RCM reaction. Consequently, a
switch to the Hoveyda–Grubbs’ second generation catalyst9 proved
rewarding and under optimized conditions afforded tetracyclic 4 as
an inseparable mixture (1:1) of diastereomers. In order to circum-
vent the problem of separation of the diastereomers 4 at this stage,
the carbonyl group in 4 was first reduced with NaBH4. Gratifyingly,
the reduction of 4 was stereoselective and the anticipated epimeric
OMe
Me
OMe
Me
OMe
Me
c
a, b
Br
Br
6
7
5
Scheme 2. Reagents and conditions: (a) PyHBr3, DCM, 0 °C, 2 h, 90%; (b) K2CO3,
crotyl bromide, acetone, reflux, 6 h, 92%; (c) PhNEt2, 180 °C, 1 h, 67%.
a sequential orchestration of the oxidative dearomatization ?
intramolecular Diels–Alder reaction (IMDA)
? ring closure
metathesis (RCM) triad along the lines outlined earlier by us.4
Appropriately substituted aromatic building block 5 could be
crafted from readily available aromatic starting materials through
routine maneuvers. It may be pointed out that the bromine substi-
tuent in aromatic precursor 5 was positioned to eventuate into a
vinylic bromide functionality that served as a latent equivalent of
the C7 carbonyl group.
The initial task was to set-up the key IMDA reaction by access-
ing the aromatic precursor 5 and subjecting it to oxidative dearo-
matization in the presence of the partner diene. Regioselective
mono-bromination of the known phenol6 6 using pyridinium tri-
bromide (PyHBr3) furnished a para-bromo derivative which was
transformed in to the aryl–crotyl ether 7 on treatment with crotyl
bromide/K2CO3 in excellent yield. Claisen rearrangement in 7 in
the presence of PhNEt2 was smooth and delivered the desired pre-
cursor 5, Scheme 2. Concurrently, the oxidative dearomatization
partner (2Z,4E)-2-methyl-2,4-hexadien-1-ol 8 was prepared from
a commercially available crotonaldehyde in two steps adopting
alcohols 11a (b-Me) and 11b (a-Me) (ratio = 1:1) were amenable to
chromatographic separation (SiO2 gel), Scheme 3.10
The stereochemistry of the C10 hydroxyl group and C1 methyl
group in 11a was confirmed through X-ray crystal structure
analysis (Fig. 1) and had the requisite attributes in the context of
our objective.11 Although both 11a and 11b were reckoned as
Me
z
O
O
O
H
OH
R
MeO
MeO
MeO
O
Br
HO
O
O
a
c
b
d
5
OMe
+
O
H
Br
Br
Br
11a, R = β-Me
11b, R = α-Me
8
9
10
4
e
H
H
H
H
H
OTES
OTES
OTES
OTES
OTES
MeO
MeO
MeO
MeO
O
MeO
O
O
O
O
O
g
f
h
OH
+
O
Br
Br
Br
Br
Br
16
15
14
13
12
i
H
H
H
H
H
OH
OTES
OH
O
Al
H
MeO
MeO
MeO
MeO
O
O
O
O
j
k
O
O
O
OH
Br
Br
Br
Br
17
18
3
Scheme 3. Reagents and conditions: (a) BTIB, THF, rt, 5 h, 62%; (b) toluene, reflux, BHT, 20 h, 80%; (c) Hoveyda–Grubbs’ catalyst-II (15 mol %), toluene, reflux, 48 h, 66%, 87%
(borsm); (d) NaBH4, DCM/MeOH (2:1), 0 °C, 8 h, 90%, (ratio = 1:1); (e) TESOTf, Et3N, DCM, 0 °C, 2 h, 93%; (f) PDC, 70% aqueous TBHP, celite, benzene, rt, 5 h, 59% (14:13 = 3:1);
(g) Et3BHLi, THF, 0 °C, 2 h, 81%; (h) SOCl2, pyridine, 0 °C, 30 min, 91%; (i) mCPBA, DCM, 1.5 h, 0 °C, 97%; (j) 40% aqueous HF, THF, rt, 6 h, 73%; (k). DIBAL-H, DCM, 0 °C, 12 h, 87%.

