Copper(II)-Catalyzed β-Borylation of Acetylenic Esters in Water

Article abstract of DOI:10.1055/s-0034-1380524

A method for the β-borylation of alkynoates has been developed. In the presence of bis(pinacolato)diboron and catalytic amounts of both copper(II) and 4-picoline, substituted alkynoates undergo borylation in a regio-, stereo-, and chemoselective fashion. The reaction is performed under mild conditions using water as solvent and open to the atmosphere to exclusively afford (Z)-β-boryl-α,β-unsaturated esters.

Full text of DOI:10.1055/s-0034-1380524

SYNTHESIS
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©
Georg Thieme Verlag Stuttgart · New York
2015, 47, 2242–2248
2242
special topic
Synthesis
C. L. Peck et al.
Special Topic
Copper(II)-Catalyzed β-Borylation of Acetylenic Esters in Water
Cheryl L. Peck
R1
B2(pin)2, CuSO4
4-picoline, H2O
O
Joseph A. Calderone
Webster L. Santos*
O
R1
OR2
pinB
OR2
open-to-air, 50 °C
17 examples
up to 98% yield
Department of Chemistry, Virginia Tech,
Blacksburg, VA 24061, USA
santosw@vt.edu
1
2
R
R
= Alk, Ar, Hetar, CH2OTBS
exclusively Z
= Me, Et, Oi-Bu, Ph, CH2CH=CH2, CH2C CMe
Received: 09.03.2015
Accepted: 12.03.2015
Published online: 23.04.2015
DOI: 10.1055/s-0034-1380524; Art ID: ss-2015-c0153_st
tory previously reported a Cu(II)-catalyzed borylation pro-
tocol of α,β-unsaturated esters and ketones using water as
8
the solvent in open-air. Because of our interest in this area,
we aimed to develop a catalytic system that could be used
to conduct borylation reactions in aqueous media. Herein,
we disclose an efficient and simple β-borylation method for
alkynoates that afford β-boryl-α,β-unsaturated esters in
good to excellent yield using an aqueous Cu(II)-catalyst sys-
tem. In addition to broad substrate scope, the protocol
yields exclusively Z-products in a chemoselective fashion.
Abstract A method for the β-borylation of alkynoates has been devel-
oped. In the presence of bis(pinacolato)diboron and catalytic amounts
of both copper(II) and 4-picoline, substituted alkynoates undergo bory-
lation in a regio-, stereo-, and chemoselective fashion. The reaction is
performed under mild conditions using water as solvent and open to
the atmosphere to exclusively afford (Z)-β-boryl-α,β-unsaturated es-
ters.
Key words boron, copper, stereoselectivity, hydroboration, alkynes
B2pin2
O
cat. CuCl/NaOt-Bu
R1
Yun
Xantphos, MeOH
OEt
Vinylboronic acids and their derivatives are vital syn-
thetic intermediates for the Suzuki–Miyaura cross-coupling
reaction and they are synthetic handles for transformations
R1
O
R1
O
Miyaura
this work
PdCl2(PPh3)
1
into other functional groups. Although borylation of
OR2
TfO
OR2
KOPh, B2pin2
toluene, 50 °C
pinB
alkynes serves as an efficient method to access vinylboro-
nates, a limited number of methods for the borylation of
B2pin2, Cu(II)
4-picoline, H2O
O
2
alkynoates have been reported (Scheme 1). In 2003,
R1
Miyaura and co-workers reported a palladium-catalyzed
OR2
open-to-air, 50 °C
cross-coupling of vinyl triflates to afford β-boryl-α,β-unsat-
Scheme 1 Strategies toward β-boryl-α,β-unsaturated esters
3
urated carbonyl compounds. Subsequently, Yun and co-
4
workers disclosed copper(I)-catalyzed borylation condi-
tions employing bis(pinacolato)diboron (B pin ) as the bo-
We initiated our investigations by employing conditions
used for borylations of α,β-unsaturated compounds (Table
1). Methyl non-2-ynoate (1a) served as the model sub-
2
2
5
ron source. Some of these methods, however, have short-
comings ranging from limited substrate scope to poor E-
and Z-stereoselectivity. Furthermore, the reactions must be
conducted under inert atmospheric conditions because of
the air- and moisture-sensitivity of the catalytic system.
