One-pot synthesis of 2,7-dioxabicyclo[2.2.1]heptanes from oxoallylsilanes

Article abstract of DOI:10.1002/ejoc.201101087

A one-pot high-yielding synthesis of silylated 2,7-dioxabicyclo[2.2.1] heptanes from oxoallylsilanes is described. The mechanism of this tandem reaction is a sequential epoxidation of the allylsilane moiety and subsequent intramolecular cyclization. This

Full text of DOI:10.1002/ejoc.201101087

FULL PAPER
DOI: 10.1002/ejoc.201101087
One-Pot Synthesis of 2,7-Dioxabicyclo[2.2.1]heptanes from Oxoallylsilanes
Francisco J. Pulido,*[a] Asunción Barbero,*[a] and Raquel Abad[a]
Keywords: Synthetic methods / Tandem reactions / Fragrance chemistry / Oxygen heterocycles / Bicyclic compounds /
Allylic compounds / Allenes
A one-pot high-yielding synthesis of silylated 2,7-dioxabi-
cyclo[2.2.1]heptanes from oxoallylsilanes is described. The
ing steps: silylcupration of allene (followed by capture of the
intermediate cuprate with enones) and treatment of the oxo-
mechanism of this tandem reaction is a sequential epoxid- allylsilanes thus obtained with MCPBA. However, under the
ation of the allylsilane moiety and subsequent intramolecular
cyclization. This simple protocol allows the synthesis of ep-
oxy-bridged tetrahydropyrans from allene in two high-yield-
same conditions, oxovinylsilanes yielded epoxysilyl ketones
in a very stereoselective manner.
Various approaches have been reported for the synthesis
of these bicyclic acetals, such as the 1,3-dipolar cycload-
dition between cyclic carbonyl ylide dipoles and aldehyde
dipolarophiles recently described by Muthusamy et al.,[12]
the synthesis of an intermediate ketodiol which then un-
dergoes cyclization under acid-catalysed conditions[13] or
the catalytic hydrogenation of a 1,2,4-trioxane frame-
work.[14]
The challenge in the synthesis of epoxy-bridged tetra-
hydropyrans lies in the appropriate arrangement of func-
tional groups in the molecule and in the stereoselectivity of
the cyclization process.
On the other hand, the use of organosilicon compounds
as valuable intermediates in the synthesis of natural prod-
ucts has grown considerably in the last few decades.[15] The
synthesis of dihydro- and tetrahydropyrans, as well as spi-
roketals, by a silyl-modified Sakurai reaction has also been
reported.[16,17] In this context, our research group has been
involved in the study of new methodologies for the synthesis
of mono- and polycyclic natural-product-like scaffolds
starting from oxoallylsilanes (Scheme 2).[18,19]
Introduction
The presence of tetrahydrofuran or -pyran skeletons in
an increasing number of natural products has prompted nu-
merous research groups to explore new synthetic methods
for the construction of these substituted ethers.[1] A rather
special example is the epoxy-bridged oxepane unit, which
has been found in a growing number of naturally existing
bioactive products, such as frontalin,[2] exo-brevicomin,[3]
zaragozic acid[4] and amberketal,[5] and play an important
role in the communication system of several insects.
Their epoxy-bridged tetrahydropyran homologues are
not so abundant, but are present in the structures of some
polycyclic bioactive compounds that exhibit medicinal, an-
tifungal or odorant properties, such as loukacinol B,[6]
xanthane epoxide,[7] chuktabularins A–D,[8] leptocladolide
C,[9] isogosterone[10] or Riesling acetal[11] (Scheme 1).
Scheme 1. Polycyclic bioactive acetals.
[a] Department of Organic Chemistry, University of Valladolid,
c/ Dr. Mergelina s/n, 47011 Valladolid, Spain
Fax: +34-983-423013
Scheme 2. Synthesis of mono- and polycarbocycles from oxoallyl-
silanes.
E-mail: pulido@qo.uva.es
barbero@qo.uva.es
6974
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6974–6979

Synthesis of 2,7-Dioxabicyclo[2.2.1]heptanes
These oxoallylsilane intermediates have been synthesized Table 1. Synthesis of silylated 2,7-dioxabicyclo[2.2.1]heptanes.[a]
through an efficient syn addition of a silylcopper reagent
to an allene (a particular example of the general metallo-
metallation of multiple bonds). The regiochemistry of the
reaction is dependent on various factors, such as the sub-
stituents on the silyl group, the nature of the cuprate (higher
R1
R2
R3
Ratio[b] 4/5
Yield [%]
order vs. lower order) and the temperature. Thus, when the
reaction is carried out using the lower order (phenyldi-
methylsilyl)copper reagent 1 at –40 °C, it involves the re-
gioselective addition of copper to the central carbon of the
allene and silicon to the terminal carbon of the system. The
intermediate vinylcopper-allylsilane 2 thus obtained is reac-
tive towards a great number of electrophiles. Note, the use
of α,β-unsaturated carbonyl compounds to capture 2 is an
efficient and high-yielding protocol for the synthesis of
oxoallylsilanes 3 (Scheme 3).
a
b
c
d
e
f
Me
Et
Me
Me
Me
Me
Ph
H
H
H
H
Me
H
H
H
95
92
91
86
84
78
72
81
Me
iPr
Bu
Ph
Ph
Me
75:25
67:33
57:44
50:50
60:40
g
h
H
H
Et
[a] The reactions were carried out by using 2 equiv. of commercial
MCPBA (from Aldrich, 77%) and 2 equiv. of NaHCO3 at 0 °C for
2 h. [b] The ratios of the diastereoisomers 4 and 5 were determined
by integration of the signals in the 1H NMR spectra of the reaction
mixtures.
Scheme 3. Synthesis of oxoallylsilanes.
In this paper we report the one-pot synthesis of epoxy-
bridged tetrahydropyrans starting from oxoallylsilanes, pre-
pared from allene and the silylcopper reagent 1. Thus, the
methodology described herein allows the synthesis of 2,7-
dioxabicyclo[2.2.1]heptanes in two high-yielding steps from
allene.
Scheme 4. Mechanism of the tandem reaction.
The stereoselectivity of the process is not particularly
high, although it always favours the endo isomer, despite
being less stable than the corresponding exo isomer. This
fact seems to indicate that the epoxidation step is not very
stereoselective leading to a mixture of both diastereoiso-
mers, the major one corresponding to epoxidation on the
face opposite the hindered R2 group (Scheme 5).
Results and Discussion
Initially, we proceeded to synthesize the oxoallylsilanes
3a–h by silylcupration of allene using the lower order sil-
ylcopper reagent 1, as described previously.[18a,20]
Treatment of the oxoallylsilanes 3a–h (1 equiv.) with
MCPBA (2 equiv.) in the presence of NaHCO3 (2 equiv.)
for 2 h at 0 °C led to epoxy-bridged tetrahydropyrans 4a–
h and 5d–h in excellent yields (Table 1). Screening of the
conditions for this reaction revealed that a reaction tem-
perature of –40 °C resulted in a very low conversion of the
starting material whereas at room temperature the desired
dioxabicycloheptanes were obtained as a complex mixture
with other byproducts.
Scheme 5. Stereoselective outcome of the reaction.
