Synthesis of alkenyl boronates from allyl-substituted aromatics using an olefin cross-metathesis protocol

Article abstract of DOI:10.1021/jo400872x

An efficient synthesis of 3-aryl-1-propenyl boronates from pinacol vinyl boronic ester and allyl-substituted aromatics by cross metathesis is reported. Although the allylbenzene derivatives are prone to isomerization reaction under metathesis conditions,

Full text of DOI:10.1021/jo400872x

Note
pubs.acs.org/joc
Synthesis of Alkenyl Boronates from Allyl-Substituted Aromatics
Using an Olefin Cross-Metathesis Protocol
Remy Hemelaere, Franco̧ is Carreaux,* and Bertrand Carboni
́
Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite
Batiment 10A, 35042 Rennes Cedex, France
́ ́ ́
de Rennes 1, 263, Avenue du General Leclerc, Campus de Beaulieu,
̂
S
* Supporting Information
ABSTRACT: An efficient synthesis of 3-aryl-1-propenyl boronates from
pinacol vinyl boronic ester and allyl-substituted aromatics by cross
metathesis is reported. Although the allylbenzene derivatives are prone to
isomerization reaction under metathesis conditions, we found that some
ruthenium catalysts are effective for this methodology. This strategy thus
provides an interesting alternative approach to alkyne hydroboration,
leading to the preparation of unknown compounds. Moreover, the boron substituent can be replaced by various functional
groups in good yields.
Functionalized alkenyl boronates constitute an important class
of organoboron compounds.1 Their utility in organic synthesis
has been illustrated many times over. For instance, alkenyl
boronates can be converted to aldehydes or ketones,2 halides,3
and the corresponding olefins.4 In particular, they have been
employed in a range of C−C bond-forming reactions such as
Suzuki−Miyaura cross-coupling reaction.5 More recently, it was
found that alcohols can be coupled with vinyl boronate esters
using catalytic Cu(OAc)2 to synthesize vinyl ethers.6 Despite
the potential synthetic interest of 3-aryl-1-propenyl boronates
3, this particular class of alkenyl boronates has surprisingly
received little attention. To the best of our knowledge, only a
few compounds have been prepared in the literature to date
(Scheme 1). Among all the synthetic methodologies described,
product (α:β, 25:75) is moderate, which has been explained by
the presence of a phenyl group on the substrate. Other less
straightforward strategies have been employed to synthesize
(E)-4,4,5,5-tetramethyl-2-(3-phenylpropen-1-yl)-[1,3,2]-dioxa-
borolane, which can also be obtained from the commercially
available boronic acid.12−14 The (Z) isomer of this compound
is accessible by the rhodium(I)-catalyzed trans-hydroboration
reaction of prop-2-ynylbenzene developed by Miyaura and co-
workers.15 In light of this information, the development of an
efficient general method for the preparation of this class of
alkenyl boronates appears a sufficiently interesting goal to
justify a thorough study.
Although the terminal alkenyl boronates can be prepared by
a number of procedures, cross metathesis (CM) of alkenes with
vinyl boronates has recently emerged as a new, efficient
catalytic method.16 Taking into account that the introduction of
a propenyl moiety on a phenyl ring is easier than the
introduction of a propynyl group due to its lower reactivity, we
envisaged that the cross-olefin metathesis reaction could be
useful for the development of a general protocol to prepare 3-
arylpropen-1-yl boronic esters 3.17 Allylbenzene derivatives, and
more specifically, 3-phenyl-1-propene, have already been used
as substrates in olefin metathesis with different electron-
deficient cross partners such as methyl vinyl ketone,
acrylonitrile, or acroleine.18 However, because of the strong
substrate dependency of the metathesis reactions, this method,
employing a vinyl boronate, can lead to a side reaction resulting
from the migration of the double bond to the internal position
of the allylic compound, which could dramatically decrease the
yield of the desired product.19 Indeed, the isomerization of
allylbenzene derivatives under metathesis conditions was
Scheme 1. Different Strategies To Prepare 3-Arylpropen-1-yl
Boronic Esters
the hydroboration of the corresponding alkynes is employed
the most.7−11 As an example, the hydroboration of 3-(2-
bromophenyl)-1-propyne with the catecholborane was real-
ized.7,8 However, in this particular case, the hydroboration
product must be converted with an additional transformation
into a stable boronic acid compound to be used efficiently in a
Suzuki coupling reaction. Hydroboration of simple allylbenzene
catalyzed by NHC−Cu complexes in presence of bis-
(pinacolato)diboron [B2(pin)2] was also reported by the
Hoveyda group.10 The selectivity in favor of the desired
Received: April 29, 2013
Revised: June 17, 2013
Accepted: June 17, 2013
Published: June 17, 2013
© 2013 American Chemical Society
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The Journal of Organic Chemistry
Note
reported, although the exact mechanism is still unknown.20 It
has been postulated that the ruthenium hydride species
generated from the decomposition of the ruthenium catalysts,
such as G-II (Grubbs second generation catalyst) or HG-II
(Hoveyda−Grubbs second generation catalyst), are responsible
for the unwanted reaction.21
As part of our program related to the use of catalytic
processes in organoboron chemistry,22 we report our efforts
that are devoted to the development of a new access path to 3.
Different ruthenium-based olefin metathesis catalysts have been
evaluated, including the catalyst M71-SIPr,23 a Hoveyda−
Grubbs type catalyst that contains an aminocarbonyl function
linked to a benzylidene ligand (Figure 1). Some representative
applications of these metathesis products are also described.
not complete after 18 h, alkenyl boronate 3a was obtained in a
pure form after flash chromatography (55% yield) with the E
isomer as major product.26 The moderate yield can also be
explained by the presence of the self-metathesis product 5,
detected by 1H NMR analysis of crude reaction product, as well
as by the formation of other unidentified products. When G-II
and HG-II are used as catalysts (3 mol %), conversion is
complete under the same experimental conditions. The
proportion of 3a in the crude product decreased in favor of
compound 4, resulting from the isomerization process (entries
2−3). The exclusive formation of isomerized product 4 is
observed at high temperature in the presence of HG-II catalyst,
confirming that decomposition products from the catalyst can
be responsible of the isomerization reaction (entry 4). To
resolve this problem, Grubbs and co-workers have developed
cross-metathesis conditions using additives that minimize the
unwanted isomerization reaction.27
We therefore studied the effect of 1,4-benzoquinone on the
metathesis reaction of 1a. Unexpectedly, the addition of this
additive (10 mol %) significantly reduced the catalytic activity
of G-II with a slight effect on the isomerization process (entry
5). Better results were obtained in the presence of HG-II under
reflux conditions in toluene. A stoichiometric quantity of 1,4-
benzoquinone allowed a significant reduction of the isomer-
ization process but, unfortunately, with a concomitant drop of
catalyst activity (entries 6−8). Finally, M71-SIPr catalyst had a
better catalytic activity than HG-II in the presence of the
additive (entry 9). By heating the reaction mixture at 60 °C
with only 0.5 equiv of 1,4-benzoquinone, the desired product
3a was predominantly formed. After purification, the yield was
slightly higher than the one obtained with the G-I catalyst but
with a similar stereoselectivity in favor of E isomer (entry 10).
