Bu4N+ alkoxide-initiated/autocatalytic addition reactions with organotrimethylsilanes

Article abstract of DOI:10.1021/jo5007637

The use of Me₃SiO^-/Bu₄N⁺ as a general activator of organotrimethylsilanes for addition reactions has been established. The broad scope of the method offers trimethylsilanes (including acetate, allyl, propargyl, benzyl, dithiane, heteroaryl, and aryl derivatives) as bench-stable organometallics that can be readily utilized as carbanion equivalents for synthesis. Reactions are achieved at rt without the requirement of specialized precautions that are commonplace for other organometallics.

Full text of DOI:10.1021/jo5007637

Article
pubs.acs.org/joc
Bu4N+ Alkoxide-Initiated/Autocatalytic Addition Reactions with
Organotrimethylsilanes
Manas Das and Donal F. O’Shea*
†Department of Pharmaceutical and Medicinal Chemistry, Royal College of Surgeons in Ireland, 123 St. Stephen’s Green, Dublin 2,
Ireland
School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
S
* Supporting Information
ABSTRACT: The use of Me3SiO−/Bu4N+ as a general
activator of organotrimethylsilanes for addition reactions has
been established. The broad scope of the method offers
trimethylsilanes (including acetate, allyl, propargyl, benzyl,
dithiane, heteroaryl, and aryl derivatives) as bench-stable
organometallics that can be readily utilized as carbanion equivalents for synthesis. Reactions are achieved at rt without the
requirement of specialized precautions that are commonplace for other organometallics.
Scheme 1. Analysis of Trimethylsilane Addition Reactions
INTRODUCTION
■
The research literature on organometallic reagent addition to an
electrophilic carbon is nothing short of vast.1 The common
conceptual purpose of generating an organometallic reagent is
the formation of a nucleophilic carbon via an electronically
polarized carbon−metal bond. A consequence of using the more
reactive organometallics of Li, Mg, Zn, Cu, Ti, Ni, and Pd is that
they can rarely be isolated or stored, leading to individualized
reaction conditions for their generation and in situ reaction. An
idealized collection of organometallic reagents evokes the
seemingly two incompatible features of bench stability and
high reactivity. Silicon organometallics, as their corresponding
organotrimethylsilanes, could provide this ideal, but significant
challenges exist in identifying mild conditions that can unlock the
carbanion reactivity of organotrimethylsilanes in a general
manner without using toxic activators or forcing conditions.
The primary attraction of using silicon as the metallic
component is the inherent bench stability of organosilanes due
to the relatively low bond polarization of the C−Si bond. The
synthetic use of organotrimethylsilanes was first established by
the pioneering work of Sakurai and others, which showed that
fluoride could promote the addition reactions of allyl-, alkynyl-,
cyano- and trifluoromethylsilanes.2 Numerous reports have
expanded on these earlier publications, but the means of
activation is most often a fluoride source.3 In this report, we
illustrate the first general addition method applicable for the
widest range of bench-stable trimethylsilane substrates. The
universal reaction conditions are mild and user-friendly, can be
carried out at room temperature, and do not rely on the use of
fluoride. Our approach to achieving this was guided by
mechanistic studies of the fluoride-promoted addition of allyl-
and, in our own work, benzyltrimethylsilanes 1 to carbonyls
(Scheme 1).4 These studies have indicated that the reaction
pathway is a fluoride-initiated formation of hypervalent silicon
species 2, which provides a carbanion equivalent that upon
carbonyl addition produces an alkoxide 3 and trimethylsilyl
fluoride.
The reaction pathway then enters an autocatalytic cycle in
which the alkoxide 3 reacts with the starting organotrimethylsi-
lane to generate another hypervalent silicon species 4, thereby
propagating the reaction and producing product 5. If the role of
fluoride is solely to initiate the reaction, while an alkoxide-
controlled autocatalytic cycle drives the reaction to completion,
then it would be plausible to expect that fluoride could be
replaced with a suitable alkoxide. This would result in a reaction
Received: April 3, 2014
© XXXX American Chemical Society
A
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sequence that is initiated by one alkoxide and then autocatalytic
turnover is achieved by the in situ-produced alkoxide. With this
analysis in mind, an investigation into alternative Lewis base
(LB) activation of organotrimethylsilanes was undertaken
(Scheme 1).5 As the most common synthetically utilized
organometallics have functional groups such as acetate, allyl,
propargyl, benzyl,6 dithiane, heteroaryl, and aryl, the substituted
trimethylsilanes 6−13 (Figure 1) were selected for evaluation of
the new method.
An initial interpretation of the failure of any of the alkoxides to
mediate the reaction could lead to the conclusion that the
autocatalytic cycle as proposed in Scheme 1 is not in operation.
But a critical remaining factor that differs in the fluoride and
alkoxide reaction conditions is the role of the countercation. For
the fluoride reagents used, the counterion was a Bu4N+ salt (entry
1), whereas inorganic potassium salts were employed for the
unsuccessfully attempted alkoxide-mediated reactions (entries
2−4). To fully replicate the countercation conditions without the
need to presynthesize Bu4N+ alkoxide salts, an in situ exchange
was devised using inexpensive Bu4NCl.8 Repeating the three
reactions with 10 mol % alkoxide and Bu4NCl, we were delighted
to obtain the product for each alkoxide in good yield after 2−3 h
of reflux (entries 5−7). Remarkably, with Me3SiOK, the weakest
base of the three, the reaction was complete at room temperature
after 2 h, providing 14a in 80% yield when Bu4NCl was included
(entry 8).
To illustrate the generality of the Bu4N+ effect, the reactions of
trimethylsilanes bearing ethyl acetate (6), allyl (7a), propargyl
(8), dithiane (10), heteroaryl (12), and aryl (13b) groups with
benzaldehyde were carried out. In each case, the reaction was
successful at either rt or 0 °C, and the corresponding product
14b−g was obtained in good to excellent yield (Table 1, entries
9−14). The exciting potential of this approach can be gauged by
the wide range of organotrimethylsilanes undergoing addition
reactions under one set of conditions. Of specific note is the
Figure 1. Trimethylsilyl organometallic reagents.
RESULTS AND DISCUSSION
■
We have previously reported that the fluoride-mediated addition
of (3-methoxybenzyl)trimethylsilane (9c) to benzaldehyde in
THF at reflux gave alcohol 14a in good yield (Table 1, entry 1).4a
Table 2. Comparison of Me3SiO−/Bu4N+- and Fluoride-
Mediated Additions
a
Table 1. Screening and Optimization of Conditions
a
time
silane
LB
bc
mol % temp
(h)
14 (% yield)
1
9c
9c
9c
9c
9c
9c
9c
9c
6
TBAT
5
10
10
10
10
10
10
10
10
10
10
10
10
10
Δ
Δ
Δ
Δ
Δ
Δ
Δ
rt
3
14a (82)
−
−
2
Me3SiOK
12
12
12
3
3
EtOK
4
tBuOK
−
5
tBuOK/Bu4NCl
EtOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
Me3SiOK/Bu4NCl
14a (70)
14a (74)
14a (78)
14a (80)
6
3
7
2
8
2
d
9
0 °C
rt
0.5
2
14b (83)
10
11
12
13
14
7a
8
14c (88)
e
0 °C
rt
1
14d (59)
10
12
13b
2
14e (87)
f
rt
5
14f (78)
rt
5
14g (86)
a
Trimethylsilane (0.6 mmol) and aldehyde (0.5 mmol), unless
b
otherwise noted. TBAT = tetrabutylammonium triphenyldifluorosi-
c
licate. A similar result was obtained with TBAF (see ref 4a).
d
e
Trimethylsilane (0.5 mmol) and aldehyde (0.6 mmol). A mixture of
f
propargyl and allenyl alcohols was isolated. Trimethylsilane (1.0
mmol) and aldehyde (0.5 mmol).
a
Trimethylsilane (0.6 mmol) and aldehyde (0.5 mmol), unless
This reaction was chosen for the development of a new non-
fluoride activation method, and an initial screen of the three
different Lewis bases tBuOK, EtOK, and Me3SiOK was carried
out. These alkoxides were chosen to encompass the alcohol pKa
range of 17, 16, and 12.7 respectively.7 Using the identical
conditions but replacing fluoride with an alkoxide failed to
produce 14a even after prolonged reaction times (entries 2−4).
b
otherwise noted. Trimethylsilane (1.0 mmol) and aldehyde (0.5
c
mmol). The reaction was performed at reflux with Me3SiOK/Bu4NCl.
d
e
A mixture of propargyl and allenyl alcohols was isolated. The
f
reaction was performed at rt. The reaction was performed at 0 °C.
g
h
Me3SiOK/Bu4NCl (20 mol %) was used. Me3SiOK/Bu4NCl (5 mol
i
j
%) was used. Worked up with water. Trimethylsilane (0.375 mmol),
aldehyde (0.25 mmol), and Me3SiOK/Bu4NCl (0.375 mmol).
B
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tolerance of the ester functional group of 6, which is often
sensitive to organometallic reactions, and the aromatic derivative
13b, which is often considered too unreactive to effectively
participate in addition reactions.
mediated reactions gave over 90% conversion to 14a within 1 h,
whereas fluoride reached only approximately 40% conversion at
this time point (Figure 2, top graph). It would be expected that
the participation of arylsilane 13b in an addition reaction would
be more challenging, yet the Me3SiO−/Bu4N+ conditions gave
complete conversion within 5 h, whereas at that time point only a
trace of product could be detected when fluoride was used to
promote the reaction (Figure 2, bottom graph). Collectively
these results illustrate that Me3SiO−/Bu4N+ is superior to
fluoride at obtaining carbanion reactivity from organotrimethyl-
silanes. This could be attributed to a significant enhancement of
the nucleophilicity of the trimethylsilyl oxide as the ammonium
salt with respect to an inorganic countercation.
Next, the electrophile scope was explored utilizing the
Me3SiO−/Bu4N+ silicon-activating conditions. Encouragingly,
diversely substituted aromatic, heteroaromatic, α,β-unsaturated,
and aliphatic aldehydes, ketones, and imines all underwent
addition reactions with the 11 different trimethylsilanes tested to
give the corresponding alcohol and amine products 16a−t
(Table 3).
To probe the practicality of Me3SiO−/Bu4N+-mediated
addition reactions, a side-by-side comparison with fluoride
activation was carried out for 15 reactions with various
trimethylsilanes and carbonyls (Table 2). The allyl (7a and
7b), propargyl (8), benzyl (9a−e), dithianyl (10), and
benzothiazole (11) derivatives were all successful with
Me3SiO−/Bu4N+ activation at rt or 0 °C, providing products
15a−j with no major differential from fluoride under reflux. A
significant difference emerged with the reactions of furan 12 and
aryl derivatives 13b−e. The results showed that the rt Me3SiO−/
Bu4N+ conditions were successful in each case, giving the
products 15k−o in good yields, in contrast to fluoride (at reflux),
for which the reactions either failed or gave the products in low
yields (Table 2).
A more detailed comparison of the two silicon-activating
conditions was carried out for the reactions of 9c and 13b with
benzaldehyde to generate 14a and 14g, respectively. The
reactions were monitored for product formation over time
using HPLC. It was revealing to see that the Me3SiO−/Bu4N+-
Because of their synthetic importance yet rarity of use in
addition reactions, specific attention was given to the aryl-
Si(Me)3 derivatives 12 and 13a−e (Table 4).9 In the case of furan
Table 3. Me3SiO−/Bu4N+-Promoted Addition to Carbonyls
a
and Imines with Various Trimethylsilanes
a
Trimethylsilane (0.6 mmol) and aldehyde (0.5 mmol), unless
b
otherwise noted. Trimethylsilane (0.5 mmol) and aldehyde (0.6
mmol). The reaction was performed at 0 °C. Trimethylsilane (1.0
mmol) and electrophile (0.5 mmol). Me3SiOK/Bu4NCl (20 mol %)
c
d
e
Figure 2. Relative percentage formation of (top) 14a and (bottom) 14g
using fluoride (red) or Me3SiO−/Bu4N+ (green) in the reactions of
benzaldehyde with 9c and 13b, respectively.
f
was used. A mixture of propargyl and allenyl alcohols was isolated.
g
The reaction was performed at reflux.
C
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a
paper for Peterson olefination reactions is underway and will be
reported in due course.
Table 4. Aryl and Heteroaryl Addition to Carbonyls
EXPERIMENTAL SECTION
■
General Information. All of the reactions involving air-sensitive
reagents were performed under nitrogen either in oven- or flame-dried
glassware using syringe−septum cap technique. All of the solvents were
purified and degassed before use. 2,2,6,6-Tetramethylpiperidine TMP-
(H) was distilled from CaH2 prior to use. THF was purified under
nitrogen over Na/benzophenone ketyl. BuLi was purchased as a 2.5 M
solution in hexanes. The exact concentration of the BuLi was
determined by titration with diphenylacetic acid in THF prior to use.
