Silicon acceleration of a tandem alkene isomerization/electrocyclic ring-opening of 2-methyleneoxetanes to α,β-unsaturated methylketones

Article abstract of DOI:10.1021/jo4014645

The first rearrangement of 2-methyleneoxetanes to α,β-unsaturated methylketones is reported. It is proposed that when these substrates are heated, the corresponding oxetenes are formed and subsequently undergo electrocyclic ring-opening to methyl vinylketones. In particular, α-silyl-α,β-unsaturated methylketones were isolated in moderate to high yields and with high stereoselectivities. Based on the proposed mechanism, density functional theory explains the differential kinetics and stereoselectivities among substrates.

Full text of DOI:10.1021/jo4014645

Article
pubs.acs.org/joc
Silicon Acceleration of a Tandem Alkene Isomerization/Electrocyclic
Ring-opening of 2‑Methyleneoxetanes to α,β-Unsaturated
Methylketones
Elisa Farber, Aleksandra Rudnitskaya, Santosh Keshipeddy, Kendricks S. Lao, Jose A. Gascon,
́
́
and Amy R. Howell*
Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269-3060, United States
S
* Supporting Information
ABSTRACT: The first rearrangement of 2-methyleneoxetanes to α,β-
unsaturated methylketones is reported. It is proposed that when these
substrates are heated, the corresponding oxetenes are formed and
subsequently undergo electrocyclic ring-opening to methyl vinylketones.
In particular, α-silyl-α,β-unsaturated methylketones were isolated in
moderate to high yields and with high stereoselectivities. Based on the
proposed mechanism, density functional theory explains the differential
kinetics and stereoselectivities among substrates.
Scheme 1. Unexpected Outcome upon Heating 1a
INTRODUCTION
We report an unexpected conversion of 2-methyleneoxetanes 1
to α,β-unsaturated methylketones 3 (Figure 1). Moreover, a
■
characteristic of 3a, a number of other signals, along with
baseline broadening, were seen. Presumably the broad peaks
were due to the formation of polymers, which would not be
surprising considering the reactivity of enones. We decided to
see if enone formation was a general outcome when 2-
methyleneoxetanes were heated.
Figure 1. Enone formation from 2-methyleneoxetanes.
silyl substituent at C-3 greatly enhanced the yields and rates of
these reactions. α-Silyl-α,β-unsaturated methylketones were
obtained in moderate to high yields with excellent stereo-
selectivities. This outcome suggests a tandem alkene isomer-
ization/four π-electron electrocyclic ring-opening pathway
involving initial transformation to 2-methyloxetenes 2, which
undergo a well-precedented electrocyclic ring-opening. To our
knowledge there are no reports of such a tandem reaction
involving oxetanes.
We have been interested in the reactivity of 2-methyleneox-
etanes 1. These compounds are attractive intermediates due to
their strained ring and electron rich exocyclic double bond.
Examples of the utility of these oxetanes include their
transformation to homopropargylic alcohols,1 α-substituted
ketones,2 functionalized ketones,3 and 1,4-dioxaspiro[2.3]-
hexanes.4
RESULTS AND DISCUSSION
■
To investigate whether other 2-methyleneoxetanes would lead
to the corresponding methyl vinylketones, 1b6 and 1c6 were
heated to 200 °C (Table 1). Methylenones 3b and 3c were
isolated in ∼30% yield, and the reactions were cleaner than the
isomerization of 1a. No byproducts were isolated, and the low
yield was again attributed to polymerization. There was no
reaction at less than 200 °C. Although the isolated yields of 3b
and 3c were low, we were interested in the mechanism of the
transformation and in seeing whether the yields could be
improved.
Based on the outcome, our assumption was that the first step
was isomerization of the exocyclic double bond to the
endocyclic one, since it has been well-documented that
exocyclic alkenes7 are converted to endocyclic alkenes upon
heating or in the presence of acid/base catalysts.8 These bond
migrations are attributed to the greater stability of the isomers
As part of our effort to explore the reactivity of 2-
methyleneoxetanes, 1a was synthesized as a substrate for an
expected Claisen rearrangement to cyclohexenone 4 (Scheme
1), since related reactions are known with the corresponding
furans and pyrans.5 However, when 1a was heated to 200 °C,
1
dienone 3a (but no 4) was observed in H and 13C NMR
Received: July 22, 2013
spectra of the reaction mixture. In addition to peaks
Published: October 10, 2013
© 2013 American Chemical Society
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Table 1. Syntheses of 2-Methyleneoxetanes 1 and Methylenones 3
yield (%) of 6
(cis/trans)
stereochem. of 6
yield (%)
of 1
temp
(°C)
time
(min)
yield (%)
of 3
stereochem.
entry compd
R
R1
used
of 3
1
b
c
d
e
f
CH2OTBDPS
c-Hex
Me
a
a
200
200
160
160
110
160
160
110
110
110
110
90
75
10
10
30
10
10
50
35
35
15
33
29
80
63
94
89
70
E
2
H
E
3
c-Hex
TMS
TMS
TBS
TMS
TMS
TMS
TMS
TMS
TMS
72 (2:3)
trans
cis
55
Z
b
4
c-Hex
43
Z
5
c-Hex
79 (1:2)
68 (5:2)
trans
trans
cis
68
34
Z
6
g
h
i
n-C7H15
n-C7H15
t-Butyl
Ph
Z
c
7
31
Z
d
e
8
67
trans
cis
50
33
Z
9
j
60
64
42
64
71
99
Z
10
11
k
l
p-CF3Ph
CH2OBn
64 (3:1)
26 (7:3)
cis
Z/E, 92:8
cis
40
Z
a
b
c
See ref 6. An inseparable mixture of 2-methyleneoxetane/enone (10:1) was isolated. An inseparable mixture of 2-methyleneoxetane/enone (5:1)
d
e
was isolated. An inseparable mixture of 2-methyleneoxetane/enone (>9:1) was isolated. Based on recovered starting material.
with the endocyclic double bond.9 The isomerization of
methylenecyclobutane to 1-methylcyclobutene has also been
reported.10 However, we did not find examples of the
isomerization of 2-methyleneoxetanes 1 to the corresponding
2-methyloxetenes 2.
Oxetenes are well-known to be unstable species, especially at
high temperatures.11,12 They usually undergo electrocyclic ring-
opening, leading to α,β-unsaturated carbonyl systems. Similarly,
the more stable cyclobutenes have been reported to produce
dienes.13 Friedrich et al.14 studied the kinetics of the ring-
opening of 2,3,4,4-tetramethyloxetene and compared it with
that of cyclobutenes. It was found that the substitution of a
methylene group from a cyclobutene with an oxygen atom
accelerated the ring-opening by a factor of 107.
R = H). Compound 1d was heated at 160 °C; after 5−10 min,
it was completely isomerized to enone 3d in an isolated yield of
80% (Scheme 2 and Table 1, entry 3). This result showed that
silicon containing 2-methyleneoxetane 1d not only provided
the corresponding methylenone in higher yield but also
underwent isomerization considerably faster than the unsily-
lated systems 1a−1c.