Having established two reliable operating conditions, we next
examined the scope and limitations of our process. A large
variety of allylbenzene derivatives (1) have been selected with
different functional groups on the phenyl ring as substrates.
Given the cost of the catalyst and an easy purification of the
desired product, the synthetic protocol with the Grubbs’
catalyst G-I (conditions A) was preferably used, as summarized
Figure 1. Structures of ruthenium catalysts used for olefin metathesis.
In order to develop a reliable protocol, 4-allyl-1,2-dimethoxy
benzene 1a was chosen first as a model substrate for our study
because this compound is particularly appropriate to undergo
an isomerization reaction in the presence of a ruthenium−
carbene catalyst.24 The cross-metathesis results obtained with 2
equiv of vinyl pinacol boronate 225 are given in Table 1. Under
standard conditions (CH2Cl2, reflux, 0.2 M), the Grubbs first-
generation catalyst G-I proved to be an efficient catalyst for the
metathesis reaction compared its effectiveness as a catalyst for
the isomerization process (entry 1). Although the reaction was
a
Table 1. Cross Metathesis of 1a with 2 Using Various Catalysts
b
c
de
,
d
f
entry
catalyst
G-I
additive (1,4-benzoquinone)
solvent
T (°C)
conversion (%)
ratio 3a/4/5
ratio E/Z of 3a
yield of 3a (%)
1
2
none
none
none
none
0.1
CH2Cl2
CH2Cl2
CH2Cl2
toluene
CH2Cl2
CH2Cl2
toluene
toluene
toluene
toluene
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
60
93
100
100
100
22
11/0/1
3.9/1
7.4/1
3/1
55
nd
nd
G-II
6.4/12.6/1
2.1/8/1
0/1/0
3
HG-II
HG-II
G-II
4
5
1/1.9/0
8.4/10.6/1
5.3/1
3.5/1
4/1
nd
nd
nd
nd
nd
60
6
HG-II
HG-II
HG-II
M71-SIPr
M71-SIPr
0.1
53
7
0.1
97
11.5/37.5/1
8.7/2.75/1
28/4.3/1
8
1
44
4/1
9
1
93
4/1
10
0.5
94
17.8/1.2/1
4/1
a
b
c
d
1
0.2 M in solvent. Equivalent relative to 1a. Conversion based on 1a as the limiting reagent. Determined by analysis of 300 MHz H NMR
e
f
spectra of product mixtures prior to purification. In all cases, no isomerization product from 3a was detected. Isolated by flash chromatography (nd
= not determined).
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Note
in Figure 2. In the hardest cases, catalyst M71-SIPr was also
tested (condition B). Yields obtained are between 55 and 89%,
than the aryl electrophiles.29 Using the readily available and
inexpensive KHF2, 7 was obtained in 65% yield as an air-stable
compound.30
In some transformations (Scheme 3), purification of the vinyl
boronate was not necessary. After completion of the CM
Scheme 3. Reaction Sequences without Purification of
Metathesis Product
reaction and evaporation of CH2Cl2, iodination (I2, NaOH) can
be realized in THF, giving rise to a cross-metathesis/iodination
sequence starting from 4-fluoroallylbenzene 1n. The corre-
sponding alkenyl iodide 8 was obtained in 62% yield for the
two steps. In all cases (6−8), the olefin stereochemistry of
metathesis product 3n was retained during these reactions.
Similarly, a cross-metathesis/oxidation sequence can be
realized, giving the corresponding aldehyde 9 in an
unoptimized overall yield (68%) due to partial decomposition
during purification by column chromatography. This last
approach can be an alternative strategy to the anti-Markovnikov
regioselective oxidation of allyl aromatics into aldehydes using
base−transition metal catalysts.31
In summary, we described in this paper an efficient and
simple route of alkenyl boronates starting from allyl aromatics
based on a cross-metathesis reaction. Two simple and
complementary operating conditions have been developed,
allowing us to increase the generality of the methodology. The
synthesis and isolation of several new functionalized 3-aryl-1-
propenyl pinacol boronates have been carried out for a broad
scope of substrates. Furthermore, various synthetic trans-
formations of the boron−carbon bond have been realized. In
the future, the boron substituent could be replaced by other
functional groups using, for example, sodium azide as a
nitrogen counterpart.32
Figure 2. Cross metathesis of various allyl aromatics with 2.
except for 1-allyl-4-methylsulfanylbenzene 1j (22%). By using
the catalyst M71-SIPr, compound 3j can be prepared with a
slightly improved yield (42%), showing the interest in having
two available protocols. It must be noted that N-Boc-3-
allylindole 1q is a very good substrate for the cross metathesis
with 2, which is a relevant result due to the fact that this
nucleus is found in various bioactive molecules of pharmaceut-
ical importance.28 The stereoselectivity of the reaction is
moderately high, in most cases in favor of the E isomer, except
when the phenyl moiety is substituted by a thioether or
sulfonamide functional group (3j and 3k). All compounds were
isolated as an inseparable mixture of isomers except in the case
of 3k.
To illustrate the synthetic interest of this family of alkenyl
boronates, some typical transformations have been realized as
shown in Scheme 2. A Suzuki cross-coupling reaction between
3n and phenyl iodide was conducted in the presence of K2CO3,
Pd(OAc)2 (5 mol %), and PPh3 (15 mol %) under reflux in
THF to give the corresponding coupled product 6 in 88% yield.
The alkenyl boronate 3n can also be readily converted to its
trifluoroborate analog; these salts are known as useful reagents
in palladium-catalyzed coupling reactions with partners other
EXPERIMENTAL SECTION
■
General Information and Materials. All commercially available
chemicals were used without further purification. Tetrahydrofuran
(THF) and toluene were distilled over sodium/benzophenone.
Dichloromethane (CH2Cl2) was distilled over P2O5. 1H and 13C
1
spectra were recorded in CDCl3 (internal standard: 7.26 ppm, H;
Scheme 2. Some Synthetic Transformations of Alkenyl
Boronate 3n
77.00 ppm, 13C), acetone-d6 (internal standard: 2.05 ppm, H; 29.84
1
ppm, 13C), 19F NMR chemical shifts to external CFCl3 (0.0 ppm), and
11B NMR chemical shifts to external BF3·OEt2 (0.0 ppm). Carbon
atoms in α to boron are often not visible in 13C NMR. High-resolution
mass spectra (HMRS) were recorded on a micro-TOF-Q II mass
analyzer or Q-TOF 2 using positive ion electrospray.