KOtBu was purchased as a 1.0 M solution in THF. Tetrabutylammo-
nium difluorotriphenylsilicate (TBAT) was used as received.
Preweighed amounts of Me3SiOK and Bu4NCl were stored in a
desiccator utilizing P2O5 as a desiccant and used immediately upon
removal from the desiccator. Aldehydes were purified by distillation or
silica gel chromatography prior to use. Chromatographic separations
were carried out under pressure on Merck silica gel 60 or aluminum
oxide 60 using flash-column techniques. Reactions were monitored by
thin-layer chromatography (TLC) carried out on 0.25 mm silica gel-
coated aluminum plates with UV light (254 nm) as the visualizing agent.
1H and 13C NMR spectra were recorded at room temperature on a 400
MHz spectrometer. HRMS measurements were acquired with a TOF
mass analyzer. Isolated yields after column chromatography are
reported. Compounds 6, 7a, 7b, 8, 9a, 10, 11, and 13a are commercially
available. Compounds 9b−e,4a 12,10 13b,11 13d,11 and 13e12 were
prepared according to the literature procedures.
a
Trimethylsilane (0.6 mmol) and aldehyde (0.5 mmol), unless
b
c
otherwise noted. Worked up with water. Trimethylsilane (0.75
mmol), aldehyde (0.25 mmol), and Me3SiOK/Bu4NCl (0.375 mmol).
d
Trimethylsilane (0.375 mmol), aldehyde (0.25 mmol), Me3SiOK/
Bu4NCl (0.375 mmol).
Trimethyl(2-(trifluoromethyl)phenyl)silane (13c).13 A solution
of 1-bromo-2-(trifluoromethyl)benzene (1.8 g, 8 mmol) in THF (80
mL) at −78 °C was treated dropwise with s-BuLi (1.3 M, 9.2 mL, 12
mmol) under a N2 atmosphere. The reaction mixture was stirred for 1 h
at −78 °C, and chlorotrimethylsilane (1.6 mL, 12 mmol) was added.
The reaction mixture was stirred for a further 1 h at −78 °C and then
slowly warmed to rt. The solvent was removed under reduced pressure,
and aq HCl (2 M, 40 mL) was added. The residue was extracted with
diethyl ether (50 × 3 mL), and the organic layers were combined,
washed with brine (50 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
12 and the ortho-substituted aryl derivatives 13b and 13c, 10 mol
% Me3SiO−/Bu4N+ was sufficient for the reaction to reach
completion, giving products 17a−j in good to excellent yields.
For the para-substituted arenes 13d and 13e, a catalytic amount
of Me3SiO−/Bu4N+ proved insufficient for the reaction to reach
completion, though increasing the amount of Me3SiO−/Bu4N+
to 1.5 equiv gave the diaryl alcohols 17k and 17l in yields of 68
and 64% respectively. A plausible rationale for this experimental
observation is the failure of the autocatalytic cycle in these
examples because of the nature of the diaryl alkoxide that is
generated in situ. But as the activating reagents Me3SiOK and
Bu4NCl are inexpensive, nontoxic, and easily separated from the
products, their use in greater than catalytic quantities when
necessary is not considered a significant drawback. Of the series
examined, the only derivative that failed under these conditions
was phenyltrimethylsilane (13a), which denotes the current
reactivity limit of the method. Investigations remain ongoing to
devise conditions to further extend the reactivity limit of our
method to promote reactions with substrates such as 13a, which
have, as would be expected, the lowest reactivity.
1
cyclohexane (100%) afforded 13c as a colorless oil (1.43 g, 82%). H
NMR (400 MHz, CDCl3): δ 7.74−7.66 (m, 2H), 7.53−7.42 (m, 2H),
0.34 (s, 9H) ppm. 13C NMR (CDCl3, 100 MHz): δ 138.5, 136.0, 135.0
(q, J = 31.0 Hz), 130.8 (q, J = 1.2 Hz), 129.1, 126.1 (q, J = 5.4 Hz), 125.1
(q, J = 273.2 Hz), 0.4 (q, J = 2.6 Hz) ppm.
2-(3-Methoxyphenyl)-1-phenylethanol (14a).4a Addition of 9c
to Benzaldehyde Using tBuOK/Bu4NCl in THF. A solution of (3-
methoxybenzyl)trimethylsilane (9c) (116 mg, 0.6 mmol) and
benzaldehyde (51 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and tBuOK (50 μL, 0.05
mmol, 1 M in THF) under N2, and the resulting solution was stirred at
reflux for 3 h. The reaction mixture was cooled to rt and the solvent
removed under reduced pressure, and 2 M HCl (10 mL) was added. The
residue was extracted with diethyl ether (15 × 3 mL), and the organic
layers were combined, washed with brine (10 mL), dried over sodium
sulfate, and concentrated to dryness. Purification by silica gel
chromatography eluting with cyclohexane/ethyl acetate (96:4) yielded
14a as a colorless oil (80 mg, 70%).
CONCLUSION
■
In summary, a new Lewis base activation of organotrimethylsi-
lanes utilizing Me3SiO−/Bu4N+ has been developed, with the key
to its success lying in the use of the Bu4N+ cation, which is
superior to fluoride in promoting trimethylsilane addition
reactions. Once initiated, reactions proceed to completion via
an autocatalytic cycle involving the in situ-formed alkoxide. For
reactions where the autocatalytic cycle is not effective, a
stoichiometric amount of the activator can be used. Taken
together, these results indicate that the use of bench-stable
trimethylsilyl organometallics, many of which are already
commercially available, may become increasingly attractive to
the wider community of synthetic chemists. Investigations into a
general asymmetric approach to using organotrimethylsilanes is
ongoing. A further expansion of the concepts presented in this
Addition of 9c to Benzaldehyde Using EtOK/Bu4NCl in THF. A
solution of (3-methoxybenzyl)trimethylsilane (9c) (116 mg, 0.6 mmol)
and benzaldehyde (51 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and EtOK (4 mg, 0.05
mmol) under N2, and the resulting solution was stirred at reflux for 3 h.
The reaction mixture was cooled to rt and the solvent removed under
reduced pressure, and 2 M HCl (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded 14a as a colorless
oil (84 mg, 74%).
D
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Addition of 9c to Benzaldehyde Using Me3SiOK/Bu4NCl in THF. A
solution of (3-methoxybenzyl)trimethylsilane (9c) (116 mg, 0.6 mmol)
and benzaldehyde (51 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at rt for 2 h.
The solvent was removed under reduced pressure, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL). The organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded 14a as a colorless oil (91 mg, 80%).
(51 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was treated with dried
Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol). The
resulting solution was stirred under N2 at rt for 2 h, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate
(90:10) yielded the product 14e as a colorless solid (98 mg, 87%, mp
59−61 °C). 1H NMR (400 MHz, CDCl3): δ 7.45−7.30 (m, 5H), 4.92
(d, J = 7.5, 1H), 4.08 (d, J = 7.5 Hz, 1H), 3.01−2.89 (m, 3H), 2.78−2.68
(m, 2H), 2.13−1.91 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ
140.3, 128.6, 128.4, 127.0, 74.9, 52.9, 28.3, 27.7, 25.5 ppm. HRMS-ESI
[M + Na]+: 249.0381, C11H14ONaS2 requires 249.0384.
1H NMR (400 MHz, CDCl3): δ 7.38−7.32 (m, 4H), 7.31−7.26 (m,
1H), 7.22 (t, J = 7.9 Hz, 1H), 6.82−6.76 (m, 2H), 6.72 (s, 1H), 4.90 (dd,
J = 8.3, 4.8 Hz, 1H), 3.77 (s, 3H, OCH3), 3.06−2.92 (m, 2H), 1.98 (s,
1H) ppm. 13C NMR (100 MHz, CDCl3): δ 159.7, 143.7, 139.5, 129.5,
128.4, 127.6, 125.9, 121.8, 115.0, 112.1, 75.2, 55.1, 46.2 ppm. HRMS-
ESI [M + Na]+: 251.1039, C15H16O2Na requires 251.1048.
Furan-2-yl(phenyl)methanol (14f).18 A solution of furan-2-
yltrimethylsilane (12) (140 mg, 1.0 mmol) and benzaldehyde (51 μL,
0.5 mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl
(14 mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol). The resulting
solution was stirred under N2 at rt for 5 h, and 0.2 M HCl (10 mL) was
added. The residue was extracted with diethyl ether (15 × 3 mL), and
the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
Ethyl 3-Hydroxy-3-phenylpropanoate (14b).14 A solution of
ethyl 2-(trimethylsilyl)acetate (6) (92 μL, 0.50 mmol) and
benzaldehyde (61 μL, 0.6 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol). The resulting solution was stirred under N2 at 0 °C for 30
min, and 1 M HCl (10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (90:10) yielded 14b as a colorless oil (81 mg,
83%). 1H NMR (400 MHz, CDCl3): δ 7.41−7.25 (m, 5H), 5.13 (dd, J =
8.7, 4.1 Hz, 1H), 4.18 (q, J = 7.2 Hz, 2H), 2.80−2.67 (m, 2H), 1.26 (t, J =
7.2 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 172.5, 142.6, 128.7,
127.9, 125.8, 70.5, 61.0, 43.5, 14.3 ppm. HRMS-ESI [M + Na]+:
217.0836, C11H14O3Na requires 217.0814.
1
yielded the product 14f as a yellow oil (68 mg, 78%). H NMR (400
MHz, CDCl3): δ 7.46−7.29 (m, 6H), 6.31 (dd, J = 3.2, 1.8 Hz, 1H), 6.11
(dt, J = 3.2, 0.7 Hz, 1H), 5.83 (s, 1H), 2.39 (br s, 1H) ppm. 13C NMR
(100 MHz, CDCl3): δ 156.1, 142.7, 140.9, 128.6, 128.2, 126.7, 110.4,
107.6, 70.3 ppm. HRMS-EI [M]+: 174.0679, C11H10O2 requires
174.0681.
(2-Chlorophenyl)(phenyl)methanol (14g).19 A solution of (2-
chlorophenyl)trimethylsilane (13b) (111 mg, 0.6 mmol) and
benzaldehyde (51 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol). The resulting solution was stirred under N2 at rt for 5 h, and
2 M HCl (10 mL) was added. The residue was extracted with diethyl
ether (15 × 3 mL), and the organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
1-Phenylbut-3-en-1-ol (14c).15 A solution of allyltrimethylsilane
(7a) (96 μL, 0.6 mmol) and benzaldehyde (51 μL, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol). The resulting solution was
stirred under N2 at rt for 2 h, and 2 M HCl (10 mL) was added. The
residue was extracted with diethyl ether (15 × 3 mL), and the organic
layers were combined, washed with brine (10 mL), dried over sodium
sulfate, and concentrated to dryness. Purification by silica gel
chromatography eluting with cyclohexane/ethyl acetate (95:5) yielded
1
acetate (95:5) yielded 14g as a colorless oil (94 mg, 86%). H NMR
(400 MHz, CDCl3): δ 7.60 (dd, J = 7.7, 1.6 Hz, 1H), 7.43−7.18 (m, 8H),
6.22 (d, J = 3.1 Hz, 1H), 2.43−2.35 (m, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 142.4, 141.1, 132.7, 129.7, 128.9, 128.6, 128.2, 127.9, 127.2,
127.0, 72.8 ppm. MS-ESI [(M + H) − H2O)]+: 201.05, C13H10Cl
requires 201.04.
1
14c as a colorless oil (65 mg, 88%). H NMR (400 MHz, CDCl3): δ
7.38−7.24 (m, 5H), 5.87−5.75 (m, 1H), 5.21−5.11 (m, 2H), 4.74 (dd, J
= 7.3, 5.7 Hz, 1H), 2.59−2.44 (m, 2H), 2.04 (br s, 1H) ppm. 13C NMR
(100 MHz, CDCl3): δ 144.0, 134.6, 128.5, 127.7, 125.9, 118.6, 73.4, 44.0
ppm. MS-ESI [M − H]−: 147.06, C10H11O requires 147.08.
2-Phenylpent-4-en-2-ol (15a).20 Addition of 7a to Acetophe-
none Using TBAT in THF at Reflux. A solution of allyltrimethylsilane
(7a) (114 mg, 1.0 mmol) and acetophenone (59 μL, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with TBAT (27 mg, 0.05 mmol),
and the resulting solution was stirred under N2 at reflux for 3 h. The
reaction mixture was cooled to rt and the solvent removed under
reduced pressure, and 2 M HCl (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded 15a as a colorless
oil (72 mg, 89%).