A plausible mechanism for this tandem reaction is a se-
quential epoxidation of the allylic double bond leading to
With these results in hand we decided to explore the reac-
an epoxyallylsilyl ketone intermediate, which, under acid tion of the corresponding oxovinylsilanes with MCPBA,
catalysis conditions, undergoes cyclization to give an inter- obtained by syn addition of the silylcuprate 1 to acetylene
mediate cyclic oxocarbenium ion, which affords the cyclic and capture of the intermediate cuprate-vinylsilane 6 with
acetal 4 by intramolecular trapping with the internal pri- α,β-unsaturated ketones. The results of this reaction are
[21]
mary alcohol. All attempts to isolate the intermediate ep- shown in Table 2. Again, the use of BF3·OEt2
or
oxyallylsilyl ketone were unsuccessful, which suggests that TMSCl[22] as activating agent was essential to afford high
the acid-catalysed cyclization step is very fast (Scheme 4). yields of the vinylsilyl ketones 7a–f.
Eur. J. Org. Chem. 2011, 6974–6979
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6975

F. J. Pulido, A. Barbero, R. Abad
FULL PAPER
Table 2. Synthesis of oxovinylsilanes 7a–f.
Jamison and co-workers[26] have reported that the regioch-
emical outcome of the cyclization of poly(α,β-silyl epoxides)
is dependent on the nature of the catalyst used and the
number of silyl epoxide units on the substrate.
Conclusions
We have developed a strategy for the synthesis of si-
lylated 2,7-dioxabicyclo[2.2.1]heptanes in two high-yielding
steps from allene. The second step is a tandem reaction in-
volving epoxidation and subsequent acid-catalysed cycliza-
tion. On the other hand, the reactions of vinylsilyl ketones
with MCPBA lead to silylated epoxy ketones in a very
stereoselective manner.
R1
R2
R3
Activating agent
Yield [%]
a
b
c
d
e
f
Me
Et
Me
Me
Me
Ph
H
H
iPr
Bu
Ph
Ph
H
H
H
H
H
H
TMSCl
TMSCl
BF3·OEt2
BF3·OEt2
BF3·OEt2
BF3·OEt2
87
85
80
82
91
78
Experimental Section
General Information: All reactions were carried out in flame-dried
glassware under nitrogen. Tetrahydrofuran was distilled from so-
dium benzophenone. MCPBA was purchased from Aldrich (77%
MCPBA, 33% MCBA and water) and used without further purifi-
cation. All compounds were obtained as colourless compounds. 1H
and 13C NMR spectra were recorded at 300 and 75 MHz, respec-
tively. Signals were assigned with the aid of the DEPT technique
and 2D COSY spectra. The stereochemistries of the compounds
were assigned on the basis of COSY and NOESY experiments.
The reactions of the vinylsilyl ketones 7a–f (1 equiv.) with
MCPBA (2 equiv.) in the presence of NaHCO3 (2 equiv.) at
0 °C for 2 h led to silylepoxy ketones 8a–f in high yields
(Table 3). Moreover, the stereoselectivity of the epoxidation
step is very high, with just one single diastereomer obtained
or a very major one, which may be attributed to the fact
that the silyl and the R2 group probably block one of the
faces of the double bond in the transition step. No trace of
the corresponding dioxabicyclo[2.2.1]heptanes were de-
Synthesis of Oxoallylsilanes and Oxovinylsilanes: A solution of
PhMe2SiLi (6 mmol) was added to a stirred suspension of CuCN
(6 mmol) in dry THF (10 mL) under nitrogen and the mixture was
stirred for 30 min at 0 °C. The solution was then cooled to –40 °C
and a slight excess of allene or acetylene gas was added from a
1
tected by H NMR analysis of the reaction mixtures. The
ring-opening of α,β-silyl epoxides by a nucleophile usually
proceeds by α attack of the carbon supporting the silyl
group.[23] This fact is in sharp contrast to the expected β balloon and stirred for an additional hour. BF3·OEt2 (6 mmol) or
TMSCl (6 mmol) was then added and, after stirring for 5 min at
–40 °C, the α,β-unsaturated carbonyl compound (7 mmol) was
added dropwise. The resulting mixture was kept at –40 °C for 1 h,
warmed to 0 °C, quenched with saturated ammonium chloride
solution (15 mL) and extracted with diethyl ether (3ϫ15 mL). The
organic layer was dried with MgSO4 and the solvent removed by
rotary evaporation. Purification by flash chromatography gave the
oxoallylsilanes 3a–h[18a,20] and the oxovinylsilanes 7a–f.
(Z)-6-Phenyldimethylsilyl-5-hexen-2-one (7a): Liquid (87%). 1H
NMR (CDCl3, 300 MHz): δ = 7.60–7.57 (m, 2 H), 7.40–7.36 (m, 3
H), 6.40 (dt, J = 14.0, 7.0 Hz, 1 H), 5.72 (d, J = 14.0 Hz, 1 H),
2.38–2.30 (m, 4 H), 2.04 (s, 3 H), 0.43 (s, 6 H) ppm. 13C NMR
(CDCl3, 150 MHz): δ = 208.0 (C), 148.6 (CH), 139.6 (C), 133.9
(CH), 129.1 (CH), 128.5 (CH), 128.0 (CH), 43.2 (CH2), 30.0 (CH3),
cleavage due to the known stabilization of carbocations β
to silicon.[24] Paquette and co-workers[25] reported that the
C–Si and the neighbouring C–O bonds in α,β-silyl epoxides
are not favourably aligned for stabilization of the de-
veloping cation β to silicon. Moreover, in our case, α-open-
ing of the silyl epoxide 8 by the carbonyl group is not
favourable for steric reasons, because the bulky silyl group
partially blocks the rear face of the epoxide, making diffi-
cult the approach of the carbonyl group. Nevertheless, the
effect of the silyl group on the corresponding intramolecu-
lar nucleophilic ring-opening of oxiranes is still uncertain.
Table 3. Reaction of oxovinylsilanes 7 with MCPBA.[a]
28.0 (CH ), –0.8 (CH ) ppm. IR (film): ν = 1718 (C=O), 1613
˜
max
2
3
(C=C), 1548 (arC–C), 1113 (Si–Ph) cm–1. MS (CI): m/z (%) = 233
[M + 1]+, 217 [M – Me]+, 155 [M – Ph]+, 135 [SiMe2Ph]+.
C14H20OSi (232.40): calcd. C 72.36, H 8.67; found C 72.75, H 9.08.
(Z)-7-Phenyldimethylsilyl-6-hepten-3-one (7b): Liquid (85%). 1H
NMR (CDCl3, 300 MHz): δ = 7.58–7.54 (m, 2 H), 7.39–7.34 (m, 3
H), 6.37 (dt, J = 14.0, 7.0 Hz, 1 H), 5.70 (d, J = 14.0 Hz, 1 H),
2.34–2.27 (m, 6 H), 1.01 (t, J = 7.5 Hz, 3 H), 0.41 (s, 6 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 210.7 (C), 148.8 (CH), 139.6
(C), 133.8 (CH), 129.0 (CH), 128.4 (CH), 128.0 (CH), 41.8 (CH2),
R1
R2
R3
Yield [%]
a
b
c
d
e
f
Me
Et
Me
Me
Me
Ph
H
H
iPr
Bu
Ph
Ph
H
H
H
H
H
H
85
81
80
82
80
75
36.0 (CH ), 28.1 (CH ), 7.9 (CH3), –0.8 (CH ) ppm. IR (film): ν
˜
max
2
2
3
= 1718 (C=O), 1602 (C=C), 1551 (arC–C), 1113 (Si–Ph) cm–1. MS
(CI): m/z (%) = 247 [M + 1]+, 231 [M – Me]+, 217 [M – Et]+, 169
[M – Ph]+, 135 [SiMe2Ph]+. C15H22OSi (246.42): calcd. C 73.11, H
9.00; found C 73.49, H 9.38.