Based on the result with 1d, we decided to investigate the
scope of the transformation of 3-silyl-2-methyleneoxetanes to
α-silyl-α,β-unsaturated methylketones (Table 1). α-Silyl-β-
lactones 6e−6l were prepared from [2 + 2]-cycloadditions of
silylketenes and a variety of aldehydes in the presence of
catalytic BF3·OEt2.16 2-Methyleneoxetanes 1e−1l were synthe-
sized by methylenation of β-lactones 6e−6l using the Petasis
reagent. It is noteworthy that during methylenation several of
the substrates provided mixtures of 2-methyleneoxetane and α-
silyl-α,β-unsaturated ketone (entries 4, 7, and 8). The
inseparable product mixtures were heated to complete the
conversion to the enones.
In an attempt to improve the yields for the tandem alkene
isomerization/electrocyclic ring-opening of 2-methyleneoxe-
tanes, 3-silyl-2-methyleneoxetane 1d was prepared (Scheme 2
Scheme 2. Isomerization of Silylated Methyleneoxetane 1d
The reactivity of the 3-silyl-2-methyleneoxetanes 1 was
investigated (Table 1). Conversions to the corresponding α-
silylenones were complete in 10−50 min at 110−160 °C, below
the temperature required for 1a−1c. With the exception of 1i,
having a bulky substituent at C-4, all of the 3-silylated 2-
methyleneoxetanes reacted in good to excellent yields with high
stereoselectivities. The size of the silyl group (entry 5) did not
affect the outcome, although the reaction was slower with TBS
(entry 4 vs 5). Except for compound 1k (entry 10), which gave
a mixture of enones (92:8 Z/E), only Z-isomers were observed
and Table 1). Baukov et al.15 reported in 1981 that 2-ethoxy-3-
silyloxetenes 5 (R = TMS) gave α-silyl-α,β-unsaturated esters
in higher yields than the corresponding unsilylated systems (5,
Figure 2. Proposed Mechanism for the Formation of Enones.
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from both cis- and trans-2-methyleneoxetanes 1. The high Z-
selectivity is discussed below.
analyzed. Comparing the potential energy surface (PES), we
observe that the significant difference in energy between the
silyl and non-silyl substrates is in the stability of the oxetene
intermediates (2c* and 2d*). The energy barriers for the
forward reactions are very similar for the conversion of each 2-
methyleneoxetane to the corresponding oxetene and for the
subsequent conversions to enones. Because of the high barriers
(∼45 kcal/mol) for the reverse reaction of the second step for
either compound, this step can be considered irreversible.
Moreover, for both 1c and 1d, the calculated rate constants for
the reverse reaction of the first step (k−1) are 2 orders of
magnitude larger than the forward reactions of the second step
(k2). This leads to a condition of pre-equilibrium, in which the
constant for the overall reaction can be expressed as
Since it was assumed that oxetenes were intermediates, we
tried to confirm their presence. Each reaction was monitored by
NMR; no oxetene was observed. A solution of 1f in toluene-d8
was heated while 1H and 13C NMR spectra were taken every 5
min. At 90 °C, only reactant and product were observed. At
lower temperatures, the reaction was very slow, and again, no
oxetene was seen by NMR. The failure to observe oxetenes may
be a reflection of a lack of build-up before consumption (vide
infra). Despite the lack of spectral evidence for oxetenes, their
intermediacy is logical, considering the outcome.
Based on previous literature reports on exocyclic alkene
isomerization and on oxetene electrocyclic ring-opening (vide
supra), a two-step mechanism is proposed (Figure 2). First, in
the presence of a trace amount of Lewis acid, an oxocarbenium
7a is formed from 1. The formation of a carbocation triggers a
chain reaction where 1 abstracts a proton at C-3 from 7a,
leading to oxetene 2 with regeneration of 7a. Therefore, only a
catalytic amount of 7a would be needed to start the reaction. In
the second step, 2 undergoes electrocyclic ring-opening,
providing enone 3.
In order to model the behavior of the 2-methyleneoxetanes 1
under high temperatures and explain the stereoselectivity,
computational models of 1b, 1d, and 1e were constructed. The
results should be applicable to other 2-methyleneoxetanes.
All geometries and energies presented in this study were
computed using density functional theory with the B3LYP
functional17 and basis set 6-311++G(d,p) as implemented in
Gaussian 09.18 Harmonic vibrational frequency calculations
were carried out at the same level of theory in order to
determine the nature of the stationary points, the zero-point
energy (ZPE), and the thermal contributions to the free energy
of activation. Note that entropy effects are taken into account
by considering the contribution from all degrees of freedom to
the partition function, which is needed in the calculation of free
energies. The pathways between the transition state structures
and their corresponding minima were identified by intrinsic
reaction coordinate (IRC)19 calculations.
k1
k−1
k =
k2
At 160 °C, we obtain kTMS/kH ≈ 9400. This result explains the
much faster and more facile isomerization of 3-silyl-2-
methyleneoxetanes.
The high Z-selectivity obtained from the isomerization of 3-
silyloxetenes has been previously observed by Baukov et al.
when α-silyl-α,β-unsaturated esters were formed.15 Both steric
and electronic effects have been shown to influence
torquoselectivity in 4e‑ electrocyclic ring-openings; however,
electronic effects play a greater role.21 Based on calculations
with cyclobutenes, Houk et al.21a showed that an electron-
donating group at C-3 or C-4 favors an outward motion,
whereas electron-withdrawing substituents can also lead to
inward rotation, which is consistent with entry 10 (Table 1).
Recently, Shindo et al.22 reported that oxetenes follow the same
trend (Figure 5) and that the rotation is influenced by orbital
interactions in the transition states. Our computational results
show that the energy of the transition state leading to the Z-
silylenones is lower than the corresponding transition state
leading to E-isomer (see Supporting Information).
The role of silicon in the migration of the double bond is
remarkable. 2-Methyleneoxetanes can be stored for long
periods of time in the freezer. Occasionally, hydrolysis to β-
hydroxymethylketones is seen. In contrast, the α-silylated 2-
methyleneoxetanes could not be stored for extended periods.
For example, 2-methyleneoxetane 1d converted completely to
the corresponding enone when stored neat in the freezer for 1
month.
All computed geometries of reactants, transition states,
intermediates, and products, as well as rate constants, are given
in the Supporting Information (Tables S1 and S2). Figure 3
shows the optimal structure for the complexation of 2-
methyleneoxetane 1d with its corresponding carbocationic
species (this complex is denoted as 1d*).
α-Silyl-α,β-unsaturated ketones are useful substrates for the
syntheses of α-substituted enones and their derivatives. α-
Silylenones have been utilized for the preparation of α-iodo-
α,β-unsaturated ketones.23 Also, unsaturated α,γ-diketones
were prepared from α-silyl-α,β-unsaturated ketones by reaction
with aroyl chlorides.24 The approach to α-silylenones described
here is useful because silyl ketenes can be prepared on a large
scale,25 and Z-3-silyl enones can be synthesized in three steps
without separating the lactone mixtures (since both isomers
provide the Z-enone).26 With some α-silylenone being
observed during the methylenation for some of the substrates,
it would seem that the methylenation and isomerization could
be accomplished as a one-pot process, either by heating longer
at 80 °C or by raising the bath temperature to 110 °C once the
methylenation was complete. This was not the case. Although
consumption of the methyleneoxetanes could be driven to
completion and the enones were the only isolable products, the
reactions were much slower, and the yields were much lower.