1-Phenylbuta-2,3-dien-1-ol [14d-(1), Major] and 1-Phenyl-
but-3-yn-1-ol [14d-(2), Minor].16 A solution of trimethyl(prop-2-yn-
1-yl)silane (8) (67 mg, 0.60 mmol) and benzaldehyde (51 μL, 0.5
mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14
mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting
solution was stirred under N2 at 0 °C for 1 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded a 70:30 mixture of
products 14d-(1,2) as a colorless oil (43 mg, 59%). 1H NMR (400 MHz,
CDCl3): δ 7.44−7.27 (m, 5H), 5.45 (q, J = 6.5 Hz, 0.7H), 5.31−5.25 (m,
0.7H), 4.98−4.91 (m, 1.4H), 4.88 (t, J = 6.3 Hz, 0.3H), 2.65 (dd, J = 6.5,
2.6 Hz, 0.6H), 2.41 (br s, 0.3H), 2.39 (s, 0.3H), 2.18 (br s, 0.7H), 2.08 (t,
J = 2.6 Hz, 0.3H) ppm. 13C NMR (100 MHz, CDCl3): δ 207.2, 143.0,
142.6, 128.7, 128.6, 128.1, 128.0, 126.2, 125.9, 95.3, 80.8, 78.4, 72.5,
72.1, 71.1, 29.6 ppm. MS-ESI [M − H]−: 145.04, C10H11O requires
145.07.
Addition of 7a to Acetophenone Using Me3SiOK/Bu4NCl in THF at
Reflux. A solution of allyltrimethylsilane (7a) (114 mg, 1.0 mmol) and
acetophenone (59 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at reflux for
3 h. The reaction mixture was cooled to rt and the solvent removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded 15a as a colorless
oil (62 mg, 77%).
Note: the isolation of mixtures of buta-2,3-dien-1-ols and but-3-yn-1-
ols from fluoride-mediated addition reactions of trimethyl(prop-2-yn-1-
yl)silane has been previously reported.16
1H NMR (400 MHz, CDCl3): δ 7.47−7.41 (m, 2H), 7.38−7.31 (m,
2H), 7.27−7.21 (m, 1H), 5.69−5.56 (m, 1H), 5.18−5.08 (m, 2H), 2.69
(dd, J = 13.7, 6.4 Hz, 1H), 2.50 (dd, J = 13.7, 8.3 Hz, 1H), 2.04 (br s,
(1,3-Dithian-2-yl)(phenyl)methanol (14e).17 A solution of (1,3-
dithian-2-yl)trimethylsilane (10) (116 mg, 0.6 mmol) and benzaldehyde
E
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1H), 1.55 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 147.8, 133.8,
128.3, 126.8, 124.9, 119.6, 73.8, 48.6, 30.1 ppm. MS-ESI [M + H]+:
163.11, C11H15O requires 163.10.
114.0, 113.9, 95.4, 81.0, 78.3, 72.1, 71.7, 71.0, 55.5, 55.4, 29.5 ppm.
HRMS-ESI [M + H]+: 177.0924, C11H13O2 requires 177.0916.
Note: the isolation of mixtures of buta-2,3-dien-1-ols and but-3-yn-1-
ols from fluoride-mediated addition reactions of trimethyl(prop-2-yn-1-
yl)silane has been previously reported.17
1-(3,4-Dimethoxyphenyl)-3-methylbut-3-en-1-ol (15b). Addi-
tion of 7b to 3,4-Dimethoxybenzaldehyde Using TBAT in THF at
Reflux. A solution of trimethyl(2-methylallyl)silane (7b) (102 μL, 0.60
mmol) and 3,4-dimethoxybenzaldehyde (83 mg, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with TBAT (27.0 mg, 0.05
mmol), and the resulting solution was stirred under N2 at reflux for 3 h.
The reaction mixture was cooled to rt and the solvent removed under
reduced pressure, and 2 M HCl (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (90:10) yielded 15b as a
colorless solid (97 mg, 87%).
1-Benzylcyclohexanol (15d).4a Addition of 9a to Cyclo-
hexanone Using TBAT in THF at rt. A solution of benzyltrimethylsilane
(9a) (164 mg, 1.0 mmol) and cyclohexanone (52 μL, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with TBAT (54 mg, 0.10 mmol),
and the resulting solution was stirred under N2 at rt for 12 h. The solvent
was removed under reduced pressure, and 2 M HCl (10 mL) was added.
The residue was extracted with diethyl ether (15 × 3 mL), and the
organic layers were combined, washed with brine (10 mL), dried over
sodium sulfate, and concentrated to dryness. Purification by silica gel
chromatography eluting with cyclohexane/ethyl acetate (96:4) yielded
15d as a colorless solid (69 mg, 71%).
Addition of 9a to Cyclohexanone Using Me3SiOK/Bu4NCl in THF at
rt. A solution of benzyltrimethylsilane (9a) (164 mg, 1.0 mmol) and
cyclohexanone (52 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (28 mg, 0.1 mmol) and TMSOK (13 mg, 0.1
mmol), and the resulting solution was stirred under N2 at rt for 5 h. The
solvent was removed under reduced pressure, and 2 M HCl (10 mL) was
added. The residue was extracted with ethyl acetate (10 × 3 mL), and
the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded 15d as a colorless solid (59 mg, 62%, mp 41−43 °C).
1H NMR (400 MHz, CDCl3): δ 7.34−7.18 (m, 5H), 2.75 (s, 2H),
1.65−1.38 (m, 10H), 1.25 (br s, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 137.1, 130.6, 128.1, 126.4, 71.1, 48.7, 37.3, 25.8, 22.1 ppm.
HRMS-EI [M]+: 190.1361, C13H18O requires 190.1358.
Addition of 7b to 3,4-Dimethoxybenzaldehyde Using Me3SiOK/
Bu4NCl in THF at rt. A solution of trimethyl(2-methylallyl)silane (7b)
(102 μL, 0.60 mmol) and 3,4-dimethoxybenzaldehyde (83 mg, 0.5
mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14
mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting
solution was stirred under N2 at rt for 3 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (90:10) yielded 15b as a
colorless solid (93 mg, 84%, mp 72−74 °C).
1H NMR (400 MHz, CDCl3): δ 6.95 (d, J = 1.7 Hz, 1H), 6.90 (dd, J =
8.2, 1.7 Hz, 1H), 6.84 (d, J = 8.2 Hz, 1H), 4.93 (s, 1H), 4.86 (s, 1H), 4.77
(dd, J = 8.7, 4.8 Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 2.49−2.36 (m, 2H),
1.80 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 149.2, 148.5, 142.6,
136.9, 118.1, 114.1, 111.1, 109.1, 71.4, 56.1, 56.0, 48.4, 22.5 ppm. IR
(neat): 3420, 1592, 1508 cm−1. HRMS-ESI [M + Na]+: 245.1157,
C13H18O3Na requires 245.1154.
2-(2-Methoxyphenyl)-1-m-tolylethanol (15e).4a Addition of 9b
to m-Tolualdehyde Using TBAT in THF at Reflux. A solution of (2-
methoxybenzyl)trimethylsilane (9b) (117 mg, 0.60 mmol) and m-
tolualdehyde (60 mg, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with TBAT (27.0 mg, 0.05 mmol), and the resulting solution was
stirred under N2 at reflux for 3 h. The reaction mixture was cooled to rt
and the solvent removed under reduced pressure, and 2 M HCl (10 mL)
was added. The residue was extracted with ethyl acetate (10 × 3 mL),
and the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded 15e as a colorless solid (74 mg, 61%).
Addition of 9b to m-Tolualdehyde Using Me3SiOK/Bu4NCl in THF
at rt. A solution of (2-methoxybenzyl)trimethylsilane (9b) (117 mg,
0.60 mmol) and m-tolualdehyde (60 mg, 0.5 mmol) in anhydrous THF
(2.0 mL) was treated with dried Bu4NCl (28 mg, 0.1 mmol) and
TMSOK (13 mg, 0.1 mmol), and the resulting solution was stirred
under N2 at rt for 3 h. The solvent was removed under reduced pressure,
and 2 M HCl (10 mL) was added. The residue was extracted with diethyl
ether (15 × 3 mL), and the organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (96:4) yielded 15e as a colorless solid (77 mg, 63%, mp 51−53
°C).
1-(4-Methoxyphenyl)buta-2,3-dien-1-ol [15c-(1), Major] and
1-(4-Methoxyphenyl)but-3-yn-1-ol [15c-(2), Minor].16 Addition
of 8 to p-Anisaldehyde Using TBAT in THF at rt. A solution of
trimethyl(prop-2-yn-1-yl)silane (8) (75 μL, 0.50 mmol) and p-
anisaldehyde (73 μL, 0.6 mmol) in anhydrous THF (2.0 mL) was
treated with TBAT (27.0 mg, 0.05 mmol), and the resulting solution was
stirred under N2 at rt for 30 min. The solvent was removed under
reduced pressure, and 2 M HCl (10 mL) was added. The residue was
extracted with ethyl acetate (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with petroleum ether/ethyl acetate (90:10) yielded an 84:16
mixture of products 15c-(1,2) as a yellow oil (78 mg, 88%). 1H NMR
(400 MHz, CDCl3): δ 7.38−7.27 (m, 2H), 6.95−6.83 (m, 2H), 5.47−
5.39 (m, 0.84H), 5.26−5.19 (m, 0.84H), 4.97−4.87 (m, 1.68H), 4.86−
4.79 (m, 0.16H), 3.82−3.78 (m, 3H), 2.65−2.60 (m, 0.32H), 2.38 (s,
0.16H), 2.16 (s, 0.84H), 2.08−2.05 (m, 0.16H) ppm.
Addition of 8 to p-Anisaldehyde Using Me3SiOK/Bu4NCl in THF at
0 °C. A solution of trimethyl(prop-2-yn-1-yl)silane (8) (75 μL, 0.50
mmol) and 4-bromobenzaldehyde (73 μL, 0.60 mmol) in anhydrous
THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and
TMSOK (7 mg, 0.05 mmol), and the resulting solution was stirred
under N2 at 0 °C for 15 min. The solvent was removed under reduced
pressure, and 2 M HCl (10 mL) was added. The residue was extracted
with diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
petroleum ether/ethyl acetate (90:10) yielded a 93:7 mixture of
products 15c-(1,2) as a yellow oil (72 mg, 82%).
1H NMR (400 MHz, CDCl3): δ 7.27−7.15 (m, 4H), 7.13−7.09 (m,
2H), 6.93−6.86 (m, 2H), 4.98−4.88 (m, 1H), 3.86 (s, 1H), 3.14−3.07
(m, 1H), 3.01−2.92 (m, 1H), 2.48 (s, 1H), 2.36 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3): δ 157.7, 144.7, 138.0, 131.6, 128.3, 128.1 (2 × C),
126.9, 126.5, 123.0, 120.9, 110.6, 74.4, 55.5, 41.3, 21.6 ppm. HRMS-ESI
[M + Na]+: 265.1196, C16H18O2Na requires 265.1204.
2-(3-Bromophenyl)-1-(3-methoxyphenyl)propan-2-ol (15f).
Addition of 9c to 3′-Bromoacetophenone Using TBAT in THF at
Reflux. A solution of (3-methoxybenzyl)trimethylsilane (9c) (194 mg,
1.0 mmol) and 3′-bromoacetophenone (64 μL, 0.5 mmol) in anhydrous
THF (2.0 mL) was treated with TBAT (27 mg, 0.05 mmol) under N2,
and the resulting solution was stirred at 70 °C for 4 h. The reaction
mixture was cooled to rt and the solvent removed under reduced
pressure, and 2 M HCl (10 mL) was added. The residue was extracted
with diethyl ether (10 × 3 mL), and the organic layers were combined,
1H NMR (400 MHz, CDCl3): δ 7.38−7.28 (m, 2H), 6.94−6.84 (m,
2H), 5.47−5.39 (m, 0.93H), 5.26−5.19 (m, 0.93H), 4.97−4.87 (m,
1.86H), 4.86−4.79 (m, 0.07H), 3.82−3.77 (m, 3H), 2.65−2.60 (m,
0.14H), 2.17−2.12 (m, 0.93H), 2.08−2.05 (m, 0.07H) ppm. 13C NMR
(100 MHz, CDCl3): δ 207.1, 159.5, 159.4, 135.2, 134.8, 127.6, 127.2,
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washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (96:4) yielded 15f as a yellow oil (138 mg,
85%).
Addition of 9e to trans-Cinnamaldehyde Using Me3SiOK/Bu4NCl
in THF at rt. A solution of (4-bromobenzyl)trimethylsilane (9e) (146
mg, 0.60 mmol) and trans-cinnamaldehyde (65 μL, 0.50 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting solution was
stirred under N2 at rt for 3 h. The solvent was removed under reduced
pressure, and 2 M HCl (10 mL) was added. The residue was extracted
with diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (96:4) yielded 15h as a colorless solid (106
mg, 70%, mp 80−82 °C).
Addition of 9c to 3′-Bromoacetophenone Using Me3SiOK/Bu4NCl
in THF at Reflux. A solution of (3-methoxybenzyl)trimethylsilane (9c)
(194 mg, 1.0 mmol) and 3′-bromoacetophenone (64 μL, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol) under N2, and the resulting
solution was stirred at reflux for 5 h. The reaction mixture was cooled to
rt and the solvent removed under reduced pressure, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (10 × 3
mL), and the organic layers were combined, washed with water (10 mL)
and brine (10 mL), dried over sodium sulfate, and concentrated to
dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (96:4) yielded 15f as a yellow oil (117 mg,
73%).