In recent years, synthetic protocols that utilize boronic
acid derivatives and employ environmentally friendly con-
ditions have been reported, eliminating the necessity for
8
strate because of its borderline aqueous solubility. Fortu-
nately, standard conditions afforded vinyl boronate 2a in
59% yield (entry 1). Nuclear Overhauser effect (NOE) stud-
ies indicated exclusive formation of the Z-product. Increase
in reaction time did not significantly affect the reaction
yield (entry 2). However, changing the number of equiva-
lents of B pin to 1.5 and increasing the temperature result-
6
organic solvents. In contrast, complementary processes
2
2
that generate boronic acid derivatives using copper as a cat-
alyst in an aqueous environment are emerging. Our labora-
ed in improved reaction yields (entries 3–6). The screening
7
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Synthesis
C. L. Peck et al.
Special Topic
study revealed that B pin (1.5 equiv), CuSO (1 mol%), and
With the optimization conditions in hand, we explored
2
2
4
4
-picoline (5 mol%) in water at 50 °C were the optimal con-
the scope and limitations of the reaction by using a wide
range of acetylenic esters (Table 2). Aliphatic alkyl groups
ranging from methyl (1b), propyl (1c), hexyl (1a), and hep-
tyl (1d) groups were efficient substrates, affording the cor-
responding (Z)-β-boryl-α,β-unsaturated esters 2a–d in
good to excellent yields (entries 1–4).
Surprisingly, the use of a dodecyl-bearing substituent
resulted in no reaction (Table 2, entry 5). Attempts to im-
prove the reaction were unsuccessful (biphasic conditions,
increased temp, etc). However, substrates with a cyclopro-
pyl or larger cyclohexyl group with either ethyl or isobutyl
ester moieties were borylated in excellent yield (entries 6–
ditions.
Table 1 Screening of Reaction Conditions
B2pin2 (x equiv)
O
CuSO4•5H2O (1 mol%)
H13C6
O
4-picoline (5 mol%)
OMe
H13C6
pinB
OMe
H2O, temp
1a
2a
2 2
B pin
(equiv) Temp. (°C) Yield (%)a
Entry
Time (h)
1
2
3
4
5
4
1.3
1.3
1.5
1.5
1.5
1.5
r.t.
r.t.
r.t.
40
50
60
59
61
67
70
76
67
8). Furthermore, cyclohexenyne 1i was borylated regiose-
6.5
6.5
4.5
3
lectively on the β-position to generate α,β,γ,δ-unsaturated
diene 2i in 98% yield. Aryl substitutions were also tolerated.
For example, substrates bearing phenyl (1j), electron-do-
nating methoxy (1k), or electron-withdrawing fluorine (1l)
groups yielded the corresponding borylated products in ex-
cellent yields (entries 10–12). Finally, tert-butyldimethylsi-
lyl-protected alcohol 1m gave product 2m in 84% yield,
confirming the good functional group compatibility of the
reaction conditions.
6
6.5
a
Isolated yield.
Table 2 Cu(II)-Catalyzed Monoboration of Alkynoates
O
4 2
CuSO •5H O (1 mol%)
R2
O
4-picoline (5 mol%)
OR1
pinB
OR1
R2
B pin (1.5 equiv)
2
2
H2O, 50 °C
exclusively Z
Entry
1
1
Substrate
Product
2
Time (h)
3
Isolated yield (%)
76
O
H13C6
O
1a
1b
1c
2a
2b
2c
OMe
pinB
pinB
OMe
OEt
H13C6
O
O
O
O
2a,b
2
4
96
84
OEt
O
H7C3
pinB
3
OEt
OEt
OEt
OEt
H7C3
O
H15C7
4
5
1d
1e
2d
2e
2
–
85
nr
pinB
H15C7
H25C12
O
H25C12
O
Oi-Bu
pinB
Oi-Bu
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C. L. Peck et al.
Special Topic
Table 2 (continued)
Entry
1
Substrate
Product
2
Time (h)
4
Isolated yield (%)
85
O
O
6
1f
OPh
2f
pinB
OPh
O
OEt
7
8
9
1g
2g
3
6
76
70
98
95
O
O
pinB
pinB
OEt
O
O
O
Oi-Bu
1h
1i
2h
2i
Oi-Bu
OEt
22
O
O
pinB
pinB
OEt
OEt
OEt
1
0a,c
1j
2j
4
OMe
O
OEt
11
1k
2k
20
91
O
MeO
pinB
OEt
F
O
OEt
1
2a
1l
2l
24
90
84
O
F
pinB
OEt
OEt
O
TBSO
O
13
1m
2m
3
OEt
TBSO
pinB
a
b
c
The reaction was performed at r.t.