General Procedures for Cross-Metathesis Reactions. Proce-
dure A. To a solution of 1 (0.35 mmol) in dry CH2Cl2 (0.2 M) under
argon atmosphere was added successively 2 (0.70 mmol) and G-I
catalyst (3 mol %). The resulting mixture was heated under a reflux
condition for 18 h. After this time, CH2Cl2 was removed under
reduced pressure, and the residue was purified via column
chromatography by using an appropriate eluent to afford the products
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Note
3b−i, 3k−l, and 3n as inseparable mixtures of E and Z isomers except
for 3k.
129.4, 137.2, 140.7, 152.2, 159.0; (Z) δ 24.9, 38.7, 69.9, 83.0, 115.3,
121.3, 127.5, 127.9, 128.6, 129.4, 137.1, 140.7, 152.5, 159.0. 11B NMR
(96 MHz, CDCl3): δ 29.8. HRMS ESI (+), CH3OH: [M + Na]+ calcd
for C22H27BO3, 373.1951; found, 373.1951.
Procedure B. To a solution of 1 (0.35 mmol) in dry toluene (0.2
M) under an argon atmosphere were added successively 2 (0.70
mmol), 1,4-benzoquinone (0.175 mmol), and M71-SIPr (3 mol %).
The resulting mixture was heated at 60 °C for 18 h. After this time,
toluene was removed under reduced pressure, and the residue was
purified on column chromatography by using an appropriate eluent to
afford 3a, 3j, and 3m, as an inseparable mixture of E and Z isomers.
4,4,5,5-Tetramethyl-2-(3-(3,4-dimethoxyphenyl)prop-1-
enyl)-[1,3,2]-dioxaborolane (3a). Procedure B. Purified using
EtOAc/cyclohexane (1:9); 65 mg (60%, E/Z = 80/20). Colorless
2-(3-(2-(Benzyloxy)phenyl)prop-1-enyl)-4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolane (3f). Procedure A. Purified using EtOAc/
1
cyclohexane (5:95); 89 mg (73%, E/Z = 90/10). Colorless oil. H
NMR (300 MHz, CDCl3): (E) δ 1.29 (s, 12H), 3.59 (dd, J = 6.2, 1.4
Hz, 2H), 5.11 (s, 2H), 5.48 (dt, J = 17.9, 1.4 Hz, 1H), 6.85 (dt, J =
17.9, 6.2 Hz, 1H), 6.91−6.96 (m, 2H), 7.17−7.23 (m, 2H), 7.32−7.48
(m, 5H); (Z) δ 1.32 (s, 12H), 3.90 (dd, J = 7.5, 1.3 Hz, 2H), 5.14 (s,
2H), 5.46 (dt, J = 13.3, 1.3 Hz, 1H), 6.68 (dt, J = 13.3, 7.5 Hz, 1H),
6.91−6.96 (m, 2H), 7.17−7.23 (m, 2H), 7.32−7.48 (m, 5H). 13C
NMR (75 MHz, CDCl3): (E) δ 24.8, 36.5, 69.9, 83.0, 111.8, 120.8,
127.2, 127.5, 127.7, 128.1, 128.5, 130.5, 137.4, 152.3, 156.4; (Z) δ
24.9, 33.0, 69.9, 82.9, 111.7, 120.9, 127.1, 127.5, 127.7, 128.1, 128.5,
130.1, 137.4, 152.7, 156.4. 11B NMR (96 MHz, CDCl3): δ 29.8.
HRMS ESI (+), CH3OH: [M + Na]+ calcd for C22H27BO3, 373.1951;
found, 373.1952.
1
oil. H NMR (400 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.43 (dd, J =
6.3, 1.6 Hz, 2H), 3.86 (s, 3H), 3.87 (s, 3H), 5.45 (dt, J = 17.8, 1.6 Hz,
1H), 6.69−6.83 (m, 4H); (Z) δ 1.32 (s, 12H), 3.70 (dd, J = 7.9, 1.3
Hz, 2H), 3.86 (s, 3H), 3.88 (s, 3H), 5.43 (dt, J = 13.3, 1.3 Hz 1H),
6.55 (dt, J = 14.0, 7.9 Hz, 1H), 6.69−6.83 (m, 3H). 13C NMR (75
MHz, CDCl3): (E) δ 24.8, 41.9, 55.8, 55.9, 83.1, 111.3, 112.2, 120.8,
131.7, 147.5, 148.9, 152.7; (Z) δ 24.9, 38.2, 55.7, 55.9, 83.0, 111.3,
112.0, 120.4, 133.3, 147.5, 148.9, 152.9. 11B NMR (96 MHz, CDCl3) δ
29.7. HRMS ESI (+), CH3OH: [M + Na]+ calcd for C17H25BO4,
327.1744; found, 327.1745.
2-(3-(4-Methoxyphenyl)prop-1-enyl)-4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolane(3g). Procedure A. Purified using EtOAc/
1
cyclohexane (5:95); 64 mg (67%, E/Z = 85/15). Colorless oil. H
NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.44 (dd, J = 6.3, 1.5
Hz, 2H), 3.80 (s, 3H), 5.44 (dt, J = 17.9, 1.5 Hz, 1H), 6.77 (dt, J =
17.9, 6.3 Hz, 1H), 6.83−6.86 (m, 2H), 7.09−7.18 (m, 2H); (Z) δ 1.32
(s, 12H), 3.72 (dd, J = 7.6, 1.3 Hz 2H), 3.80 (s, 3H), 5.42 (dt, J = 13.3,
1.3 Hz, 1H), 6.54 (dt, J = 13.3, 7.6 Hz, 1H), 6.83−6.86 (m, 2H),
7.09−7.18 (m, 2H). 13C NMR (75 MHz, CDCl3): (E) δ 24.8, 41.4,
55.3, 83.1, 113.9, 129.9, 131.1, 153.0, 158.1; (Z) δ 24.9, 38.0, 55.3,
83.0, 113.8, 129.4, 130.5, 153.1, 157.90. 11B NMR (96 MHz, CDCl3):
δ 29.6. HRMS ESI (+), CH3OH: [M + Na]+ calcd for C16H23BO3,
297.1638; found, 297.1640.
2-Methoxy-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)allyl)phenol (3b). Procedure A. Purified using EtOAc/cyclohexane
(1:4); 66 mg (65%, E/Z = 83/17). Colorless oil. 1H NMR (300 MHz,
CDCl3): (E) δ 1.27 (s, 12H), 3.41 (dd, J = 6.3, 1.6 Hz, 2H), 3.87 (s,
3H), 5.45 (dt, J = 17.8, 1.6 Hz, 1H), 5.56 (br s, 1H, OH), 6.67−6.86
(m, 4H); (Z) δ 1.32 (s, 12H), 3.69 (dd, J = 7.7, 1.3 Hz, 2H), 3.88 (s,
3H), 5.42 (dt, J = 13.5, 1.3 Hz, 1H), 5.54 (br s, 1H, OH), 6.55 (dt, J =
13.5, 7.7 Hz, 1H), 6.67−6.86 (m, 3H). 13C NMR (75 MHz, CDCl3):
(E) δ 24.8, 42.0, 55.9, 83.1, 111.5, 114.3, 121.6, 130.9, 144.0, 146.5,
152.9; (Z) δ 24.9, 38.3, 55.8, 83.0, 111.2, 114.2, 121.2, 132.5, 143.8,
146.5, 153.0. 11B NMR (96 MHz, CDCl3): δ 29.8. HRMS ESI (+),
CH3OH: [M + Na]+ calcd for C16H23BO4, 313.1587; found, 313.1585.