1H NMR (400 MHz, CDCl3): δ 7.44 (d, J = 7.1 Hz, 2H), 7.39−7.21
(m, 5H), 7.13 (d, J = 7.1 Hz, 2H), 6.57 (d, J = 16.0 Hz, 1H), 6.24 (dd, J =
16.0, 6.4 Hz, 1H), 4.54−4.45 (m, 1H), 2.95−2.80 (m, 2H), 1.71 (s, 1H)
ppm. 13C NMR (100 MHz, CDCl3): δ 136.7, 136.4, 131.5, 131.3, 131.1,
130.8, 128.6, 127.8, 126.5, 120.5, 73.3, 43.4 ppm. HRMS-ESI [M − H]−:
301.0215, C16H14OBr requires 301.0228.
1H NMR (400 MHz, CDCl3): δ 7.58 (s, 1H), 7.38 (d, J = 7.9 Hz, 1H),
7.31 (d, J = 7.9 Hz, 1H), 7.23−7.12 (m, 2H), 6.77 (d, J = 7.8 Hz, 1H),
6.62 (d, J = 7.8 Hz, 1H), 6.50 (s, 1H), 3.70 (s, 3H), 3.08 (d, J = 13.2 Hz,
1H), 2.97 (d, J = 13.2 Hz, 1H), 1.92 (s, 1H), 1.54 (s, 3H) ppm. 13C NMR
(100 MHz, CDCl3): δ 159.4, 150.0, 137.6, 129.7, 129.6, 129.2, 128.4,
123.7, 122.9, 122.4, 115.9, 112.6, 74.1, 55.1, 50.3, 29.4 ppm. IR (neat):
3490, 2952, 1585 cm−1. HRMS-ESI [M + Na]+: 343.0324,
C16H17O2NaBr requires 343.0310.
4-(2-Hydroxy-2-(5-methylfuran-2-yl)ethyl)-N,N-diisopropyl-
benzamide (15g). Addition of 9d to 5-Methylfurfural Using TBAT in
THF at Reflux. A solution of N,N-diisopropyl-4-((trimethylsilyl)-
methyl)benzamide (9d) (175 mg, 0.60 mmol) and 5-methylfurfural
(50 μL, 0.50 mmol) in anhydrous THF (2.0 mL) was treated with
TBAT (27 mg, 0.05 mmol) under N2, and the resulting solution was
stirred at 70 °C for 2 h. The reaction mixture was cooled to rt and the
solvent removed under reduced pressure, and 2 M HCl (10 mL) was
added. The residue was extracted with diethyl ether (15 × 3 mL), and
the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (90:10)
yielded 15g as a yellow oil (114 mg, 70%).
Addition of 9d to 5-Methylfurfural Using Me3SiOK/Bu4NCl in THF
at rt. A solution of N,N-diisopropyl-4-((trimethylsilyl)methyl)-
benzamide (9d) (175 mg, 0.60 mmol) and 5-methylfurfural (50 μL,
0.50 mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl
(14 mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol), the resulting
solution was stirred under N2 at rt for 3 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (90:10) yielded 15g as a yellow
oil (112 mg, 68%).
(E)-1-(1,3-Dithian-2-yl)-3-phenylprop-2-en-1-ol (15i). Addi-
tion of 10 to trans-Cinnamaldehyde Using TBAT in THF at Reflux.
A solution of (1,3-dithian-2-yl)trimethylsilane (10) (116 mg, 0.6 mmol)
and trans-cinnamaldehyde (63 μL, 0.5 mmol) in anhydrous THF (2.0
mL) was treated with TBAT (27 mg, 0.05 mmol), and the resulting
solution was stirred under N2 at reflux for 3 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 15i as a colorless
solid (104 mg, 82%).
Addition of 10 to trans-Cinnamaldehyde Using Me3SiOK/Bu4NCl
in THF at rt. A solution of (1,3-dithian-2-yl)trimethylsilane (10) (116
mg, 0.6 mmol) and trans-cinnamaldehyde (63 μL, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol), the resulting solution was
stirred under N2 at rt for 3 h. The solvent was removed under reduced
pressure, and 2 M HCl (10 mL) was added. The residue was extracted
with diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (95:5) yielded 15i as a colorless solid (110
mg, 87%, mp 58−60 °C).
1H NMR (400 MHz, CDCl3): δ 7.45−7.38 (m, 2H), 7.35−7.21 (m,
3H), 6.74 (d, J = 15.8 Hz, 1H), 6.35 (dd, J = 15.8, 6.5 Hz, 1H), 4.59−
7.52 (m, 1H), 4.02 (d, J = 6.8 Hz, 1H), 3.00−2.91 (m, 2H), 2.82−2.72
(m, 2H), 2.67 (d, J = 3.7 Hz, 1H), 2.15−1.92 (m, 2H) ppm. 13C NMR
(100 MHz, CDCl3): δ 136.4, 132.9, 128.7, 128.0, 126.8, 73.4, 52.2, 28.4,
28.1, 25.7 ppm. IR (neat): 3434, 2938, 2883, 1494 cm−1. HRMS-ESI [M
+ Na]+: 275.0538, C13H16ONaS2 requires 275.0540.
Benzothiazol-2-yl(phenyl)methanol (15j). Addition of 11 to
Benzaldehyde Using TBAT in THF at rt. A solution of 2-(trimethylsilyl)-
benzothiazole (11) (124 mg, 0.6 mmol) and benzaldehyde (51 μL, 0.5
mmol) in anhydrous THF (2.0 mL) was treated with TBAT (27 mg,
0.05 mmol), and the resulting solution was stirred under N2 at rt for 3 h.
The solvent was removed under reduced pressure, and 1 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate
(90:10) yielded 15j as a colorless solid (98 mg, 81%).
Addition of 11 to Benzaldehyde Using Me3SiOK/Bu4NCl in THF at 0
°C. A solution of 2-(trimethylsilyl)benzothiazole (11) (124 mg, 0.6
mmol) and benzaldehyde (51 μL, 0.5 mmol) in anhydrous THF (2.0
mL) was treated with dried Bu4NCl (7 mg, 0.025 mmol) and TMSOK
(3.5 mg, 0.025 mmol), and the resulting solution was stirred under N2 at
0 °C for 3 h. The solvent was removed under reduced pressure, and 1 M
HCl (10 mL) was added. The residue was extracted with diethyl ether
(15 × 3 mL), and the organic layers were combined, washed with brine
(10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
1H NMR (400 MHz, CDCl3): δ 7.24−7.16 (m, 4H), 6.07 (d, J = 3.1
Hz, 1H), 5.89−5.86 (m, 1H), 4.81 (dd, J = 7.9, 5.5 Hz, 1H), 3.68 (br s,
2H), 3.19−3.05 (m, 2H), 2.75 (s, 1H), 2.29 (s, 3H), 1.31 (s, 12H) ppm.
13C NMR (100 MHz, CDCl3): δ 171.1, 153.9, 151.6, 138.6, 136.9, 129.5,
125.7, 107.2, 106.0, 68.5, 42.0, 20.7, 13.5 ppm. IR (neat): 3308, 2943,
1710, 1599 cm−1. HRMS-ESI [M + H]+: 330.2078, C20H28O3N requires
330.2069.
(E)-1-(4-Bromophenyl)-4-phenylbut-3-en-2-ol (15h).4a Addi-
tion of 9e to trans-Cinnamaldehyde Using TBAT in THF at Reflux. A
solution of (4-bromobenzyl)trimethylsilane (9e) (146 mg, 0.60 mmol)
and trans-cinnamaldehyde (63 μL, 0.50 mmol) in anhydrous THF (2.0
mL) was treated with TBAT (27 mg, 0.05 mmol) under N2, and the
resulting solution was stirred at reflux for 4 h. The reaction mixture was
cooled to rt and the solvent removed under reduced pressure, and 2 M
HCl (10 mL) was added. The residue was extracted with diethyl ether
(15 × 3 mL), and the organic layers were combined, washed with brine
(10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (96:4) yielded 15h as a colorless solid (108 mg, 71%).
G
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acetate (90:10) yielded 15j as a colorless solid (90 mg, 75%, mp 108−
110 °C).
at Reflux. A solution of trimethyl(2-(trifluoromethyl)phenyl)silane
(13c) (131 mg, 0.6 mmol) and 4-fluorobenzaldehyde (62 mg, 0.50
mmol) in anhydrous THF (2.0 mL) was treated with TBAT (27 mg,
0.05 mmol) under N2, and the resulting solution was stirred at reflux for
6 h. The reaction mixture was cooled to rt and the solvent removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 15m as a colorless
oil (12 mg, 9%).
Addition of 13c to 4-Fluorobenzaldehyde Using Me3SiOK/Bu4NCl
in THF at rt. A solution of trimethyl(2-(trifluoromethyl)phenyl)silane
(13c) (131 mg, 0.6 mmol) and 4-fluorobenzaldehyde (62 mg, 0.50
mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14
mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol) under N2, and the
resulting solution was stirred at rt for 5 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 15m as a colorless
oil (108 mg, 80%).
1H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.1 Hz, 1H), 7.84 (dd, J =
8.1 Hz, 1H), 7.57−7.50 (m, 2H), 7.46 (t, J = 7.7 Hz, 1H), 7.42−7.31 (m,
4H), 6.15 (s, 1H), 3.84 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
174.8, 152.7, 141.1, 135.5, 129.0, 128.9, 126.9, 126.3, 125.3, 123.3, 121.9,
74.6 ppm. IR (neat): 3161, 2924, 2715, 1501 cm−1. HRMS-ESI [M +
Na]+: 264.0448, C14H11NONaS requires 264.0459.
[(3,4-Dimethoxyphenyl)(furan-2-yl)methoxy]trimethylsilane
(15k). Addition of 12 to 3,4-Dimethoxybenzaldehyde Using TBAT in
THF at Reflux. A solution of furan-2-yltrimethylsilane (12) (140 mg, 1.0
mmol) and 3,4-dimethoxybenzaldehyde (83 mg, 0.50 mmol) in
anhydrous THF (2.0 mL) was treated with TBAT (27 mg, 0.05
mmol) under N2, and the resulting solution was stirred at reflux for 4 h.
The reaction mixture was cooled to rt and the solvent removed under
reduced pressure, and 10 mL of water was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 15k as a colorless
oil (64 mg, 42%).
Addition of 12 to 3,4-Dimethoxybenzaldehyde Using Me3SiOK/
Bu4NCl in THF at rt. A solution of furan-2-yltrimethylsilane (12) (140
mg, 1.0 mmol) and 3,4-dimethoxybenzaldehyde (83 mg, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting solution was
stirred under N2 at rt for 5 h. Water (10 mL) was added, and the residue
was extracted with diethyl ether (15 × 3 mL). The organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 15k as a colorless
oil (116 mg, 76%).
1H NMR (400 MHz, CDCl3): δ 7.67 (d, J = 7.9 Hz, 1H), 7.63 (d, J =
7.9 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.36−7.29
(m, 2H), 7.05−6.98 (m, 2H), 6.29 (s, 1H), 2.20 (br s, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ 162.3 (d, J = 246.1 Hz), 142.4, 138.6 (d, J =
3.2 Hz), 132.6 (q, J = 1.1 Hz), 129.5, 128.3 (d, J = 8.1 Hz), 128.0, 127.7
(q, J = 30.3 Hz), 125.8 (q, J = 5.8 Hz), 124.5 (q, J = 274.0 Hz), 115.4 (d, J
= 21.5 Hz), 70.4 (q, J = 2.4 Hz) ppm. IR (neat): 3267, 1508 cm−1.
HRMS-ESI [M − H]−: 269.0584, C14H9OF4 requires 269.0590.
(4-Chlorophenyl)(4-(dimethylamino)phenyl)methanol (15n).
A solution of (4-chlorophenyl)trimethylsilane (13d) (70 mg, 0.375
mmol) and 4-(dimethylamino)benzaldehyde (37 mg, 0.25 mmol) in
anhydrous THF (1.0 mL) was treated with dried Bu4NCl (104 mg,
0.375 mmol) and TMSOK (48 mg, 0.375 mmol), and the resulting
solution was stirred under N2 at 0 °C for 5 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The resulting
mixture was stirred for 30 min and neutralized with saturated aq
NaHCO3 solution. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
aluminum oxide chromatography eluting with petroleum ether/ethyl
acetate (80:20) yielded the product 15n as a colorless solid (43 mg, 66%,
1H NMR (400 MHz, CDCl3): δ 7.35 (s, 1H), 6.98 (d, J = 1.9 Hz, 1H),
6.92 (dd, J = 8.2, 1.9 Hz, 1H), 6.83 (d, J = 8.2 Hz, 1H), 6.28 (dd, J = 3.2,
1.9 Hz, 1H), 6.06 (d, J = 3.2 Hz, 1H), 5.73 (s, 1H), 3.88−3.86 (m, 6H),
0.11 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ 156.9, 148.94, 148.6,
142.3, 134.5, 118.9, 110.8, 110.2, 109.9, 107.1, 70.2, 56.02, 55.98, 0.1
ppm. IR (neat): 2938, 1515, 1459 cm−1. HRMS-EI [M]+: 306.1281,
C16H22O4Si requires 306.1287.