To further understand the difference in reactivity between
silyl- and non-silylmethyleneoxetanes, computed energy
profiles of transition states and intermediates for 1c and 1d
(Figure 4) were analyzed.20 Since our calculations revealed that
the energy profiles for 1d and 1e (trans and cis isomers,
respectively) are identical, only the profile for 1d is shown and
Figure 3. Graphical representation of the optimized structure of 1d*
initiating the chain reaction.
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Figure 4. Potential energy surface (PES) diagrams for the stepwise production of 3c (blue and higher set of lines) and 3d (pink and lower set of
lines).
mL, 59.2 mmol). The resulting solution was cooled to −78 °C, and n-
BuLi (29.5 mL, 59.2 mmol, 2 M in hexane) was added dropwise
through an addition funnel. The resulting solution was stirred for 1 h
at −78 °C. Then, methylhexanoate (7.90 mL, 53.8 mmol) was added
dropwise. The resulting dark yellow solution was stirred at −78 °C for
1.5 h. Then, acrolein (5.40 mL, 80.7 mmol) was added. After 15−20
min, the reaction was quenched with 1 M aqueous HCl solution (10
Figure 5. Electronic Effects on Torquoselectivity.
mL) at −78 °C, and the solution was allowed to warm to rt. The
aqueous layer was separated and extracted with Et2O (2 × 15 mL).
For example, after β-lactone 6j was completely consumed, the
flask was transferred to an oil bath at 110 °C. Conversion to
enone 3j was not complete even after 12 h. That the rate
decrease was not a concentration effect was determined by
conducting the tandem alkene isomerization/electrocyclic ring-
opening at 110 °C at the same concentration as the
methylenation with substrate 1j. Only enone 3j was present
when the reaction was checked at 30 min. This suggests that
either excess Petasis reagent or byproducts from the
methylenation reaction compete for the catalytic carriers,
slowing down the reaction. That the yield is lower if the
reaction is slower is not surprising. Our earlier studies on the
preparation of 2-methyleneoxetanes had shown that methyle-
nation yields decreased if reactions were left too long,
particularly if reactions were run at higher temperatures.27
In summary, novel tandem alkene isomerization/four π-
electron electrocyclic ring-openings of 2-methyleneoxetanes to
methyl vinylketones have been reported. Additionally, reactions
of substituted 3-silyl-2-methyleneoxetanes are considerably
faster and more efficient than the corresponding non-silicon-
containing compounds. α-Silylenones were isolated in high
yields and with excellent stereoselectivities, the isomerizations
proceeding without solvent at moderate temperatures. DFT
calculations were consistent with the experimental results and
provided an explanation for the origin of differential kinetics
between silyl and non-silyl substrates.
The combined organic extracts were washed with brine (15 mL), dried
(MgSO4), and concentrated. The crude product was purified by flash
chromatography on silica gel (petroleum ether/ethyl acetate, 9:1) to
give methyl (3R*,4R*)-2-butyl-3-hydroxypent-4-enoate (4.3 g, 43%)
as a yellow oil and methyl (3S*,4R*)-2-butyl-3-hydroxypent-4-enoate
(4.3 g, 43%) as a yellow oil. Methyl (3R*,4R*)-2-butyl-3-hydroxypent-
4-enoate: 1H NMR (300 MHz, CDCl3) δ 5.81 (ddd, J = 16.7, 10.5, 6.1
Hz, 1H), 5.25 (d, J = 17.1 Hz, 1H) 5.14 (d, J = 10.5 Hz, 1H), 4.26 (m,
1H), 3.65 (s, 3H), 2.58 (m, 1H), 2.50 (ddd, J = 9.8, 5.0, 5.0 Hz, 1H),
1.71−1.55 (m, 2H), 1.33−1.19 (m, 4H), 0.84 (t, J = 6.8 Hz, 3H); 13C
NMR (75 MHz, CDCl3) δ 175.3, 137.9, 116.6, 73.5, 51.8, 51.4, 30.0,
27.2, 22.8, 14.0. Methyl (3S*,4R*)-2-butyl-3-hydroxypent-4-enoate:
1H NMR (400 MHz, CDCl3) δ 5.70 (ddd, J = 17.0, 10.4, 6.4 Hz, 1H),
5.15 (d, J = 17.2 Hz, 1H), 5.04 (d, J = 10.4 Hz, 1H), 4.06 (dd, J = 12.5,
6.5 Hz, 1H), 3.56 (s, 3H), 3.01 (d, J = 5.1 Hz, 1H), 2.35 (ddd, J = 9.7,
6.9, 5.1 Hz, 1H), 1.54−1.36 (m, 2H), 1.23−1.08 (m, 4H), 0.75 (t, J =
7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 175.8, 138.8, 116.6, 73.8,
51.9, 51.4, 29.6, 29.0, 22.6, 14.0.
(3S*,4R*)-2-Butyl-3-hydroxy-4-pentenoic acid. Aqueous NaOH
(23 mL, 2 M) was added to a solution of methyl (3S*,4R*)-2-butyl-3-
hydroxypent-4-enoate (1.2 g, 6.3 mmol) in THF/MeOH (215 mL,
1:2) at rt. The resulting mixture was stirred at 50 °C in a pre-
equilibrated oil bath overnight. The solution was cooled to rt, and
aqueous HCl (1 M) was added to pH = 3−4. MeOH and THF were
removed under reduced pressure, and EtOAc (60 mL) was added to
the residue. The two layers were separated, and the aqueous layer was
extracted with EtOAc (4 × 40 mL). The combined organic layers were
dried (MgSO4) and concentrated under reduced pressure to give
(2R*,3S*)-2-butyl-3-hydroxy-4-pentenoic acid (1.02 g, quant.) as a
brown oil. The crude product was utilized in the next reaction without
purification: 1H NMR (400 MHz, CDCl3) δ 5.78 (ddd, J = 17.0, 10.4,
6.5 Hz, 1H), 5.24 (d, J = 17.1 Hz, 1H), 5.14 (d, J = 10.4 Hz, 1H), 4.17
(dd, J = 6.7, 6.7 Hz, 1H), 2.42 (ddd, J = 9.4, 7.0, 5.1 Hz, 1H), 1.84 (m,
1H). 1.63−1.47 (m, 2H), 1.31−1.22 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H);
EXPERIMENTAL SECTION
■
Preparation of cis-3-Butyl-4-vinyloxetan-2-one (6a) from
Methyl 2-Butyl-3-hydroxypent-4-enoate. Methyl 2-Butyl-3-hy-
droxypent-4-enoate.28 A 500 mL 3-neck round-bottom flask under
N2 was charged with dry THF (270 mL) and diisopropylamine (8.40
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1
13C NMR (100 MHz, CDCl3) δ 179.7, 138.2, 117.1, 73.8, 51.4, 29.4,
28.8, 22.6, 13.9.