2-[3-(4-Benzyloxy-3-methoxyphenyl)prop-1-enyl]-4,4,5,5-
tetramethyl-[1,3,2]-dioxaborolane (3c). Procedure A. Purified
using EtOAc/cyclohexane (5:95); 74 mg (56%, E/Z = 75/25). Pale
2-(3-(2-Methoxyphenyl)prop-1-enyl)-4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolane (3h). Procedure A. Purified using EtOAc/
1
cyclohexane (5:95); 85 mg (89%, E/Z = 87/13). Colorless oil. H
NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.51 (dd, J = 6.2, 1.6
Hz, 2H), 3.83 (s, 3H), 5.44 (dt, J = 17.9, 1.6 Hz, 1H), 6.80 (dt, J =
17.9, 6.2 Hz, 1H), 6.85−6.93 (m, 2H), 7.12−7.15 (m, 1H), 7.18−7.24
(m, 1H); (Z) δ 1.33 (s, 12H), 3.80 (dd, J = 7.5, 1.6 Hz, 2H), 3.85 (s,
3H), 5.42 (dt, J = 13.2, 1.6 Hz, 1H), 6.60 (dt, J = 13.3, 7.5 Hz, 1H),
6.85−6.93 (m, 2H), 7.12−7.15 (m, 1H), 7.18−7.24 (m, 1H). 13C
NMR (75 MHz, CDCl3): (E) δ 24.8, 36.4, 55.3, 83.0, 110.3, 120.5,
127.5, 127.6, 130.3, 152.3, 157.3; (Z) δ 24.9, 32.9, 55.3, 82.9, 110.3,
120.5, 127.2, 127.6, 130.0, 152.6, 157.3. 11B NMR (96 MHz, CDCl3):
δ 29.7. HRMS ESI (+), CH3OH: [M + Na]+ calcd for C16H23BO3,
297.1638; found, 297.1635.
4,4,5,5-Tetramethyl-2-(3--tolylprop-1-enyl)-[1,3,2]-dioxabor-
olane (3i). Procedure A. Purified using EtOAc/cyclohexane (5:95);
63 mg (70%, E/Z = 87/17). Colorless oil. 1H NMR (300 MHz,
CDCl3): (E) δ 1.28 (s, 12H), 2.35 (s, 3H), 3.47 (dd, J = 6.3, 1.5 Hz,
2H), 5.47 (dt, J = 17.8, 1.5 Hz, 1H), 6.78 (dt, J = 17.8, 6.3 Hz, 1H),
7.07−7.14 (m, 4H); (Z) δ 1.33 (s, 12H), 2.35 (s, 3H), 3.75 (dd, J =
7.6, 1.3 Hz, 2H), 5.45 (dt, J = 13.2, 1.3 Hz, 1H), 6.56 (dt, J = 13.2, 7.6
Hz, 1H), 7.07−7.14 (m, 4H). 13C NMR (75 MHz, CDCl3): (E) δ
21.0, 24.8, 41.9, 83.1, 128.8, 129.1, 135.6, 136.0, 152.8; (Z) δ 21.0,
24.9, 38.2, 83.0, 128.5, 129.1, 135.8, 135.9, 153.0. 11B NMR (96 MHz,
CDCl3): δ 29.7. HRMS ESI (+), CH3OH: [M + Na]+ calcd for
C16H23BO2, 281.1689; found, 281.1686.
1
yellow oil. H NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.42
(dd, J = 6.3, 1.5 Hz, 2H), 3.89 (s, 3H), 5.15 (s, 2H), 5.46 (dt, J = 17.8,
1.5 Hz, 1H), 6.64−6.84 (m, 4H), 7.28−7.47 (m, 5H); (Z) δ 1.32 (s,
12H), 3.69 (dd, J = 7.6, 1.1 Hz, 2H), 3.89 (s, 3H), 5.15 (s, 2H), 5.43
(dt, J = 13.2, 1.1 Hz, 1H), 6.55 (dt, J = 13.2, 7.6 Hz, 1H), 6.64−6.84
(m, 3H), 7.28−7.47 (m, 5H). 13C NMR (75 MHz, CDCl3): (E) δ
24.8, 41.9, 56.0, 71.2, 83.1, 112.8, 114.3, 120.8, 127.2, 127.7, 128.5,
132.3, 137.4, 146.6, 149.6, 152.7; (Z) δ 24.9, 38.3, 55.9, 71.2, 83.0,
112.5, 114.3, 120.4, 127.2, 127.7, 128.5, 133.9, 137.4, 146.5, 149.6,
152.9. 11B NMR (96 MHz, CDCl3): δ 29.8. HRMS ESI (+), CH3OH:
[M + Na]+ calcd for C23H29BO4, 403.2057; found, 403.2057.
2-(3-(Benzo[d][1,3]dioxol-6-yl)prop-1-enyl)-4,4,5,5-tetra-
methyl-[1,3,2]-dioxaborolane (3d). Procedure A. Purified using
EtOAc/cyclohexane (5:95); 79 mg (79%, E/Z = 88/12). Colorless oil.
1H NMR (400 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.39 (dd, J = 6.3,
1.5 Hz, 2H), 5.44 (dt, J = 17.8, 1.5 Hz, 1H), 5.92 (s, 2H), 6.61−6.78
(m, 4H); (Z) δ 1.31 (s, 12H), 3.67 (dd, J = 7.6, 1.1 Hz, 2H), 5.42 (dt,
J = 13.2, 1.1 Hz, 1H), 5.92 (s, 2H), 6.51 (dt, J = 13.2, 7.6 Hz, 1H),
6.61−6.78 (m, 3H). 13C NMR (75 MHz, CDCl3): (E) δ 24.8, 41.9,
83.1, 100.8, 108.2, 109.4, 121.7, 132.8, 145.9, 147.6, 152.5; (Z) δ 24.9,
38.3, 83.0, 100.7, 108.1, 109.0, 121.3, 134.5, 145.7, 147.6, 152.80. 11B
NMR (96 MHz, CDCl3): δ 29.7. HRMS ESI (+), CH3OH: [M + Na]+
calcd for C16H21BO4, 311.1431; found, 311.1435.
4,4,5,5-Tetramethyl-2-[3-(3-benzyloxyphenyl)prop-1-enyl]-
4,4,5,5-tetramethyl-[1,3,2]-dioxaborolane (3e). Procedure A.
