On the way to an oxidative Hosomi-Sakurai reaction

Article abstract of DOI:10.1055/s-0028-1087369

An oxidative allylation process mediated by a hypervalent iodine reagent has been performed on polysubstituted phenols. This reaction, occurring in useful to good yields, leads to a rapid access to dienones containing a quaternary carbon center. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087369

3226
LETTER
On the Way to an Oxidative Hosomi–Sakurai Reaction
O
xidative Hosom
y
i–Sakurai
R
r
Laboratoire de Méthodologie et Synthèse de Produits Naturels, Université du Québec à Montréal, C.P. 8888, Succ. Centre-Ville,
Montréal, Québec H3C 3P8, Canada
Fax +1(514)9874054; E-mail: canesi.sylvain@uqam.ca
Received 18 August 2008
O
O
OH
OH
Abstract: An oxidative allylation process mediated by a hyper-
valent iodine reagent has been performed on polysubstituted phe-
nols. This reaction, occurring in useful to good yields, leads to a
rapid access to dienones containing a quaternary carbon center.
Nu
[ O ]
– Nu
a
[ ? ]
or
b
R
Nu
R
1
R
2
R
4
Key words: hypervalent iodine, allyltrimethylsilane, substitued
phenols, oxidative allylation
3
Scheme 1
Allylation processes are generally recognized as impor-
tant tools for organic synthesis; one of the most famous is
the Hosomi–Sakurai reaction.1 This reaction has opened
up many new opportunities in synthetic chemistry. In-
deed, the allyl moiety is known to be a good precursor of
carbonyl. This reaction consists in the addition of mild nu-
cleophiles such as allylsilanes, propargylsilanes, and enol
ethers onto electrophilic species activated by Lewis acids.
An interesting development of this reaction would be to
extend its application to aromatic derivatives. A possible
avenue to achieve this objective would involve the forma-
tion of an electrophilic intermediate from the correspond-
ing aromatic ring. An indication of how this objective
could be achieved is apparent in the work of Kita,2 who
has shown that phenols3 may be activated under the influ-
ence of hypervalent iodine reagents such as iodobenzene
diacetate4 (DIB) leading to 2. Electrophilic species 2 tends
to react at the 4-position (cf. reaction mode b), at least
with heteronucleophiles. We recently determined that
carbon-based nucleophiles5 in a bimolecular process at-
tack the presumed intermediate 2 at a position adjacent to
the carbonyl group (pathway a), resulting in the formation
of product 4 (Scheme 1). As demonstrated by Kita,6 this
reaction generally occurs best in solvents such as tri-
fluoroethanol (TFE) or hexafluoroisopropanol (HFIP).
Formally, this type of transformation can be termed an
‘aromatic ring umpolung’. While a phenol normally reacts
as a nucleophile, suitable oxidative activation can convert
it to reactive electrophilic intermediate 2, which may be
intercepted by mild nucleophiles.
an intramolecular process as a key step in the synthesis of
platensimycin7 by Nicolaou et al. Moreover, a first ap-
proach to this reaction was developed by Quideau and
coworkers8 in aprotic solvents with phenyliodine bistri-
fluoracetate (PIFA), which has provided some noteworthy
examples of oxidative allylation on substituted 1-naph-
thol. By generalizing and extending this reaction to differ-
ent aromatic compounds in a bimolecular process, we
would introduce novel opportunities in the field of chem-
ical synthesis. Indeed, the corresponding dienone 3, an in-
teresting functionalizable core containing a prochiral
quaternary center, can be easily dissymmetrized.9 This
main skeleton is present in numerous natural products:
lycoramine,10 platencin,11 etc. To perform this reaction ef-
ficiently with phenols, different aspects must be consid-
ered. First, in protic and poorly nucleophilic solvents,
such as TFE or HFIP (Kita’s conditions), intermediate 2
should be stabilized by the solvent long enough to react
with allylsilane. Second, the regioselectivity of the nu-
cleophilic attack of allylsilane must be considered. As
presented in Scheme 1, carbon-based nucleophiles, such
as allylsilanes,12 attack the presumed intermediate 2 at the
least hindered position adjacent to the carbonyl group
(pathway a). To perform an oxidative allylation process, it
seems reasonable to block the ortho positions to avoid the
cycloaddition process. Thus, to test the regioselectivity of
the reaction, 2,4,6-trimethylphenol (6) was oxidized and
led to a mixture (4:1) of 7 and 8 in 41% yield (Scheme 2).