G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1749–1752
1751
H
H
OH
OH
MeO
HO
O
O
a
Ref. 3b
18
OH
OH
O
O
2
1
Scheme 4. Reagents and conditions: (a) (i) tBuLi, TMEDA, B(OiPr)3, THF, À78 °C, 2 h;
(ii) NaOH, H2O2, 34%.
to the metal–halogen exchange reaction, yet the potential payoff
in term of achieving concurrent internal protection (through ex-
change with access tBuLi present) motivated us to execute the
transformation without recourse to protecting group maneuver.
Arrival at 2 heralded our acquisition of the methyl ether of the nat-
ural product 11-O-debenzoyltashironin 1, which can be regarded
as the formal synthesis of the natural product as transformation
of 2 to 1 has been indicated in the patent literature.3b
In conclusion, we have delineated a short three step strategy to
rapidly assemble the core tetracyclic scaffold present in bioactive tas-
hironins through tandem oxidative dearomatization-IMDA-RCM
sequence. A set of stereo- and regioselective transformations and
functional group equivalency concept have been garnered to eventu-
ate in a concise synthesis of 11-O-methyldebenzoyltashironin.
Figure 1. ORTEP diagram of the compound 11a with 30% ellipsoidal probability.
serviceable for further evolution toward the target, we initially
decided to forge ahead with the former. The C10 hydroxyl func-
tionality in 11a was protected as TES ether 12 with the intent that
this bulky appendage will be required to play a critical stereodi-
recting role in the subsequent steps of our synthesis.
Allylic oxidation of 12 using PDC/TBHP12 provided two regioiso-
meric a,b-unsaturated enones 13 and 14 in a 1:3 ratio, Scheme 3.
Initially the major enone 14 remained reticent toward commonly
used reducing agents but we could manage to circumvent the im-
passe by exposing the enone 14 to super hydride (Et3BHLi) to fur-
nish doubly reduced product 15 stereoselectively and in good
yield. As planned, the bulky TES group had sterically shielded the
‘top’ face of enone 14 to direct the hydride delivery from the bot-
tom face to eventuate in a b-methyl group at C1 and the b-hydroxyl
group at C3 in 15. Brief exposure of 15 to thionyl chloride-pyridine
milieu rendered the desired olefin 16 in a regioselective manner.
The expedient arrival of 16 set the stage for the stereoselective
Acknowledgments
P.M. and G.M. thank the CSIR, Government of India for the
award of a research and Bhatnagar fellowships, respectively. G.M.
acknowledges the support from the Eli Lilly and Jubilant-Bhartia
Foundation at the University of Hyderabad. We thank Dr. Saikat
Sen for determining the X-ray crystal structures. We also thank
Professor S. P. Cook for helpful correspondence.
epoxidation with mCPBA13 from the less hindered
a-face to furnish
the epoxide 3 in excellent yield. At this stage, the TES protection
was jettisoned through exposure of the epoxide 3 to aqueous HF
to furnish 17 and we now opted for an unorthodox reductive open-
ing of the epoxide ring through ‘top’ face delivery of the hydride
from DIBAL-H coordinated to the C10 hydroxyl group (see, Scheme
3). Indeed, 18 was realized from 17 quite smoothly and the
structure of 18 was secured through X-ray crystal structure analy-
sis (Fig. 2).11
Inching toward the end game, the vinylic bromide moiety in the
bicyclo[2.2.2] octane segment of 18, strategically positioned as a
latent carbonyl group, had to be unmasked. This was achieved
through halogen-metal exchange with excess tBuLi in TMEDA
and quench with B(OiPr)3 to furnish a borate intermediate,14 which
was concomitantly treated with alkaline H2O2 to afford directly 11-
O-methyldebenzoyltashironin 2 along with some undesired debro-
minated product, Scheme 4. Although we were conscious of the
fact that the free C10 hydroxyl group in 18 would be detrimental
References and notes
1. (a) Huang, J.-M.; Yokoyama, R.; Yang, C.-S.; Fukuyama, Y. J. Nat. Prod. 2001, 64,
428–431; (b) Huang, J.-M.; Yang, C.-S.; Tanaka, M.; Fukuyama, Y. Tetrahedron
2001, 57, 4691–4698.