Purified using EtOAc/cyclohexane (5:95); 87 mg (71%, E/Z = 86/
14). Colorless oil. 1H NMR (300 MHz, CDCl3): (E) δ 1.29 (s, 12H),
3.48 (dd, J = 6.3, 1.5 Hz, 2H), 5.07 (s, 2H), 5.50 (dt, J = 17.8, 1.5 Hz,
1H), 6.74−6.92 (m, 4H), 7.21−7.26 (m, 1H), 7.36−7.49 (m, 5H); (Z)
δ 1.33 (s, 12H), 3.78 (dd, J = 7.5, 1.3 Hz, 2H), 5.07 (s, 2H), 5.48 (dt, J
= 13.2, 1.3 Hz, 1H), 6.58 (dt, J = 13.2, 7.5 Hz, 1H), 6.74−6.92 (m,
3H), 7.21−7.26 (m, 1H), 7.36−7.49 (m, 5H). 13C NMR (75 MHz,
CDCl3): (E) δ 24.8, 42.3, 69.9, 83.1, 115.6, 121.6, 127.6, 127.9, 128.6,
4,4,5,5-Tetramethyl-2-(3-(4-(methylthio)phenyl)prop-1-
enyl)-[1,3,2]-dioxaborolane (3j). Procedure B. Purified using
EtOAc/cyclohexane (5:95); 42 mg (42%, E/Z = 70/30). Colorless
1
oil. H NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 2.48 (s, 3H),
3.45 (dd, J = 6.2, 1.5 Hz, 2H), 5.44 (dt, J = 17.8, 1.5 Hz, 1H), 6.74 (dt,
J = 17.8, 6.3 Hz, 1H), 7.10−7.24 (m, 4H); (Z) δ 1.31 (s, 12H), 2.48
(s, 3H), 3.73 (dd, J = 7.6, 1.2 Hz, 2H), 5.41−5.48 (m, 1H), 6.53 (dt, J
= 14.0, 7.5 Hz, 1H), 7.10−7.24 (m, 4H). 13C NMR (75 MHz,
CDCl3): (E) δ 16.3, 24.8, 41.6, 83.1, 127.2, 129.5, 135.8, 136.2, 152.4;
(Z) δ 16.4, 24.9, 41.6, 83.0, 127.3, 129.2, 135.5, 136.5, 152.2. 11B NMR
(96 MHz, CDCl3): δ 29.7. HRMS ESI (+), CH3OH: [M + Na]+ calcd
for C16H23BO2S, 313.1409; found, 313.1411.
6789
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The Journal of Organic Chemistry
Note
4-Nitro-N-{2-[3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-
yl)allyl]phenyl}benzenesulfonamide (3k). Procedure A. Purified
using EtOAc/cyclohexane (1:4); 96 mg (62%, separable mixture of E/
CH3OH: [M + Na]+ calcd for C15H16BF5O2, 357.1061; found,
357.1064.
4,4,5,5-Tetramethyl-2-[3-(4-trifluoromethylphenyl)prop-1-
enyl]-[1,3,2]-dioxaborolane (3p). Procedure A. Purified using
EtOAc/cyclohexane (5:95); 76 mg (70%, E/Z = 92/8). Colorless
1
Z = 70/30). Brown oil. H NMR (300 MHz, CDCl3): (E) δ 1.27 (s,
12H), 3.12 (dd, J = 5.4, 1.7 Hz, 2H), 5.21 (dt, J = 18.0, 1.7 Hz, 1H),
6.52 (br s, 1H), 6.53 (dt, J = 18.0, 5.4 Hz, 1H), 7.09 (dd, J = 7.4, 1.6
Hz, 1H), 7.17−7.21 (m, 1H), 7.22−7.28 (m, 1H), 7.40 (dd, J = 7.8,
1.3 Hz, 1H), 7.91 (d, J = 8.9 Hz, 2H), 8.30 (d, J = 8.9 Hz, 2H); (Z) δ
1.27 (s, 6H), 1.44 (s, 6H), 3.26 (dd, J = 8.1, 1.2 Hz, 2H), 5.28 (m,
1H), 6.18 (dt, J = 13.1, 8.1 Hz, 1H), 7.11−7.18 (m, 2H), 7.22−7.25
(m, 1H), 7.65 (d, J = 8.1 Hz, 1H), 7.81 (d, J = 8.9 Hz, 1H), 8.22−8.25
(m, 3H). 13C NMR (75 MHz, CDCl3): (E) δ 24.8, 37.7, 83.5, 124.3,
124.9, 127.3, 128.1, 128.4, 131.2, 131.9, 133.8, 145.2, 149.4, 150.2; (Z)
δ 24.7, 34.3, 83.4, 123.9, 124.3, 126.5, 127.7, 128.4, 130.5, 131.8, 134.0,
145.2, 150.4, 151.7. 11B NMR (96 MHz, CDCl3): δ 29.5. HRMS ESI
(+), CH3OH: [M + Na]+ calcd for C21H25BN2O6S, 467.1424; found,
467.1421.
1
oil. H NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.54 (dd, J =
6.2, 1.6 Hz, 2H), 5.46 (dt, J = 17.8, 1.6 Hz, 1H), 6.74 (dt, J = 17.8, 6.2
Hz, 1H), 7.29 (d, J = 8.9 Hz, 2H), 7.55 (d, J = 8.2 Hz, 2H); (Z) δ 1.32
(s, 12H), 3.83 (dd, J = 7.5, 1.3 Hz, 2H), 5.50 (dt, J = 13.2, 1.3 Hz,
1H), 6.53 (dt, J = 13.2, 7.5 Hz, 1H), 7.35 (d, J = 8.6 Hz, 2H), 7.55 (d,
J = 8.2 Hz, 2H). 13C NMR (75 MHz, CDCl3): (E) δ 24.8, 38.8, 83.2,
124.3 (d, J = 243.7 Hz), 125.3 (q, J = 3.8 Hz), 128.6 (d, J = 32.2 Hz),
129.2, 143.2, 151.0; (Z) δ 24.9, 41.9, 83.1, 124.29 (d, J = 243.7 Hz),
125.3 (q, J = 3.8 Hz), 128.6 (d, J = 32.2 Hz), 128.9, 143.1, 151.2. 19F
NMR (282 MHz, CDCl3): (E) δ −62.4; (Z) δ −62.2. 11B NMR (96
MHz, CDCl3): δ 29.5. HRMS ESI (+), CH3OH: [M + Na]+ calcd for
C16H20BF3O2, 335.1406; found, 335.1406.
tert-Butyl-3-(3-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-
yl)allyl)-1H-indole-1-carboxylate (3q). Procedure A. Purified using
EtOAc/cyclohexane (5:95); 108 mg (81%, E/Z = 86/14). Colorless
4,4,5,5-Tetramethyl-2-(3-phenylprop-1-enyl)-[1,3,2]-dioxa-
borolane (3l). Procedure A. Purified using EtOAc/cyclohexane
1
(5:95); 60 mg (70%, E/Z = 85/15). Colorless oil. H NMR (300
1
oil. H NMR (300 MHz, CDCl3): (E) δ 1.28 (s, 12H), 1.69 (s, 9H),
MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.50 (dd, J = 6.2, 1.5 Hz, 2H),
5.46 (dt, J = 17.8, 1.5 Hz, 1H), 6.78 (dt, J = 17.8, 6.2 Hz, 1H), 7.18−
7.33 (m, 5H); (Z) δ 1.33 (s, 12H), 3.80 (dd, J = 7.6, 0.8 Hz, 2H), 5.46
(dt, J = 13.4, 0.8 Hz, 1H), 6.55−6.61 (m, 1H), 7.18−7.33 (m, 5H).