[a] The reactions were carried out by using 2 equiv. of commercial
MCPBA (from Aldrich, 77%) and 2 equiv. of NaHCO3 at 0 °C for
2 h.
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Eur. J. Org. Chem. 2011, 6974–6979

Synthesis of 2,7-Dioxabicyclo[2.2.1]heptanes
(Z)-4-Isopropyl-6-phenyldimethylsilyl-5-hexen-2-one (7c): Liquid
1-Methyl-4-phenyldimethylsilylmethyl-2,7-dioxabicyclo[2.2.1]-
(80%). 1H NMR (CDCl3, 300 MHz): δ = 7.60–7.57 (m, 2 H), 7.37– heptane (4a): Liquid (95 %). 1H NMR (CDCl3, 300 MHz): δ =
7.35 (m, 3 H), 6.24 (dd, J = 14.0, 10.5 Hz, 1 H), 5.71 (d, J =
7.55–7.51 (m, 2 H), 7.40–7.35 (m, 3 H), 3.43 (d, J = 6.3 Hz, 1 H),
14.0 Hz, 1 H), 2.60–2.52 (m, 1 H), 2.42 (dd, J = 15.2, 5.9 Hz, 1 H), 3.20 (dd, J = 6.3, 3.2 Hz, 1 H), 1.89 (ddd, J = 11.7, 8.7, 5.1 Hz, 1
2.25 (dd, J = 15.2, 7.5 Hz, 1 H), 1.99 (s, 3 H), 1.58 (sept., J =
6.3 Hz, 1 H), 0.82 (d, J = 6.3 Hz, 3 H), 0.80 (d, J = 6.3 Hz, 3 H),
0.45 (s, 6 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 208.3 (C),
151.1 (CH), 139.8 (C), 134.0 (CH), 129.0 (CH), 128.7 (CH), 127.9
H), 1.77–1.69 (m, 3 H), 1.58 (s, 3 H), 1.55 (s, 2 H), 0.39 (s, 3 H),
0.38 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 138.3 (C),
134.2 (CH), 129.2 (CH), 127.8 (CH), 107.0 (C), 86.7 (C), 75.5
(CH2), 37.8 (CH2), 35.1 (CH2), 21.2 (CH2), 18.6 (CH3), –1.7 (CH3),
(CH), 46.5 (CH2), 44.6 (CH), 31.8 (CH), 30.7 (CH3), 20.0 (CH3), –1.6 (CH ) ppm. IR (film): ν
= 1548 (arC–C), 1252 (Si–CH3),
˜
3
max
19.2 (CH ), –0.6 (CH ), –0.8 (CH ) ppm. IR (film): ν = 1714
˜
max
1110 (Si–Ph) cm–1. MS (CI): m/z = 263 [M + 1]+, 262 [M]+, 247
3
3
3
(C=O), 1606 (C=C), 1106 (Si–Ph) cm–1. MS (CI): m/z (%) = 275 [M – Me]+, 185 [M – Ph]+, 135 [PhMe2Si]+. C15H22O2Si (262.42):
[M + 1]+, 259 [M – Me]+, 197 [M – Ph]+, 139 [M – PhMe2Si]+, 135
[SiMe2Ph]+. C17H26OSi (274.48): calcd. C 74.39, H 9.55; found C
74.78, H 9.93.
calcd. C 68.65, H 8.45; found C 69.06, H 8.84.
1-Ethyl-4-phenyldimethylsilylmethyl-2,7-dioxabicyclo[2.2.1]heptane
(4b): Liquid (92%). 1H NMR (CDCl3, 300 MHz): δ = 7.56–7.53
(m, 2 H), 7.40–7.36 (m, 3 H), 3.46 (d, J = 6.4 Hz, 1 H), 3.20 (dd,
(Z)-4-Butyl-6-phenyldimethylsilyl-5-hexen-2-one (7d): Liquid (82%).
1H NMR (CDCl3, 300 MHz): δ = 7.58–7.55 (m, 2 H), 7.36–7.34 J = 6.4, 3.1 Hz, 1 H), 1.91 (q, J = 7.5 Hz, 2 H), 1.89–1.68 (m, 3
(m, 3 H), 6.11 (dd, J = 14.0, 10.1 Hz, 1 H), 5.66 (d, J = 14.0 Hz,
1 H), 2.62–2.54 (m, 1 H), 2.30 (dd, J = 15.4, 7.4 Hz, 1 H), 2.20
(dd, J = 15.4, 5.9 Hz, 1 H), 1.94 (s, 3 H), 1.33–1.09 (m, 6 H), 0.83
(t, J = 6.5 Hz, 3 H), 0.43 (s, 3 H), 0.41 (s, 3 H) ppm. 13C NMR
(CDCl3, 150 MHz): δ = 208.0 (C), 153.4 (CH), 139.7 (C), 134.0
H), 1.59–1.49 (m, 1 H), 1.55 (s, 2 H), 1.04 (t, J = 7.5 Hz, 3 H), 0.40
(s, 3 H), 0.39 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 138.6
(C), 133.7 (CH), 129.4 (CH), 128.1 (CH), 109.8 (C), 86.6 (C), 75.7
(CH2), 35.8 (CH2), 35.1 (CH2), 25.8 (CH2), 21.2 (CH2), 8.6 (CH3),
–1.4 (CH ), –1.5 (CH ) ppm. IR (film): νmax = 1548 (arC–C), 1255
˜
3
3
(CH), 129.1 (CH), 128.0 (CH), 127.6 (CH), 49.4 (CH2), 39.5 (CH), (Si–CH3), 1113 (Si–Ph) cm–1. MS (CI): m/z = 277 [M + 1]+, 261
34.8 (CH2), 30.5 (CH3), 29.6 (CH2), 23.0 (CH2), 14.1 (CH3), –0.7
(CH3), –0.9 (CH3) ppm. MS (CI): m/z (%) = 289 [M + 1]+, 273
[M – Me]+, 231 [M – Bu]+, 211 [M – Ph]+, 153 [M – PhMe2Si]+,
135 [SiMe2Ph]+. C18H28OSi (288.50): calcd. C 74.94, H 9.78; found
C 75.36, H 10.15.
[M – Me]+, 199 [M – Ph]+, 135 [SiMe2Ph]+. C16H24O2Si (276.45):
calcd. C 69.51, H 8.75; found C 69.94, H 9.16.