(2-Chlorophenyl)(mesityl)methanol (15l).21 Addition of 13b to
Mesitaldehyde Using TBAT in THF at Reflux. A solution of (2-
chlorophenyl)trimethylsilane (13b) (111 mg, 0.6 mmol) and
mesitaldehyde (74 μL, 0.50 mmol) in anhydrous THF (2.0 mL) was
treated with TBAT (27 mg, 0.05 mmol) under N2, and the resulting
solution was stirred at reflux for 6 h. The reaction mixture was cooled to
rt and the solvent removed under reduced pressure, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 15l as a colorless solid (11 mg, 8%).
1
mp 79−81 °C). H NMR (400 MHz, CDCl3): δ 7.35−7.26 (m, 4H),
7.17 (d, J = 8.7 Hz, 2H), 6.68 (d, J = 8.8 Hz, 2H), 5.74 (s, 1H), 2.93 (s,
6H), 2.1 (br s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 150.4, 142.9,
132.9, 131.6, 128.5, 127.9, 127.8, 112.6, 75.5, 40.7 ppm. IR (neat): 3273,
2883, 1515 cm−1. HRMS-ESI [M + H]+: 262.1006, C15H17NOCl
requires 262.0999.
(4-Bromophenyl)(naphthalen-2-yl)methanol (15o). A solution
of (4-bromophenyl)trimethylsilane (13e) (86 mg, 0.375 mmol) and 2-
naphthaldehyde (39 mg, 0.25 mmol) in anhydrous THF (1.0 mL) was
treated with dried Bu4NCl (104 mg, 0.375 mmol) and TMSOK (48 mg,
0.375 mmol), and the resulting solution was stirred under N2 at 0 °C for
5 h. The solvent was removed under reduced pressure, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 15o as a colorless solid (53 mg, 68%, mp 73−75 °C). 1H NMR
(400 MHz, CDCl3): δ 7.88−7.78 (m, 4H), 7.53−7.44 (m, 4H), 7.39
(dd, J = 8.5, 1.7 Hz, 1H), 7.30 (d, J = 8.5 Hz, 2H), 5.96 (s, 1H), 2.35 (s,
1H) ppm. 13C NMR (100 MHz, CDCl3): δ 142.7, 140.8, 133.4, 133.1,
131.7, 128.7, 128.5, 128.2, 127.8, 126.5, 126.3, 125.3, 124.7, 121.7, 75.9
ppm. IR (neat): 3308, 2911, 1480 cm−1. HRMS-EI [M]+: 312.0155,
C17H13OBr requires 312.0150.
Addition of 13b to Mesitaldehyde Using Me3SiOK/Bu4NCl in THF
at rt. A solution of (2-chlorophenyl)trimethylsilane (13b) (111 mg, 0.6
mmol) and mesitaldehyde (74 μL, 0.50 mmol) in anhydrous THF (2.0
mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK
(7 mg, 0.05 mmol) under N2, and the resulting solution was stirred at rt
for 5 h. The solvent was removed under reduced pressure, and 2 M HCl
(10 mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 15l as a colorless solid (103 mg, 79%, mp 91−93 °C).
1H NMR (400 MHz, CDCl3): δ 7.47−7.41 (m, 1H), 7.38−7.32 (m,
1H), 7.25−7.18 (m, 2H), 6.85 (s, 2H), 6.38 (d, J = 3.7 Hz, 1H), 2.38 (d, J
= 3.7 Hz, 1H), 2.28 (s, 3H), 2.26 (s, 6H) ppm. 13C NMR (100 MHz,
CDCl3): δ 140.0, 137.5, 137.3, 134.2, 133.2, 130.3, 129.9, 129.2, 128.7,
126.6, 70.6, 21.2, 21.0 ppm. IR (neat): 3448, 2917, 1438 cm−1. HRMS-
ESI [M + Na]+: 283.0854, C16H17ONaCl requires 283.0866.
(4-Fluorophenyl)(2-(trifluoromethyl)phenyl)methanol
(15m). Addition of 13c to 4-Fluorobenzaldehyde Using TBAT in THF
Methyl 4-(3-Ethoxy-1-hydroxy-3-oxopropyl)benzoate
(16a).22 A solution of ethyl 2-(trimethylsilyl)acetate (6) (92 μL, 0.5
mmol) and methyl 4-formylbenzoate (99 mg, 0.60 mmol) in anhydrous
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THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and
TMSOK (7 mg, 0.05 mmol). The resulting solution was stirred under
N2 at 0 °C for 15 min, and 1 M HCl (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (80:20) yielded 16a as a colorless
oil (100 mg, 79%). 1H NMR (400 MHz, CDCl3): δ 8.01 (d, J = 8.2 Hz,
2H), 7.45 (d, J = 8.2 Hz, 2H), 5.18 (t, J = 6.3 Hz, 1H), 4.18 (q, J = 7.1 Hz,
2H), 3.90 (s, 3H), 3.51 (br s, 1H), 2.72 (d, J = 6.3 Hz, 2H), 1.25 (t, J =
7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ 172.3, 167.0, 147.7, 130.0,
129.7, 125.7, 70.0, 61.2, 52.2, 43.2, 14.3 ppm. HRMS-ESI [M + Na]+:
275.0882, C13H16O5Na requires 275.0895.
Ethyl 3-(4-(Dimethylamino)phenyl)-3-hydroxypropanoate
(16b). A solution of ethyl 2-(trimethylsilyl)acetate (6) (92 μL, 0.5
mmol) and 4-(dimethylamino)benzaldehyde (90 mg, 0.60 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol). The resulting solution was
stirred under N2 at 0 °C for 30 min, and 1 M HCl (10 mL) was added.
The resulting mixture was neutralized with saturated NaHCO3 solution.
The residue was extracted with diethyl ether (15 × 3 mL), and the
organic layers were combined, washed with brine (10 mL), dried over
sodium sulfate, and concentrated to dryness. Purification by aluminum
oxide chromatography eluting with cyclohexane/ethyl acetate (90:10)
yielded 16b as a yellow oil (72 mg, 61%). 1H NMR (400 MHz, CDCl3):
δ 7.25 (d, J = 8.7 Hz, 2H), 6.72 (d, J = 8.7 Hz, 2H), 5.05 (dd, J = 9.4, 3.6
Hz, 1H), 4.18 (q, J = 7.1 Hz, 2H), 2.94 (s, 6H), 2.78 (dd, J = 16.1, 9.4 Hz,
1H), 2.67 (dd, J = 16.1, 3.6 Hz, 1H), 1.27 (t, J = 7.1 Hz, 3H) ppm. 13C
NMR (100 MHz, CDCl3): δ 172.7, 150.5, 130.5, 126.8, 112.7, 70.4, 60.9,
43.4, 40.8, 14.3 ppm. IR (neat): 3385, 2932, 1696, 1592 cm−1. HRMS-
ESI [M + Na]+: 260.1266, C13H19NO3Na requires 260.1263.
0.05 mmol), and the resulting solution was stirred under N2 at rt for 3 h.
The solvent was removed under reduced pressure, and 2 M HCl (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 16e as a yellow oil (68 mg, 50%). 1H NMR (400 MHz, CDCl3):
δ 4.87 (s, 1H), 4.81 (s, 1H), 4.55−4.48 (m, 1H), 4.27 (s, 1H), 4.23−4.07
(m, 8H), 2.40 (d, J = 6.9 Hz, 2H), 2.03 (d, J = 2.6 Hz, 1H), 1.79 (s, 3H)
ppm. 13C NMR (100 MHz, CDCl3): δ 142.9, 113.3, 93.6, 68.5, 68.1,
67.9, 67.6, 67.0, 65.8, 47.0, 22.7 ppm. IR (neat): 3455, 3078, 2925, 1647
cm−1. HRMS-EI [M]+: 270.0699, C15H18OFe requires 270.0707.
N-(3-Methyl-1-phenylbut-3-en-1-yl)aniline (16f).25 A solution
of trimethyl(2-methylallyl)silane (7b) (170 μL, 1.0 mmol) and (E)-N-
benzylideneaniline (91 mg, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (28 mg, 0.1 mmol) and TMSOK (13 mg, 0.1
mmol), and the resulting solution was stirred under N2 at rt for 4 h. The
solvent was removed under reduced pressure, and water (10 mL) was
added. The residue was extracted with diethyl ether (15 × 3 mL), and
the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by
aluminum oxide chromatography eluting with petroleum ether/
dichloromethane (92:8) yielded 16f as a colorless oil (85 mg, 72%).
1H NMR (400 MHz, CDCl3): δ 7.39 (dd, J = 8.0, 0.9 Hz, 2H), 7.35−
7.29 (m, 2H), 7.25−7.20 (m, 1H), 7.10−7.03 (m, 2H), 6.64 (t, J = 7.3
Hz, 1H), 6.48 (d, J = 7.7 Hz, 2H), 4.91 (s, 1H), 4.86 (s, 1H), 4.38 (dd, J =
10.2, 4.5 Hz, 1H), 4.13 (br s, 1H), 2.51 (dd, J = 14.3, 4.0 Hz, 1H), 2.39
(dd, J = 14.3, 10.2 Hz, 1H), 1.75 (s, 3H) ppm. 13C NMR (100 MHz,
CDCl3): δ 147.8, 144.5, 142.6, 129.1, 128.8, 127.1, 126.2, 117.5, 114.2,
113.6, 55.7, 48.3, 21.8 ppm. HRMS-ESI [M + H]+: 238.1607, C17H20N
requires 238.1596.
(E)-1-Phenylhexa-1,5-dien-3-ol (16c).23 A solution of allyltrime-
thylsilane (7a) (96 μL, 0.6 mmol) and trans-cinnamaldehyde (63 μL, 0.5
mmol) in anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14
mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting
solution was stirred under N2 at rt for 3 h. The solvent was removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded 16c as a yellow oil
(63 mg, 72%). 1H NMR (400 MHz, CDCl3): δ 7.38 (d, J = 7.8 Hz, 2H),
7.31 (t, J = 7.3 Hz, 2H), 7.27−7.20 (m, 1H), 6.61 (d, J = 15.9 Hz, 1H),
6.24 (dd, J = 15.9, 6.3 Hz, 1H), 5.93−5.79 (m, 1H), 5.22−5.14 (m, 2H),
4.36 (dd, J = 12.4, 6.3 Hz, 1H), 2.49−2.33 (m, 2H), 1.79 (s, 1H) ppm.
13C NMR (100 MHz, CDCl3): δ 136.8, 134.2, 131.7, 130.5, 128.7, 127.8,
1-(4-Chlorophenyl)buta-2,3-dien-1-ol [16g-(1), Major] and 1-
(4-Chlorophenyl)but-3-yn-1-ol [16g-(2), Minor].16 A solution of
trimethyl(prop-2-yn-1-yl)silane (8) (67 mg, 0.60 mmol) and 4-
chlorobenzaldehyde (70 mg, 0.5 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at 0 °C for 3
h. The solvent was removed under reduced pressure, and 2 M HCl (10
mL) added. The residue was extracted with diethyl ether (15 × 3 mL),
and the organic layers were combined, washed with brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded a 70:30 mixture of products 16g-(1,2) as a yellow oil (53 mg,
59%). 1H NMR (400 MHz, CDCl3): δ 7.36−7.30 (m, 4H), 5.40 (q, J =
6.5 Hz, 0.7H), 5.28−5.23 (m, 1H), 4.98−4.89 (m, 1.4H), 4.86 (t, J = 6.3
Hz, 0.3H), 2.64−2.60 (m, 0.6H), 2.42 (br s, 0.3H), 2.18 (br s, 0.7H),
2.08 (t, J = 2.6 Hz, 0.3H) ppm. 13C NMR (100 MHz, CDCl3) δ 207.3,
141.4, 141.0, 133.8, 133.6, 128.8, 128.7, 127.6, 127.3, 95.1, 80.3, 78.6,
71.8, 71.5, 71.4, 29.6 ppm. HRMS-ESI [M − H]−: 179.0271, C10H8OCl
requires 179.0264.
126.6, 118.7, 71.8, 42.2 ppm. MS-ESI [M − H]−: 173.13, C12H13O
requires 173.09.