B
2
pin
pin
2
(1.1 equiv) was used.
2
(1.3 equiv) was used.
B
2
To assess the limitations of the reaction, 2-pyridyl sub-
stituted substrate 1n was subjected to the same conditions
Scheme 2). In this case, the resulting products underwent
protodeboration: mono- and diboration followed by spon-
taneous protodeboration generated semihydrogenated 2n
and fully reduced 3n. Surprisingly, the double bond geome-
try of 2n was found to be E, possibly a result of isomeri-
zation leading to the more stable trans isomer. Whereas
(
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C. L. Peck et al.
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TBS-protected 1m was readily borylated, the corresponding
propargylic alcohol 1o underwent β-borylation. However,
only the cyclized butenolide 2o was isolated in low yield.
the reaction medium to afford (Z)-β-borylated products ex-
clusively. Furthermore, acetylenic esters were transformed
chemoselectivity into the desired products in the presence
of competing functional groups. Further investigations on
the substrate scope and applications of the method are un-
derway.
O
OEt
N
O
2
n 17% (36%)a
1H and 13C NMR spectra were recorded with a Bruker Avance II 500
MHz, Agilent MR 400 MHz, or Agilent DD2 400 MHz spectrometer in
CDCl3 with TMS as an internal reference. B NMR spectra were re-
OEt
+
O
11
N
OEt
corded with a Varian Inova 400 MHz spectrometer in CDCl with bo-
3
1n
ron trifluoride diethyl etherate as an external standard. High-resolu-
tion mass spectra (HRMS) were obtained with an Agilent LC-ESI-TOF.
Bis(pinacolato)diboron was donated by AllylChem and used as re-
ceived. Copper sulfate pentahydrate, 4-picoline, and other commer-
cially available reagents were used as received.
N
3
n 29% (51%)a
O
O
O
OEt
General Procedure
pinB
OH
In a 1 dram vial, methyl non-2-ynoate (88 mg, 1.0 equiv), 4-picoline
1o
2o 15%
(2.55 μL, 0.05 equiv), half the amount of bis(pinacolato)diboron (198
Scheme 2 Reaction conditions: B pin (1.5 equiv), CuSO (1 mol%),
mg total, 1.5 equiv), and CuSO stock solution (1.3 mg/mL, 1 mL, 0.01
4
2
2
4
a
4
-picoline (5 mol%), H O, 50 °C. NMR yield.
equiv) were mixed and stirred vigorously at 50 °C. The remaining half
of bis(pinacolato)diboron was added over a period of 10 min. After 3
h, hexanes (1 mL) was added to quench the reaction. The aqueous lay-
er was extracted three times with hexanes. The organic layer was
washed five times with H O, dried over Na SO , filtered, and concen-
2
The selective borylation on the β-position of enyne 1i
prompted us to further explore the selectivity of the reac-
tion (Scheme 3). Given that copper(I)-catalyzed borylations
2
2
4
trated in vacuo. Column chromatography was used to purify the
product.
9
of nonactivated alkenes and alkynes have been reported, it
was unclear whether a copper(II) catalyst system was suffi-
ciently selective in the presence of competing functional
groups. Thus, 3-phenylpropiolate substrates containing al-
lyl (1p) or propargyl (1q) groups were synthesized. When
these substrates were subjected to the borylation condi-
tions, products 2p and 2q were isolated in excellent yields;
exquisite reactivity at the more activated alkyne was ob-
served, demonstrating the chemoselectivity of the reaction.
Methyl (Z)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)non-2-
enoate (2a)
Yield: 115 mg (76%); colorless oil; bp 299.2 °C; R = 0.56 (hexanes–
f
EtOAc, 90:10).
1
H NMR (400 MHz, CDCl ): δ = 0.87 (t, J = 6.7 Hz, 3 H, CH ), 1.27 (s,
3
3
1
2 H, CH -Bpin), 1.27–1.37 (m, 6 H, CH CH CH ), 1.37–1.46 (m, 2 H,
3
2
2
2
CH ), 2.66 (t, J = 7.3 Hz, 2 H, CH CCH), 3.70 (s, 3 H, OCH ), 6.39 [s, 1 H,
2
2
3
CCH(C=O)].
13
C NMR (101 MHz, CDCl ): δ = 14.2 (CH ), 22.4 (CH ), 24.8 (CH -
3
3
2
3
O
O
Bpin), 29.5 (CH ), 29.7 (CH ), 30.2 (CH ), 31.9 (CH ), 51.2 (OCH ), 84.2
2
2
2
2
3
(C-Bpin), 129.3 [CH(C=O)], 166.6 (C=O).