1,3,3-Trimethyl-4-phenyldimethylsilylmethyl-6,7-dioxabicyclo-
1
[2.2.1]heptane (4c): Liquid (91%). H NMR (CDCl3, 300 MHz): δ
= 7.60–7.55 (m, 2 H), 7.39–7.36 (m, 3 H), 3.86 (d, J = 7.0 Hz, 1
H), 3.27 (d, J = 7.0 Hz, 1 H), 1.76 (d, J = 12.1 Hz, 1 H), 1.54 (s, 3
(Z)-4-Phenyl-6-phenyldimethylsilyl-5-hexen-2-one
(7e):
Liquid
(91%). 1H NMR (CDCl3, 300 MHz): δ = 7.61–7.58 (m, 2 H), 7.39– H), 1.53 (d, J = 12.1 Hz, 1 H), 1.36 (d, J = 14.9 Hz, 1 H), 1.06 (s,
7.37 (m, 3 H), 7.28–7.18 (m, 3 H), 7.04–7.02 (m, 2 H), 6.51 (dd, J
= 13.6, 10.5 Hz, 1 H), 5.72 (d, J = 13.6 Hz, 1 H), 3.95 (ddd, J =
10.5, 8.8, 6.1 Hz, 1 H), 2.81 (dd, J = 15.8, 8.8 Hz, 1 H), 2.57 (dd,
3 H), 1.03 (d, J = 14.9 Hz, 1 H), 0.99 (s, 3 H), 0.46 (s, 3 H), 0.42
(s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 139.7 (C), 133.5
(CH), 128.9 (CH), 127.7 (CH), 107.6 (C), 90.6 (C), 70.4 (CH2), 52.8
J = 15.8, 6.1 Hz, 1 H), 1.91 (s, 3 H), 0.50 (s, 6 H) ppm. 13C NMR (CH2), 41.8 (C), 27.8 (CH3), 23.4 (CH3), 19.3 (CH3), 13.5 (CH2),
(CDCl3, 150 MHz): δ = 206.6 (C), 151.6 (CH), 143.1 (C), 139.4
–1.1 (CH ), –1.5 (CH ) ppm. IR (film): νmax = 1252 (Si–CH3), 1110
˜
3 3
(C), 134.1 (CH), 129.3 (CH), 128.8 (CH), 128.1 (CH), 127.7 (CH), (Si–Ph) cm–1. MS (CI): m/z = 291 [M + 1]+, 290 [M]+, 289 [M – 1]
127.4 (CH), 126.6 (CH), 50.3 (CH2), 44.9 (CH), 30.5 (CH3), –0.7 +, 275 [M – Me]+, 213 [M – Ph]+, 155 [M – PhMe2Si]+, 135 [Si-
(CH ), –0.9 (CH ) ppm. IR (film): νmax = 1718 (C=O), 1605 (C=C), Me2Ph]+. C17H26O2Si (290.48): calcd. C 70.29, H 9.02; found C
˜
3
3
1548 (arC–C), 1113 (Si–Ph) cm–1. MS (CI): m/z (%) = 309 69.86, H 9.39.
[M + 1]+, 294 [M – Me]+, 279 [M – 2Me]+, 232 [M – Ph]+, 135
(3S)-3-Isopropyl-1-methyl-4-phenyldimethylsilylmethyl-6,7-dioxa-
[SiMe2Ph]+. C20H24OSi (308.50): calcd. C 77.87, H 7.84; found C
78.29, H 8.22.
bicyclo[2.2.1]heptane (4d): Liquid (65 %). 1H NMR (CDCl3,
300 MHz): δ = 7.57–7.49 (m, 2 H), 7.36–7.26 (m, 3 H), 3.84 (d, J
= 6.6 Hz, 1 H), 3.22 (dd, J = 6.6, 2.4 Hz, 1 H), 1.94–1.84 (m, 2 H),
(Z)-1,3-Diphenyl-5-phenyldimethylsilyl-4-penten-1-one (7f): Liquid
(78%). 1H NMR (CDCl3, 300 MHz): δ = 7.60–7.12 (m, 15 H), 6.68 1.63–1.54 (m, 2 H), 1.53 (s, 3 H), 1.37 (d, J = 15.0 Hz, 1 H), 1.29
(ddd, J = 13.6, 10.5, 1.8 Hz, 1 H), 5.80 (dd, J = 13.6, 2.0 Hz, 1 H),
4.30–4.14 (m, 1 H), 3.47 (dd, J = 16.3, 7.5 Hz, 1 H), 3.18 (dd, J =
16.3, 6.1 Hz, 1 H), 0.49 (s, 3 H), 0.48 (s, 3 H) ppm. 13C NMR
(CDCl3, 150 MHz): δ = 198.0 (C), 151.6 (C), 143.5 (C), 139.4 (C),
137.2 (C), 134.1 (CH), 133.2 (CH), 129.2 (CH), 128.8 (CH), 128.3
(d, J = 15.0 Hz, 1 H), 0.89 (d, J = 6.7 Hz, 3 H), 0.77 (d, J =
6.7 Hz, 3 H), 0.33 (s, 3 H), 0.30 (s, 3 H) ppm. 13C NMR (CDCl3,
150 MHz): δ = 138.4 (C), 133.8 (CH), 129.0 (CH), 127.9 (CH),
107.6 (C), 89.0 (C), 71.1 (CH2), 54.3 (CH), 45.4 (CH2), 27.6 (CH),
23.6 (CH3), 21.4 (CH3), 21.2 (CH2), 19.2 (CH3), –0.7 (CH3), –1.0
(CH), 128.1 (CH), 127.9 (CH), 127.5 (CH), 126.5 (CH), 45.5 (CH2), (CH ) ppm. IR (film): ν
= 1551 (arC–C), 1252 (Si–CH3), 1108
˜
3
max
44.9 (CH), –0.8 (CH ) ppm. IR (film): ν
= 1721 (C=O), 1606 (Si–Ph) cm–1. MS (CI): m/z = 305 [M + 1]+, 304 [M]+, 289 [M –
˜
3
max
(C=C), 1548 (arC–C), 1113 (Si–Ph) cm–1. MS (CI): m/z (%) = 371
[M + 1]+, 355 [M – Me]+, 293 [M – Ph]+, 235 [M – SiMe2Ph]+, 135
[SiMe2Ph]+. C25H26OSi (370.57): calcd. C 81.03, H 7.07; found C
81.44, H 7.36.
Me]+, 227 [M – Ph]+, 169 [M – PhMe2Si]+, 135 [SiMe2Ph]+.
(3R)-3-Isopropyl-1-methyl-4-phenyldimethylsilylmethyl-6,7-dioxa-
bicyclo[2.2.1]heptane (5d): Liquid (21 %). 1H NMR (CDCl3,
300 MHz): δ = 7.57–7.51 (m, 2 H), 7.37–7.35 (m, 3 H), 3.35 (d, J
= 6.3 Hz, 1 H), 3.18 (d, J = 6.3 Hz, 1 H), 1.90–1.82 (m, 2 H), 1.78–
1.69 (m, 1 H), 1.55 (s, 3 H), 1.54–1.49 (m, 1 H), 1.48 (s, 2 H), 0.75
(d, J = 6.7 Hz, 3 H), 0.64 (d, J = 6.7 Hz, 3 H), 0.38 (s, 6 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 138.8 (C), 133.7 (CH), 129.4
(CH), 128.0 (CH), 106.9 (C), 88.3 (C), 76.0 (CH2), 49.1 (CH), 37.4
(CH2), 27.1 (CH), 21.4 (CH3), 18.7 (CH3), 17.4 (CH2), 16.2 (CH3),
Reactions of Oxoallylsilanes or Oxovinylsilanes with MCPBA: A
suspension of oxosilane 3a–h or 7a–f (6 mmol), MCPBA (12 mol)
and NaHCO3 (12 mmol) in dichloromethane (15 mL) was stirred
for 2 h at 0 °C. The reaction mixture was then washed with 5%
NaHCO3 solution, water and brine. The organic layer was dried
with over MgSO4 and the solvent removed by rotary evaporation.
