A new, highly stereoselective synthesis of β-unsubstituted (Z)-γ-alkylidene-butenolides using bromine as a removable stereocontrol element

Article abstract of DOI:10.1055/s-2007-968004

Several β-unsubstituted (Z)-γ-alkylidenebutenolides have been prepared in highly stereocontrolled fashion by implementing a steric directing group stratagem in the vinylogous aldol condensation of butenolides with aldehydes. Applications to the synthesis of the antitumor heptene (S)-melodorinol and a thiophenelactone from Chamaemelum nobile L. are described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-968004

LETTER
219
A New, Highly Stereoselective Synthesis of b-Unsubstituted (Z)-g-Alkylidene-
butenolides Using Bromine as a Removable Stereocontrol Element
S
tereosele
o
ctive
S
ynthe
h
sis of
b
-Unsu
n
bstituted (
Z
)-
g
-Alk
B
ylidenebutenolid
o
e
s
ukouvalas,* Paola P. Beltrán, Nicolas Lachance, Sébastien Côté, François Maltais, Martin Pouliot
Département de Chimie, Université Laval, Quebec City, Quebec G1K 7P4, Canada
Fax +1(418)6567916; E-mail: john.boukouvalas@chm.ulaval.ca
Received 1 November 2006
methods offer stereochemical predictability and high
Abstract: Several b-unsubstituted (Z)-g-alkylidenebutenolides
have been prepared in highly stereocontrolled fashion by imple-
menting a steric directing group stratagem in the vinylogous aldol
condensation of butenolides with aldehydes. Applications to the
synthesis of the antitumor heptene (S)-melodorinol and a
thiophenelactone from Chamaemelum nobile L. are described.
levels of selectivity, they all require access to stereo-
defined precursors that may involve several steps and/or
the separation of diastereoisomers.1b,8
R
R
R
X
Key words: aldol reaction, bromobutenolides, dehalogenation,
2-silyloxyfurans, stereoselectivity
X
O
O
O
O
O
O
H
Ar
B:
Ar
Ar
syn
Z
The stereoselective construction of g-alkylidenebuteno-
lides continues to stand as an important objective in syn-
thetic organic chemistry due to the diverse structures and
biological activities of many members of this class.1,2
Most naturally occurring g-alkylidenebutenolides have
the Z-configuration, and many of them lack a b-sub-
stituent, as represented by eremolactone (1),1a the anti-
tumor heptene (S)-melodorinol (2),3 and the noncytotoxic
cholesterol biosynthesis inhibitor xerulin4 (3; Figure 1).
R
R
R
X
Ar
Ar
O
O
O
O
O
O
H
X
Ar
B:
E
anti
R = i-Pr, Ar; X = OTBS
(not observed)
Scheme 1
In the course of our work on the total synthesis of
nostoclides and rubrolides,9 we found that mixtures of
syn- and anti-g-(a-silyloxyalkyl)butenolides bearing a b-
isopropyl or aryl substituent readily undergo b-elimina-
tion in the presence of DBU to afford solely (Z)-g-alkyl-
idenebutenolides. The consistently high stereoselectivity
seen in these reactions9,10 can best be explained by an
E1cb mechanism9a whereby the formation of the Z-isomer
is favored due to the steric bias provided by the b-sub-
stituent (Scheme 1).11 We now report an extension of the
mechanistic principle to the synthesis of b-unsubstituted
(Z)-g-alkylidenebutenolides by using bromine as a re-
movable steric directing group.12
H
PhCOO
O
O
OH
O
O
1
2
O
3
O
Figure 1
Although the Z-isomers are generally more stable than
their E-counterparts, in the absence of a b-substituent the
preference for formation of the Z-isomer is usually small.1