13C NMR (75 MHz, CDCl3): (E) δ 24.8, 42.3, 83.1, 126.1, 128.4,
128.9, 139.1, 152.5; (Z) δ 24.9, 38.7, 83.0, 125.9, 128.4, 128.6, 139.1,
152.7. 11B NMR (96 MHz, CDCl3): δ 29.5. These data are in
agreement with those reported in the literature.33
3.57 (dd, J = 6.0, 1.5 Hz, 2H), 5.57 (dt, J = 17.7, 1.5 Hz, 1H), 6.85 (dt,
J = 17.8, 6.0 Hz, 1H), 7.22−7.28 (m, 1H), 7.31−7.36 (m, 1H), 7.42
(br s, 1H), 7.51−7.53 (m, 1H), 8.15 (d, J = 7.3 Hz, 1H); (Z) δ 1.35 (s,
12H), 1.69 (s, 9H), 3.86 (dd, J = 7.5, 1.1 Hz, 2H), 5.50−5.55 (m, 1H),
6.65 (dt, J = 13.8, 7.5 Hz, 1H), 7.22−7.28 (m, 1H), 7.31−7.36 (m,
1H), 7.42 (br s, 1H), 7.64−7.67 (m, 1H), 8.15 (d, J = 7.3 Hz, 1H). 13C
NMR (75 MHz, CDCl3): (E) δ 24.8, 28.2, 31.3, 83.1, 83.3, 115.2,
118.0, 119.2, 122.4, 123.3, 124.3, 130.5, 135.6, 149.8, 150.8; (Z) δ
24.9, 28.2, 30.2, 83.1, 83.3, 115.2, 118.0, 119.3, 122.2, 123.3, 124.3,
130.5, 135.6, 149.8, 151.6. 11B NMR (96 MHz, CDCl3): δ 29.8.
HRMS ESI (+), CH3OH: [M + Na]+ calcd for C22H30BNO4,
406.2166; found, 406.2167
1-Fluoro-4-(3-phenylallyl)benzene (6). To a solution of 2-(3-
(4-fluorophenyl)prop-1-enyl)-4,4,5,5-tetramethyl-[1,3,2]-dioxaboro-
lane 3n (50 mg, 0.19 mmol) in anhydrous THF (2.0 mL) were added
Pd(OAc)2 (2.14 mg, 9.53 μmol, 0.05 equiv), PPh3 (7.50 mg, 28.60
μmol, 0.15 equiv), K2CO3 (39 mg, 0.28 mmol, 1.50 equiv), and phenyl
iodide (32.00 μL, 0.28 mmol, 1.50 equiv). The resulting mixture was
heated under reflux conditions for 18 h. After this time, water was
added to quench the reaction, and the mixture was extracted with
Et2O. Organic phases were washed with brine, dried over MgSO4, and
concentrated under a vacuum. Crude product was purified by column
chromatography using cyclohexane/EtOAc (98:2) as the eluent to
afford the desired product 6 as a colorless oil (35 mg, 88%). 1H NMR
(300 MHz, CDCl3): (E) δ 3.54 (d, J = 6.4 Hz, 2H), 6.24 (dt, J = 15.7,
6.7 Hz, 1H), 6.36 (dt, J = 15.7, 1.4 Hz, 1H), 6.99−7.08 (m, 2H),
7.20−7.40 (m, 7H); (Z) δ 3.67 (d, J = 7.3 Hz, 2H), 5.74 (dt, J = 11.5,
7.3 Hz, 1H), 6.51 (dt, J = 11.5, 1.9 Hz, 1H), 6.99−7.08 (m, 2H),
7.20−7.40 (m, 7H). 13C NMR (75 MHz, CDCl3): (E) δ 38.5, 115.2
(d, J = 21.0 Hz), 126.1, 127.2, 128.5, 129.0, 130.0 (d, J = 8.0 Hz),
131.2, 135.7 (d, J = 3.2 Hz), 137.3, 161.5 (d, J = 244.0 Hz); (Z) δ 38.5,
115.6 (d, J = 21.8 Hz), 126.4, 126.9, 128.7, 129.0, 129.7 (d, J = 8.0
Hz), 131.2, 135.7 (d, J = 3.2 Hz), 137.3, 161.5 (d, J = 244.0 Hz). 19F
NMR (282 MHz, CDCl3): (E) δ −117.26; (Z): δ −114.26. These data
are in agreement with those reported in the literature.34
2-(3-(2-Methoxyphenyl)prop-1-enyl)-4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolane (3m). Procedure B. Purified using EtOAc/
cyclohexane (1:9); 58 mg (55%, E/Z = 85/15). Yellow powder. Mp =
1
99 °C. H NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 2.31 (s,
3H), 3.40 (dd, J = 6.3, 1.4 Hz, 2H), 5.47 (dt, J = 17.8, 1.4 Hz, 1H),
6.68 (dt, J = 17.8, 6.3 Hz, 1H), 7.04−7.07 (m, 1H), 7.16−7.32 (m,
3H); (Z) δ 1.31 (s, 12H), 2.32 (s, 3H), 3.70 (dd, J = 7.3, 1.0 Hz, 2H),
5.47 (m, 1H), 6.48 (dt, J = 13.2, 7.3 Hz, 1H), 7.04−7.07 (m, 1H),
7.16−7.32 (m, 3H). 13C NMR (75 MHz, CDCl3): (E) δ 21.0, 24.8,
36.7, 83.2, 122.4, 126.2, 127.5, 130.8, 131.0, 149.0, 150.7, 169.3; (Z) δ
21.0, 24.9, 36.7, 83.1, 122.3, 126.2, 127.3, 130.5, 131.0, 149.0, 150.7,
169.3. 11B NMR (96 MHz, CDCl3): δ 29.7. HRMS ESI (+), CH3OH:
[M + Na]+ calcd for C17H23BO4, 325.1587; found, 325.1587.