Purification by flash chromatography gave the dioxabicyclohept-
anes 4a–h and 5d–h or epoxysilyl ketones 8a–f.
–1.2 (CH ), –1.3 (CH ) ppm. IR (film): νmax = 1551 (arC–C), 1249
˜
3
3
(Si–CH3), 1113 (Si–Ph) cm–1. MS (CI): m/z = 305 [M + 1]+, 304
Eur. J. Org. Chem. 2011, 6974–6979
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6977

F. J. Pulido, A. Barbero, R. Abad
FULL PAPER
[M]+, 303 [M – 1]+, 289 [M – Me]+, 227 [M – Ph]+, 169 [M –
(C), 140.1 (C), 138.5 (C), 133.9 (CH), 129.3 (CH), 128.9 (CH), 128.6
(CH), 128.4 (CH), 128.3 (CH), 128.0 (CH), 127.9 (CH), 126.0 (CH),
108.2 (C), 90.6 (C), 71.2 (CH2), 53.1 (CH), 44.5 (CH2), 18.1 (CH2),
PhMe2Si]+, 135 [SiMe2Ph]+.
(3R)-3-Butyl-1-methyl-4-phenyldimethylsilylmethyl-6,7-dioxabi-
cyclo[2.2.1]heptane (4e): Liquid (56 %). 1H NMR (CDCl3,
300 MHz): δ = 7.59–7.56 (m, 2 H), 7.38–7.36 (m, 3 H), 3.84 (d, J
= 6.8 Hz, 1 H), 3.22 (dd, J = 6.8, 2.1 Hz, 1 H), 1.90 (dd, J = 12.2,
11.3 Hz, 1 H), 1.89–1.78 (m, 1 H), 1.56 (s, 3 H), 1.45 (dd, J = 12.2,
–0.8 (CH ), –1.0 (CH ) ppm. IR (film): ν = 1548 (arC–C), 1252
˜
max
3
3
( S i – C H 3 ) , 1 1 1 0 ( S i – P h ) c m – 1 . M S ( C I ) : m / z =
399 [M – 1]+, 385 [M – Me]+, 323 [M – Ph]+, 135 [SiMe2Ph]+.
C26H28O2Si (400.59): calcd. C 77.96, H 7.05; found C 78.37, H 7.43.
4.8 Hz, 1 H), 1.30 (s, 2 H), 1.35–1.19 (m, 6 H), 0.86 (t, J = 7.0 Hz, (3R)-1,3-Diphenyl-4-phenyldimethylsilylmethyl-6,7-dioxabicyclo-
1
3 H), 0.44 (s, 3 H), 0.41 (s, 3 H) ppm. 13C NMR (CDCl3,
150 MHz): δ = 139.7 (C), 133.7 (CH), 129.1 (CH), 127.9 (CH),
[2.2.1]heptane (5g): Liquid (36%). H NMR (CDCl3, 300 MHz): δ
= 7.59–7.20 (m, 15 H), 3.76 (d, J = 6.6 Hz, 1 H), 3.54 (d, J =
108.1 (C), 89.1 (C), 71.3 (CH2), 47.2 (CH), 44.0 (CH2), 31.6 (CH2), 6.6 Hz, 1 H), 3.17 (dd, J = 8.4, 4.2 Hz, 1 H), 2.94 (dd, J = 12.7,
30.5 (CH2), 22.0 (CH2), 19.3 (CH3), 18.4 (CH2), 14.2 (CH3), –1.1 8.4 Hz, 1 H), 2.23 (dd, J = 12.7, 4.2 Hz, 1 H), 1.22 (d, J = 15.0 Hz,
(CH ), –1.2 (CH ) ppm. IR (film): ν = 1551 (arC–C), 1252 (Si–
˜
max
1 H), 1.15 (d, J = 15.0 Hz, 1 H), 0.33 (s, 3 H), 0.32 (s, 3 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 144.0 (C), 139.1 (C), 133.7 (C),
134.4 (CH), 129.2 (CH), 128.6 (CH), 128.6 (CH), 128.5 (CH), 128.1
(CH), 127.9 (CH), 126.9 (CH), 126.2 (CH), 108.2 (C), 90.1 (C),
75.6 (CH2), 52.5 (CH), 49.9 (CH2), 17.0 (CH2), –1.0 (CH3), –1.2
3
3
CH3), 1110 (Si–Ph) cm–1. MS (CI): m/z = 319 [M + 1]+, 318 [M]+,
303 [M – Me]+, 261 [M – Bu]+, 241 [M – Ph]+. C19H30O2Si (318.53):
calcd. C 71.64, H 9.49; found C 72.06, H 9.87.
(3S)-3-Butyl-1-methyl-4-phenyldimethylsilylmethyl-6,7-dioxabi-
cyclo[2.2.1]heptane (5e): Liquid (28 %). 1H NMR(CDCl3,
300 MHz): δ = 7.55–7.53 (m, 2 H), 7.38–7.36 (m, 3 H), 3.38 (d, J
= 6.6 Hz, 1 H), 3.24 (d, J = 6.6 Hz, 1 H), 2.07 (dd, J = 12.3, 7.9 Hz,
1 H), 1.65–1.59 (m, 1 H), 1.55 (s, 3 H), 1.46 (d, J = 14.0 Hz, 1 H),
1.42 (d, J = 14.0 Hz, 1 H), 1.31 (dd, J = 12.3, 3.5 Hz, 1 H), 1.29–
(CH ) ppm. IR (film): ν
= 1252 (Si–CH3), 1113 (Si–Ph) cm–1.
max
˜
3
MS (CI): m/z = 401 [M + 1]+, 385 [M – Me]+, 323 [M – Ph]+, 135
[SiMe2Ph]+.
(3R)-1-Ethyl-3-methyl-4-phenyldimethylsilylmethyl-6,7-dioxabi-
cyclo[2.2.1]heptane (4h): Liquid (49 %). 1H NMR (CDCl3,
1.14 (m, 6 H), 0.86 (t, J = 7 Hz, 3 H), 0.39 (s, 3 H), 0.38 (s, 3 300 MHz): δ = 7.58–7.52 (m, 2 H), 7.37–7.34 (m, 3 H), 3.87 (d, J
H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 138.6 (C), 133.7 (CH),
= 6.9 Hz, 1 H), 3.18 (dd, J = 6.9, 1.8 Hz, 1 H), 1.89–1.86 (m, 1 H),
129.5 (CH), 128.0 (CH), 106.9 (C), 88.4 (C), 75.5 (CH2), 44.6 1.85–1.81 (m, 3 H), 1.37–1.35 (m, 1 H), 1.25 (s, 2 H), 1.03–0.99 (m,
(CH2), 44.3 (CH), 32.0 (CH2), 28.7 (CH2), 22.9 (CH2), 19.0 (CH3), 9 H), 0.41 (s, 3 H), 0.39 (s, 3 H) ppm. 13C NMR (CDCl3,
17.8 (CH2), 14.4 (CH3), –1.3 (CH3), –1.4 (CH3) ppm. IR (film): 150 MHz): δ = 139.7 (C), 133.6 (CH), 129.0 (CH), 127.8 (CH),
ν
= 1548 (arC–C), 1249 (Si–CH3), 1113 (Si–Ph) cm–1. MS (CI): 110.6 (C), 89.0 (C), 70.2 (CH2), 43.1 (CH2), 41.2 (CH), 26.1 (CH2),
˜
max
m/z = 319 [M + 1]+, 318 [M]+, 303 [M – Me]+, 261 [M – Bu]+, 241
17.8 (CH2), 14.8 (CH3), 8.4 (CH3), –1.2 (CH3), –1.3 (CH3) ppm.