As a consequence, traditional synthetic approaches in-
volving alkylidenation of preformed oxacycles, such as
butenolides and 2-silyloxyfurans, are notoriously nonste-
reoselective.1a,5,6 Useful solutions to this problem include
the inherently stereospecific anti-elimination of diaste-
reomerically pure syn-g-(a-hydroxyalkyl)butenolides,1b,2c
the metallocyclization–protolysis of (Z)-2-en-4-ynoic
acids,1a,d and the Stille coupling of (Z)-halomethylidene-
butenolides with organotin reagents.7 While these
The serviceability of this strategy was initially demon-
strated by the preparation of benzylidenebutenolide 7a
from silyloxyfuran 413 (Scheme 2). In accord with a gen-
eral trend,9a,14 the TBSOTf-mediated Mukaiyama aldol
reaction of 4 with benzaldehyde delivered a 3.3:1 mixture
of the syn- and anti-bromobutenolides 5 in 91% yield.15
Treatment of this mixture with DBU in dichloromethane
provided (Z)-ylidenebutenolide 6a as the only detectable
isomer in 94% yield after chromatography. Smooth de-
bromination to 7a was achieved by either Pd(0)-catalyzed
reduction with tri-n-butyltin hydride (Bu3SnH)16 or
Brückner’s procedure (Zn, AcOH–THF, sonication).7a
While the former method gave the highest yield (97%),
the latter was cleaner making product purification easier.
SYNLETT 2007, No. 2, pp 0219–0222
0
1.
0
2.
2
0
0
7
Advanced online publication: 24.01.2007
DOI: 10.1055/s-2007-968004; Art ID: S18306ST
© Georg Thieme Verlag Stuttgart · New York

220
J. Boukouvalas et al.
LETTER
Br
Br
X
In contrast to aromatic aldehydes, simple alkanals did not
undergo condensation with 8 under these conditions.
Their conversion to (Z)-alkylidenebutenolides could be
achieved with little additional effort through Mukaiyama
aldol reaction with silyloxyfuran 413 or 920 (Table 2).
Dehydration of the so obtained mixtures of syn- and anti-
alcohols 1015 with mesyl chloride in the presence of tri-
ethylamine–DMAP (0 °C) or pyridine (r.t.) furnished 11
(Z:E > 40:1) in good to excellent yields.21
i
ii
Ph
OTBS
O
O
O
O
O
R2
Ph
R1
4
syn-5 R1 = H, R2 = OTBS
anti-5 R1 = OTBS, R2 = H
6a X = Br
7a X = H
iii
or iv
Scheme 2 Reagents and conditions: (i) PhCHO (1 equiv), TBSOTf
(1.1 equiv), CH2Cl2, –78 °C, 2 h, 91%; (ii) DBU (2 equiv), CH2Cl2,
r.t., 1 h, 94%; (iii) Bu3SnH (1.4 equiv), (Ph3P)4Pd (0.02 equiv),
CH2Cl2, r.t., 1 h, 97%; (iv) Zn dust, AcOH, THF, r.t., sonication, 45
min, 85–88%.
Table 2 Preparation of (Z)-g-Alkylidenebutenolides from
4-Bromo-2-(tert-butyldimethylsilyloxy)furans
Br
R'
RCHO
BF3·OEt2
Br
R'
Br
R'
The promise of this approach was further manifested by
the direct alkylidenation of b-bromobutenolide 8 using a
new variant of the one-pot procedure that we had previ-
ously developed for condensing b-arylbutenolides with
aromatic aldehydes.9b Thus, sequential treatment of 8 with
TBSOTf–triethylamine, the appropriate aldehyde and
DBU,17 delivered the corresponding g-alkylidene-b-bro-
mobutenolides 6 with excellent stereocontrol (Table 1).
Attempts to condense the parent, non-brominated a,b-
butenolide with benzaldehyde or p-anisaldehyde under
the same conditions led to complex mixtures containing
little, if any, of the desired product (7a: 0%; 7b: ca. 5–
10%). These results suggest that in addition to performing
the intended steric directing role, the b-bromine also
provides a strong accelerating effect to the condensation
process.