2. (a) Zuccato, C.; Cattaneo, E. Nat. Rev. Neurol. 2009, 5, 311–322; (b) Bohn, M. C.;
Choi-Lundberg, D. L. Gene Ther. Mol. Biol. 1998, 1, 265–277.
3. Total synthesis: (a) Cook, S. P.; Polara, A.; Danishefsky, S. J. J. Am. Chem. Soc.
2006, 128, 16440–16441; (b) Danishefsky, S. J.; Cook, S. P. PTC Int. Appl. 2006,
159pp; (c) Polara, A.; Cook, S. P.; Danishefsky, S. J. Tetrahedron Lett. 2008, 49,
5906–5908.
4. (a) Mehta, G.; Maity, P. Tetrahedron Lett. 2007, 48, 8865–8868; (b) Mehta, G.;
Maity, P. Tetrahedron Lett. accompanying communication.
5. (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, 48, 8297–8300.
6. Bertrand, F.; Basketter, D. A.; Roberts, D. W.; Lepoittevin, J. P. Chem. Res. Toxicol.
1997, 10, 335–343.
7. (a) Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405–4408; (b) Hensel, M.
J.; Fuchs, C. L. Synth. Commun. 1986, 16, 1285–1295.
8. (a) Pelter, A.; Elgendy, S. Tetrahedron Lett. 1988, 29, 677–680; (b) Tamura, Y.;
Yakura, T.; Haruta, J.; Kita, Y. J. Org. Chem. 1987, 52, 3927–3930; (c) Hsu, P. Y.;
Peddinti, R. K.; Chittimala, S. K.; Liao, C. C. J. Org. Chem. 2005, 70, 9156–9167;
(d) Carlini, R.; Higgs, K.; Rodrigo, R.; Taylor, N. Chem. Commun. 1998, 65–66; For
a recent review on cyclohexadienone ketals, see: (e) Magdziak, D.; Meek, S. J.;
Pettus, T. R. R. Chem. Rev. 2004, 104, 1383–1429.
9. (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J.; Hoveyda, A. H. J. Am. Chem.
Soc. 1999, 121, 791–799; (b) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett.
2000, 41, 9973–9976; (c) Harrity, J. P. A.; La, D.; Cefalo, D. R.; Visser, M. S.;
Hoveyda, A. H. J. Am. Chem. Soc. 1998, 120, 2343–2351.
10. All new compounds were fully characterized on the basis of IR, 1H NMR, 13C
NMR and HRMS spectral data. Spectral data of selected compounds: 11a mp
126.4–127.3 °C; IR (neat) 3466, 2950, 2904, 1381, 1027 cmÀ1
;
1H NMR
(300 MHz, CDCl3) d 6.77 (s, 1H), 5.77–5.81 (m, 1H), 5.60–5.62 (m, 1H), 3.82 (s,
2H), 3.54 (dd, J = 1.2, 9.6 Hz, 1H), 3.44 (s, 3H), 2.83 (br s, 1H), 2.48 (d, J = 9.6 Hz,
1H), 2.46 (br s, 1H), 1.37 (d, J = 7.2 Hz, 3H), 1.33 (s, 3H), 0.98 (s, 3H); 13C NMR
(75 MHz, CDCl3) d 140.5, 138.2, 124.7, 122.8, 106.7, 74.5, 72.1, 62.1, 57.8, 56.3,
51.8, 44.1, 43.4, 20.4, 14.9, 12.6; HRMS(ES) m/z Calcd for
C16H21BrO3Na
(M+Na): 363.0572. Found: 363.0554; 12 IR (neat) 2954, 2922, 1712,
Figure 2. ORTEP diagram of the compound 18 with 30% ellipsoidal probability.