[M – Ph]+.
(3S)-1-Ethyl-3-methyl-4-phenyldimethylsilylmethyl-6,7-dioxabi-
(3S)-1-Methyl-3-phenyl-4-phenyldimethylsilylmethyl-6,7-dioxabi- cyclo[2.2.1]heptane (5h): Liquid (32 %). 1H NMR (CDCl3,
cyclo[2.2.1]heptane (4f): Liquid (45 %). 1H NMR (CDCl3, 300 MHz): δ = 7.55–7.52 (m, 2 H), 7.39–7.34 (m, 3 H), 3.38 (d, J
300 MHz): δ = 7.40–7.27 (m, 10 H), 3.86 (d, J = 7.0 Hz, 1 H), 3.21
(ddd, J = 11.0, 6.1, 2.2 Hz, 1 H), 3.13 (dd, J = 7.0, 2.2 Hz, 1 H),
2.23 (dd, J = 12.3, 6.1 Hz, 1 H), 2.19 (dd, J = 12.3, 11.0 Hz, 1 H),
1.70 (s, 3 H), 1.40 (d, J = 14.9 Hz, 1 H), 1.12 (d, J = 14.9 Hz, 1
= 6.5 Hz, 1 H), 3.22 (d, J = 6.5 Hz, 1 H), 2.12 (dd, J = 12.1, 8.1 Hz,
1 H), 1.86 (q, J = 7.5 Hz, 2 H), 1.85–1.80 (m, 1 H), 1.48 (d, J =
14.4 Hz, 1 H), 1.41 (d, J = 14.4 Hz, 1 H), 1.22 (dd, J = 12.1, 3.6 Hz,
1 H), 1.01 (t, J = 7.5 Hz, 3 H), 0.85 (d, J = 6.9 Hz, 3 H), 0.39 (s,
H), 0.46 (s, 3 H), 0.45 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): 3 H), 0.38 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 138.6
δ = 139.6 (C), 138.7 (C), 133.8 (CH), 129.1 (CH), 128.8 (CH), 128.4 (C), 133.4 (CH), 129.2 (CH), 127.8 (CH), 109.2 (C), 87.6 (C), 74.8
(CH), 127.9 (CH), 126.9 (CH), 108.8 (C), 90.0 (C), 70.6 (CH2),
53.5 (CH), 43.7 (CH2), 19.2 (CH3), 18.1 (CH2), –0.9 (CH3), –1.1 8.4 (CH ), –1.5 (CH ), –1.6 (CH ) ppm. IR (film): ν
˜
max
(CH2), 44.7 (CH2), 38.2 (CH), 25.6 (CH2), 18.7 (CH3), 17.0 (CH2),
= 1548
3
3
3
(CH ) ppm. IR (film): ν
= 1548 (arC–C), 1249 (Si–CH3), 1113 (arC–C), 1252 (Si–CH3), 1113 (Si–Ph) cm–1. MS (CI): m/z = 291
˜
3
max
(Si–Ph) cm–1. MS (CI): m/z = 339 [M + 1]+, 338 [M]+, 323 [M –
[M + 1]+, 290 [M]+, 289 [M – 1]+, 275 [M – Me]+, 261 [M – Et]+,
213 [M – Ph]+, 155 [M – SiMe2Ph]+, 135 [SiMe2Ph]+. C17H26O2Si
(290.48): calcd. C 70.29, H 9.02; found C 70.71, H 9.35.
Me]+, 261 [M – Ph]+, 135 [SiMe2Ph]+.
(3R)-1-Methyl-3-phenyl-4-phenyldimethylsilylmethyl-6,7-dioxabi-
cyclo[2.2.1]heptane (5f): Liquid (33 %). 1H NMR (CDCl3, (5R,6S)-6-Phenyldimethylsilyl-5,6-epoxy-2-hexanone (8a): Liquid
300 MHz): δ = 7.39–7.15 (m, 10 H), 3.57 (d, J = 6.5 Hz, 1 H), 3.36
(d, J = 6.5 Hz, 1 H), 3.00 (dd, J = 8.8, 4.3 Hz, 1 H), 2.56 (dd, J =
12.7, 8.8 Hz, 1 H), 1.85 (dd, J = 12.7, 4.3 Hz, 1 H), 1.69 (s, 3 H),
(85%). 1H NMR (CDCl3, 300 MHz): δ = 7.57–7.55 (m, 2 H), 7.40–
7.38 (m, 3 H), 3.21–3.10 (m, 1 H), 2.58–2.43 (m, 3 H), 2.09 (s, 3
H), 1.89–1.79 (m, 1 H), 1.58–1.51 (m, 1 H), 0.43 (s, 3 H), 0.41 (s,
1.12 (s, 2 H), 0.27 (s, 3 H), 0.26 (s, 3 H) ppm. 13C NMR (CDCl3, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 207.8 (C), 137.0 (C),
150 MHz): δ = 144.2 (C), 139.1 (C), 133.8 (CH), 129.2 (CH), 128.9
134.0 (CH), 129.7 (CH), 128.2 (CH), 56.9 (CH), 50.8 (CH), 40.7
(CH), 128.5 (CH), 127.9 (CH), 126.7 (CH), 107.2 (C), 89.8 (C), (CH2), 30.0 (CH3), 25.7 (CH2), –2.6 (CH3), –3.2 (CH3) ppm. IR
75.4 (CH2), 52.4 (CH), 49.5 (CH2), 18.8 (CH3), 17.2 (CH2), –1.0 (film): ν
= 1715 (C=O), 1256 (Si–CH3), 1110 (Si–Ph) cm–1. MS
˜
max
(CH ), –1.2 (CH ) ppm. IR (film): ν = 1548 (arC–C), 1252 (Si–
˜
max
(CI): m/z = 249 [M + 1]+, 248 [M]+, 233 [M – Me]+ , 171
[M – Ph]+, 135 [SiMe2Ph]+. C14H20O2Si (248.40): calcd. C 67.70,
H 8.12; found C 68.11, H 8.39.
3
3
CH3), 1116 (Si–Ph) cm–1. MS (CI): m/z = 339 [M + 1]+, 338 [M]+,
323 [M – Me]+, 261 [M – Ph]+, 135 [SiMe2Ph]+. C21H26O2Si
(338.52): calcd. C 74.51, H 7.74; found C 74.94, H 8.12.