Although a mixture of compounds 7 and 8 was obtained,
this result is encouraging because it demonstrates the fea-
sibility of this approach. In order to increase the selectiv-
ity, it seems rational to use adequate bulky groups, such as
tert-butyl, to conduct the reaction exclusively at one posi-
tion. Under these conditions, the desired dienones are pro-
duced in high yield (Scheme 3). Indeed, such hindered
structures have already been used efficiently in oxidative
dearomatization of phenols.13 These structures appear to
be good precursors for an efficient oxidative Hosomi–
Sakurai-type process. Additionally, this reaction seems to
occur as well in the ortho or para positions. These exper-
Indeed on the basis of this concept, two reactions may be
in competition: aromatic substitution (pathway a) versus
oxidative addition (pathway b). Therefore, at this point, it
would be interesting to verify the regioselectivity of mild
nucleophiles such as allylsilanes with species such as 2.
One noteworthy similar approach has already been used in
SYNLETT 2008, No. 20, pp 3226–3230
1
6
.1
2
.2
0
0
8
Advanced online publication: 26.11.2008
DOI: 10.1055/s-0028-1087369; Art ID: S07408ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxidative Hosomi–Sakurai Reaction
3227
PhI(OAc)2
TFE or HFIP
Table 1 Representative Experiments for the Oxidation of 4-Alkyl-
2-6-di-tert-butyl Phenols 11
OH
TMS
(+/–)
O
ref. 12
O
OH
R
R
TMS
PhI(OAc)2
TFE
t-Bu
t-Bu
t-Bu
t-Bu
1
5
O
TMS
O
OH
PhI(OAc)2
HFIP
R
R
11
13
+
TMS
Entry
11
R
Yield of 13 (%)
13a 84
41%
6
7
8
1
2
3
4
5
6
7
11a
11b
11c
11d
11e
11f
Me
Scheme 2
n-Pent
13b 79
i-Pr
13c 74
iments have demonstrated that the steric effect of the sub-
stituents controls the regioselectivity of this reaction. The
reaction seems more efficient when the attack occurs in
the para position.
CH2CH2OH
CH2OTBDMS
CH2CH2NHTs
CH2CO2Me
13d 71
13e 81
13f 61
Since compound 11 is more substituted than compound 1,
its oxidation occurs more slowly due to the presence of
bulky substituents in the ortho positions; in some cases it
is difficult to convert all the starting materials. However,
this reaction provides higher yields of the desired prod-
ucts. This observation could be rationalized considering
that potential electrophilic intermediate 12 would be more
stable than the species 2 due to the presence of two addi-
tional electron-donor groups. As expected, the ratio of
byproducts has decreased significantly. To extend the
scope of this reaction, different 4-alkyl-2-6-di-tert-butyl
phenols 11 were successfully oxidized. A summary of
representative experiments appears in Table 1.14 It is wor-
thy of note that the reaction tolerates moderately nucleo-
philic functionalities such as alcohols, sulfonamides, and
esters.
11g
13g 70
O
OH
OH
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
H+
– H+
+
R
R
R
13
14
15
Scheme 4
In order to avoid being restricted to tert-butyl groups, we
have investigated possible protective groups that would
have the potentiality to block the desired positions while
being subsequently removable. An interesting choice
would be the halides: as a matter of fact, they could be ef-
ficiently introduced onto an aromatic ring. In particular,
bromides could be useful to generate some C–C bonds by
means of palladium chemistry. This synthetic strategy
could be useful for the total synthesis of numerous natural
products. Unfortunately, oxidation of 2-6-dibromo cresol
led to inextricable byproducts. However, bromides can
The source of hypervalent iodine, iodobenzene diacetate,
is a key aspect of this reaction. Indeed, during the process,
it releases 2 equivalents of acetic acid, promoting some di-
enone–phenol rearrangement.15 While this rearrangement
occurs slowly with acetic acid, it can be accelerated in the
presence of stronger acids such as trifluoroacetic acid.
This may be the reason why PIFA would not be the most
appropriate oxidizing reagent (Scheme 4).