+
R
R
CH2Cl2
–78 °C
OTBS
O
O
O
O
O
OH
OH
4 R' = H
9 R' = Me
syn-10
anti-10
MsCl, Et3N, DMAP
CH2Cl2, 0 °C
X
R'
11 X = Br
12 X = H
Bu3SnH, (Ph3P)4Pd
CH2Cl2, r.t.
O
O
R
R
R¢
Yield (%)a of 10 Yield (%)a,b Yield (%)a,b
(syn:anti)
of 11
of 12
Me(CH2)3
Me(CH2)3
Ph(CH2)2
PhCH2
H
91 (10a; 5.0:1)
87 (10b; 5.2:1)
82 (10c; 5.5:1)
75 (10d; 4.2:1)
98 (11a)
91 (11b)
99 (11c)
76d (11d)
96 (12a)
97 (12b)
89 (12c)
77 (12d)
Me
H
Using this protocol, lactone 7c, a constituent of Chamae-
melum nobile L. and popular target for testing new meth-
odology,18 was prepared from 5-methylthiophene-2-
carboxaldehyde in 76% yield over two steps (Table 1).
Likewise, (E)-cinnamaldehyde was easily converted into
7d,19 which has only recently been prepared stereoselec-
tively by Stille coupling.7a
H
c
H
–
65d (11e)
93 (12e)
O
O
a Yields refer to chromatographically purified products. Aldols
10a–d were obtained as diastereomeric mixtures after chromatogra-
phy on silica gel.
Table 1 Stereocontrolled Access to (Z)-g-Alkylidenebutenolides
from b-Bromo-a,b-butenolide (8)
Br
X
TBSOTf, Et3N, CH2Cl2, 0 °C
then RCHO, –78 °C
b The Z/E ratio was over 40:1 according to 1H NMR.
c Not determined; see text.
d Dehydration was carried out using MsCl in pyridine at r.t.
O
O
then DBU, –78 °C to r.t.
O
O
R
6 X = Br
7 X = H
8
Zn, AcOH, THF
r.t., sonication
The crude diastereomeric aldol products can be carried
forward without chromatographic purification, as illus-
trated by the entirely stereoselective conversion of (R)-
2,3-isopropylidene glyceraldehyde to 11e (65%, 2 steps)
in the context of a new synthesis of (S)-melodorinol (2).
Debromination of 11e provided the requisite relay ace-
tonide 12e3a (93%, Table 2) whose hydrolysis and ensuing
benzoylation afforded 2 as a pale yellow oil {[a]26D +91.0,
(c = 0.98, CHCl3); Lit. [a]D +86.4,3a [a]D +92.53b} in 61%
yield for the two steps (Scheme 3).
R
Yield (%)a,b of 6
Yield (%)a of 7
86d (7a)
Ph
68c (6a)
85 (6b)
p-MeOPh
87 (7b)
83 (6c)
70 (6d)
91 (7c)
S
77d (7d)
Ph
a Yields refer to chromatographically purified products.
b The Z/E ratio was over 40:1 according to 1H NMR.
c A second portion of TBSOTf (1.1 equiv) was added after the
aldehyde.
In summary, this new methodology enables stereo-
controlled access to a variety of b-unsubstituted (Z)-g-
alkylidenebutenolides from readily available, non-stereo-
defined precursors. Moreover, the intermediate (Z)-g-
alkylidene-b-bromobutenolides are interesting in their
d Data from ref. 7a.
Synlett 2007, No. 2, 219–222 © Thieme Stuttgart · New York

LETTER
Stereoselective Synthesis of b-Unsubstituted (Z)-g-Alkylidenebutenolides
221
(8) Vaz, B.; Alvarez, R.; Brückner, R.; de Lera, A. R. Org. Lett.
2005, 7, 545.