O
O
11
B NMR (128 MHz, CDCl ): δ = 30.1.
Ph
Ph
3
HRMS (ESI): m/z [M + H]+ calcd for C16H29BO : 297.2275; found:
1p
4
1q
297.2248.
CuSO4•5H2O (1 mol%)
-picoline (5 mol%)
4
Ethyl (Z)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)but-2-
B2pin2 (1.5 equiv)
enoate (2b)
Yield: 120 mg (96%); colorless oil; R = 0.45 (hexanes–EtOAc, 90:10).
1H and 13C NMR data are consistent with the reported data.4
f
Ph
O
Ph
O
pinB
O
1
pinB
O
H NMR (500 MHz, CDCl ): δ = 1.27 (s, 12 H, CH -Bpin), 1.28 (t, J =
3
3
7
.1 Hz, 3 H, OCH CH ), 2.17 [d, J = 1.8 Hz, 3 H, CH CH(CO)], 4.17 (d, J =
2
3
3
2p 89%
2q 82%
7.1 Hz, 2 H, OCH ), 6.44 [q, J = 1.8 Hz, 1 H, CH(CO)].
2
Scheme 3 Chemoselectivity of the reaction
Ethyl (Z)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)hex-2-
enoate (2c)
Yield: 116 mg (84%); pale-yellow oil; bp 281 °C; R = 0.65 (hexanes–
EtOAc, 90:10).
In summary, we have developed a simple, mild, and effi-
cient copper(II)-catalyzed borylation method for acetylenic
esters. The reaction is performed in air and utilizes water as
f
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C. L. Peck et al.
Special Topic
1
13
H NMR (500 MHz, CDCl ): δ = 0.93 (t, J = 7.4 Hz, 3 H, CH ), 1.26 (s,
C NMR (101 MHz, CDCl ): δ = 19.3 [(CH ) ], 24.9 (C-Bpin), 26.1
3
3
3
3 3
1
2 H, CH -Bpin), 1.27 (t, J = 7.1 Hz, 3 H, CH ), 1.41–1.50 (m, 2 H,
(CH ), 26.4 (CH ), 27.9 (OCH CH), 31.5 (CH ), 40.2 (CHCCH ), 70.3
3
3
2 2 2 2 2
CH CH CH ), 2.64 (t, J = 7.6 Hz, 2 H, CH CH C), 4.16 (q, J = 7.1 Hz, 2 H,
(OCH ), 83.9 (CH -Bpin), 127.8 [CH(C=O)], 166.5 (C=O).
2 3
3
2
2
2
2
OCH ), 6.41 [s, 1 H, CH(C=O)].
11
2
B NMR (128 MHz, CDCl ): δ = 30.3.
3
13
C NMR (126 MHz, CDCl ): δ = 14.2 (CH ), 14.3 (CH ), 22.9 (CH ), 24.7
HRMS (ESI): m/z [M + H]+ calcd for C19H33BO : 337.2561; found:
337.2545.
3
3
3
2
4
(
CH -Bpin), 31.9 (CH ), 59.8 (OCH ), 84.0 (C-Bpin), 130.0 [CH(C=O)],
3
2
2
166.1 (C=O).
1
1
B NMR (128 MHz, CDCl ): δ = 29.9.
3
Ethyl (Z)-3-(Cyclohex-1-en-1-yl)-3-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)acrylate (2i)
+
HRMS (ESI): m/z [M + H] calcd for C14H25BO : 269.18; found: 269.08.
4
Yield: 155 mg (98%); yellow oil; bp >220 °C (dec); R = 0.53 (hexanes–
f
Ethyl (Z)-3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)dec-2-
EtOAc, 90:10).
enoate (2d)
1
H NMR (400 MHz, CDCl ): δ = 1.25 (t, J = 7.1 Hz, 3 H, CH ), 1.26 (s,
3
3
Yield: 144 mg (85%); pale-yellow liquid; bp 232.7 °C; R = 0.72 (hex-
12 H, CH -Bpin), 1.56–1.63 (m, 2 H, CH ), 1.64–1.71 (m, 2 H, CH ),
f
3
2
2
anes–EtOAc, 90:10).
2.02–2.15 (m, 4 H, CH CH ), 4.14 (q, J = 7.1 Hz, 2 H, OCH ), 5.42–5.46
2 2 2
1
(m, 1 H, CH
2
CHC), 6.31 [s, 1 H, CH(C=O)].