25.8, 25.5, 17.0, −6.6, −7.5. Cis diastereomer: H NMR (400 MHz,
CDCl3) δ 4.19 (dd, J = 9.6, 6.1 Hz, 1H), 3.39 (d, J = 6.1 Hz, 1H),
1.97−1.93 (m, 1H), 1.78−1.58 (m, 5H), 1.26−1.16 (m, 3H), 1.09−
0.93 (m, 2H), 0.94 (s, 9H), 0.18 (s, 3H), 0.13 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 170.7, 76.8, 42.8, 40.5, 29.6, 28.5, 26.6, 26.0, 25.3,
25.1, 17.0, −4.7, −5.5.
cis-3-Butyl-4-vinyloxetan-2-one (6a). Benzenesulfonyl chloride
(1.85 g, 10.5 mmol) was added dropwise to a solution of
(2R*,3S*)-2-butyl-3-hydroxy-4-pentenoic acid (0.60 g, 3.5 mmol) in
dry pyridine (72 mL) at 0−5 °C under N2. The resulting solution was
stirred at 0−5 °C overnight. Then, it was poured onto crushed ice
(100 mL) and stirred for 15 min. Et2O (50 mL) was added, and the
layers were separated. The aqueous layer was extracted with Et2O (3 ×
70 mL). The combined organic extracts were washed with saturated
aqueous NaHCO3 (2 × 50 mL), 10% aqueous CuSO4 (8 × 100 mL),
and H2O (1 × 50 mL), dried (MgSO4), and concentrated. The residue
was purified by flash chromatography on silica gel (petroleum ether/
EtOAc, 95:5) to provide cis-3-butyl-4-vinyloxetan-2-one (6a) (0.38 g,
38%) as a clear oil: IR (neat) 2959, 2933, 2863, 1826, 1116, 857 cm−1;
1H NMR (400 MHz, CDCl3) δ 5.97 (ddd, J = 17.2, 10.4, 7.0 Hz, 1H),
5.43 (d, J = 17.1 Hz, 1H), 5.32 (d, J = 10.5 Hz, 1H), 4.59 (dd, J = 5.4,
5.4 Hz, 1H), 3.30 (m, 1H), 1.87−1.69 (m, 2H), 1.43−1.25 (m, 4H),
0.87 (t, J = 6.9 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 171.2, 134.3,
120.0, 77.6, 57.6, 29.0, 27.4, 22.4, 13.9; HRMS (TOF) calcd for
C9H15O2 (M+ + H) m/z 155.1067, found 155.1056.
4-Heptyl-3-trimethylsilyloxetan-2-one (6g and 6h). Purification
by flash chromatography on silica gel (petroleum ether/EtOAc, 98:2)
provided trans-4-heptyl-3-trimethylsilyloxetan-2-one (6g) (0.10 g,
19%) as a clear oil and cis-4-heptyl-3-trimethylsilyloxetan-2-one (6h)
(0.26 g, 49%) as a clear oil. Trans diastereomer: IR (neat) 2956, 2928,
2858, 1808, 1253 cm−1; 1H NMR (300 MHz, CDCl3) δ 4.21 (ddd, J =
6.5, 6.5, 4.2 Hz, 1H), 2.87 (d, J = 4.1 Hz, 1H), 1.93−1.81 (m, 1H),
1.72−1.61 (m, 1H), 1.30−1.25 (m, 10H), 0.85 (t, J = 6.8 Hz, 3H),
0.15 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 171.0, 72.9, 48.5, 35.9,
31.9, 29.4, 29.3, 25.3, 22.8, 14.2, −2.8; HRMS (TOF) calcd for
C13H27O2Si (M+ + H) m/z 243.1780, found 243.1759. Cis
diastereomer: IR (neat) 2928, 2857, 1803, 1253, 1123 cm−1; 1H
NMR (300 MHz, CDCl3) δ 4.52 (ddd, J = 9.8, 6.0, 4.6 Hz, 1H), 3.28
(d, J = 6.0 Hz, 1H), 1.77−1.68 (m, 2H), 1.53−1.44 (m, 1H), 1.34−
1.21 (m, 9 H), 0.83 (t, J = 6.9 Hz, 3 H), 0.17 (s, 9H); 13C NMR (100
MHz, CDCl3) δ 171.1, 74.2, 46.5, 33.7, 31.8, 29.3, 29.2, 26.4, 22.7,
14.2, −1.0; HRMS (TOF) calcd for C13H26NaO2Si (M+ + Na) m/z
265.1594, found 265.1610.
t-Butyldimethylsilylketene.29 Ethylmagnesium chloride (79 mL,
157 mmol, 2 M in THF) was added dropwise to a solution of
ethoxyacetylene (10 g, 143 mmol) in dry THF (320 mL) at 0 °C
under N2. The resulting solution was stirred for 3 h while warming to
rt. Then, t-butyldimethylsilyl chloride (24.0 g, 157 mmol) was slowly
added, and the solution was stirred overnight (16 h) and then
concentrated in vacuo. The magnesium salts precipitated upon the
addition of petroleum ether, and the resulting slurry was filtered
through a pad of Celite, washing with petroleum ether. The filtrate was
concentrated in vacuo and carefully distilled under high vacuum to
provide t-butyldimethylsilylethoxyacetylene (6.5 g, 25%) as a clear,
colorless oil. It was then slowly distilled (140−180 °C bath
temperature, 1 atm) to give t-butyldimethylsilylketene (4.4 g, 20%)
trans-4-t-Butyl-3-trimethylsilyloxetan-2-one (6i).27 No purifica-
tion was needed. The desired trans-4-t-butyl-3-trimethylsilyloxetan-2-
one (6i) (0.49 g, 67%) was isolated as a white solid: H NMR (400
1
MHz, CDCl3) δ 3.89 (d, J = 4.2 Hz, 1H), 2.91 (d, J = 4.1 Hz, 1H),
0.88 (s, 9H), 0.09 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 170.9,
79.7, 43.1, 33.3, 24.3, −3.0.
cis-4-Phenyl-3-trimethylsilyloxetan-2-one (6j).32 Purification by
flash chromatography on silica gel (petroleum ether/EtOAc, 98:4)
provided cis-4-phenyl-3-trimethylsilyloxetan-2-one (6j) (0.48 g, 60%)
as a clear oil: 1H NMR (400 MHz, CDCl3) δ 7.34 (m, 5H), 5.66 (d, J
= 6.6 Hz, 1H), 3.69 (d, J = 6.4 Hz, 1H), −0.15 (s, 9H); 13C NMR
(100 MHz, CDCl3) δ 170.6, 137.1, 128.7, 128.5, 125.6, 72.8, 49.9,
−1.7.
1
as a clear, colorless oil: H NMR (400 MHz, CDCl3) δ 1.71 (s, 1H),
0.96 (s, 9H), 0.10 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 179.3,
26.1, 17.8, −3.0, −4.3.
Typical Procedure for the Syntheses of β-Lactones 6b−6l. 4-
Cyclohexyl-3-trimethylsilyloxetan-2-one (6d/6e).30 BF3·OEt2 (3.7
μL, 0.030 mmol) was added dropwise to a solution of
trimethylsilylketene31 (0.46 mL, 3.2 mmol), cyclohexylcarboxaldehyde
(0.32 mL, 2.7 mmol), and dry CH2Cl2 (2.5 mL) at 0 °C under N2.