O
OH
PhI(OAc)2
TFE
t-Bu
t-Bu
TMS
t-Bu
t-Bu
9
10
42%
O
O
OH
t-Bu
t-Bu
PhI(OAc)2
TFE
t-Bu
t-Bu
t-Bu
t-Bu
+
TMS
84%
11a
12a
13a
Scheme 3
Synlett 2008, No. 20, 3226–3230 © Thieme Stuttgart · New York

3228
C. Sabot et al.
LETTER
Table 3 Synthesis of Compound 21
Table 2 Treatment of Di-TMS-phenols under Oxidative Conditions
O
O
OH
OH
PhI(OAc)2
PhI(OAc)2
TFE
R1
R2
R2
TMS
R1
TMS
TMS
TMS
HFIP
TMS
TMS
R
R
R
R
20
21
16
17
Entry 20
R
R1
Cl
Br
I
R2
Yield of 21 (%)
21a 65
Entry
16
R
Yield of 17 (%)
17a 52
1
2
3
4
5
6
20a
20b
Me
Me
Me
i-Pr
Me
n-Bu
t-Bu
t-Bu
t-Bu
t-Bu
TMS
TMS
1
2
3
4
16a
16b
16c
16d
Me
21b 51
Et
17b 46
20c
20d
20e
20f
21c 45
Ph
17c 37
Br
Br
Br
21d 42
CH2CH2OH
17d 41
21e 53
easily be changed into a trimethylsilyl group,16 a motif
quite similar to tert-butyl with the advantage of being eas-
ily removable. Consequently, different di-TMS-phenols
have been treated under the oxidative conditions. A sum-
mary of representative experiments appears in Table 2.17
21f 52
form 25 is a weaker contributor to the overall delocalized
system (Scheme 6). Indeed, alkyls are known to be better
electron-donor groups than halides. The use of TFE as sol-
vent in reactions involving 20 results in the formation of
an important part of the addition of TFE on the substrate
(compound 3, pathway b, Scheme 1, in agreement with
Kita’s observations).6 This problem can be easily avoided
by using a less nucleophilic solvent such as HFIP.
While this reaction also proceeds with trimethylsilyl
groups, it remains less efficient than with their tert-butyl
analogues. Compounds that have partially lost one or two
trimethylsilyl groups were recovered as byproduct. How-
ever, oxidation of 16 appears synthetically useful to gen-
erate functionalizable structures such as 18. Indeed, 17a
easily produces 18 in 73% yield under a TBAF/CsF treat-
ment (Scheme 5).
O
O
O
t-Bu
Br
t-Bu
Br
t-Bu
Br
+
+
+
O
O
TMS
TMS
TBAF, CsF
73%
23
24
25
Scheme 6
17a
18
Moreover, this process can be extended to alennyltrimeth-
ylsilane 28. The latter was easily afforded for the first time
by treatment of the Fleming silylcuprate reagent19 with
propargyl bromide in 60% yield (Scheme 7).
Scheme 5
The trimethylsilyl group appears to be a suitable protec-
tive group for this reaction and contributes to the develop-
ment of a general oxidative allylation process for phenols.
To explore the scope and limit of this reaction, we were
interested in combining different protective groups.
Hence various mixed phenols were oxidized. While the
oxidation of di-halogen-phenols is not efficient, a combi-
nation of halogen and tert-butyl or trimethylsilyl groups
produces the desired compound 21 in useful yield
(Table 3). It should be noted that compound 20e,f can be
easily obtained from the dibrominated phenols16 and the
subsequent oxidation quickly leads to highly polyfunc-
tionalized cores 21e,f.18 They may be useful for rapid ac-
cess to the total synthesis of numerous natural products.
They appear to be the best compromise for potential fur-
ther applications.
Br
THF, –78°C
60%
SiPhMe2
+
(Me2PhSi)2CuLi
26
27
28
Scheme 7
A summary of representative oxidative experiments with
28 and different polysubstitued phenols appears in
Table 4.20 However, this process is inefficient with halo-
genoalkene such as 2-bromoallyltrimethylsilane. This re-
sult could be explained due to the withdrawing effect of
the halogen, which deactivates the nucleophilic character
of the alkene moiety.
In conclusion, an approach to accomplish an oxidative al-
lylation process extended to phenols is now available. The
transformation provides new strategic opportunities in the
chemical synthesis of substances, and results in ongoing
Regarding compound 20, no addition has been observed
on the carbon containing the halide. The selectivity ob-
served might be explained by the fact that the mesomer
Synlett 2008, No. 20, 3226–3230 © Thieme Stuttgart · New York

LETTER
Oxidative Hosomi–Sakurai Reaction
3229
Biomol. Chem. 2003, 1, 1647. (e) Dohi, T.; Morimoto, K.;
Kiyono, Y.; Maruyama, A.; Tohma, H.; Kita, Y. Chem.