2-(3-(4-Fluorophenyl)prop-1-enyl)-4,4,5,5-tetramethyl-
[1,3,2]-dioxaborolane (3n). Procedure A. Purified using EtOAc/
cyclohexane (5:95); 69 mg (76%, E/Z = 93/7). Colorless oil. 1H
NMR (300 MHz, CDCl3): (E) δ 1.27 (s, 12H), 3.46 (dd, J = 6.2, 1.6
Hz, 2H), 5.44 (dt, J = 17.9, 1.6 Hz, 1H), 6.78 (dt, J = 17.8, 6.2 Hz,
1H), 6.95−7.10 (m, 2H), 7.11−7.21 (m, 2H); (Z) δ 1.32 (s, 12H),
3.74 (dd, J = 7.6, 1.2 Hz, 2H), 5.45 (dt, J = 13.2, 1.2 Hz, 1H), 6.52 (dt,
J = 13.3, 7.5 Hz, 1H), 6.95−7.10 (m, 2H), 7.11−7.21 (m, 2H). 13C
NMR (75 MHz, CDCl3): (E) δ 24.8, 41.3, 83.2, 115.2 (d, J = 21.1
Hz), 130.3 (d, J = 7.7 Hz), 134.7 (d, J = 3.2 Hz), 152.1, 161.5 (d, J =
243.7 Hz); (Z) δ 24.9, 37.8, 83.1, 115.1 (d, J = 21.1 Hz), 129.9 (d, J =
7.8 Hz), 136.3 (d, J = 3.0 Hz), 152.4, 161.5 (d, J = 243.7 Hz). 19F
NMR (282 MHz, CDCl3): (E) δ −117.3; (Z) δ −117.7. 11B NMR (96
MHz, CDCl3): δ 29.7. HRMS ESI (+), CH3OH: [M + Na]+ calcd for
C15H20BFO2, 285.1438; found, 285.1437.
Potassium-3-(4-fluorophenyl)propenyl-1-trifluoroborate (7).
To a solution of 3n (97 mg, 0.37 mmol) in methanol (3.5 M) at 0 °C
were added KHF2 (87 mg, 1.11 mmol, 3 equiv) and water (80 μL).
The ice bath was removed, and the mixture was stirred at room
temperature for 4 h. After this time, methanol and water were removed
under reduced pressure, and the crude product was washed with
acetone and then filtrated. Acetone was then removed under reduced
pressure, and the crude product was washed with Et2O and then
filtrated to give the desired product 7 as a white powder (58 mg, 65%).
Mp = 240 °C. 1H NMR (300 MHz, acetone-d6): (E) δ 3.12 (d, J = 6.2
Hz, 2H), 5.28−5.37 (m, 1H), 5.69 (dt, J = 16.7, 6.2 Hz, 1H), 6.78−
6.89 (m, 2H), 7.04 (dd, J = 8.7, 5.7 Hz, 2H); (Z) δ = 3.37 (d, J = 7.1
Hz, 2H), 5.28−5.37 (m, 1H), 5.52−5.59 (m, 1H), 6.78−6.89 (m, 2H),
7.12 (dd, J = 8.7, 5.7 Hz, 2H). 13C NMR (75 MHz, acetone-d6): (E) δ
4,4,5,5-Tetramethyl-2-(3-(perfluorophenyl)prop-1-enyl)-
[1,3,2]-dioxaborolane (3o). Procedure A. Purified using EtOAc/
1
cyclohexane (5:95); 76 mg (65%, E/Z = 84/16). Colorless oil. H
NMR (300 MHz, CDCl3): (E) δ 1.26 (s, 12H), 3.53 (dd, J = 5.7, 1.6
Hz, 2H), 5.40 (dd, J = 17.8, 1.6 Hz, 1H), 6.62 (dt, J = 17.8, 5.7 Hz,
1H); (Z) δ 1.32 (s, 12H), 3.88 (dd, J = 7.1, 1.5 Hz, 2H), 5.49 (dt, J =
13.2, 1.3 Hz, 1H), 6.34 (dt, J = 13.2, 7.1 Hz, 1H). 13C NMR (75 MHz,
CDCl3): (E) δ 23.7, 26.9, 82.4, 111.2 (dt, J = 19.0, 3.7 Hz), 120.0,
134.8 (m), 138.3 (m), 142.4 (m), 145.7; (Z) δ 23.8, 24.4, 82.3, 111.2
(dt, J = 19.0, 3.7 Hz), 120.0 (CH), 137.3 (m), 140.6 (m), 145.6 (m),
146.3. 19F NMR (282 MHz, CDCl3): (E) δ −162.7 (dt, J = 21.3, 7.6
Hz), −157.2 (t, J = 20.6 Hz), −143.5 (dd, J = 21.9, 8.9 Hz); (Z) δ
−163.0 (dt, J = 22.6, 8.1 Hz), −157.9 (t, J = 20.7 Hz), −143.5 (dd, J =
22.1, 8.1 Hz). 11B NMR (96 MHz, CDCl3): δ 29.6. HRMS ESI (+),
6790
dx.doi.org/10.1021/jo400872x | J. Org. Chem. 2013, 78, 6786−6792

The Journal of Organic Chemistry
Note
42.1, 115.4 (d, J = 21.1 Hz), 127.8 (d, J = 181.0 Hz), 131.0 (d, J = 7.9
Hz), 134.7 (q, J = 4.6 Hz), 139.0 (d, J = 3.1 Hz), 161.9 (d, J = 240.0
Hz); (Z) δ 37.7, 115.2 (d, J = 20.8 Hz), 127.8 (d, J = 181.0 Hz), 131.1
(d, J = 7.8 Hz), 136.3 (q, J = 4.5 Hz), 140.3 (d, J = 2.6 Hz), 161.8 (d, J
= 240.0 Hz). 19F NMR (376 MHz, acetone-d6): (E) δ −120.1, −141.3
(m); (Z) δ −120.6, −135.6 (m). 11B NMR (96 MHz, acetone-d6): δ
3.0. HRMS (ESI): [M + 2K]+ calcd for C9H8BF4K, 280.9929; found,
280.9928.
Kaufmann, D., Ed.; Thieme: Stuttgart, Germany, 2004; Vol. 6. (b)
Boronic Acids: Preparation and Applications in Organic Synthesis,
Medicine and Materials, 2nd ed.; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, Germany, 2011.
(2) (a) Rangaishenvi, M. V.; Singaram, B.; Brown, H. C. J. Org. Chem.
1991, 56, 3286−3294. (b) Njardarson, J. T.; Biswas, K.; Danishefsky,
S. J. Chem. Commun. 2002, 2759−2761.
(3) Brown, H. C.; Hamaoka, T.; Ravindran, N. J. Am. Chem. Soc.
1973, 95, 6456−6457 and references cited therein.
(4) (a) Brown, H. C.; Campbell, J. B., Jr. Aldrichimica Acta 1981, 14,
3−11. (b) Brown, H. C.; Bhat, N. G. J. Org. Chem. 1988, 53, 6009−
6013.
(5) Carboni, B.; Carreaux, F. In Science of Synthesis: Cross Coupling
and Heck-Type Reactions; Molander, G., Ed; Thieme: New York, 2013;
Vol 1, pp 265−321.
(6) (a) Shade, R. E.; Hyde, A. M.; Olsen, J.-C.; Merlic, C. A. J. Am.