1752
1154 cmÀ1
G. Mehta, P. Maity / Tetrahedron Letters 52 (2011) 1749–1752
;
1H NMR (300 MHz, CDCl3) d 6.84 (s, 1H), 5.94 (d, J = 1.5 Hz, 1H),
1H), 2.52–2.58 (m, 1H), 2.09–2.16 (m, 1H), 1.85–1.89 (m, 1H), 1.63–1.71 (m,
2H), 1.28 (s, 3H), 1.27 (d, J = 7.2 Hz, 3H), 0.99 (s, 3H); 13C NMR (100 MHz,
CDCl3) d 136.4, 126.6, 106.5, 87.9, 73.2, 72.0, 61.4, 56.3, 52.9, 51.8, 36.4, 32.3,
4.25 (d, J = 8.7 Hz, 1H), 3.65–3.67 (m, 2H), 3.44 (s, 3H), 2.04 (d, J = 1.5 Hz, 3H),
2.02 (s, 1H), 1.34 (s, 3H), 1.11 (s, 3H), 0.91 (t, J = 7.8 Hz, 9H), 0.49–0.58 (m, 6H);
13C NMR (100 MHz, CDCl3) d 201.8, 165.8, 133.8, 132.2, 126.1, 106.3, 74.2, 70.0,
65.1, 58.5, 58.0 (2C), 42.7, 21.6, 15.9, 15.4, 6.8 (3C), 5.1 (3C); HRMS(ES) m/z
Calcd for C22H33BrO4SiNa (M+Na): 491.1229. Found: 491.1214; 14 IR (neat)
31.2, 15.4, 14.7, 14.2; HRMS(ES) m/z Calcd for
C16H23BrO4Na (M+Na):
381.0677. Found: 381.0656; 2 IR (neat) 3493, 2924, 2852, 1712, 1018 cmÀ1
;
1H NMR (400 MHz, CDCl3) d 3.99 (d, J = 9.2 Hz, 1H), 3.87 (d, J = 6.2 Hz, 1H), 3.83
(d, J = 9.2 Hz, 1H), 3.38 (s, 3H), 3.33 (d, J = 6.3 Hz, 1H), 2.53 (d, J = 18.7 Hz, 1H),
2.22–2.30 (m, 2H), 2.07–2.11 (m, 1H), 1.96 (d, J = 18.7 Hz, 1H), 1.66–1.75 (m,
1H), 1.51–1.57 (m, 1H), 1.22 (d, J = 7.1 Hz, 3H), 1.09 (s, 3H), 0.97 (s, 3H); 13C
NMR (100 MHz, CDCl3) d 211.2, 108.3, 85.3, 74.7, 74.0, 60.9, 54.5, 52.4, 51.8,
43.6, 38.4, 34.3, 30.9, 14.2, 13.7, 9.3; HRMS(ES) m/z Calcd for C16H24O5Na
(M+Na): 319.1521. Found: 319.1534.
3425, 2951, 2877, 1451 cmÀ1 1H NMR (300 MHz, CDCl3) d 6.48 (s, 1H), 5.11 (d,
;
J = 7.5 Hz, 1H), 4.57 (d, J = 12.6 Hz, 1H), 4.24–4.33 (m, 1H), 3.77 (d, J = 1.5 Hz,
1H), 3.64 (d, J = 7.8 Hz, 1H), 3.38 (s, 3H), 2.53–2.64 (m, 1H), 1.78–1.92 (m, 1H),
1.65 (s, 1H), 1.41 (ddd, J = 1.2, 9.3, 14.1 Hz, 1H), 1.33 (s, 3H), 1.19 (d, J = 7.2 Hz,
3H), 0.98 (t, J = 8.1 Hz, 9H), 0.94 (s, 3H), 0.66–0.75 (m, 6H); 13C NMR (100 MHz,
CDCl3) d 140.0, 123.6, 107.7, 76.1, 71.7, 70.5, 58.7, 58.4, 54.3, 52.8, 46.9, 46.7,
37.9, 19.0, 15.1, 14.5, 6.8 (3C), 4.9 (3C); HRMS(ES) m/z Calcd for
11. X-ray data was collected at 291 K on a Bruker Kappa APEX II diffractometer
C
22H37BrO4SiNa (M+Na): 495.1542. Found: 495.1557; 16 IR (neat) 2950,
with graphite monochromated MoK radiation (k = 0.7107 Å). The crystal
a