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Org. Chem. 2004, 8, 113. (g) Ciufolini, M. A.; Canesi, S.;
Ousmer, M.; Braun, N. A. Tetrahedron 2006, 62, 5318.
(h) Nicolaou, K. C.; Edmonds, D. J.; Li, A.; Tria, G. S.
Angew. Chem. 2007, 119, 4016. (i) Ciufolini, M. A.; Braun,
N. A.; Canesi, S.; Ousmer, M.; Chang, J.; Chai, D. Synthesis
2007, 3759. (j) Bérard, D.; Jean, A.; Canesi, S. Tetrahedron
Lett. 2007, 48, 8238. (k) Bérard, D.; Giroux, M. A.; Racicot,
L.; Sabot, C.; Canesi, S. Tetrahedron 2008, 7537.
(l) Quideau, S.; Pouységu, L.; Deffieux, D. Synlett 2008,
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Lamidey, A. M.; Miqueu, K.; Sotiropoulos, J. M.; Quideau,
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Ciufolini, M. A. J. Org. Chem. 2008, 4299.
Table 4 Summary of Representative Oxidative Experiments with
Compound 28
O
OH
PhI(OAc)2
HFIP
t-Bu
t-Bu
t-Bu
t-Bu
SiPhMe2
28
R
R
11
29
Entry
11
R
Yield of 29 (%)
29a 81
1
2
3
11a
11h
11i
Me
n-Bu
29h 77
CH2CH2CHCH2
29i 75
investigations; their applications in total synthesis of nat-
ural products will be disclosed in due course.
Experimental Procedure
To a stirred solution of phenol (0.2 mmol) in TFE or HFIP (0.5 mL)
at r.t. was added allylsilane (137 mg, 1.2 mmol, 6 equiv), followed
DIB (97 mg, 0.3 mmol, 1.5 equiv) dissolved in TFE or HFIP (0.4
mL) over 20 s (Table 3). After 10 min stirring, 64–97 mg of DIB
(from 1–1.5 equiv) in TFE or HFIP (0.25 mL) were added to the re-
action mixture, depending of the phenol side chain. The solution
was stirred for further 5 min and quenched with sat. aq NaHCO3 (2
mL). The aqueous phase was extracted with EtOAc (3 × 5 mL),
washed with brine (5 mL), dried over Na2SO4 and concentrated. The
crude product was purified by chromatography (n-hexane–CH2Cl2).
(5) Jean, A.; Cantat, J.; Bérard, D.; Bouchu, D.; Canesi, S. Org.
Lett. 2007, 9, 2553.
(6) (a) Kita, Y.; Tohma, H.; Kikuchi, K.; Inagaki, M.; Yakura,
T. J. Org. Chem. 1991, 56, 435. (b) Hamamoto, H.;
Anilkumar, G.; Tohma, H.; Kita, Y. Chem. Eur. J. 2002, 8,
5377.
(7) Nicolaou, K. C.; Edmonds, D. J.; Li, A.; Tria, G. S. Angew.
Chem. 2007, 119, 4016.
(8) (a) Quideau, S.; Looney, M. A.; Pouységu, L. Org. Lett.
1999, 1, 1651. (b) Quideau, S.; Pouységu, L.; Oxoby, M.;
Looney, M. A. Tetrahedron 2001, 57, 319.
Acknowledgment
Acknowledgment is made to the Donors of the American Chemical
Society Petroleum Research Fund (ACS PRF) for support of this
research. We are also very grateful to the Natural Sciences and
Engineering Research Council of Canada (NSERC) and to the pro-
vincial government of Quebec (FQRNT).
(9) (a) Canesi, S.; Bouchu, D.; Ciufolini, M. A. Angew. Chem.
Int. Ed. 2004, 43, 4336. (b) Imbos, R.; Minnaard, A. J.;
Feringa, B. L. J. Am. Chem. Soc. 2002, 124, 184.
(c) Hayashi, Y.; Gotoh, H.; Tamura, T.; Yamaguchi, H.;
Masui, R.; Shoji, M. J. Am. Chem. Soc. 2005, 127, 16028.
(d) Liu, Q.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 2552.