1) AcOH–H2O (1:1)
r.t., 48 h (98%)
O
O
O
O
(9) (a) Boukouvalas, J.; Maltais, F.; Lachance, N. Tetrahedron
Lett. 1994, 35, 7897. (b) Boukouvalas, J.; Lachance, N.;
Ouellet, M.; Trudeau, M. Tetrahedron Lett. 1998, 39, 7665.
(10) For recent synthetic applications, see: (a) Bellina, F.;
Anselmi, C.; Viel, S.; Mannina, L.; Rossi, R. Tetrahedron
2001, 57, 9997. (b) Wu, J.; Zhu, Q.; Wang, L.; Fathi, R.;
Yang, Z. J. Org. Chem. 2003, 68, 670. (c) Bellina, F.;
Anselmi, C.; Martina, F.; Rossi, R. Eur. J. Org. Chem. 2003,
2290. (d) Boukouvalas, J.; Pouliot, M. Synlett 2005, 343.
(11) In the absence of a b-substituent, stereoselectivities can vary
both in magnitude and direction: (a) Takayama, H.;
Kuwajima, T.; Kitajima, M.; Nonato, M. G.; Aimi, N.
Heterocycles 1999, 50, 75. (b) Takayama, H.; Ichikawa, T.;
Kuwajima, T.; Kitajima, M.; Seki, H.; Aimi, N.; Nonato, M.
G. J. Am. Chem. Soc. 2000, 122, 8635. (c) Barbosa, L. C.
A.; Demuner, A. J.; de Alvarenga, E. S.; Oliveira, A.; King-
Diaz, B.; Lotina-Hennsen, B. Pest Manag. Sci. 2006, 62,
214.
2) PhCOCl, py, 0 °C
72 h (62%)
12e
2
O
OH
O
PhCOO
Scheme 3
own right since they can be transformed to a range of
b-substituted homologues by cross-coupling reac-
tions,7a,9b,22 and also due to the recent discovery that cer-
tain members of this class are potent quorum sensing (QS)
inhibitors23 with potential utility for the treatment of an-
thrax and other bacterial infections.24 Such applications
are under study and the results will be reported in due
course.
(12) Bromine has previously performed this role in CBS-
reduction and TADA reactions: (a) Nicolaou, K. C.;
Bertinato, A. D.; Piscopio, A. D.; Chakraborty, T. K.;
Minowa, N. Chem. Commun. 1993, 619. (b) He, F.; Bo, Y.;
Altom, J. D.; Corey, E. J. J. Am. Chem. Soc. 1999, 121,
6771. (c) Parker, K. A.; Fokas, D. J. Org. Chem. 2006, 71,
449. (d) Frank, S. A.; Roush, W. R. J. Org. Chem. 2002, 67,
4316.
Acknowledgment
We thank the Natural Sciences and Engineering Research Council
of Canada (NSERC), Merck Frosst Canada and Eisai Research In-
stitute (Andover, MA, USA) for financial support. We also thank
NSERC for postgraduate scholarships to N.L., S.C. and M.P.
References and Notes
(13) Jas, G. Synthesis 1991, 965.
(14) (a) López, C. S.; Álvarez, R.; Vaz, B.; Faza, O. N.; de Lera,
R. J. Org. Chem. 2005, 70, 3654. (b) Boeckman, R. K. Jr.;
Pero, J. E.; Boehmler, D. J. J. Am. Chem. Soc. 2006, 128,
11032.
(15) The major isomers (syn) of all aldol products described
herein (5 and 10a–d) were clearly distinguished from their
anti counterparts by the upfield shift of their g-proton
(Dd ≈ 0.2–0.3 ppm). Their stereochemistry was deduced by
debromination of syn-10a/anti-10a to the corresponding
butenolides syn-13a/anti-13a whose stereostructures were
unambiguously assigned from the diagnostic shift of the b-
proton5a (Scheme 4).