The resulting solution was stirred at 0 °C until the aldehyde was
consumed (reaction monitored by TLC). Then, pH 7 buffer solution
(2.5 mL) was added. The two layers were separated, and the aqueous
layer was extracted with CH2Cl2 (3 × 5 mL). The combined organic
extracts were dried (MgSO4) and concentrated. The residue was
purified by flash chromatography on silica gel (petroleum ether/
EtOAc, 96:4) to give trans-4-cyclohexyl-3-trimethylsilyloxetan-2-one
(6d) (0.26 g, 43%) as a white solid and cis-4-cyclohexyl-3-
trimethylsilyloxetan-2-one (6e) (0.18 g, 29%) as a white solid. Trans
diastereomer: 1H NMR (300 MHz, CDCl3) δ 3.88 (dd, J = 7.8, 3.9 Hz,
1H), 2.92 (d, J = 3.8 Hz, 1 H), 1.92 (m, 1H), 1.75−1.65 (m, 3H),
1.56−1.49 (m, 2H), 1.25−1.10 (m, 3H), 1.00−0.83 (m, 2H), 0.13 (s,
9H); 13C NMR (75 MHz, CDCl3) δ 171.2, 76.6, 46.5, 43.0, 28.7, 27.5,
26.1, 25.6, 25.3, −2.8. Cis diastereomer: 1H NMR (400 MHz, CDCl3)
δ 4.14 (dd, J = 10.4, 5.9 Hz, 1H), 3.23 (d, J = 5.9 Hz, 1H), 1.92 (m,
1H), 1.73−1.67 (m, 2H), 1.65−1.57 (m, 3H), 1.23−1.11 (m, 3H),
0.97−0.82 (m, 2H), 0.17 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
171.1, 78.0, 46.0, 40.8, 29.0, 28.7, 26.0, 25.2, 25.1, −0.8.
4-Cyclohexyl-3-t-butyldimethylsilyloxetan-2-one (6f, Cis Iso-
mer).27 Purification by flash chromatography on silica gel (petroleum
ether/EtOAc, 97:3) provided trans-4-cyclohexyl-3-t-butyldimethylsily-
loxetan-2-one (6f) (0.73 g, 53%) as a white solid and cis-4-cyclohexyl-
3-t-butyldimethylsilyloxetan-2-one (0.37 g, 26%) as a white solid.
Trans diastereomer: 1H NMR (400 MHz, CDCl3) δ 3.95 (dd, J = 7.6,
4.1 Hz, 1H), 3.00 (d, J = 4.1 Hz, 1H), 1.95 (m, 1H), 1.78−1.74 (m,
2H), 1.69−1.66 (m, 1H), 1.60−1.51 (m, 2H), 1.30−1.09 (m, 3H),
1.04−0.8 (m, 2H), 0.93 (s, 9H), 0.11 (s, 3H), 0.04 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 171.3, 76.6, 43.7, 43.3, 28.6, 28.2, 26.6, 26.2,
4-(p-Trifluoromethylphenyl)-3-trimethylsilyloxetan-2-one (6k,
Trans Isomer). Purification by flash chromatography on silica gel
(petroleum ether/EtOAc, 9:1) provided cis-4-(p-trifluoromethylphen-
yl)-3-trimethylsilyloxetan-2-one (6k) (0.69 g, 47%) as a white solid
and trans-4-(p-trifluoromethylphenyl)-3-trimethylsilyloxetan-2-one
(0.25 g, 17%) as a clear oil. Trans diastereomer: 1H NMR (500
MHz, CDCl3) δ 7.65 (d, J = 7.2 Hz, 2H), 7.46 (d, J = 7.2 Hz, 2H),
5.26 (bs, 1H), 3.22 (bs, 1H), 0.26 (s, 9H); 13C NMR (125 MHz,
2
1
CDCl3) δ 169.9, 142.8, 131.2 (q, JC−F = 32.4 Hz), 126.2 (q, JC−F
=
3
4.2 Hz), 126.1, 125.6, 124.0 (q, JC−F = 272.2 Hz), 71.4, 53.2, −2.7.
Cis diastereomer: mp 78−82 °C; IR (neat) 2964, 2918, 1797, 1324
1
cm−1; H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.9 Hz, 2H), 7.46
(d, J = 7.9 Hz, 2H), 5.70 (d, J = 6.5 Hz, 1H), 3.75 (d, J = 6.5 Hz, 1H),
−0.15 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 169.9, 141.3, 131.0 (q,
1
3
2JC−F = 33.0 Hz), 126.2, 125.6 (q, JC−F = 3.7 Hz), 124.0 (q, JC−F
=
270.7 Hz), 72.1, 50.4, −1.7; HRMS (TOF) calcd for C13H16F3O2Si
(M+ + H) m/z 289.0866, found 289.0862.
4-Benzyloxymethyl-3-trimethylsilyloxetan-2-one (6l, Trans Iso-
mer). Purification by flash chromatography on silica gel (petroleum
ether/EtOAc, 9:1) provided cis-4-benzyloxymethyl-3-trimethylsilylox-
etan-2-one (6l) (0.17 g, 19%) as a clear oil and trans-4-
benzyloxymethyl-3-trimethylsilyloxetan-2-one (0.077 g, 6%) as a
clear oil. Trans diastereomer: IR (neat) 2956, 2898, 2862, 1804,
1
1454, 1254 cm−1; H NMR (400 MHz, CDCl3) 7.36−7.27 (m, 5H),
4.59 (s, 2H), 4.41 (ddd, J = 4.9, 4.2, 3.7 Hz, 1H), 3.75 (dd, J = 11.4,
3.5 Hz, 1H), 3.69 (dd, J = 11.4, 5.0 Hz, 1H), 3.16 (d, J = 4.2 Hz, 1H),
0.17 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 170.2, 137.7, 128.7,
128.1, 127.8, 73.9, 71.0, 70.9, 45.3, −2.7; HRMS (TOF) calcd for
C14H21O3Si (M+ + H) m/z 265.1254, found 265.1247. Cis
diastereomer:33 1H NMR (400 MHz, CDCl3) 7.36−7.29 (m, 5H),
4.74 (ddd, J = 6.0, 6.0, 6.0 Hz, 1H), 4.60 (d, J = 11.9 Hz, 1H), 4.55 (d,
J = 11.9 Hz, 1H), 3.75 (m, 2H), 3.37 (d, J = 6.5 Hz, 1H), 0.16 (s, 9H);
11217
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Article
13C NMR (100 MHz, CDCl3) δ 170.4, 137.4, 128.7, 128.2, 128.2, 73.8,
72.0, 69.9, 45.6, −0.9.
Et3N, 97.5:2:0.5) provided a mixture of cis-4-heptyl-2-methylene-3-
trimethylsilyloxetane (1h) and (Z)-4-heptyl-3-trimethylsilylbut-3-en-2-
one (3h) (5:1, 50 mg, 31%) as a clear oil: IR (neat) 2956, 2926, 2856,
1678, 1250 cm−1; 1H NMR (400 MHz, CDCl3) δ 4.90 (m, 1H), 3.98
(m, 1H), 3.53 (m, 1H), 3.03 (m, 1H), 2.54 (m, 1H), 2.25 (m, 1H)
1.84 (m, 1H), 1.59 (m, 1H), 1.49−1.37 (m, 2H), 1.25 (m, 6H), 0.84
(t, J = 7.3 Hz, 3H), 0.12 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
165.8, 82.4, 77.0, 37.2, 35.1, 32.0, 29.6, 29.4, 26.0, 22.8, 14.3, −1.1.