(e) Vo, N. T.; Pace, R. D. M.; O’Hara, F.; Gaunt, M. J. J. Am.
Chem. Soc. 2008, 130, 404.
References and Notes
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Wang, M.; Wang, B.; Zhang, S. Y. Org. Lett. 2004, 6, 4691.
(11) Nicolaou, K. C.; Scott Tria, G.; Edmonds, D. J. Angew.
Chem. Int. Ed. 2008, 47, 1780.
(12) Bérard, D.; Racicot, L.; Sabot, C.; Canesi, S. Synlett 2008,
1076.
(13) Ozanne-Beaudenon, A.; Quideau, S. Angew. Chem. Int. Ed.
(1) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 1295.
(2) (a) Tamura, Y.; Yakura, T.; Haruta, J.; Kita, Y. J. Org.
Chem. 1987, 52, 3927. (b) Kita, Y.; Tohma, H.; Hatanaka,
K.; Takada, T.; Fujita, S.; Mitoh, S.; Sakurai, H.; Oka, S.
J. Am. Chem. Soc. 1994, 116, 3684. (c) Kita, Y.; Takada, T.;
Gyoten, M.; Tohma, H.; Zenk, M. H.; Eichhorn, J. J. Org.
Chem. 1996, 61, 5854. (d) Kita, Y.; Gyoten, M.; Ohtsubo,
M.; Tohma, H.; Takada, T. Chem. Commun. 1996, 1481.
(e) Takada, T.; Arisawa, M.; Gyoten, M.; Hamada, R.;
Tohma, H.; Kita, Y. J. Org. Chem. 1998, 63, 7698.
(f) Arisawa, M.; Utsumi, S.; Nakajima, M.; Ramesh, N. G.;
Tohma, H.; Kita, Y. Chem. Commun. 1999, 469. (g) Akai,
S.; Kawashita, N.; Morita, N.; Nakamura, Y.; Iio, K.; Kita,
Y. Heterocycles 2002, 58, 75. (h) Dohi, T.; Maruyama, A.;
Takenaga, N.; Senami, K.; Minamitsuji, Y.; Fujioka, H.;
Caemmerer, S. B.; Kita, Y. Angew. Chem. Int. Ed. 2008, 47,
3787.
2005, 44, 7065.
(14) Analytical Data
IR: ca. 1645 (CO) cm–1.
Compound 13b: 1H NMR (300 MHz, CDCl3): d = 6.33 (s,
2 H), 5.43 (m, 1 H), 4.92 (m, 2 H), 2.23 (d, 2 H, J = 7.8 Hz),
1.53 (m, 2 H), 1.19 (m, 22 H), 0.99 (m, 2 H), 0.80 (t, 3 H,
J = 6.6 Hz). 13C NMR (150 MHz, CDCl3): d = 187.3, 148.2,
145.7, 133.5, 118.1, 45.3, 44.1, 40.1, 35.1, 32.4, 29.9, 24.3,
22.7, 14.2. ESI-HRMS: m/z calcd for C22H36ONa [M + Na]+:
339.2658; found: 339.2662.
(3) (a) Moreno, I.; Tellitu, I.; SanMartín, R.; Domínguez, E.
Synlett 2001, 1161. (b) Tohma, H.; Iwata, M.; Maegawa, T.;
Kita, Y. Tetrahedron Lett. 2002, 43, 9241. (c) Akai, S.;
Kawashita, N.; Morita, N.; Nakamura, Y.; Iio, K.; Kita, Y.
Heterocycles 2002, 58, 75. (d) Tohma, H.; Iwata, M.;
Maegawa, T.; Kiyono, Y.; Maruyama, A.; Kita, Y. Org.
Compound 13c: 1H NMR (300 MHz, CDCl3): d = 6.39 (s,
2 H), 5.43 (m, 1 H), 4.93 (m, 2 H), 2.32 (d, 2 H, J = 7.5 Hz),
1.83 (h, 1 H, J = 6.6 Hz), 1.21 (s, 18 H), 0.84 (d, 6 H, J = 6.6
Hz). 13C NMR (150 MHz, CDCl3): d = 187.4, 148.8, 144.3,
133.8, 117.8, 46.4, 42.4, 36.3, 35.3, 29.9, 18.2. ESI-HRMS:
Synlett 2008, No. 20, 3226–3230 © Thieme Stuttgart · New York

3230
C. Sabot et al.
LETTER
m/z calcd for C20H33O [M + H]+: 289.2525; found: 289.2529.