N-(1-(4-Methoxyphenyl)but-3-enyl)aniline (16d).24 A solution
of allyltrimethylsilane (7a) (114 mg, 1.0 mmol) and (E)-N-(4-
methoxybenzylidene)aniline (106 mg, 0.5 mmol) in anhydrous THF
(2.0 mL) was treated with dried Bu4NCl (28 mg, 0.1 mmol) and
TMSOK (13 mg, 0.1 mmol), and the resulting solution was stirred
under N2 at rt for 4 h. The solvent was removed under reduced pressure,
and water (10 mL) was added. The residue was extracted with diethyl
ether (15 × 3 mL), and the organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by aluminum oxide chromatography eluting with cyclo-
hexane/ethyl acetate (98:2) yielded 16d as a colorless oil (92 mg, 72%).
1H NMR (400 MHz, CDCl3): δ 7.30−7.23 (m, 2H), 7.11−7.03 (m,
2H), 6.85 (d, J = 7.8 Hz, 1H), 6.63 (t, J = 7.3 Hz, 1H), 6.49 (d, J = 7.8 Hz,
1H), 5.82−5.69 (m, 1H), 5.21−5.09 (m, 2H), 4.33 (t, J = 6.4 Hz, 1H),
4.11 (br s, 1H), 3.78 (s, 3H), 2.62−2.42 (m, 2H) ppm. 13C NMR (100
MHz, CDCl3): δ 158.7, 147.5, 135.7, 134.9, 129.2, 127.5, 118.3, 117.4,
114.1, 113.6, 56.7, 55.4, 43.5 ppm. HRMS-ESI [M + H]+: 254.1541,
C17H20NO requires 254.1545.
Note: the isolation of mixtures of buta-2,3-dien-1-ols and but-3-yn-1-
ols from fluoride-mediated addition reactions of trimethyl(prop-2-yn-1-
yl)silanes has been previously reported.16
1-(Furan-2-yl)-2-phenylethanol (16h).26 A solution of benzyl-
trimethylsilane (9a) (99 mg, 0.60 mmol) and furfural (42 μL, 0.5 mmol)
in anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg,
0.05 mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting solution
was stirred under N2 at rt for 3 h. The solvent was removed under
reduced pressure, and 1 M HCl (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (96:4) yielded 16h as a colorless
oil (78 mg, 83%). 1H NMR (400 MHz, CDCl3): δ 7.40 (s, 1H), 7.33−
7.15 (m, 5H), 6.34−6.30 (m, 1H), 6.23−6.19 (m, 1H), 4.94−4.88 (m,
1H), 3.19 (dd, J = 13.6, 5.4 Hz, 1H), 3.11 (dd, J = 13.6, 8.1 Hz, 1H), 1.99
(br s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 155.9, 142.1, 137.5,
129.5, 128.6, 126.8, 110.4, 106.5, 68.9, 42.3 ppm. HRMS-ESI [M +
Na]+: 211.0740, C12H12O2Na requires 211.0735.
3-Methyl-1-ferrocenylbut-3-en-1-ol (16e). A solution of
trimethyl(2-methylallyl)silane (7b) (102 μL, 0.6 mmol) and ferroce-
nealdehyde (107 mg, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
I
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Article
N-(2-Phenyl-1-(pyridin-4-yl)ethyl)aniline (16i). A solution of
benzyltrimethylsilane (9a) (164 mg, 1.0 mmol) and N-phenyl-1-(4-
pyridyl)methanimine (91 mg, 0.5 mmol) in anhydrous THF was treated
with dried Bu4NCl (28 mg, 0.1 mmol) and TMSOK (13 mg, 0.1 mmol),
and the resulting solution was stirred under N2 at rt for 5 h. The solvent
was removed under reduced pressure, and water (10 mL) was added.
The residue was extracted with diethyl ether (15 × 3 mL), and the
organic layers were combined, washed with brine (10 mL), dried over
sodium sulfate, and concentrated to dryness. Purification by aluminum
oxide chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 16i as a colorless solid (100 mg, 73%, mp 92−94 °C). 1H NMR
(400 MHz, CDCl3): δ 8.54−8.49 (m, 2H), 7.32−7.19 (m, 5H), 7.12−
7.02 (m, 4H), 6.66 (t, J = 7.3 Hz, 1H), 6.40 (d, J = 7.5 Hz, 2H), 4.61−
4.53 (m, 1H), 4.15 (br s, 1H), 3.15−2.97 (m, 2H) ppm. 13C NMR (100
MHz, CDC3): δ 152.6, 150.0, 146.6, 136.6, 129.2, 129.1, 128.7, 127.1,
121.7, 118.1, 113.6, 58.4, 44.4 ppm. IR (neat): 3259, 3015, 1599 cm−1.
HRMS-ESI [M + H]+: 275.1540, C19H19N2 requires 275.1548.
121.8, 115.1, 113.8, 112.1, 74.8, 55.3, 55.1, 46.1 ppm. HRMS-ESI [M +
Na]+: 281.1140, C16H18O3Na requires 281.1154.
N-(1-(4-Fluorophenyl)-2-(3-methoxyphenyl)ethyl)aniline
(16m). A solution of (3-methoxybenzyl)trimethylsilane (9c) (194 mg,
1.0 mmol) and (E)-N-(4-fluorobenzylidene)aniline (99 mg, 0.5 mmol)
in anhydrous THF was treated with dried Bu4NCl (14 mg, 0.05 mmol)
and TMSOK (7 mg, 0.05 mmol) under N2, and the resulting mixture
was stirred at rt for 5 h. The solvent was removed under reduced
pressure, and water (10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by aluminum oxide chromatography eluting with
cyclohexane/ethyl acetate (96:4) yielded 16m as a yellow oil (118 mg,
73%). 1H NMR (400 MHz, CDCl3): δ 7.31−7.25 (m, 2H), 7.20 (t, J =
7.9 Hz, 1H), 7.06 (t, J = 7.5 Hz, 2H), 6.99 (t, J = 8.2 Hz, 2H), 6.77 (dd, J
= 8.2, 2.0 Hz, 1H), 6.71 (d, J = 7.5 Hz, 1H), 6.67−6.60 (m, 2H), 6.44 (d,
J = 8.1 Hz, 2H), 4.59−4.53 (m, 1H), 4.13 (s, 1H), 3.74 (s, 3H), 3.06 (dd,
J = 13.8, 5.9 Hz, 1H), 2.98 (dd, J = 13.8, 7.9 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3): δ 162.0 (d, J = 244.7 Hz), 159.8, 147.2, 139.1 (d, J =
3.0 Hz), 139.0, 129.7, 129.2, 128.1 (d, J = 7.9 Hz), 121.7, 117.8, 115.5 (d,
J = 21.4 Hz), 115.1, 113.8, 112.4, 58.7, 55.3, 45.4 ppm. IR (neat): 3406,
2925, 1501, cm−1. HRMS-EI [M]+: 321.1525, C21H20NOF requires
321.1529.
1-(4-Chlorophenyl)-2-(2-methoxyphenyl)ethanol (16j).4a
A
solution of (2-methoxybenzyl)trimethylsilane (9b) (117 mg, 0.60
mmol) and 4-chlorobenzaldehyde (70 mg, 0.5 mmol) in anhydrous
THF (2.0 mL) was treated with dried Bu4NCl (28 mg, 0.1 mmol) and
TMSOK (13 mg, 0.1 mmol), and the resulting solution was stirred
under N2 at rt for 3 h. The solvent was removed under reduced pressure,
and 2 M HCl (10 mL) was added. The residue was extracted with diethyl
ether (15 × 3 mL), and the organic layers were combined, washed with
water (10 mL) and brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 16j as a colorless
4-(2-(4-Fluorophenyl)-2-hydroxyethyl)-N,N-diisopropylben-
zamide (16n). A solution of N,N-diisopropyl-4-((trimethylsilyl)-
methyl)benzamide (9d) (175 mg, 0.60 mmol) and p-fluorobenzalde-
hyde (54 μL, 0.5 mmol) in anhydrous THF (2.0 mL) was treated with
dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg, 0.05 mmol), and
the resulting solution was stirred under N2 at rt for 3 h. The solvent was
removed under reduced pressure, and 2 M HCl (10 mL) was added. The
residue was extracted with diethyl ether (15 × 3 mL), and the organic
layers were combined, washed with water (10 mL) and brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate
(90:10) yielded 16n as a colorless solid (145 mg, 84%, mp 125−127
1
solid (66 mg, 50%, mp 62−64 °C). H NMR (400 MHz, CDCl3): δ
7.31−7.20 (m, 5H), 7.03 (d, J = 7.5 Hz, 1H), 6.91−6.85 (m, 2H), 4.97−
4.90 (m, 1H), 3.84 (s, 3H), 3.09 (dd, J = 13.6, 4.1 Hz, 1H), 2.93 (dd, J =
13.6, 8.4 Hz, 1H), 2.60 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
157.7, 143.1, 132.9, 131.7, 128.4, 128.3, 127.3, 126.2, 120.9, 110.6, 73.8,
55.5, 41.3 ppm. HRMS-ESI [M + Na]+: 285.0660, C15H15O2ClNa
requires 285.0658.
1
°C). H NMR (400 MHz, CDCl3): δ 7.32−7.13 (m, 6H), 7.04−6.97
4-Methoxy-N-(2-(2-methoxyphenyl)-1-phenylethyl)aniline
(16k). A solution of (2-methoxybenzyl)trimethylsilane (9b) (194 mg,
1.0 mmol) and (E)-N-(4-methoxyphenyl)-1-phenylmethanimine (106
mg, 0.5 mmol) in anhydrous THF was treated with dried Bu4NCl (28
mg, 0.1 mmol) and TMSOK (13 mg, 0.1 mmol) under N2, and the
resulting mixture was stirred at rt for 5 h. The solvent was removed
under reduced pressure, and water (10 mL) was added. The residue was
extracted with diethyl ether (15 × 3 mL), and the organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by aluminum oxide chromatog-
raphy eluting with cyclohexane/ethyl acetate (96:4) yielded 16k as a
colorless oil (74 mg, 44%). 1H NMR (400 MHz, CDCl3): δ 7.38 (d, J =
7.4 Hz, 2H), 7.30 (t, J = 7.6 Hz, 2H), 7.25−7.15 (m, 2H), 7.02 (dd, J =
7.3, 1.3 Hz, 1H), 6.89−6.81 (m, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.38 (d, J
= 8.8 Hz, 2H), 4.48 (dd, J = 8.7, 5.0 Hz, 1H), 3.87 (s, 3H), 3.65 (s, 3H),
3.12−2.98 (m, 2H) ppm. 13C NMR (100 MHz, CDCl3): δ 157.7, 151.9,
144.4, 131.1, 128.6, 128.1, 127.0, 127.0, 126.6, 120.8, 114.8, 114.6, 110.6,
60.2, 55.9, 55.4, 40.1 ppm. HRMS-ESI [M + Na]+: 356.1616,
C22H23NO2Na requires 356.1626.
(m, 2H), 4.87 (t, J = 6.6 Hz, 1H), 3.69 (br s, 2H), 3.00 (d, J = 6.6 Hz,
2H), 2.11 (s, 1H), 1.31 (br s, 12H) ppm. 13C NMR (100 MHz, CDCl3):
δ 170.9, 162.2 (d, J = 245.7 Hz), 139.4 (d, J = 3.1 Hz), 138.4, 137.3,
129.5, 127.5 (d, J = 8.1 Hz), 125.9, 115.2 (d, J = 21.4 Hz), 74.5, 45.9, 20.7
ppm. IR (neat): 3353, 2975, 1600, 1504 cm−1. HRMS-ESI [M + H]+:
344.2019, C21H27O2NF requires 344.2026.
(E)-N,N-Diisopropyl-4-(4-phenyl-2-(phenylamino)but-3-
enyl)benzamide (16o). A solution of N,N-diisopropyl-4-
((trimethylsilyl)methyl)benzamide (9d) (291 mg, 1.0 mmol) and
(E)-N,3-diphenylprop-2-en-1-imine (104 mg, 0.5 mmol) in anhydrous
THF was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK
(7 mg, 0.05 mmol) under N2, and the resulting solution was stirred at rt
for 5 h. The solvent was removed under reduced pressure, and water (10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
aluminum oxide chromatography eluting with pentane/dichloro-
methane (92:8) yielded 16o as a colorless solid (152 mg, 71%, mp
130−132 °C). 1H NMR (400 MHz, CDCl3): δ 7.33−7.18 (m, 9H), 7.14
(t, J = 7.7 Hz, 2H), 6.69 (t, J = 7.3 Hz, 1H), 6.63 (d, J = 7.9 Hz, 2H), 6.52
(d, J = 15.9 Hz, 1H), 6.17 (dd, J = 15.9, 6.0 Hz, 1H), 4.30 (q, J = 6.3 Hz,
1H), 3.80 (s, 1H), 3.61 (br s, 2H), 3.02 (d, J = 6.5 Hz, 2H), 1.35 (br s,
12H) ppm. 13C NMR (100 MHz, CDCl3): δ 171.0, 147.3, 138.4, 137.4,
136.9, 131.1, 130.7, 129.7, 129.3, 128.6, 127.6, 126.5, 126.0, 117.8, 113.8,
56.4, 42.2, 20.9 ppm. IR (neat): 3315, 2938, 1606, 1494 cm−1. HRMS-
ESI [M + H]+: 427.2751, C29H35N2O requires 427.2749.