H NMR (400 MHz, CDCl ): δ = 0.87 (t, J = 6.9 Hz, 3 H, CH ), 1.21–1.36
3
3
13
(
m, 23 H, CH CH CH CH , CH , CH -Bpin), 1.37–1.46 (m, 2 H, CH ),
C NMR (101 MHz, CDCl ): δ = 14.4 (CH ), 22.1 (CH ), 22.8 (CH ), 24.8
2 2 2 2 3 3 2
3
3
2
2
2
.65 (t, J = 7.5 Hz, 2 H, CH CCH), 4.16 (q, J = 7.2 Hz, 2 H, OCH ), 6.39 [s,
(CH -Bpin), 25.5 (CH ), 28.1 (CH ), 60.2 (OCH ), 84.2 (C-Bpin), 123.7
3 2 2 2
2
2
1
H, CH(C=O)].
[CH(C=O)], 130.1 (CH CHC), 137.6 (CHCCC), 167.1 (C=O).
2
13
11
C NMR (101 MHz, CDCl ): δ = 14.3 (CH ), 14.4 (CH ), 22.8 (CH ), 24.9
B NMR (128 MHz, CDCl ): δ = 30.0.
3
3
3
2
3
(
5
CH -Bpin), 29.4 (CH ), 29.9 (CH ), 29.8 (CH ), 30.2 (CH ), 32.0 (CH ),
HRMS (ESI): m/z [M + H]+ calcd for C17H27BO : 307.2070; found:
307.2075.
3
2
2
2
2
2
4
9.9 (OCH ), 84.1 (C-Bpin), 129.9 [CH(C=O)], 166.2 (C=O).
2
1
1
B NMR (128 MHz, CDCl ): δ = 30.2.
3
HRMS (ESI): m/z [M + H]+ calcd for C18H33BO : 325.2546; found:
Ethyl (Z)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
4
325.2560.
yl)acrylate (2j)
Yield: 148 mg (95%); yellow oil; R = 0.31 (hexanes–EtOAc, 90:10).
f
Phenyl (Z)-3-Cyclopropyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)acrylate (2f)
1
H NMR (400 MHz, CDCl ): δ = 1.06 (t, J = 7.1, 3 H, CH ), 1.27 (s, 12 H,
3
3
CH -Bpin), 4.02 (q, J = 7.1 Hz, 2 H, CH ), 6.64 [s, 1 H, CH(C=O)], 7.18–
3
2
Yield: 139 mg (85%); white solid; mp 105.1–108.6 °C; Rf = 0.57
7.23 (m, 2 H, ArH), 7.23–7.32 (m, 3 H, ArH).
(
1
hexanes–EtOAc, 90:10).
13
C NMR (101 MHz, CDCl ): δ = 14.0 (CH ), 24.9 (CH -Bpin), 60.3
3
3
3
H NMR (400 MHz, CDCl ): δ = 0.88–0.93 (m, 2 H, CH ), 1.01–1.06 (m,
(CH ), 84.6 (C-Bpin), 127.4 (CH-Ar), 127.8 (CH-Ar), 128.1 (CH-Ar),
3
2
2
2
H, CH ), 1.27 (s, 12 H, CH -Bpin), 3.05–3.15 (m, 1 H, CH CHC), 6.56
132.4 [CH(C=O)], 138.8 (CH-Ar), 166.5 (C=O).
2
3
2
[
7
s, 1 H, CH(C=O)], 7.10–7.14 (m, 2 H, ArH), 719–7.24 (m, 1 H, ArH),
.35–7.41 (m, 2 H, ArH).
11
B NMR (128 MHz, CDCl ): δ = 29.7.
3
+
HRMS (ESI): m/z [M + H] calcd for C17H23BO : 303.17; found: 303.06.
4
1
3
C NMR (400 MHz, CDCl ): δ = 9.2 [(CH ) CHC], 14.3 [(CH ) CHC],
3
2
2
2 2
2
4.8 (CH -Bpin), 84.2 (C-Bpin), 121.9 (CH-Ar), 125.7 (CH-Ar), 126.7
3
Ethyl (Z)-3-(4-Methoxyphenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)acrylate (2k)
(CH-Ar), 129.4 [CH(C=O)], 150.9 (CH-Ar), 165.0 (C=O).
11
B NMR (128 MHz, CDCl ): δ = 29.1.
3
Yield: 156 mg (91%); yellow liquid; bp 308 °C; R = 0.34 (hexanes–
f
HRMS (ESI): m/z [M + H]+ calcd for C18H23BO : 315.1762; found:
4
EtOAc, 90:10).