Compound 13d: 1H NMR (300 MHz, CDCl3): d = 6.44 (s,
2 H), 5.48 (m, 1 H), 4.97 (m, 2 H), 3.42 (t, 2 H, J = 7.2 Hz),
2.30 (d, 2 H, J = 7.8 Hz), 1.92 (t, 2 H, J = 7.2 Hz), 1.27 (s,
18 H). 13C NMR (150 MHz, CDCl3): d = 186.9, 148.4, 145.0,
132.7, 118.8, 60.0, 45.4, 42.9, 42.8, 35.2, 29.8 ESI-HRMS:
m/z calcd for C19H30O2Na [M + Na]+: 313.2138; found:
313.2138.
145.4, 133.8, 132.5, 119.5, 45.3, 42.9, 35.3, 29.5, 25.6. ESI-
HRMS: m/z calcd for C14H20ClO [M + H]+: 239.1197; found:
239.1185.
Compound 21b: 1H NMR (300 MHz, CDCl3): d = 7.18 (d,
1 H, J = 3.0 Hz), 6.56 (d, 1 H, J = 3.0 Hz), 5.53 (m, 1 H), 5.04
(m, 2 H), 2.33 (d, 2 H, J = 6.9 Hz), 1.27 (s, 3 H), 1.22 (s,
9 H). 13C NMR (150 MHz, CDCl3): d = 178.9, 153.6, 149.0,
145.1, 132.5, 126.4, 119.5, 45.1, 44.4, 35.4, 29.5, 25.5. ESI-
HRMS: m/z calcd for C14H20BrO [M + H]+: 283.0692;
found: 283.0688.
Compound 13e: 1H NMR (300 MHz, CDCl3): d = 6.50 (s,
2 H), 5.49 (m, 1 H), 4.97 (m, 2 H), 3.48 (s, 2 H), 2.35 (d,
2 H, J = 7.2 Hz), 1.22 (s, 18 H), 0.88 (s, 9 H), 0.03 (s, 6 H).
13C NMR (150 MHz, CDCl3): d = 187.2, 148.8, 143.0, 133.4,
118.3, 69.1, 45.7, 40.5, 35.2, 29.9, 26.1, 18.5, –5,1. ESI-
HRMS: m/z calcd for C24H43O2Si [M + H]+: 391.3026;
found: 391.3008.
Compound 21c: 1H NMR (300 MHz, CDCl3): d = 7.50 (d,
1 H, J = 2.7 Hz), 6.57 (d, 1 H, J = 2.7 Hz), 5.54 (m, 1 H), 5.04
(m, 2 H), 2.32 (d, 1 H, J = 6.9 Hz), 2.29 (d, 1 H, J = 7.8 Hz),
1.27 (s, 3 H), 1.21 (s, 9 H). 13C NMR (150 MHz, CDCl3):
d = 179.6, 161.9, 149.3, 143.8, 132.5, 119.5, 107.6, 46.1,
45.0, 35.5, 29.5, 25.3. ESI-HRMS: m/z calcd for C14H20IO
[M + H]+: 331.0553; found: 331.0549.
Compound 13f: 1H NMR (300 MHz, CDCl3): d = 7.56 (d,
2 H, J = 7.5 Hz), 7.20 (d, 2 H, J = 7.5 Hz), 6.25 (s, 2 H), 5.35
(m, 1 H), 4.87 (m, 2 H), 4.29 (m, 1 H), 2.55 (q, 2 H, J = 6.6
Hz), 2.32 (s, 3 H), 2.17 (d, 2 H, J = 7.5 Hz), 1.79 (t, 2 H, J =
6.6 Hz), 1.10 (s, 18 H). 13C NMR (150 MHz, CDCl3): d =
186.5, 149.1, 144.2, 144.0, 136.6, 132.3, 130.1, 127.3,
119.0, 45.3, 43.1, 40.1, 39.7, 35.2, 29.8, 21.8. ESI-HRMS:
m/z calcd for C26H37NO3SNa [M + Na]+: 466.2386; found:
466.2378.