1-(4-Bromophenyl)-3,3-dimethylbutan-2-ol (16p). A solution
of (4-bromobenzyl)trimethylsilane (9e) (243 mg, 1.0 mmol) and
pivalaldehyde (55 μL, 0.5 mmol) in anhydrous THF (2 mL) was treated
with dried Bu4NCl (28 mg, 0.1 mmol) and TMSOK (13 mg, 0.1 mmol),
and the resulting solution was stirred under N2 at rt for 6 h. The solvent
was removed under reduced pressure, and 2 M HCl (10 mL) added. The
residue was extracted with ethyl acetate (10 × 3 mL), and the organic
layers were combined, washed with water (10 mL) and brine (10 mL),
2-(3-Methoxyphenyl)-1-(4-methoxyphenyl)ethanol (16l).27
A
solution of (3-methoxybenzyl)trimethylsilane (9c) (117 mg, 0.60
mmol) and p-anisaldehyde (61 μL, 0.5 mmol) in anhydrous THF (2.0
mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK
(7 mg, 0.05 mmol), and the resulting solution was stirred under N2 at rt
for 3 h. The solvent was removed under reduced pressure, and 2 M HCl
(10 mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (92:8)
1
yielded 16l as a colorless oil (93 mg, 72%). H NMR (400 MHz,
CDCl3): δ 7.30−7.24 (m, 2H), 7.21 (t, J = 7.9 Hz, 1H), 6.88 (d, J = 8.7
Hz, 2H), 6.81−6.75 (m, 2H), 6.73 (s, 1H), 4.85 (dd, J = 7.7, 5.6 Hz, 1H),
3.80 (s, 3H), 3.77 (s, 3H), 3.03−2.92 (m, 2H), 1.91 (s, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ 159.7, 159.1, 139.7, 136.0, 129.4, 127.1,
J
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The Journal of Organic Chemistry
Article
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded 16p as a colorless solid (102 mg, 79%, mp 48−50 °C). 1H NMR
(400 MHz, CDCl3): δ 7.43 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H),
3.39 (d, J = 10.7 Hz, 1H), 2.84 (dd, J = 13.7, 1.6 Hz, 1H), 2.44 (dd, J =
13.7, 10.7 Hz, 1H), 0.99 (s, 9H) ppm. 13C NMR (100 MHz, CDCl3): δ
139.2, 131.7, 131.2, 120.2, 80.7, 37.9, 35.1, 25.9 ppm. IR (neat): 3455,
2952, 1480 cm−1. HRMS-ESI [M + Na]+: 279.0365, C12H17BrONa
requires 279.0360.
N-(2-(4-Bromophenyl)-1-phenylethyl)-4-methoxyaniline
(16q). A solution of (4-bromobenzyl)trimethylsilane (9e) (243 mg, 1.0
mmol) and (E)-N-(4-methoxyphenyl)-1-phenyl-methanimine (106 mg,
0.5 mmol) in anhydrous THF was treated with dried Bu4NCl (28 mg,
0.1 mmol) and TMSOK (13 mg, 0.1 mmol) under N2, and the resulting
mixture was stirred at rt for 5 h. The solvent was removed under reduced
pressure, and water (10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by aluminum oxide chromatography eluting with
cyclohexane/ethyl acetate (96:4) yielded 16q as a yellow oil (82 mg,
43%). 1H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 8.3 Hz, 2H), 7.32−
7.20 (m, 5H), 6.95 (d, J = 8.3 Hz, 2H), 6.65 (d, J = 8.9 Hz, 2H), 6.42 (d, J
= 8.9 Hz, 2H), 4.51−4.45 (m, 1H), 3.67 (s, 3H), 3.07−2.95 (m, 2H)
ppm. 13C NMR (100 MHz, CDCl3): δ 152.3, 143.2, 141.36, 136.9,
131.6, 131.1, 128.7, 127.3, 126.6, 120.7, 115.0, 114.8, 60.0, 55.8, 44.5
ppm. IR (neat): 3399, 2925, 1508 cm−1. HRMS-ESI [M + H]+:
382.0814, C21H21NOBr requires 382.0807.
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate
1
(90:10) yielded 16t as a colorless oil (114 mg, 71%). H NMR (400
MHz, CDCl3): δ 7.96 (d, J = 8.2 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 7.54−
7.32 (m, 6H), 6.11 (s, 1H), 4.21 (br s, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 174.4, 152.6, 140.0, 135.3, 132.1, 128.5, 126.4, 125.5, 123.2,
122.9, 122.0, 73.8 ppm. HRMS-ESI [M + Na]+: 341.9561,
C14H10BrNONaS requires 341.9564.
(Furan-2-yl(4-(phenoxymethyl)phenyl)methoxy)trimethylsi-
lane (17a). A solution of furan-2-yltrimethylsilane (12) (140 mg, 1.0
mmol) and 4-(phenoxymethyl)benzaldehyde (106 mg, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05
mmol) and TMSOK (7 mg, 0.05 mmol), and the resulting solution was
stirred under N2 at rt for 5 h. Water (10 mL) was added, and the residue
was extracted with diethyl ether (15 × 3 mL). The organic layers were
combined, washed with brine (10 mL), dried over sodium sulfate, and
concentrated to dryness. Purification by silica gel chromatography
eluting with petroleum ether/ethyl acetate (97:3) yielded 17a as a
colorless oil (145 mg, 82%). 1H NMR (400 MHz, CDCl3): δ 7.45−7.28
(m, 8H), 6.95 (d, J = 8.6 Hz, 2H), 6.27 (dd, J = 3.1, 1.8 Hz, 1H), 6.06
(dd, J = 3.1, 0.6 Hz, 1H), 5.73 (s, 1H), 5.05 (s, 2H), 0.10 (s, 9H) ppm.
13C NMR (100 MHz, CDCl3): δ 158.4, 157.0, 142.2, 137.2, 134.4, 128.7,
128.1, 127.8, 127.6, 114.6, 110.2, 107.1, 70.2, 70.0, 0.1 ppm. IR (neat):
2952, 1606, 1508 cm−1. HRMS-ESI [M + Na]+: 375.1399,
C21H24O3NaSi requires 375.1392.
1-(3-Bromophenyl)-1-(1,3-dithian-2-yl)ethanol (16r). A solu-
tion of (1,3-dithian-2-yl)trimethylsilane (10) (192 mg, 1.0 mmol) and
m-bromoacetophenone (63 μL, 0.5 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at reflux for
3 h. The reaction mixture was cooled to rt and the solvent removed
under reduced pressure, and 2 M HCl (10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with water (10 mL) and brine (10 mL), dried
over sodium sulfate, and concentrated to dryness. Purification by silica
gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
yielded 16r as a yellow oil (104 mg, 65%). 1H NMR (400 MHz, CDCl3):
δ 7.7 (s, 1H), 7.50−7.36 (m, 2H), 7.23 (t, J = 7.9 Hz, 1H), 4.40 (s, 1H),
2.89 (s, 1H), 2.88−2.73 (m, 4H), 2.11−1.98 (m, 1H), 1.91−1.75 (m,
1H), 1.71 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3): δ 147.1, 130.7,
129.6, 128.9, 124.3, 122.6, 76.4, 59.7, 30.4, 30.2, 27.5, 25.4 ppm. IR
(neat): 3441, 2889, 1563 cm−1. HRMS-ESI [M + Na]+: 340.9655,
C12H15BrOS2Na requires 340.9645.
(4-Bromophenyl)(furan-2-yl)methanol (17b). A solution of
furan-2-yltrimethylsilane (12) (140 mg, 1.0 mmol) and 4-bromoben-
zaldehyde (93 mg, 0.5 mmol) in anhydrous THF (2.0 mL) was treated
with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg, 0.05
mmol), and the resulting solution was stirred under N2 at rt for 5 h. HCl
(0.1 M, 10 mL) was added, and the residue was extracted with diethyl
ether (15 × 3 mL). The organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (95:5) yielded 17b as a colorless oil (105 mg, 83%). 1H NMR
(400 MHz, CDCl3): δ 7.50 (d, J = 8.4 Hz, 2H), 7.41−7.38 (m, 1H), 7.32
(d, J = 8.4 Hz, 2H), 6.32 (dd, J = 3.2, 1.9 Hz, 1H), 6.12 (d, J = 3.2 Hz,
1H), 5.80 (s, 1H), 2.40 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
155.5, 142.9, 139.9, 131.7, 128.4, 122.1, 110.5, 107.8, 69.6 ppm. IR
(neat): 3427, 2917, 1703, 1487 cm−1. HRMS-EI [M]+: 251.9791,
C11H9BrO2 requires 251.9786.
(2-Chlorophenyl)(naphthalen-2-yl)methanol (17c).29 A solu-
tion of (2-chlorophenyl)trimethylsilane (13b) (111 mg, 0.6 mmol) and
2-naphthaldehyde (78 mg, 0.5 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at rt for 5 h.
HCl (2 M, 10 mL) was added, and the residue was extracted with diethyl
ether (15 × 3 mL). The organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (95:5) yielded 17c as a colorless oil (118 mg, 87%). 1H NMR
(400 MHz, CDCl3): δ 7.88 (s, 1H), 7.84−7.78 (m, 3H), 7.62 (dd, J =
7.8, 1.4 Hz, 1H), 7.50−7.43 (m, 3H), 7.36 (dd, J = 7.8, 1.4 Hz, 1H), 7.30
(td, J = 7.6, 1.4 Hz, 1H), 7.26−7.20 (m, 1H), 6.40 (d, J = 3.8 Hz, 1H),
2.45 (d, J = 3.8 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 141.0,
139.7, 133.4, 133.1, 132.8, 129.8, 129.0, 128.5, 128.4, 128.3, 127.8, 127.3,
126.3, 126.2, 125.8, 125.0, 72.9 ppm. HRMS-ESI [M + Na]+: 291.0546,
C17H13ONaCl requires 291.0553.
N-((1,3-Dithian-2-yl)(4-methoxyphenyl)methyl)aniline (16s).
A solution of (1,3-dithian-2-yl)trimethylsilane (10) (192 mg, 1.0 mmol)
and (E)-N-(4-methoxybenzylidene)aniline (106 mg, 0.5 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (28 mg, 0.1
mmol) and TMSOK (13 mg, 0.1 mmol), and the resulting solution was
stirred under N2 at 0 °C for 4 h. The solvent was removed under reduced
pressure, and water (10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (97:3) yielded 16s as a yellow oil (113 mg,
68%). 1H NMR (400 MHz, CDCl3): δ 7.37−7.31 (m, 2H), 7.12−7.05
(m, 2H), 6.88 (d, J = 7.8 Hz, 2H), 6.66 (t, J = 7.3 Hz, 1H), 6.52 (d, J = 7.8
Hz, 1H), 4.71 (s, 1H), 4.63 (s, 1H), 4.47−4.43 (m, 1H), 3.79 (s, 1H),
2.95−2.73 (m, 4H), 2.14−2.05 (m, 1H), 1.93−1.80 (m, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ 159.3, 147.0, 131.7, 129.2, 128.4, 117.8,
114.0, 113.7, 61.4, 55.3, 54.8, 30.8, 30.6, 25.9 ppm. IR (neat): 3385,
2903, 1501 cm−1. HRMS-ESI [M + H]+: 332.1135, C18H22NOS2
requires 332.1143.
(2-Chlorophenyl)(4-fluorophenyl)methanol (17d).30 A solu-
tion of (2-chlorophenyl)trimethylsilane (13b) (111 mg, 0.6 mmol) and
4-fluorobenzaldehyde (62 mg, 0.5 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at rt for 5 h.
HCl (2 M, 10 mL) was added, and the residue was extracted with diethyl
ether (15 × 3 mL). The organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (95:5) yielded 17d as a colorless oil (102 mg, 86%). 1H NMR
Benzothiazol-2-yl(4-bromophenyl)methanol (16t).28 A solu-
tion of 2-(trimethylsilyl)benzothiazole (11) (124 mg, 0.6 mmol) and 4-
bromobenzaldehyde (93 mg, 0.5 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.025 mmol), and the resulting solution was stirred under N2 at 0 °C for
3 h. The solvent was removed under reduced pressure, and 1 M HCl (10
K
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The Journal of Organic Chemistry
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(400 MHz, CDCl3): δ 7.59 (dd, J = 7.7, 1.6 Hz, 1H), 7.38−7.28 (m, 4H),
7.26−7.21 (m, 1H), 7.05−6.98 (m, 2H), 6.20 (d, J = 2.9 Hz, 1H), 2.35
(d, J = 3.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 162.2 (d, J =
246.2 Hz), 157.1, 140.8, 137.9 (d, J = 3.2 Hz), 129.6, 128.9, 128.6 (d, J =
8.2 Hz), 127.8, 127.1, 115.3 (d, J = 21.4 Hz), 72.0 ppm. HRMS-ESI [M
− H]−: 235.0326, C13H9ClFO requires 235.0326.