trans-4-t-Butyl-2-methylene-3-trimethylsilyloxetane (1i). Purifica-
tion by flash chromatography on silica gel (petroleum ether/EtOAc/
Et3N, 97.5:2:0.5) provided trans-4-t-butyl-2-methylene-3-trimethylsily-
loxetane (1i) and (Z)-4-t-butyl-3-trimethylsilylbut-3-en-2-one (3i)
(∼9:1, 136 mg, 50%) as a yellow oil: IR (neat) 2957, 2898, 1679, 1251
Typical Procedure for the Preparation of 2-Methyleneox-
etanes (1). trans-4-Cyclohexyl-2-methylene-3-trimethylsilyloxetane
(1d). Dimethyltitanocene34 (4.0 mL, 2.0 mmol, 0.50 M in toluene)
and trans-4-cyclohexyl-3-trimethylsilyloxetan-2-one (6d) (0.22 g, 1.0
mmol) were stirred at 80 °C under N2 in the dark for 2 h. Additional
dimethyltitanocene (1−6 equiv) was added until complete con-
sumption of 6d was observed by TLC (petroleum ether/EtOAc/
Et3N). The solution was cooled to rt, and petroleum ether (8 mL) was
added, at which point a yellow precipitate formed. The resulting
mixture was stirred for 18 h at rt. The solid residue was filtered
through a pad of Celite, rinsing with petroleum ether. The solvent was
removed under reduced pressure to 5 mL (approximate volume), and
the residue was purified by flash chromatography on silica gel
(petroleum ether/EtOAc/Et3N, 97.5:2:0.5) to give trans-4-cyclohexyl-
2-methylene-3-trimethylsilyloxetane (1d) (127 mg, 55%) as a clear oil:
1
cm−1; H NMR (400 MHz, CDCl3) δ 4.17 (d, J = 5.1 Hz, 1H), 3.95
(dd, J = 2.8, 2.8 Hz, 1H), 3.48 (dd, J = 3.1, 1.9 Hz, 1H), 2.67 (m, 1H),
0.9 (bs, 9H), 0.08 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.7,
88.1, 76.7, 34.4, 33.3, 24.1, −3.2; HRMS (TOF) calcd for C11H23OSi
(M+ + H) m/z 199.1513, found 199.1535.
1
IR (neat) 2927, 2853, 1678, 1451, 1249 cm−1; H NMR (400 MHz,
CDCl3) δ 4.14 (dd, J = 8.1, 5.0 Hz, 1H), 3.95 (m, 1H), 3.49 (m, 1H),
2.63 (m, 1H), 1.91 (m, 1H), 1.75−1.60 (m, 4H), 1.55 (m, 1H), 1.30−
1.08 (m, 3H), 0.93−0.77 (m, 2H), 0.06 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 166.0, 84.9, 77.2, 44.1, 36.5, 28.3, 26.9, 26.5, 25.8, 25.5,
−3.3; HRMS (TOF) calcd for C13H25OSi (M+ + H) m/z 225.1669,
found 225.1675.
cis-2-Methylene-4-phenyl-3-trimethylsilyloxetane (1j). Purifica-
tion by flash chromatography on silica gel (petroleum ether/EtOAc/
Et3N, 97.5:2:0.5) provided cis-2-methylene-4-phenyl-3-trimethylsily-
loxetane (1j) (210 mg, 64%) as a yellow oil: IR (neat) 3065, 3030,
1
2955, 2899, 1681, 1250 cm−1; H NMR (400 MHz, CDCl3) δ 7.38−
7.35 (m, 4H), 7.32−7.28 (m, 1H), 6.03 (d, J = 7.9 Hz, 1H), 4.23 (dd, J
= 2.8, 2.8 Hz, 1H), 3.69 (dd, J = 3.3, 2.0 Hz, 1H), 3.46 (ddd, J = 7.9,
2.2, 2.2 Hz, 1H), −0.19 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
165.5, 139.9, 128.3, 128.1, 125.7, 81.1, 77.9, 40.3, −1.9; HRMS (TOF)
calcd for C13H19OSi (M+ + H) m/z 219.1200, found 219.1219.
cis-2-Methylene-4-(p-trifluoromethylphenyl)-3-trimethylsilyloxe-
tane (1k). Purification by flash chromatography on silica gel
(petroleum ether/EtOAc/Et3N, 94:5:1) provided cis-2-methylene-4-
(p-trifluoromethylphenyl)-3-trimethylsilyloxetane (1k) (121 mg, 42%)
as an orange oil: IR (neat) 2958, 2902, 1684, 1621, 1417, 1325 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.2 Hz, 2H), 7.46 (d, J =
8.2 Hz, 2H), 6.03 (d, J = 8.0 Hz, 1H), 4.22 (dd, J = 3.5, 2.7 Hz, 1H),
3.69 (dd, 3.6, 2.0 Hz, 1H), 3.47 (ddd, J = 7.9, 2.2, 2.2 Hz, 1H), −0.22
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 164.8, 144.0, 130.4 (q, 2JC−F
= 32.4 Hz), 126.1, 125.3 (1JC−F = 3.8 Hz), 124.3 (3JC−F = 272.1 Hz),
80.4, 78.5, 40.2, −2.0; HRMS (TOF) calcd for C14H18F3OSi (M+ + H)
m/z 287.1074, found 287.1049.
cis-3-Butyl-2-methylene-4-vinyloxetane (1a). Purification by flash
chromatography on silica gel (petroleum ether/EtOAc/Et3N,
98:1.5:0.5) provided cis-3-butyl-4-vinyl-2-methyleneoxetane (1a) (50
mg, 36%) as a yellow oil: IR (neat) 2959, 2930, 2874, 2859, 1662,
1
1178 cm−1; H NMR (400 MHz, CDCl3) δ 6.05 (ddd, J = 17.1, 10.4,
6.7 Hz, 1H), 5.33 (d, J = 17.1 Hz, 1H), 5.22 (d, J = 10.4 Hz, 1H), 4.78
(dd, J = 5.8, 5.8 Hz, 1H), 4.09 (dd, J = 3.3, 2.4 Hz, 1H), 3.74 (dd, J =
3.4, 1.7 Hz, 1H), 3.11−3.06 (m, 1H), 1.72−1.67 (m, 2H), 1.32−1.26
(m, 4H), 0.89 (t, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ
167.3, 137.0, 117.7, 85.7, 78.9, 48.7, 31.7, 29.0, 22.7, 14.1; HRMS
(TOF) calcd for C10H17O (M+ + H) m/z 153.1274, found 153.1236.
cis-4-Cyclohexyl-2-methylene-3-trimethylsilyloxetane (1e). Purifi-
cation by flash chromatography on silica gel (petroleum ether/EtOAc/
Et3N, 97.5:2:0.5) provided a mixture of cis-4-cyclohexyl-2-methylene-
3-(trimethylsilyl)oxetane (1e) and (Z)-4-cyclohexyl-3-trimethylsilyl-
but-3-en-2-one (3e) (10:1, 97 mg, 43%) as a yellow oil. cis-4-
Cyclohexyl-2-methylene-3-(trimethylsilyl)oxetane (1e): 1H NMR
(400 MHz, CDCl3) δ 4.51 (dd, J = 10.5, 6.9 Hz, 1H), 3.99 (dd, J =
2.8, 2.8 Hz, 1H), 3.56 (dd, J = 3.0, 1.8 Hz, 1H), 2.96 (ddd, J = 6.8, 1.9,
1.9 Hz, 1H), 1.93 (m, 1H), 1.77−1.58 (m, 5H), 1.28−1.09 (m, 3H),
0.88−0.73 (m, 2H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3) δ
165.5, 85.9, 77.1, 41.8, 37.3, 28.3, 26.5, 25.5, 25.3, −0.9.
cis-4-Benzyloxymethyl-2-methylene-3-trimethylsilyloxetane (1l).