2878, 1450, 1146 cmÀ1 1H NMR (400 MHz, CDCl3) d 6.24 (s, 1H), 5.47 (s, 1H),
;
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. Crystal data of
11a: C16H21BrO3, M = 341.23, monoclinic, P21/c, a = 9.9357(17), b = 7.3053(12),
3.88 (s, 2H), 3.86 (s, 1H), 3.35 (s, 3H), 2.46 (ddd, J = 2.2, 8.1, 14.7 Hz, 1H), 2.28
(q, J = 7.7 Hz, 1H), 2.11–2.17 (m, 1H), 1.28 (d, J = 6.6 Hz, 3H), 1.27 (s, 3H), 1.02
(s, 3H), 0.93 (t, J = 7.8 Hz, 9H), 0.57–0.70 (m, 6H); 13C NMR (100 MHz, CDCl3) d
150.2, 138.3, 123.3, 121.3, 109.3, 77.9, 75.2, 60.9, 56.4, 51.9, 48.5, 41.9, 40.3,
16.2, 15.0, 13.8, 7.0 (3C), 5.2 (3C); HRMS(ES) m/z Calcd for C22H35BrO3SiNa
c = 20.603(4) Å, b = 97.355(3)°, V = 1483.1(5) Å3, Z = 4,
q
calcd = 1.528 g/cm3,
10,672 reflections measured, 2747 unique (Rint = 0.024), R1 = 0.0314 and
wR2 = 0.0766 for 2227 observed reflections, CCDC no. 796424. Crystal data of
(M+Na): 477.1386. Found: 477.1384; 3 IR (neat) 2953, 2878, 1456, 1141 cmÀ1
;
1H NMR (400 MHz, CDCl3) d 6.30 (s, 1H), 3.79 (1/2ABq, J = 9.5 Hz, 1H), 3.78 (s,
1H), 3.73 (1/2ABq, J = 7.9 Hz, 1H), 3.44 (s, 1H), 3.41 (s, 3H), 2.04 (dd, J = 7.2,
12.5 Hz, 1H), 1.88–1.97 (m, 1H), 1.72–1.78 (m, 1H), 1.35 (s, 3H), 1.14 (d,
J = 7.2 Hz, 3H), 0.95 (t, J = 7.9 Hz, 9H), 0.79 (s, 3H), 0.61–0.72 (m, 6H); 13C NMR
(100 MHz, CDCl3) d 135.0, 124.7, 108.1, 76.3, 74.3 (2C), 59.3, 56.3, 53.8, 52.2,
46.4, 36.6, 34.3, 16.1, 13.6, 11.9, 7.1 (3C), 5.2 (3C); HRMS(ES) m/z Calcd for
18:
C
16H23BrO4, M = 359.24, monoclinic, P21/n, a = 7.613(2), b = 19.155(6),
c = 10.867(3) Å, b = 93.295(6)°, V = 1581.9(8) Å3, Z = 4,
q
calcd = 2.612 g/cm3,
11,641 reflections measured, 2920 unique (Rint = 0.053), R1 = 0.0801 and
wR2 = 0.2111 for 1769 observed reflections, CCDC no. 796423.
12. Chidambaram, N.; Chandrasekaran, S. J. Org. Chem. 1987, 52, 5048–5051.
13. Prilezhaev, N. Chem. Ber. 1909, 42, 4811–4815.
C
22H35BrO4SiNa (M+Na) 493.1386. Found: 493.1399; 18 mp 132.8–133.2 °C; IR
(KBr) 3481, 2926, 2853, 1093 cmÀ1 1H NMR (400 MHz, CDCl3) d 6.39 (s, 1H),
3.87 (d, J = 9.2 Hz, 2H), 3.56 (d, J = 7.5 Hz, 1H), 3.35 (s, 3H), 3.14 (d, J = 7.5 Hz,
14. (a) Tietze, L. F.; Wiegand, J. M.; Vock, C. A. Eur. J. Org. Chem. 2004, 4107–4112;
(b) Organ, M. G.; Bratovanov, S. Tetrahedron Lett. 2000, 41, 6945–6949.
;