315.1765.
1
H NMR (400 MHz, CDCl ): δ = 1.14 (t, J = 7.1 Hz, 3 H, CH ), 1.29 (s,
3
3
1
2 H, CH -Bpin), 3.80 (s, 3 H, CH O), 4.07 (q, J = 7.1 Hz, 2 H, OCH ),
3
3
2
Ethyl (Z)-3-Cyclohexyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-
-yl)acrylate (2g)
6.58 [s, 1 H, CH(C=O)], 6.83–6.87 (m, 2 H, ArH), 7.19–7.23 (m, 2 H,
2
ArH).
Yield: 120 mg (76%); pale-yellow oil; R = 0.50 (hexanes–EtOAc,
9
13
f
C NMR (101 MHz, CDCl ): δ = 14.2 (OCH CH ), 24.9 (CH -Bpin), 55.3
3 2 3 3
0:10). H and 13C NMR data are consistent with the reported data.4
1
(CH O), 60.3 (OCH ), 84.6 (C-Bpin), 113.3 (CH-Ar), 129.8 [CH(C=O)],
3
2
1
H NMR (400 MHz, CDCl ): δ = 1.27 (s, 12 H, CH -Bpin), 1.28 (t, J =
130.8 (CH-Ar), 131.2 (CH-Ar), 159.3 (CH OC), 166.7 (C=O).
3
3
3
7
4
.1 Hz, 3 H, OCH CH ), 1.58–1.44 (m, 6 H, CH CH CH ), 1.77–1.62 (m,
11
2
3
2
2
2
B NMR (128 MHz, CDCl ): δ = 30.5.
3
H, CH CH ), 3.44–3.34 [m, 1 H, CHCCH(CO)], 4.16 (q, J = 7.1 Hz, 2 H,
2
2
HRMS (ESI): m/z [M + H]+ calcd for C18H25BO : 333.1868; found:
5
OCH ), 6.23 [s, 1 H, CH(CO)].
2
333.1875.
Isobutyl (Z)-3-Cyclohexyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaboro-
lan-2-yl)acrylate (2h)
Ethyl (Z)-3-(4-Fluorophenyl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)acrylate (2l)
Yield: 121 mg (70%); colorless oil; bp 338 °C; R = 0.64 (hexanes–
f
Yield: 150 mg (90%); pale-yellow solid; mp 57.2–61.4 °C; R = 0.43
f
EtOAc, 90:10).
(hexanes–EtOAc, 90:10).
1
H NMR (400 MHz, CDCl ): δ = 0.95 [d, J = 6.7 Hz, 6 H, CH(CH ) ], 1.28
3
3 3
1
H NMR (400 MHz, CDCl ): δ = 1.12 (t, J = 7.1 Hz, 3 H, CH ), 1.28 (s,
3
3
(
s, 12 H, CH -Bpin), 1.43–1.61 (m, 6 H, CH CH CH ), 1.63–1.76 (m,
3
2
2
2
1
6
2 H, CH -Bpin), 4.06 (q, J = 7.1 Hz, 2 H, OCH ), 6.65 [s, 1 H, CH(C=O)],
.97–7.03 (m, 2 H, ArH), 7.17–7.23 (m, 2 H, ArH).
3
2
4
H, CH CH ), 1.89–2.00 (m, 1 H, OCH CH), 3.34–3.44 [m, 1 H,
2 2 2
CHCCH(C=O)], 3.89 (d, J = 6.6 Hz, 2 H), 6.24 [s, 1 H, CH(C=O)].
©
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2
247
Synthesis
C. L. Peck et al.
Special Topic
1
3
C NMR (101 MHz, CDCl ): δ = 14.1 (CH ), 24.9 (CH -Bpin), 60.4
Allyl (Z)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-
yl)acrylate (2p)
3
3
3
2
2
(OCH ), 84.7 (C-Bpin), 114.6 (CH-Ar, J = 21.5 Hz), 114.9 (CH-Ar, J =
2
1.5 Hz), 129.9 (CH-Ar, 3J = 8.1 Hz), 130.0 (CH-Ar, J = 8.1 Hz), 132.5
3
2
Yield: 146 mg (89%); colorless liquid; bp >277 °C (dec); R = 0.52
f
4
4
[
(
1
CH(C=O)], 134.5 (CH-Ar, J = 3.4 Hz), 134.5 (CH-Ar, J = 3.4 Hz), 161.2
F-CH-Ar, J = 247 Hz), 163.6 (F-CH-Ar, J = 247 Hz), 166.3 (C=O).