Compound 21d: 1H NMR (300 MHz, CDCl3): d = 7.16 (d,
1 H, J = 2.7 Hz), 6.55 (1 H, d, J = 2.7 Hz), 5.47 (m, 1 H), 5.01
(m, 2 H), 2.40 (m, 2 H), 1.93 (hept, 1 H, J = 6.6 Hz), 0.93 (d,
3 H, J = 6.6 Hz), 0.89 (d, 3 H, J = 6.6 Hz). 13C NMR (150
MHz, CDCl3): d = 179.3, 151.8, 147.4, 147.1, 132.6, 127.6,
119.1, 51.4, 41.8; 36.2, 35.7, 29.6, 18.4, 18.2. ESI-HRMS:
m/z calcd for C16H23BrO2Na [M + Na]+: 333.0824; found:
333.0822.
Compound 13g: 1H NMR (300 MHz, CDCl3): d = 6.49 (s,
2 H), 5.50 (m, 1 H), 4.01 (m, 2 H), 3.54 (s, 3 H), 2.54 (s, 2
H), 2.35 (d, 2 H, J = 7.2 Hz), 1.21 (s, 18 H). 13C NMR (150
MHz, CDCl3): d = 186.7, 170.7, 148.1, 143.4, 132.5, 119.3,
51.7, 44.6, 44.3, 42.0, 35.2, 29.8. ESI-HRMS: m/z calcd for
C20H31O3 [M + H]+: 319.2267; found: 319.2267.
Compound 21e: 1H NMR (300 MHz, CDCl3): d = 7.21 (d,
1 H, J = 3.0 Hz), 6.89 (d, 1 H, J = 3.0 Hz), 5.55 (m, 1 H), 5.05
(m, 2 H), 2.33 (d, 2 H, J = 7.2 Hz), 1.27 (s, 3 H), 0.18 (s,
9 H). 13C NMR (150 MHz, CDCl3): d = 181.7, 162.9, 154.9,
139.6, 132.3, 125.4, 119.6, 46.0, 44.7, 25.0, –1.1. ESI-
HRMS: m/z calcd for C13H19BrOSiNa [M + Na]+: 321.0280;
found: 321.0278.
(15) Clemo, G. R.; Haworth, R. D.; Walton, E. J. Chem. Soc.
1930, 1110.
(16) Thadani, A. N.; Huang, Y.; Rawal, V. H. Org. Lett. 2007, 9,
3873.
Compound 21f: 1H NMR (300 MHz, CDCl3): d = 7.16 (d,
1 H, J = 2.7 Hz), 6.84 (d, 1 H, J = 2.7 Hz), 5.53 (m, 1 H), 5.03
(m, 2 H), 2.35 (d, 2 H, J = 7.2 Hz), 1.65 (t, 2 H, J = 9.0 Hz),
1.25 (m, 2 H), 1.10 (m, 2 H), 0.85 (t, 3 H, J = 7.2 Hz), 0.19
(s, 9 H). 13C NMR (150 MHz, CDCl3): d = 182.1, 162.4,
154.3, 141.3, 132.2, 126.1, 119.4, 50.4, 44.1, 38.9, 27.2,
23.3, 14.1, –1.1. ESI-HRMS: m/z calcd for C16H25BrOSiNa
[M + Na]+: 363.0750; found: 363.0752.
(17) Analytical Data
Compound 17a: 1H NMR (300 MHz, CDCl3): d = 6.86 (s,
2 H), 5.52 (m, 1 H), 4.99 (m, 2 H), 2.26 (d, 2 H, J = 7.2 Hz),
1.20 (s, 3 H), 0.16 (s, 18 H). 13C NMR (150 MHz, CDCl3):
d = 192.0, 162.4, 140.7, 133.3, 118.6, 45.2, 41.4, 25.5, –0.9.
ESI-HRMS: m/z calcd for C16H29OSi2 [M + H]+: 293.1751;
found: 293.1753.
(19) Fleming, I.; Roessler, F. J. Chem. Soc., Chem. Commun.
1980, 276.
(20) Analytical Data
Compound 17b: 1H NMR (300 MHz, CDCl3): d = 6.77 (s,
2 H), 5.51 (m, 1 H), 4.99 (dd, 1 H, J = 8.7, 1.2 Hz), 4.96 (dd,
1 H, J = 18.0, 1.2 Hz), 2.29 (d, 2 H, J = 7.2 Hz), 1.63 (q,
2 H, J = 7.8 Hz), 0.68 (t, 3 H, J = 7.8 Hz), 0.16 (s, 18 H).
13C NMR (150 MHz, CDCl3): d = 192.4, 161.3, 143.0, 133.3,
118.3, 46.1, 44.3, 32.1, 9.3, –0.8. ESI-HRMS: m/z calcd for
C17H31OSi2 [M + H]+: 307.1908; found: 307.1909.