Purification by flash chromatography on silica gel (petroleum ether/
EtOAc/Et3N, 97.5:2:0.5) provided cis-4-benzyloxymethyl-2-methyl-
ene-3-trimethylsilyloxetane (1l) (40 mg, 40%) as a yellow oil: IR
1
(neat) 2954, 2858, 1679, 1251 cm−1; H NMR (400 MHz, CDCl3) δ
7.34−7.32 (m, 4H), 7.30−7.20 (m, 1H), 5.12 (ddd, J = 7.3, 7.3, 4.2
Hz, 1H), 4.58 (d, J = 11.8 Hz, 1H), 4.52 (d, J = 11.8 Hz, 1H), 4.05 (m,
1H), 3.77 (dd, J = 10.7, 7.3 Hz, 1H), 3.68 (dd, J = 10.7, 4.3 Hz, 1H),
3.58 (dd, J = 3.5, 2.0 Hz, 1H), 3.12 (ddd, J = 7.7, 2.2, 2.2 Hz, 1H), 0.11
(s, 9H); 13C NMR (100 MHz, CDCl3) δ 165.6, 137.9, 128.6, 128.1,
128.0, 80.3, 77.8, 73.7, 71.6, 35.7, −1.2; HRMS (TOF) calcd for
C15H23O2Si (M+ + H) m/z 263.1462, found 263.1453.
trans-3-t-Butyldimethylsilyl-4-cyclohexyl-2-methyleneoxetane
(1f). Purification by flash chromatography on silica gel (petroleum
ether/EtOAc/Et3N, 97.5:2:0.5) provided trans-3-t-butyldimethylsilyl-
4-cyclohexyl-2-methyleneoxetane (1f) (110 mg, 68%) as a yellow oil:
1
IR (neat) 2927, 2855, 1812, 1676, 1250 cm−1; H NMR (400 MHz,
CDCl3) δ 4.24 (dd, J = 7.2, 4.9 Hz, 1H), 3.99 (dd, J = 2.8, 2.8 Hz, 1H),
3.54 (dd, J = 3.2, 1.9 Hz, 1H), 2.77 (ddd, J = 4.3, 1.9, 1.9 Hz, 1H), 1.93
(m, 1H), 1.77−1.74 (m, 2H), 1.69−1.57 (m, 3H), 1.29−1.09 (m, 3H),
1.01−0.87 (m, 2H), 0.90 (s, 9H), 0.07 (s, 3H), 0.03 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 166.4, 84.9, 78.2, 44.2, 33.4, 27.9, 27.8, 27.1,
26.5, 26.1, 25.7, 17.2, −7.4, −7.5; HRMS (TOF) calcd for C16H31OSi
(M+ + H) m/z 267.2144, found 267.2131.
Typical Procedure for the Preparation of α,β-Unsaturated
Ketones 3b and 3c. (E)-5-t-Butyldiphenylsilyloxy-3-methylpent-3-
en-2-one (3b). trans-4-t-Butyldiphenylsilyloxymethyl-3-methyl-2-
methyleneoxetane (1b) (61 mg, 1.7 mmol; neat) was heated in a
sand bath at 200 °C under N2 until the starting material was consumed
(by NMR). It was then cooled to rt and purified by flash
chromatography on silica gel (petroleum ether/EtOAc, 95:5) to give
(E)-5-t-butyldiphenylsilyloxy-3-methylpent-3-en-2-one (3b) (20 mg,
33%) as a clear oil: IR (neat) 3071, 2931, 2858, 1675, 1428 cm−1; 1H
NMR (400 MHz, CD2Cl2) δ 7.69−7.67 (m, 4H), 7.46−7.38 (m, 6H),
6.69 (t, J = 5.3 Hz, 1H), 4.46 (d, J = 5.5 Hz, 2H), 2.25 (s, 3H), 1.53 (s,
3H), 1.06 (s, 9H); 13C NMR (400 MHz, CD2Cl2) δ 199.6, 142.7,
136.8, 136.1, 133.9, 130.4, 128.3, 62.2, 27.1, 25.7, 19.5, 11.5; HRMS
(TOF) calcd for C22H28NaO2Si (M+ + Na) m/z 375.1751, found
375.1757.
trans-4-Heptyl-2-methylene-3-trimethylsilyloxetane (1g). Purifi-
cation by flash chromatography on silica gel (petroleum ether/EtOAc/
Et3N, 97.5:2:0.5) provided trans-4-heptyl-2-methylene-3-trimethylsily-
loxetane (1g) (30 mg, 34%) as a clear oil: IR (neat) 2956, 2929, 2857,
1
1678, 1251 cm−1; H NMR (400 MHz, CDCl3) δ 4.49 (ddd, J = 6.1,
6.1, 6.1 Hz, 1H), 3.97 (m, 1H), 3.51 (m, 1H), 2.57 (m, 1H), 1.85 (m,
1H), 1.66 (m, 1H), 1.27 (m, 10H), 0.86 (t, J = 6.8 Hz, 3H), 0.08 (s,
9H); 13C NMR (100 MHz, CDCl3) δ 165.8, 81.2, 77.5, 38.6, 37.4,
32.0, 29.6, 29.4, 24.7, 22.8, 14.3, −3.3. HRMS (TOF) calcd for
C14H29OSi (M+ + H) m/z 241.1982, found 241.1973.
(E)-3-Cyclohexylbut-3-en-2-one (3c).35 Purification by flash
chromatography on silica gel (petroleum ether/EtOAc, 95:5) provided
cis-4-Heptyl-2-methylene-3-trimethylsilyloxetane (1h). Purifica-
tion by flash chromatography on silica gel (petroleum ether/EtOAc/
1
(E)-3-cyclohexylbut-3-en-2-one (1c) (11 mg, 29%) as a clear oil: H
11218
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Article
NMR (400 MHz, CD2Cl2) δ 6.70 (dd, J = 16.2, 6.7 Hz, 1H), 6.00 (d, J
= 16.1 Hz, 1H), 2.22 (s, 3H), 2.19 (m, 1H), 1.76−1.60 (m, 5H),
1.32−1.09 (m, 5H); 13C NMR (100 MHz, CDCl3) δ 199.4, 153.6,
129.0, 40.8, 32.0, 27.1, 26.1, 25.9.