(hexanes–EtOAc, 90:10).
1
1
1
H NMR (400 MHz, CDCl ): δ = 1.28 (s, 12 H, CH -Bpin), 4.49 (dt, J =
3
3
1
B NMR (128 MHz, CDCl ): δ = 29.6.
3
5.6, 1.4 Hz, 2 H, OCH ), 5.10–5.18 (m, 2 H, CHCH ), 5.74 (ddt, J = 17.2,
2
2
HRMS (ESI): m/z [M + H]+ calcd for C17H22BFO : 321.1695; found:
10.4, 5.7 Hz, 1 H, OCH CHCH ), 6.68 [s, 1 H, CH(C=O)], 7.20–7.24 (m,
4
2 2
321.167.
2 H, ArH), 7.27–734 (m, 3 H, ArH).
13
C NMR (101 MHz, CDCl ): δ = 24.7 (CH -Bpin), 64.9 (OCH ), 84.5 (C-
3
3
2
Ethyl (Z)-4-[(tert-Butyldimethylsilyl)oxy]-3-(4,4,5,5-tetramethyl-
,3,2-dioxaborolan-2-yl)but-2-enoate (2m)
Yield: 162 mg (84%); pale-yellow liquid; bp 290.8 °C; Rf = 0.53
hexanes–EtOAc, 90:10).
Bpin), 118.1 (CHCH ), 127.3 (CH-Ar), 127.7 (CH-Ar), 127.9 (CH-Ar),
2
1
131.6 [CH(C=O)], 131.8 (CHCH ), 138.5 (CH-Ar), 165.8 (C=O).
2
11
B NMR (128 MHz, CDCl ): δ = 29.8.
3
(
HRMS (ESI): m/z [M + H]+ calcd for C18H23BO : 315.1762; found:
4
1
H NMR (400 MHz, CDCl ): δ = 0.07 [s, 6 H, Si(CH ) C(CH ) ], 0.90 [s,
315.1758.
3
3
2
3 3
9
H, Si(CH ) C(CH ) ], 1.26 (t, J = 7.1 Hz, 3 H, OCH CH ), 1.28 (s, 12 H,
3 2 3 3 2 3
CH -Bpin), 4.16 (q, J = 7.1 Hz, 2 H, OCH ), 4.82 (d, J = 2.0 Hz, 2 H,
3
2
But-2-yn-1-yl (Z)-3-Phenyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxa-
borolan-2-yl)acrylate (2q)
OCH C), 6.19 [t, J = 2.0 Hz, 1 H, CH(C=O)].
2
13C
OCH CH ), 18.6 [Si(CH ) C(CH ) ], 24.9 (CH -Bpin), 26.2 [Si(CH )
NMR (101 MHz, CDCl ): δ = –5.1 [Si(CH3) C(CH ) ], 14.4
3 2 3 3
Yield: 139 mg (82%); white solid; mp 86.1–92.5 °C; Rf = 0.55
(hexanes–EtOAc, 90:10).
(
2
3
3
2
3
3
3
3
2
C(CH ) ], 60.2 (OCH C), 62.2 (OCH ), 84.2 (C-Bpin), 126.8 [CH(C=O)],
3
3
2
2
1
H NMR (400 MHz, CDCl ): δ = 1.28 (s, 12 H, CH -Bpin), 1.82 (t, J =
3
3
165.9 (C=O).
2
.4 Hz, 3 H, CH ), 4.57 (q, J = 2.4 Hz, 2 H, OCH ), 6.68 [s, 1 H, CH(C=O)],
3
2
11
B NMR (128 MHz, CDCl ): δ = 30.3.
3
7.21–7.26 (m, 2 H, ArH), 7.27–7.34 (m, 3 H, ArH).
HRMS (ESI): m/z [M + H]+ calcd for C18H35BO Si: 371.2420; found:
13
5
C NMR (101 MHz, CDCl ): δ = 3.8 (CH ), 24.9 (CH -Bpin), 52.7
3
3
3
371.2384.
(
OCH ), 73.1 (CCCH ), 83.2 (CCCH ), 84.7 (C-Bpin), 127.6 (CH-Ar),
2 3 3
127.8 (CH-Ar), 128.2 (CH-Ar), 131.1 [CH(C=O)], 138.3 (CH-Ar), 165.4
Ethyl (E)-3-(pyridin-2-yl)acrylate (2n)
(C=O).