Chem. Soc. 2010, 132, 1202−1203. (b) Chan, D. G.; Winternheimer,
D. J.; Merlic, C. A. Org. Lett. 2011, 13, 2778−2781.
(7) Bhagwat, S. S.; Lee, C.-H.; Perner, R. J.; Gu, Y.-G. WO
2001057040, 2001.
(8) Perner, R. J.; Lee, C.-H.; Jiang, M.; Gu, Y.-G.; Didomenico, S.;
Bayburt, E. K.; Alexander, K. M.; Kohlhaas, K. L.; Jarvis, M. F.;
Kowaluk, E. L.; Bhagwat, S. S. Bioorg. Med. Chem. Lett. 2005, 15,
2803−2807.
(9) Kuribayashi, T.; Fukuda, T.; Tsuji, T.; Sasaki, K.; Takano, R. WO
2011132633, 2011.
1-Fluoro-4-(3-iodo-allyl)benzene (8). To a solution of crude
mixture 3n in technical grade THF (3.0 mL) was added a 3 M NaOH
solution (0.35 mL, 1.05 mmol, 3 equiv). The resulting mixture was
stirred at room temperature for 10 min before the addition of a 0.2 M
iodine solution in THF (2.53 mL, 0.70 mmol, 2 equiv). The resulting
mixture was stirred at room temperature for 30 min. After this time, a
saturated solution of Na2S2O3 was added, and the mixture was
extracted with Et2O. Organic phases were washed with brine, dried
over MgSO4, and concentrated under a vacuum. Crude product was
purified by column chromatography using cyclohexane as the eluent to
afford the desired product 8 as a colorless oil (57 mg, 62%). 1H NMR
(300 MHz, CDCl3): (E) δ 3.36 (d, J = 6.7 Hz, 2H), 6.09 (dt, J = 14.3,
1.5 Hz, 1H), 6.68 (dt, J = 14.3, 6.7 Hz, 1H), 6.98−7.05 (m, 2H),
7.12−7.17 (m, 2H); (Z) δ 3.49 (d, J = 6.3 Hz, 2H), 6.31−6.41 (m,
2H), 6.98−7.05 (m, 2H), 7.12−7.17 (m, 2H). 13C NMR (75 MHz,
CDCl3): (E) δ 41.3, 76.4, 115.4 (d, J = 21.3 Hz), 130.0 (d, J = 8.0 Hz),
133.6 (d, J = 3.3 Hz), 144.6, 161.5 (d, J = 244.7 Hz); (Z) δ 41.3, 76.4,
115.4 (d, J = 21.3 Hz), 130.0 (d, J = 8.0 Hz), 133.6 (d, J = 3.3 Hz),
144.6, 161.5 (d, J = 244.7 Hz). 19F NMR (376 MHz, CDCl3): (E) δ
−116.5; (Z) δ −116.7. HRMS ASAP (+), 150 °C: [M]+. calcd for
C9H8FI, 261.9654; found, 261.9655.
(10) Jang, H.; Zhugralin, A. R.; Lee, Y.; Hoveyda, A. H. J. Am. Chem.
Soc. 2011, 133, 7859−7871.
(11) Haberberger, M.; Enthaler, S. Chem.Asian J. 2013, 8, 50−54.
(12) From alkynyl diaminoboranes: Lhermitte, F.; Carboni, B. Synlett
1996, 377−379.
(4-Fluoro-phenyl)acetaldehyde (9). To a solution of crude
product of 3n in a THF/H2O mixture (1:1, 3.0 mL) was added
NaBO3·4H2O (63.4 mg, 0.39 mmol, 1.1 equiv). The resulting mixture
was stirred at room temperature for 4 h. After this time, water was
added, and the reaction mixture was extracted with Et2O. Organic
phases were washed with brine, dried over MgSO4, and concentrated
under a vacuum. Crude product was purified by column chromatog-
raphy using cyclohexane/EtOAc (80:20) as the eluent to afford the
(13) From phenylacetylene: Endo, K.; Hirokami, M.; Shibata, T.
Synlett 2009, 1331−1335.
(14) From phenylacetaldehyde: Anderson, D. R.; Mahoney, M. W.;
Phillion, D. P.; Rogers, T. E.; Meyers, M. J.; Poda, G.; Hedge, S. G.;
Singh, M.; Reitz, D. B.; Wu, K. K.; Buchler, I. P.; Xie, J.; Vernier, W. F.
WO 2004058762, 2004.
1
desired product 9 as a colorless oil (36 mg, 68%). H NMR (300
(15) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000,
122, 4990−4991.
MHz, CDCl3): δ 2.76−2.81 (m, 2H), 2.95 (t, J = 7.4 Hz, 2H), 6.96−
7.02 (m, 2H), 7.15−7.19 (m, 2H), 9.83 (t, J = 1.3 Hz, 1H). 13C NMR
(75 MHz, CDCl3): δ 27.3, 45.4, 115.4 (d, J = 21.3 Hz), 129.7 (d, J =
7.8 Hz), 132.2 (d, J = 3.2 Hz), 161.6 (d, J = 245.0 Hz), 201.2. 19F
NMR (282 MHz, CDCl3): δ −116.9. These data are in agreement
with those reported in the literature.35
(16) (a) Blackwell, H. E.; O’Leary, D. J.; Chatterjee, A. K.;
Washenfelder, R. A.; Bussmann, D. A.; Grubbs, R. H. J. Am. Chem. Soc.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H, 13C, 11B, and 19F NMR spectra of all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(17) During the course of this project, synthesis by metathesis
reaction of just one example of this class of compounds was described
using particular conditions. A large excess of vinyl pinacol boronate
was used relative to the allylic aromatic compound (7 equiv per double
bond on the starting substrate) in the presence of 8 mol % of the
neolyst 1 catalyst. See: Avetta, C. T.; Shorthill, B. J.; Ren, C.; Glass, T.
E. J. Org. Chem. 2012, 77, 851−857.
(18) (a) Blanco, O. M.; Castedo, L. Synlett 1999, 557−558.
(b) Ettari, R.; Micale, N. J. Organomet. Chem. 2007, 692, 3574−3576.
(c) Voigtritter, K.; Ghorai, S.; Lipshutz, B. H. J. Org. Chem. 2011, 76,
4697−4702.
AUTHOR INFORMATION
Corresponding Author
*E-mail: francois.carreaux@univ-rennes1.fr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
(19) The isomerization process was observed during the cross-
metathesis reaction of 2-propenyl pinacol boronate with some olefins.
See: Funk, T. W. Ph.D. Dissertation, California Institute of
Technology, Pasadena, CA, 2007.
■
This work was supported by the University of Rennes 1 and the
CNRS. We thank Omega Cat System for generously providing
us with catalyst M71-SIPr and F. Caijo and M. Mauduit for
(20) Hong, S. H.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2004,
́
their helpful discussions. R.H. also thanks “la Region Bretagne”
for a research fellowship.
126, 7414−7415.
(21) Donohoe, T. J.; O’Riordan, T. J. C.; Rosa, C. P. Angew. Chem.,
Int. Ed. 2009, 48, 1014−1017.
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