(6R,7S)-7-Phenyldimethylsilyl-6,7-epoxy-3-heptanone (8b): Liquid
(81%). 1H NMR (CDCl3, 300 MHz): δ = 7.57–7.53 (m, 2 H), 7.38–
(3S)-1,3-Diphenyl-4-phenyldimethylsilylmethyl-6,7-dioxabicyclo-
1
[2.2.1]heptane (4g): Liquid (36%). H NMR (CDCl3, 300 MHz): δ 7.35 (m, 3 H), 3.12 (td, J = 8.0, 4.9 Hz, 1 H), 2.51–2.48 (m, 1 H),
= 7.57–7.18 (m, 15 H), 4.05 (d, J = 7.0 Hz, 1 H), 3.39–3.19 (m, 2
H), 2.64 (dd, J = 12.3, 5.2 Hz, 1 H), 2.48 (dd, J = 12.3, 11.6 Hz, 1 1 H), 1.60–1.50 (m 1 H), 1.02 (t, J = 7.3 Hz, 3 H), 0.42 (s, 3 H),
H), 1.50 (d, J = 14.9 Hz, 1 H), 1.20 (d, J = 14.9 Hz, 1 H), 0.56 (s,
0.40 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 210.5 (C),
3 H), 0.48 (s, 3 H) ppm. 13C NMR (CDCl3, 150 MHz): δ = 143.1 137.5 (C), 134.0 (CH), 129.7 (CH), 128.2 (CH), 57.0 (CH), 50.8
2.41 (d, J = 4.9 Hz, 1 H), 2.35 (q, J = 7.3 Hz, 2 H), 1.92–1.80 (m,
6978
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 6974–6979

Synthesis of 2,7-Dioxabicyclo[2.2.1]heptanes
(CH), 39.3 (CH2), 36.0 (CH2), 25.8 (CH2), 7.9 (CH3), –2.6 (CH3),
[1]
a) J. P. Wolfe, M. B. Hay, Tetrahedron 2007, 63, 261; b) T. L. B.
Boivin, Tetrahedron 1987, 43, 3309; c) I. I. Larrosa, P. Romea,
F. Urpí, Tetrahedron 2008, 64, 2683.
S. Singh, P. J. Guiry, Tetrahedron 2010, 66, 5701.
R. M. Silverstein, R. G. Brownlee, T. E. Bellas, D. L. Wood,
L. E. Browne, Science 1968, 159, 889.
–3.2 (CH ) ppm. IR (film): νmax = 1718 (C=O), 1545 (arC–C), 1113
˜
3
(Si–Ph) cm–1. MS (CI): m/z = 263 [M + 1]+, 262 [M]+, 261
[M – 1]+, 247 [M – CH3]+, 233 [M – Et]+, 232 [M – 2CH3]+, 185
[M – Ph]+, 135 [PhMe2Si]+, 127 [M – PhMe2Si]+.
[2]
[3]
(4S,5R,6S)-4-Isopropyl-6-phenyldimethylsilyl-5,6-epoxy-2-hexanone
(8c): Liquid (80%). 1H NMR (CDCl3, 300 MHz): δ = 7.69–7.52
(m, 2 H), 7.39–7.37 (m, 3 H), 3.05 (dd, J = 9.6, 4.8 Hz, 1 H), 2.55–
2.36 (m, 3 H), 2.08 (s, 3 H), 1.72–1.58 (m, 2 H), 0.82 (d, J = 6.7 Hz,
3 H), 0.78 (d, J = 6.7 Hz, 3 H), 0.45 (s, 3 H), 0.43 (s, 3 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 208.7 (C), 136.9 (C), 134.2 (CH),
129.7 (CH), 128.1 (CH), 61.2 (CH), 52.9 (CH), 43.9 (CH2), 41.6
(CH), 30.4 (CH3), 30.1 (CH), 20.4 (CH3), 19.2 (CH3), –2.8 (CH3),
[4]
A. Armstrong, T. J. Blench, Tetrahedron 2002, 58, 9321.
[5] a) A. H. Conner, B. A. Nagasampagi, J. W. Rowe, Phytochemis-
try 1980, 19, 1121; b) G. Ohloff, The Fragrance of Ambergris,
in: Fragrance Chemistry: Science of the Sense of Smell (Ed.:
E. T. Theimer), Academic Press, New York, 1982, p. 535.
[6]
A. Loukaci, O. Kayser, K.-U. Bindseil, K. Siems, J. Frevert,
P. M. Abreu, J. Nat. Prod. 2000, 63, 52.
A. A. Mahmoud, Phytochemistry 1997, 45, 1633.
C.-R. Zhang, S.-P. Yang, S.-G. Liao, C.-Q. Fan, Y. Wu, J.-M.
Yue, Org. Lett. 2007, 9, 3383.
[7]
[8]
–3.3 (CH ) ppm. IR (film): νmax = 1721 (C=O), 1548 (arC–C), 1249
˜
3
(Si–CH3), 1113 (Si–Ph) cm–1. MS (CI): m/z = 291 [M + 1]+, 290
[M]+, 289 [M – 1]+, 275 [M – Me]+, 213 [M – Ph]+, 155 [M –
PhMe2Si]+, 135 [SiMe2Ph]+. C17H26O2Si (290.48): calcd. C 70.29,
H 9.02; found C 70.70, H 9.43.
[9]
A. F. Ahmed, R.-T. Shiue, G.-H. Wang, C.-F. Dai, Y.-H. Kuo,
J.-H. She, Tetrahedron 2003, 59, 7337.
[10]
[11]
Y. Tomono, H. Hirota, N. Fusetani, J. Org. Chem. 1999, 64, 2272.
H.-U. Humpf, P. Winterhalter, P. J. Schreier, Agric. Food Chem.
1991, 39, 1833.
S. Muthusamy, S. A. Babu, C. Gunanathan, B. Ganguly, E.
Suresh, P. Dastidar, J. Org. Chem. 2002, 67, 8019.
a) W. Francke, F. Schröder, P. Philipp, H. Meyer, V. Sinnwell,
G. Gries, Bioorg. Med. Chem. 1996, 4, 363; b) Z. Bobcza-Tom-
aszewski, Tetrahedron Lett. 1986, 27, 3767; c) D. Gautam, B. V.
Rao, Tetrahedron Lett. 2010, 51, 4199.
(4R,5R,6S)-4-Butyl-6-phenyldimethylsilyl-5,6-epoxy-2-hexanone
(8d): Liquid (82%). 1H NMR (CDCl3, 300 MHz): δ = 7.60–7.57
(m, 2 H), 7.38–7.36 (m, 3 H), 2.95 (dd, J = 9.2, 4.8 Hz, 1 H), 2.55
(dd, J = 15.8, 5.7 Hz, 1 H), 2.48 (d, J = 4.8 Hz, 1 H), 2.38 (d, J =
15.8, 7.5 Hz, 1 H), 2.05 (s, 3 H), 1.67–1.60 (m, 1 H), 1.27–1.07 (m, 6
H), 0.82 (t, J = 7.0 Hz, 3 H), 0.44 (s, 6 H) ppm. 13C NMR (CDCl3,
150 MHz): δ = 208.3 (C), 136.9 (C), 134.1 (CH), 129.7 (CH), 128.1
(CH), 62.0 (CH), 52.4 (CH), 47.0 (CH2), 36.7 (CH), 32.2 (CH2),
30.4 (CH3), 29.3 (CH2), 23.2 (CH2), 14.1 (CH3), –2.7 (CH3), –3.4
[12]
[13]
[14] M. J. Riveira, A. La-Venia, M. P. Mischne, J. Org. Chem. 2008,
73, 8678.