Compound 17c: 1H NMR (300 MHz, CDCl3): d = 7.30 (m,
5 H), 7.00 (s, 2 H), 5.56 (m, 1 H), 5.05 (m, 2 H), 2.80 (d,
2 H, J = 7.2 Hz), 0.18 (18 H). 13C NMR (150 MHz, CDCl3):
d = 192.1, 160.7, 141.1, 140.8, 132.9, 129.3, 127.6, 127.0,
119.0, 48.6, 42.3, –0.9. ESI-HRMS: m/z calcd for
C21H31OSi2 [M + H]+: 355.1908; found: 355.1914.
Compound 17d: 1H NMR (300 MHz, CDCl3): d = 6.86 (s,
2 H), 5.47 (m, 1 H), 4.98 (m, 2 H), 3.42 (t, 2 H, J = 6.9 Hz),
2.29 (d, 2 H, J = 7.2 Hz), 1.92 (t, 2 H, J = 6.9 Hz), 0.14 (s,
18 H). 13C NMR (150 MHz, CDCl3): d = 192.1, 160.9, 142.7,
132.5, 119.1, 60.0, 44.7, 44.4, 42.0, –0.9. ESI-HRMS: m/z
calcd for C17H31O2Si2 [M + H]+: 323.1857; found: 323.1853.
(18) Analytical Data
Compound 29a: 1H NMR (300 MHz, CDCl3): d = 6.52 (s,
2 H), 2.33 (d, 2 H, J = 2.3 Hz), 2.03 (t, 1 H, J = 2.3 Hz), 1.28
(s, 3 H), 1.23 (s, 9 H). 13C NMR (150 MHz, CDCl3): d =
186.1, 146.6, 144.7, 79.8, 71.2, 38.5, 34.6, 30.9, 29.4, 25.3.
ESI-HRMS: m/z calcd for C18H27O [M + H]+: 259.2056;
found: 259.2042.
Compound 29h: 1H NMR (300 MHz, CDCl3): d = 6.44 (s,
2 H), 2.34 (d, 2 H, J = 2.3 Hz), 2.00 (t, 1 H, J = 2.3 Hz), 1,68
(t, 2 H, J = 8.2 Hz), 1.23 (s + q, 20 H, J = 8.2 Hz), 1.00 (sext,
2 H, J = 8.2 Hz), 0.84 (t, 3 H, J = 8.2 Hz). 13C NMR (150
MHz, CDCl3): d = 186.5, 148.1, 143.8, 79.7, 71.1, 42.3,
38.3, 34.8, 30.2, 29.4, 26.5, 22.9, 13.8. ESI-HRMS: m/z
calcd for C21H33O [M + H]+: 301.2526; found: 301.2533.
Compound 29i: 1H NMR (300 MHz, CDCl3): d = 6.44 (s,
2 H), 5,73 (m, 1 H), 4.96 (d, 1 H, J = 18.7 Hz), 4,93 (d, 1 H,
J = 10.5 Hz), 2.37 (d, 2 H, J =2.3 Hz), 2.03 (t, 1 H, J = 2.3
Hz), 1.81 (t, 2 H, J = 8.2 Hz), 1.43 (t, 2 H, J = 8.2 Hz), 1.24
(s, 18 H). 13C NMR (150 MHz, CDCl3): d = 186.4, 148.5,
143.3, 127.6, 114.8, 79.5, 71.4, 42.2, 37.7, 34.9, 30.4, 29.4,
28.8. ESI-HRMS: m/z calcd for C21H31O [M + H]+:
299.2369; found: 299.2376.
Compound 21a: 1H NMR (300 MHz, CDCl3): d = 6.91 (d,
1 H, J = 2.7 Hz), 6.55 (1 H, d, J = 2.7 Hz), 5.55 (m, 1 H), 5.04
(m, 2 H), 2.34 (d, 2 H, J = 8.1 Hz), 1.27 (s, 3 H), 1.23 (s,
9 H). 13C NMR (150 MHz, CDCl3): d = 179.1, 149.1, 149.0,
Synlett 2008, No. 20, 3226–3230 © Thieme Stuttgart · New York

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