142.7, 142.3, 132.3 (q, J = 1.1 Hz), 129.5, 128.4, 127.7, 127.6 (q, J = 30.2
Hz), 127.5, 126.4, 125.5 (q, J = 5.8 Hz), 124.4 (q, J = 274.4 Hz), 70.8 (q,
J = 2.4 Hz) ppm. MS-ESI [(M + H) − H2O)]+: 235.08, C14H10F3
requires 235.07.
Mesityl(2-(trifluoromethyl)phenyl)methanol (17i). A solution
of trimethyl(2-(trifluoromethyl)phenyl)silane (13c) (131 mg, 0.6
mmol) and mesitaldehyde (74 μL, 0.50 mmol) in anhydrous THF
(2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and
TMSOK (7 mg, 0.05 mmol) under N2, and the resulting solution was
stirred at rt for 5 h. The solvent was removed under reduced pressure,
and HCl (2 M, 10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (95:5) yielded 17i as a colorless oil (106 mg,
72%). 1H NMR (400 MHz, CDCl3): δ 7.75−7.71 (m, 1H), 7.47−7.36
(m, 3H), 6.87 (s, 2H), 6.59 (d, J = 4.5 Hz, 1H), 2.29 (s, 3H), 2.27−2.23
(m, 7H) ppm. 13C NMR (100 MHz, CDCl3): δ 140.7, 137.4, 137.0,
134.7, 132.0 (q, J = 1.1 Hz), 130.4, 129.5, 128.5 (q, J = 30.3 Hz), 127.9,
127.1 (q, J = 6.1 Hz), 124.9 (q, J = 274 Hz), 70.2, 21.5, 21.0 ppm.
HRMS-ESI [M − H]−: 293.1147, C17H16F3O requires 293.1153.
2,2-Dimethyl-1-(2-(trifluoromethyl)phenyl)propan-1-ol
(17j).9b A solution of trimethyl(2-(trifluoromethyl)phenyl)silane (13c)
(164 mg, 0.75 mmol) and pivalaldehyde (28 μL, 0.25 mmol) in
anhydrous THF (2.0 mL) was treated with dried Bu4NCl (104 mg,
0.375 mmol) and TMSOK (48 mg, 0.375 mmol), and the resulting
solution was stirred under N2 at 0 °C for 5 h. The solvent was removed
under reduced pressure, and HCl (2 M, 10 mL) was added. The residue
was extracted with diethyl ether (15 × 3 mL), and the organic layers
were combined, washed with brine (10 mL), dried over sodium sulfate,
and concentrated to dryness. Purification by silica gel chromatography
eluting with cyclohexane/ethyl acetate (95:5) yielded 17j as a colorless
oil (51 mg, 88%). 1H NMR (400 MHz, CDCl3): δ 7.8 (d, J = 7.9 Hz,
1H), 7.63 (d, J = 7.9 Hz, 1H), 7.55 (t, J = 7.6 Hz, 1H), 7.38 (t, J = 7.6 Hz,
1H), 4.92 (s, 1H), 1.93 (s, 1H), 0.98 (s, 9H) ppm. 13C NMR (100 MHz,
CDCl3): δ 141.7, 131.4 (q, J = 1.1 Hz), 129.6, 128.5 (q, J = 29.6 Hz),
127.6, 125.8 (q, J = 6.0 Hz), 124.6 (q, J = 274.1 Hz), 75.8 (q, J = 2.4 Hz),
36.5, 26.6 ppm. HRMS-EI [M]+: 232.1082, C12H15F3O requires
232.1075.
1-(2-Chlorophenyl)-2,2-dimethylpropan-1-ol (17e). A solution
of (2-chlorophenyl)trimethylsilane (13b) (140 mg, 0.75 mmol) and
pivalaldehyde (28 μL, 0.25 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (104 mg, 0.375 mmol) and TMSOK (48 mg,
0.375 mmol), and the resulting solution was stirred under N2 at 0 °C for
5 h. The solvent was removed under reduced pressure, and HCl (2 M, 10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (96:4)
1
yielded 17e as a colorless oil (42 mg, 84%). H NMR (400 MHz,
CDCl3): δ 7.55 (dd, J = 7.8, 1.7 Hz, 1H), 7.32 (dd, J = 7.8, 1.3 Hz, 1H),
7.27 (td, J = 7.6, 1.3 Hz, 1H), 7.21−7.16 (m, 1H), 5.03 (d, J = 3.0 Hz,
1H), 1.86 (d, J = 3.0 Hz, 1H), 0.98 (s, 9H) ppm. 13C NMR (100 MHz,
CDCl3): δ 140.1, 129.6, 129.4, 128.5, 126.4, 123.3, 76.8, 37.1, 25.9 ppm.
HRMS-EI [M]+: 198.0807, C11H15ClO requires 198.0811.
(E)-1-(2-Chlorophenyl)-3-phenylprop-2-en-1-ol (17f). A solu-
tion of (2-chlorophenyl)trimethylsilane (13b) (111 mg, 0.6 mmol) and
trans-cinnamaldehyde (66 mg, 0.5 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK (7 mg,
0.05 mmol), and the resulting solution was stirred under N2 at rt for 5 h.
HCl (2 M, 10 mL) was added, and the residue was extracted with diethyl
ether (15 × 3 mL). The organic layers were combined, washed with
brine (10 mL), dried over sodium sulfate, and concentrated to dryness.
Purification by silica gel chromatography eluting with cyclohexane/ethyl
acetate (95:5) yielded 17f as a yellow oil (99 mg, 81%). 1H NMR (400
MHz, CDCl3): δ 7.61 (dd, J = 7.7, 1.7 Hz, 1H), 7.40−7.26 (m, 6H),
7.25−7.19 (m, 2H), 6.72 (d, J = 15.9 Hz, 1H), 6.34 (dd, J = 15.9, 6.2 Hz,
1H), 5.80 (d, J = 6.2 Hz, 1H), 2.18 (s, 1H) ppm. 13C NMR (100 MHz,
CDCl3): δ 140.2, 136.6, 132.5, 131.1, 129.8, 129.7, 129.0, 128.7, 128.0,
127.8, 127.41, 126.8, 71.5 ppm. IR (neat): 3399, 3022, 2917, 1655 cm−1.
HRMS-EI [M]+: 244.0667, C15H13ClO requires 244.0655.
Naphthalen-2-yl(2-(trifluoromethyl)phenyl)methanol (17g).
A solution of trimethyl(2-(trifluoromethyl)phenyl)silane (13c) (131
mg, 0.6 mmol) and 2-naphthaldehyde (78 mg, 0.50 mmol) in anhydrous
THF (2.0 mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and
TMSOK (7 mg, 0.05 mmol) under N2, and the resulting solution was
stirred at rt for 5 h. The solvent was removed under reduced pressure,
and HCl (2 M, 10 mL) was added. The residue was extracted with
diethyl ether (15 × 3 mL), and the organic layers were combined,
washed with brine (10 mL), dried over sodium sulfate, and concentrated
to dryness. Purification by silica gel chromatography eluting with
cyclohexane/ethyl acetate (92:8) yielded 17g as a colorless oil (130 mg,
86%). 1H NMR (400 MHz, CDCl3): δ 7.93 (s, 1H), 7.87−7.76 (m, 3H),
7.70 (d, J = 7.9 Hz, 1H), 7.63 (d, J = 7.9 Hz, 1H), 7.56−7.45 (m, 3H),
7.43−7.36 (m, 2H), 6.49 (d, J = 3.5 Hz, 1H), 2.44 (d, J = 3.5 Hz, 1H)
ppm. 13C NMR (100 MHz, CDCl3): δ 142.4, 140.2, 133.3, 132.9, 132.5
(q, J = 1.1 Hz), 130.0, 128.3, 127.9 (q, J = 30.3 Hz), 128.0, 127.8, 126.4,
126.2, 125.7 (q, J = 5.8 Hz), 125.0, 124.8, 124.6 (q, J = 274 Hz), 71.0 (q, J
= 2.4 Hz) ppm. IR (neat): 3259, 3050, 1305 cm−1. HRMS-EI [M]+:
302.0904, C18H13F3O requires 302.0918.
(4-Chlorophenyl)(3-methoxyphenyl)methanol (17k).32 A sol-
ution of (4-chlorophenyl)trimethylsilane (13d) (70 mg, 0.375 mmol)
and m-anisaldehyde (34 mg, 0.25 mmol) in anhydrous THF (2.0 mL)
was treated with dried Bu4NCl (104 mg, 0.375 mmol) and TMSOK (48
mg, 0.375 mmol), and the resulting solution was stirred under N2 at 0 °C
for 5 h. The solvent was removed under reduced pressure, and 2 M HCl
(10 mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate
1
(90:10) yielded 17k as a colorless oil (42 mg, 68%). H NMR (400
MHz, CDCl3): δ 7.34−7.22 (m, 5H), 6.94−6.89 (m, 2H), 6.81 (dd, J =
8.0, 2.0 Hz, 1H), 5.78 (s, 1H), 3.78 (s, 3H), 2.26 (br s, 1H) ppm. 13C
NMR (100 MHz, CDCl3): δ 160.0, 145.2, 142.2, 133.5, 129.8, 128.7,
128.0, 119.0, 113.3, 112.3, 75.7, 55.4, 29.8 ppm. HRMS-ESI [M − H]−:
247.0530, C14H12O2Cl requires 247.0526.
(4-Bromophenyl)(phenyl)methanol (17l).18 A solution of (4-
bromophenyl)trimethylsilane (13e) (86 mg, 0.375 mmol) and
benzaldehyde (26 μL, 0.25 mmol) in anhydrous THF (2.0 mL) was
treated with dried Bu4NCl (104 mg, 0.375 mmol) and TMSOK (48 mg,
0.375 mmol), and the resulting solution was stirred under N2 at 0 °C for
5 h. The solvent was removed under reduced pressure, and HCl (2 M, 10
mL) was added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (95:5)
yielded 17l as a colorless solid (42 mg, 64%, mp 44−46 °C). 1H NMR
(400 MHz, CDCl3): δ 7.45 (d, J = 8.5 Hz, 2H), 7.35−7.22 (m, 7H), 5.78
(s, 1H), 2.27 (br s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ 143.5,
142.8, 131.7, 128.8, 128.3, 128.0, 126.7, 121.6, 75.8 ppm. HRMS-ESI [M
− H]−: 260.9906, C13H10OBr requires 260.9915.
Phenyl(2-(trifluoromethyl)phenyl)methanol (17h).31 A solu-
tion of trimethyl(2-(trifluoromethyl)phenyl)silane (13c) (131 mg, 0.6
mmol) and benzaldehyde (51 μL, 0.50 mmol) in anhydrous THF (2.0
mL) was treated with dried Bu4NCl (14 mg, 0.05 mmol) and TMSOK
(7 mg, 0.05 mmol) under N2, and the resulting solution was stirred at rt
for 5 h. The solvent was removed under reduced pressure, and HCl (2
M, 10 mL) added. The residue was extracted with diethyl ether (15 × 3
mL), and the organic layers were combined, washed with brine (10 mL),
dried over sodium sulfate, and concentrated to dryness. Purification by
silica gel chromatography eluting with cyclohexane/ethyl acetate (92:8)
1
yielded 17h as a colorless oil (105 mg, 83%). H NMR (400 MHz,
CDCl3): δ 7.69−7.61 (m, 2H), 7.54 (t, J = 7.6 Hz, 1H), 7.41−7.23 (m,
6H), 6.31 (s, 1H), 2.36 (s, 1H) ppm. 13C NMR (100 MHz, CDCl3): δ
L
dx.doi.org/10.1021/jo5007637 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(24) Huang, J.-M.; Wang, X.-X.; Dong, Y. Angew. Chem., Int. Ed. 2011,
50, 924.
(25) Sai, M.; Oshima, K.; Yorimitsu, H. Angew. Chem., Int. Ed. 2011, 50,
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C spectra for all new compounds. This material is
available free of charge via the Internet at http://pubs.acs.org.
3294.
(26) Zhou, C.; Wang, Z. Synthesis 2005, 1649.
(27) Adams, H.; Gilmore, N. J.; Jones, S.; Muldowney, M. P.; von
Reuss, S. H.; Vemula, R. Org. Lett. 2008, 10, 1457.
(28) Wu, X.; Mahalingam, A. K.; Alterman, M. Tetrahedron Lett. 2005,
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(29) Sui, Y.-Z.; Zhang, X.-C.; Wu, J.-W.; Li, S.; Zhou, J.-N.; Li, M.;
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(30) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org.
Lett. 2006, 8, 1479.
AUTHOR INFORMATION
Corresponding Author
*E-mail: donalfoshea@rcsi.ie.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the European Research Association ERA-Chemistry
and the Irish Research Council (IRC) for financial support.
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dx.doi.org/10.1021/jo5007637 | J. Org. Chem. XXXX, XXX, XXX−XXX