−0.02 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 206.3, 151.3, 147.1,
2
1
141.7, 130.6 (q, JC−F = 32.6 Hz), 128.9, 125.3 (q, JC−F = 3.6 Hz),
3
124.2 (q, JC−F = 272.6 Hz), 28.2, 0.65; HRMS (TOF) calcd for
C14H18F3OSi (M+ + H) m/z 287.1074, found 287.1095. E-stereo-
isomer: IR (neat) 2959, 2927, 1682, 1617, 1414, 1325 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.55 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz,
2H), 6.76 (s, 1H), 2.03 (s, 3H), 0.23 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 210.1, 153.6, 140.4, 136.4, 130.4 (q, 2JC−F = 32.3 Hz), 128.7,
Typical Procedure for the Preparation of α,β-Unsaturated
Ketones 3d and 3g. (Z)-4-Cyclohexyl-3-trimethylsilylbut-3-en-2-
one (3d). trans-4-Cyclohexyl-2-methylene-3-trimethylsilyloxetane (1d)
(56 mg, 2.5 mmol) (neat) was heated in a pre-equilibrated oil bath at
160 °C for 10 min under N2. It was then cooled to rt and purified by
flash chromatography on silica (petroleum ether/EtOAc, 97:3) to give
(Z)-4-cyclohexyl-3-trimethylsilylbut-3-en-2-one (3d) (45 mg, 80%) as
1
3
125.7 (q, JC−F = 3.7 Hz), 124.0 (q, JC−F = 272.4 Hz), 31.4, −1.5;
HRMS (TOF) calcd for C14H18F3OSi (M+ + H) m/z 287.1074, found
287.1084.
1
a clear oil: IR (neat) 2928, 2852, 1663, 1598, 1450, 1248 cm−1; H
(Z)-4-Benzyloxymethyl-3-trimethylsilylbut-3-en-2-one (3l). De-
rived from cis-4-benzyloxymethyl-2-methylene-3-trimethylsilyloxetane
(1l). No purification needed. (Z)-4-Benzyloxymethyl-3-trimethylsilyl-
but-3-en-2-one (3l) (30 mg, 99%) was isolated as a light brown oil: IR
NMR (400 MHz, CDCl3) δ 6.57 (d, J = 10.2 Hz, 1H), 2.37 (m, 1H),
2.21 (s, 3H), 1.75−1.60 (m, 5H), 1.28−1.08 (m, 5H), 0.17 (s, 9H);
13C NMR (100 MHz, CDCl3) δ 206.6, 158.9, 143.8, 40.7, 32.8, 28.1,
1
(neat) 2952, 2856, 1664, 1248 cm−1; H NMR (400 MHz, CDCl3) δ
26.0, 25.7, 1.1; HRMS (TOF) calcd for C13H25OSi (M+ + H) m/z
225.1669, found 225.1683.
7.37−7.27 (m, 5H), 6.89 (t, J = 5.7 Hz, 1H), 4.54 (s, 2H), 4.24 (d, J =
5.7 Hz, 2 H), 2.25 (s, 3H), 0.14 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 205.6, 149.6, 147.2, 137.8, 128.7, 128.2, 128.1, 73.3, 69.0,
27.9, 0.6; HRMS (TOF) calcd for C15H23O2Si (M+ + H) m/z
263.1462, found 263.1457.
(Z)-4-Heptyl-3-trimethylsilylbut-3-en-2-one (3g). Derived from
trans-4-heptyl-2-methylene-3-trimethylsilyloxetane (1g). No purifica-
tion was needed, and (Z)-4-heptyl-3-trimethylsilylbut-3-en-2-one (3g)
(25 mg, 89%) was isolated as a yellow oil: IR (neat) 2956, 2926, 2856,
1663, 1599, 1247 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.81 (t, J = 7.3
Hz, 1H), 2.24 (m, 4H), 1.41 (m, 2H), 1.26 (m, 9H), 0.86 (m, 3H),
0.11 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 206.2, 154.4, 145.8,
32.0, 29.6, 29.4, 28.0, 22.8, 14.3, 1.0; HRMS (TOF) calcd for
C14H29OSi (M+ + H) m/z 241.1982, found 241.1964.
ASSOCIATED CONTENT
■
S
* Supporting Information
General experimental methods and H and 13C NMR spectra
1
for all new compounds, structures and relative energies of the
reactants, products, and transition states in both E- and Z-
isomers, tables of atom coordinates and absolute energies, and
evaluation of rate constants. This material is available free of
charge via the Internet at http://pubs.acs.org.
Typical Procedure for the Preparation of α,β-Unsaturated
Ketones 3f and 3i−3l. (Z)-3-t-Butyldimethylsilyl-4-cyclohexylbut-
3-en-2-one (3f). A solution of trans-4-cyclohexyl-3-(t-butyldimethyl-
silyl)-2-methyleneoxetane (1f) (68 mg, 0.26 mmol) in toluene-d8
(0.52 mL) was heated to reflux in a pre-equilibrated oil bath at 120−
135 °C under N2 until the starting material was consumed (by NMR).
The solution was then cooled to rt, and the solvent removed in vacuo.
No purification was needed. The desired (Z)-3-t-butyldimethylsilyl-4-
cyclohexylbut-3-en-2-one (3f) (64 mg, 94%) was isolated as a yellow
AUTHOR INFORMATION
Corresponding Author
*E-mail: amy.howell@uconn.edu. Phone: 860-486-3460. Fax:
860-486-2981.
■
1
oil: IR (neat) 2928, 2854, 1668, 1595, 1248 cm−1; H NMR (400
MHz, toluene-d8) δ 6.45 (d, J = 10.6 Hz, 1H), 2.32 (dtt, J = 10.6, 10.6,
3.5 Hz, 1H), 2.00 (s, 3H), 1.63−1.55 (m, 5H), 1.20−1.08 (m, 3H),
1.02 (s, 9H), 0.98−0.86 (m, 2H), 0.21 (s, 6H); 13C NMR (100 MHz,
toluene-d8) δ 206.6, 158.9, 143.8, 40.7, 32.8, 28.1, 26.0, 25.7, −1.1;
HRMS (TOF) calcd for C16H30NaOSi (M+ + Na) m/z 289.1958,
found 289.1957.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(Z)-4-t-Butyl-3-trimethylsilylbut-3-en-2-one (3i). Derived from
trans-4-t-butyl-2-methylene-3-(trimethylsilyl)oxetane (1i). Purification
by flash chromatography on silica gel (petroleum ether/EtOAc, 96:4)
provided (Z)-4-t-butyl-3-(trimethylsilyl)but-3-en-2-one (3i) (11 mg,
33% based on unreacted starting material) as a clear oil: IR (neat)
2959, 1675, 1585, 1251 cm−1; 1H NMR (400 MHz, CDCl3) δ 6.43 (s,
1H), 2.21 (s, 3H), 1.12 (s, 9H), 0.22 (s, 9H); 13C NMR (100 MHz,
CDCl3) δ 209.5, 158.3, 145.1, 34.7, 30.8, 30.0, 2.8; HRMS (TOF)
calcd for C11H23OSi (M+ + H) m/z 199.1513, found 199.1527.
(Z)-4-Phenyl-3-trimethylsilylbut-3-en-2-one (3j). Derived from cis-
2-methylene-4-phenyl-3-trimethylsilyloxetane (1j). Purification by
flash chromatography on silica gel (petroleum ether/EtOAc, 97:3)
provided (Z)-4-phenyl-3-trimethylsilylbut-3-en-2-one (3j) (35 mg,
64%) as a clear oil: IR (neat) 3026, 2953, 2898, 1665, 1587, 1588,
This manuscript is based upon work partially supported by the
National Science Foundation (NSF) under Grant Nos. CHE-
0111522 and CHE-1048717. J.A.G. acknowledges financial
support from the Camille and Henry Dreyfus foundation and
NSF CAREER Award CHE-0847340.
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