1
1
Yield: 16 mg (17%); colorless liquid; R = 0.66 (hexanes–EtOAc, 1:1).
B NMR (128 MHz, CDCl ): δ = 30.1.
3
f
1
H and C NMR data are consistent with the reported data.10
13
HRMS (ESI): m/z [M + H]+ calcd for C19H23BO : 327.1762; found:
327.175.
4
1
H NMR (400 MHz, CDCl ): δ = 1.33 (t, J = 7.1 Hz, 3 H, OCH CH ), 4.27
3
2
3
(
q, J = 7.1 Hz, 2 H, OCH ), 6.91 [d, J = 15.7 Hz, 1 H, CH(CO)], 7.28–7.23
2
(m, 1 H, ArH), 7.42 (d, J = 7.7 Hz, 1 H, ArH), 7.68 [d, J = 15.7 Hz, 1 H,
CHCH(CO)], 7.69 (td, J = 7.7 Hz, 1 H, ArH), 8.64 (d, J = 4.5 Hz, 1 H).
Acknowledgment
Ethyl 3-(Pyridin-2-yl)propanoate (3n)
We thank AllyChem for donation of bis(pinacolato)diboron. Financial
support of this work is provided by the National Science Foundation
(CHE-1414458).
Yield: 27 mg (29%); colorless liquid; R = 0.17 (hexanes–EtOAc, 1:1).
f
1
H and 13C NMR data are consistent with the reported data.11
1
H NMR (400 MHz, CDCl ): δ = 1.22 (t, J = 7.1 Hz, 3 H, OCH CH ), 2.80
3
2
3
(
2
t, J = 7.5 Hz, 2 H, CH ), 3.12 (t, J = 7.5 Hz, 2 H, CH ), 4.12 (q, J = 7.1 Hz,
H, OCH ), 7.14–7.10 (m, 1 H, ArH), 7.20 (d, J = 7.7 Hz, 1 H, ArH), 7.60
2
2
2
Supporting Information
(td, J = 7.7, 1.9 Hz, 1 H, ArH), 8.52 (d, J = 4.9 Hz, 1 H, ArH).
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1380524.
S
u
p
p
o
nrtIo
i
g
f
rm oaitn
S
u
p
p
ortioIgnfmr oaitn
5-Ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)furan-
2
(5H)-one (2o)
References
Yield: 19 mg (15%); white solid; mp 64.9–68.1 °C; R = 0.19 (hexanes–
f
EtOAc, 70:30).
(
1) (a) Hall, D. Boronic Acids: Preparation, Applications in Organic
1
H NMR (400 MHz, CDCl ): δ = 0.94 (t, J = 7.4 Hz, 3 H, CH ), 1.30 (s,
3
3
Synthesis, Medicine and Materials; Wiley-VCH: Weinheim, 2011,
2nd ed.. (b) Takaya, J.; Iwasawa, N. ACS Catal. 2012, 2, 1993.
(c) Beletskaya, I.; Moberg, C. Chem. Rev. 2006, 106, 2320.
6
H, CH -Bpin), 1.31 (s, 6 H, CH -Bpin), 1.63 (m, 1 H, CH CH ), 2.07
3
3
3
2
(dqd, J = 14.7, 7.4, 3.7 Hz, 1 H, CH CH ), 5.11 (ddd, J = 7.5, 3.7, 2.1 Hz,
3 2
1
H, OCH), 6.49 [d, J = 2.1 Hz, 1 H, CHC(C=O)].
(d) Burks, H. E.; Morken, J. P. Chem. Commun. 2007, 4717.
13
C NMR (101 MHz, CDCl ): δ = 9.2 (CH ), 24.7 (CH -Bpin), 25.0 (CH -
(e) Brown, J. M.; Nguyen, B. N. Stereoselective Synthesis 1: Stereo-
selective Reactions of Carbon—Carbon Double Bonds In Science of
Synthesis; Vol. 1; de Vries, J. G., Ed.; Thieme: Stuttgart, 2011,
295.
3
3
3
3
Bpin), 26.2 (CH ), 85.0 (C-Bpin), 87.2 (OCH), 131.9 [CH(C=O)], 151.4
2
(C=O).
HRMS (ESI): m/z [M + H]+ calcd for C12H19BO : 239.1449; found:
4
(
2) (a) Thomas, R. L.; Souza, F. E. S.; Marder, T. B. J. Chem. Soc.,
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7) For examples of borylation of α,β-unsaturated carbonyl com-
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©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 2242–2248