(1) Reviews on the synthesis of g-alkylidenebutenolides:
(a) Negishi, E.; Kotora, M. Tetrahedron 1997, 53, 6707.
(b) Brückner, R. Chem. Commun. 2001, 141. (c) Brückner,
R. Curr. Org. Chem. 2001, 5, 679. (d) Rossi, R.; Bellina, F.
In Targets in Heterocyclic Systems: Chemistry and
Properties, Vol. 5; Attanasi, O. A.; Spinelli, D., Eds.;
Società Chimica Italiana: Roma, 2002, 169–198.
(2) For more recent work, see: (a) Anastasia, L.; Xu, C.;
Negishi, E. Tetrahedron Lett. 2002, 43, 5673. (b) Rousset,
S.; Abarbri, M.; Thibonnet, J.; Parrain, J.-L.; Duchêne, A.
Tetrahedron Lett. 2003, 44, 7633. (c) Olpp, T.; Brückner, R.
Angew. Chem. Int. Ed. 2005, 44, 1553. (d) Takayama, H.;
Sudo, R.; Kitajima, M. Tetrahedron Lett. 2005, 46, 5795.
(e) Doroh, B.; Sulikowski, G. A. Org. Lett. 2006, 8, 903.
(f) Albrecht, U.; Nguyen, V. T. H.; Langer, P. Synthesis
2006, 1111. (g) Olpp, T.; Brückner, R. Angew. Chem. Int.
Ed. 2006, 45, 4023.
Br
Br
+
Bu
Bu
O
O
O
O
H
H
HO
HO
syn-10a
anti-10a
(3) Natural melodorinol consists of a ca. 2.5:1 mixture of the R
and S enantiomers: (a) Lu, X.; Chen, G.; Xia, L.; Guo, G.
Tetrahedron: Asymmetry 1997, 8, 3067. (b) See also:
Pohmakort, M.; Tuchinda, P.; Premkaisorn, P.;
(5:1)
δ 4.88
δ 5.12
Bu3SnH, (Ph3P)4Pd
(82%)
Limpongpan, A.; Reutrakul, V. Heterocycles 1999, 51, 795.
(4) Synthesis of xerulin and its relatives: (a) Siegel, K.;
Brückner, R. Synlett 1999, 1227. (b) Negishi, E.;
δ 7.47
δ 7.55
H
H
+
Bu
Bu
O
O
O
O
Alimardanov, A.; Xu, C. Org. Lett. 2000, 2, 65. (c) Rossi,
R.; Belina, F.; Catanese, A.; Mannina, L.; Valensin, D.
Tetrahedron 2000, 56, 479. (d) Sorg, A.; Siegel, K.;
Brückner, R. Chem. Eur. J. 2005, 11, 1610.
H
H
HO
HO
syn-13a
(5:1)
anti-13a
Scheme 4
(5) (a) Hjelmgaard, T.; Persson, T.; Rasmussen, T. B.; Givskov,
M.; Nielsen, J. Bioorg. Med. Chem. 2003, 11, 3261.
(b) Piper, S.; Risch, N. ARKIVOC 2003, (i), 86.
(6) High Z-selectivity has been obtained in some cases under
equilibration conditions: (a) Pohmakort, M.; Tuchinda, P.;
Premkaisorn, P.; Reutrakul, V. Tetrahedron 1998, 54,
11297. (b) Sundar, N.; Kundu, M. K.; Reddy, P. V.;
Mahendra, G.; Bhat, S. V. Synth. Commun. 2002, 32, 1881.
(7) (a) Sorg, A.; Siegel, K.; Brückner, R. Synlett 2004, 321.
(b) Sorg, A.; Blank, F.; Brückner, R. Synlett 2005, 1286.
(16) Uenishi, J.; Kawahama, R.; Yonemitsu, O.; Tsuji, J. J. Org.
Chem. 1998, 63, 8965.