[15] E. Langkopf, D. Schinzer, Chem. Rev. 1995, 95, 1375.
[16] a) I. E. Marko, A. Mekhalfia, Tetrahedron Lett. 1992, 33, 1799;
b) I. E. Marko, A. Mekhalfia, D. J. Bavston, H. Adams, J. Org.
Chem. 1992, 57, 2211; c) I. E. Marko, M. Bailey, F. Murphy,
J.-P. Declercq, B. Tinant, J. Feneau-Dupont, A. Krief, W. Du-
mont, Synlett 1995, 123.
[17] a) I. E. Marko, D. J. Bayston, Tetrahedron Lett. 1993, 34, 6595;
b) I. E. Marko, D. J. Bayston, Tetrahedron 1994, 50, 7141.
[18] a) A. Barbero, C. García, F. J. Pulido, Tetrahedron 2000, 56,
2739; b) A. Barbero, P. Castreño, F. J. Pulido, J. Am. Chem.
Soc. 2005, 127, 8022; c) A. Barbero, Y. Blanco, F. J. Pulido,
J. Org. Chem. 2005, 70, 6876; d) A. Barbero, P. Castreño, G.
Fernández, F. J. Pulido, J. Org. Chem. 2005, 70, 10747.
[19] a) A. Barbero, F. J. Pulido, Acc. Chem. Res. 2004, 37, 817; b)
A. Barbero, F. J. Pulido, Synthesis 2004, 779.
[20] a) A. Barbero, P. Castreño, F. J. Pulido, Org. Lett. 2003, 5,
4045; b) F. J. Pulido, A. Barbero, P. Castreño, Eur. J. Org.
Chem. 2010, 1307.
[21] a) E. Nakamura, M. Yamanaka, S. Mori, J. Am. Chem. Soc.
2000, 122, 1826; b) K. Maruyama, Y. Yamamoto, J. Am. Chem.
Soc. 1977, 99, 8068.
(CH ) ppm. IR (film): νmax = 1714 (C=O), 1541 (arC–C), 1246 (Si–
˜
3
CH3), 1113 (Si–Ph) cm–1. MS (CI): m/z = 305 [M + 1]+, 304 [M]+,
303 [M – 1]+, 289 [M – Me]+, 247 [M – Bu]+, 227 [M – Ph]+, 135
[SiMe2Ph]+. C18H28O2Si (304.50): calcd. C 71.00, H 9.27; found C
71.39, H 9.65.
(4S,5R,6S)-4-Phenyl-6-phenyldimethylsilyl-5,6-epoxy-2-hexanone
(8e): Liquid (80%). 1H NMR (CDCl3, 300 MHz): δ = 7.50–7.47
(m, 2 H), 7.39–7.30 (m, 3 H), 7.30–7.21 (m, 3 H), 7.12–7.09 (m, 2
H), 3.42 (dd, J = 9.6, 4.8 Hz, 1 H), 2.97–2.82 (m, 3 H), 2.49 (d, J
= 4.8 Hz, 1 H), 1.96 (s, 3 H), 0.39 (s, 3 H), 0.35 (s, 3 H) ppm. 13C
NMR (CDCl3, 150 MHz): δ = 206.8 (C), 140.9 (C), 136.7 (C), 134.3
(CH), 129.8 (CH), 128.8 (CH), 128.1 (CH), 127.9 (CH), 127.2
(CH), 61.5 (CH), 52.6 (CH), 49.2 (CH2), 42.3 (CH), 30.4 (CH3),
–2.8 (CH ), –3.1 (CH ) ppm. IR (film): ν = 1714 (C=O), 1602
˜
max
3
3
(C=C), 1551 (arC–C), 1252 (Si–CH3), 1116 (Si–Ph) cm–1. MS (CI):
m/z = 325 [M + 1]+, 324 [M]+, 309 [M – Me]+, 247 [M – Ph]+, 135
[SiMe2Ph]+. C20H24O2Si (324.49): calcd. C 74.03, H 7.45; found C
74.42, H 7.83.
[22] a) A. Alexakis, J. Berlan, Y. Besace, Tetrahedron Lett. 1986, 27,
1047; b) E. J. Corey, N. W. Boaz, Tetrahedron Lett. 1985, 26,
6015; E. J. Corey, N. W. Boaz, Tetrahedron Lett. 1985, 26, 6019.
[23] Among others, see: a) P. F. Hudrlik, A. M. Hudrlik, in: Ad-
vances in Silicon Chemistry (Ed.: G. L. Larson), JAI Press,
Greenwich, 1993, vol. 2, pp. 1–89; b) P. F. Hudrlik, D. Ma,
R. S. Bhamidipati, A. M. Hudrlik, J. Org. Chem. 1996, 61,
8655; c) P. F. Hudrlik, C.-H. Wan, G. P. Withers, Tetrahedron
Lett. 1976, 17, 1453.
(4S,5R,6S)-1,3-Diphenyl-5-phenyldimethylsilyl-4,5-epoxy-1-
pentanone (8f): Liquid (75%). 1H NMR (CDCl3, 300 MHz): δ =
7.57–7.18 (m, 15 H), 3.60–3.49 (m, 3 H), 3.17 (td, J = 9.2, 4.8 Hz,
1 H), 2.56 (d, J = 4.8 Hz, 1 H), 0.42 (s, 3 H), 0.35 (s, 3 H) ppm.
13C NMR (CDCl3, 150 MHz): δ = 198.0 (C), 141.1 (C), 137.2 (C),
136.7 (C), 134.1 (CH), 133.1 (CH), 129.6 (CH), 128.7 (CH), 128.3
(CH), 128.1 (CH), 127.0 (CH), 61.6 (CH), 52.7 (CH), 44.3 (CH2),
42.6 (CH), –2.9 (CH ), –3.1 (CH ) ppm. IR (film): ν = 1680
˜
max
3
3
[24] Among others, see: a) C. Eaborn, F. Feichtmayr, M. Horn, J. N.
Murrell, J. Organomet. Chem. 1974, 77, 39; b) P. F. Hudrlik, D.
Peterson, Tetrahedron Lett. 1974, 15, 1133.
(C=O), 1548 (arC–C), 1252 (Si–CH3), 1110 (Si–Ph) cm–1. MS (CI):
m/z = 371 [M – Me]+, 309 [M – Ph]+, 135 [SiMe2Ph]+.
[25] W. E. Fristad, T. R. Bailey, L. A. Paquette, R. Gleiter, M. C.
Böhm, J. Am. Chem. Soc. 1979, 101, 4420.
[26] T. P. Heffron, G. L. Simpson, E. Merino, T. F. Jamison, J. Org.
Chem. 2010, 75, 2681.
Acknowledgments
We thank the Ministerio de Educación
(CTQ2009-09302) and the Junta de Castilla y León (GR170 and
VA074A08) for financial support.
y Ciencia (MEC)
Received: July 25, 2011
Published Online: October 11, 2011
Eur. J. Org. Chem. 2011, 6974–6979
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6979