(17) Typical Procedure: To a solution of 813 (147 mg, 0. 903
mmol) in anhyd CH2Cl2 (3 mL) at 0 °C were successively
added TBSOTf (207 mL, 0. 903 mmol) and Et3N (125 mL,
0. 903 mmol). The mixture was stirred for 30 min at 0 °C,
then cooled to –78 °C, and then p-anisaldehyde (100 mL,
0.821 mmol) was added. After stirring at –78 °C for 1 h,
Synlett 2007, No. 2, 219–222 © Thieme Stuttgart · New York

222
J. Boukouvalas et al.
LETTER
DBU (251 mL, 1.64 mmol) was added and the resulting dark
purple solution was allowed to warm to r.t. and stirred for an
additional 1.5 h before quenching with 15% aq tartaric acid.
The aqueous phase was extracted with CH2Cl2 (3 ×) and the
combined organic layers were washed with sat. aq NaHCO3,
dried over MgSO4 and concentrated under reduced pressure.
The residue was purified by flash column chromatography
(silica gel; EtOAc–CH2Cl2–hexanes, 1:3:10) to afford 6b
(196 mg, 85%) as a pale red-brown solid; mp 129–130 °C.
1H NMR (400 MHz, CDCl3): d = 3.86 (s, 3 H), 6.33 (s, 1 H),
6.35 (s, 1 H), 6.95 (d, J = 8.6 Hz, 2 H), 7.79 (d, J = 8.6 Hz,
2 H). 13C NMR (100 MHz, CDCl3): d = 55.2, 113.5, 114.3,
117.4, 124.8, 132.7, 138.1, 145.0, 160.9, 167.3. MS (CI):
m/z = 281 [MH+]. Anal. Calcd for C12H9BrO3: C, 51.27; H,
3.23. Found: C, 51.29; H, 2.99.
(21) Data for 11a: orange oil. 1H NMR (400 MHz, CDCl3): d =
0.93 (t, J = 7.3 Hz, 3 H), 1.37 (m, 2 H), 1.49 (m, 2 H), 2.41
(q, J = 7.6 Hz, 2 H), 5.62 (dt, J = 0.5, 8.0 Hz, 1 H), 6.34 (d,
J = 0.5 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d = 13.7, 22.3,
26.1, 30.8, 117.3, 119.6, 136.9, 148.1, 167.0. HRMS (EI):
m/z calcd for C9H11BrO2: 229.9942; found: 229.9938.
Data for 11b: orange oil. 1H NMR (300 MHz, CDCl3): d =
0.90 (t, J = 7.1 Hz, 3 H), 1.31–1.50 (m, 4 H), 1.96 (s, 3 H),
2.37 (q, J = 7.4 Hz, 2 H), 5.47 (t, J = 7.9 Hz, 1 H). 13C NMR
(75 MHz, CDCl3): d = 10.2, 13.7, 22.3, 25.8, 31.0, 114.5,
128.1, 132.2, 147.0, 167.9. HRMS (EI): m/z calcd for
C10H13BrO2: 244.099; found: 244.0098.
Data for 11c: yellow oil. 1H NMR (300 MHz, CDCl3): d =
2.65 (m, 2 H), 2.72 (m, 2 H), 5.54 (t, J = 7.6 Hz, 1 H), 6.25
(s, 1 H), 7.11–7.25 (m, 5 H). 13C NMR (75 MHz, CDCl3): d
= 28.0, 34.7, 115.7, 119.8, 126.2, 128.2, 128.4, 136.9, 140.3,
148.3, 166.8. HRMS (EI): m/z calcd for C13H11BrO2:
277.9942; found: 277.9938.
Data for 6c: yellow solid; mp 138–139 °C. 1H NMR (400
MHz, CDCl3): d = 2.55 (br d, J = 1.0 Hz, 3 H), 6.33 (s, 1 H),
6.55 (s, 1 H), 6.78 (dq, J = 3.7, 1.0 Hz, 1 H), 7.26 (d, J = 3.7
Hz, 1 H). 13C NMR (100 MHz, CDCl3): d = 15.7, 107.6,
117.7, 126.6, 133.0, 133.5, 136.7, 144.2, 147.8, 166.8. MS
(CI): m/z = 271 [MH+]. Anal. Calcd for C10H7BrO2S: C,
44.30; H, 2.60; S, 11.83. Found: C, 44.25; H, 2.43; S, 12.19.
Compounds 6a (white solid; mp 84–85 °C) and 6d (yellow
oil) exhibited NMR data commensurate with those reported
by Brückner.7a
Data for 11d: white solid; mp 66–67 °C. 1H NMR (300 MHz,
CDCl3): d = 3.74 (d, J = 8.1 Hz, 2 H), 5.76 (t, J = 8.1 Hz, 1
H), 6.40 (s, 1 H), 7.22–7.36 (m, 5 H). 13C NMR (75 MHz,
CDCl3): d = 32.6, 114.9, 120.3, 126.8, 128.6, 128.8, 137.1,
137.9, 148.2, 166.8. Anal. Calcd for C12H9BrO2: C, 54.55;
H, 3.44. Found: C, 54.76; H, 3.53.
Data for 11e: white solid; mp 29–31 °C; [a]D23 +32.5 (c =
1.03, CHCl3). 1H NMR (300 MHz, CDCl3): d = 1.40 (s, 3 H),
1.47 (s, 3 H), 3.73 (dd, J = 6.7, 8.2 Hz, 1 H), 4.23 (dd, J =
6.7, 8.2 Hz, 1 H), 5.12 (dt, J = 6.7, 8.2 Hz, 1 H), 5.64 (d, J =
8.2 Hz, 1 H), 6.43 (s, 1 H). 13C NMR (75 MHz, CDCl3): d =
25.4, 26.5, 69.0, 70.6, 110.0, 112.8, 121.2, 137.0, 148.9,
165.9. HRMS (CI): m/z calcd for C10H11BrO4: 274.9919;
found: 274.9915.
(18) (a) Negishi, E.; Xu, C.; Tan, Z.; Kotora, M. Heterocycles
1997, 48, 209; and references cited therein. (b) von der
Ohe, F.; Brückner, R. New J. Chem. 2000, 24, 659. (c) See
also ref. 6b.
(19) Xu, D.; Sharpless, K. B. Tetrahedron Lett. 1994, 35, 4685.
(20) Silyloxyfuran 9 was prepared in 98% yield by silylation
(TBSOTf, Et3N, CH2Cl2, r.t.) of the readily available b-
bromo-a-methylbutenolide: Svendsen, J. S.; Sydnes, L. K.
Acta Chem. Scand. 1990, 44, 202.
(22) Boukouvalas, J.; Côté, S.; Ndzi, B. Tetrahedron Lett. 2007,
48, 105; and references cited therein.
(23) Ma, Z.; Morris, T. W.; Combrink, K. D. Ann. Rep. Med.
Chem. 2004, 39, 197.
(24) Jones, M. B.; Jani, R.; Ren, D.; Wood, T. K.; Blaser, M. J.
J. Infect. Dis. 2005, 191, 1881.
Data for 9: colorless oil. 1H NMR (300 MHz, CDCl3): d =
0.22 (s, 6 H), 0.97 (s, 9 H), 1.80 (s, 3 H), 6.86 (s, 1 H).). 13
NMR (75 MHz, CDCl3): d = –4.5, 7.4, 17.9, 25.4, 94.0,
104.3, 129.2, 152.4. HRMS (EI): m/z calcd for
C11H19BrO2Si: 290.0338; found: 290.0331.
C
Synlett 2007, No. 2, 219–222 © Thieme Stuttgart · New York

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