Metal free catalytic hydroboration of multiple bonds in methanol using N-heterocyclic carbenes under open atmosphere

Article abstract of DOI:10.1039/c3ob41499j

An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed with wide substrate scope. Reactions of various aldimines, ketimines, α,β-unsaturated carbonyl compounds, and alkynes were successfully executed with bis(pinacolato)diboron and N-heterocyclic carbenes in methanol without requiring a transition metal or inert atmosphere.

Full text of DOI:10.1039/c3ob41499j

Organic &
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Metal free catalytic hydroboration of multiple bonds in
methanol using N-heterocyclic carbenes under open
atmosphere†
Cite this: Org. Biomol. Chem., 2013, 11,
6350
Kun Wen,a Jinbo Chen,a Feng Gao,a Pinaki S. Bhadury,a Erkang Fanb and
Zhihua Sun*a
Received 21st July 2013,
Accepted 24th July 2013
An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed
with wide substrate scope. Reactions of various aldimines, ketimines, α,β-unsaturated carbonyl com-
pounds, and alkynes were successfully executed with bis(pinacolato)diboron and N-heterocyclic carbenes
in methanol without requiring a transition metal or inert atmosphere.
DOI: 10.1039/c3ob41499j
www.rsc.org/obc
Introduction
Results and discussion
Stable N-heterocyclic carbenes (NHC) have recently been
employed in many typical organic transformations as potent
alternatives to tertiary phosphines in metal–ligand catalysis.1,2
Largely due to their electron richness, NHCs exhibit a wide
range of reactivity in the field of organocatalysis. In this
context, the activation of diboron for direct hydroboration of a
carbonyl or related functional groups (CvO, CvN, or their
α,β-unsaturated derivatives) or alkenes and alkynes by NHCs
has attracted significant attention in recent years.3–42 We
recently prepared a series of N-aryl substituted NHCs based on
a benzimidazole core43 for carrying out the catalytic hydrobora-
tion of N-sulfinyl aldimines and ketimines in a one-pot pro-
cedure.18 The reaction required an inert atmosphere and a
Cu(I) catalyst to link with the appropriate NHC ligand precursor.
In addition, the reaction was conducted in the aprotic solvent
toluene and the required proton for hydroboration was prob-
ably supplied during aqueous work up. In order to develop an
easy to operate NHC-catalyzed hydroboration technique under
open atmosphere without requiring the use of a metal and to
further widen the substrate scope, herein we conducted regio-
selective hydroboration of a series of unsaturated substrates
with bis(pinacolato)diboron in protic solvents such as metha-
nol which could provide the necessary proton for the addition.
First, we studied non-catalytic base promoted hydroboration of
N-tert-butanesulfinyl tert-butylaldimine 1a to form 3a with bis-
(pinacolato)diboron (2, B2pin2). The reaction was conducted in
d4-MeOH at room temperature and the progress was moni-
tored against an internal standard, 1,3,5-trimethoxybenzene,
as described by Ellman et al.9 A wide range of bases were
tested and it was found that Cs2CO3 or DBU afforded the
product 3a in up to 12% yield (see Table S1 in ESI†). Some
bases, such as hydroxides, can cause rapid hydrolysis of
B2pin2, without generating the product. It is interesting to
note that both inorganic and organic bases could lead to the
formation of the desired product suggesting that activation of
B2pin2 was caused by base and not by any particular metal ion.
Further increase of the amount of the base or temperature did
not cause any significant improvement in the yield. So, we next
turned our attention to investigating the same reaction under
catalytic conditions using 10% triphenylphosphine or selected
NHC precursors (pre-NHC 4–8, Table 1) as potential catalysts.
The reactions were carried out on a 2 mmol scale in MeOH at
room temperature for 24 h. While practically no product was
generated with PPh3, various pre-NHCs (entries 2–9) led to the
formation of 3a with yields ranging from 15–88%. The best
result was achieved with DBU as the base and NHC precursor
8 (entry 7). The same combination also gave optimum result in
our previous report in toluene.18
As stated before, to ascertain the role of protic solvents in
the reaction, we further compared the formation of 3a in
different solvents under similar conditions. Compared to an
88% yield in MeOH (Table 1), the isolated yield of 3a in EtOH,
CF2HCH2OH and CF3CH2OH reached 65%, 72% and 68%
respectively. As expected, in the absence of a proton source the
desired product was not formed at all when the reactions were
aCollege of Chemistry and Chemical Engineering, Shanghai University of Engineering
Science, 333 Longteng Road, Shanghai 201620, China. E-mail: sungaris@gmail.com;
Fax: +86-21-67791432; Tel: +86-21-67791432
bDepartment of Biochemistry, University of Washington, Seattle, Washington 98195,
USA
†Electronic supplementary information (ESI) available: A table listing screening
results with various base and spectra (NMR and MS) of compounds. See DOI:
10.1039/c3ob41499j
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Table 1 Activation of B2pin2 with catalystsa
Table 2 Synthesis of α-aminoboronates from aldimines and ketimines under
optimal conditionsa
Entry
R1
R2
Product
Yield (%)
dr
1
2
3
4
5
6
7
8
CH3
H
H
H
H
3b
3c
3d
3e
3f
3g
3h
3i
85
90
85
83
82
79
68
65
>99 : 1
>99 : 1
99 : 1
>99 : 1
99 : 1
73 : 27
69 : 31
71 : 29
Cyclopentyl
Phthalimido-(CH2)4
4-Cl-C6H4
4-MeO-C6H4
Et
Ph
Ph-(CH2)2
H
CH3
CH3
Ph
Entry
Base
Catalyst
Isolated yield (%)
a Reaction conditions: ligand precursor 8 (81 mg, 0.2 mmol), DBU
(30 mg, 0.2 mmol), reactant (2.0 mmol) and bis(pinacolato)diboron
(559 mg, 2.2 mmol), room temperature for 24 h in 20 mL methanol.
1
2
3
4
5
6
7
8
9
Cs2CO3
NaOMe
Cs2CO3
DBU
DBU
DBU
DBU
TEA
Cs2CO3
PPh3
Trace
15
22
18
20
45
88
68
72
4
5
5
6
7
8
8
8
a Reaction conditions: ligand precursor (0.2 mmol), Base (0.2 mmol),
N-t-butylsulfinyl trimethylacetaldimine (378 mg, 2.0 mmol) and
bis(pinacolato)diboron (559 mg, 2.2 mmol), room temperature for
24 h in 20 mL methanol.
Fig. 1 11B NMR of B2pin2 (2) with base and/or pre-NHC in d4-MeOH (each at
0.2 M). (A) 2 alone; (B) 2 and DBU; (C) 2 and 8; and (D) 2, 8, and DBU.
performed in the aprotic solvents benzene, toluene, CH3CN,
THF, 1,4-dioxane, DMF and DMSO. The reaction also failed in
water or aqueous alcoholic solvents (H2O, or 2 : 1 MeOH–H2O)
which may be attributed to rapid hydrolysis of diboron 2 in a
homogeneous aqueous solution.
treatment was attributed to [Bpin2]− arising from decompo-
sition of 2.15 ESI-TOF MS analysis of a methanolic solution
that contained 2, 8, and DBU detected a molecular ion of
657.3675 with an isotope pattern consistent with molecular
formula of C40H47B2N2O5 (exact mass 657.3666). This suggests
Having established the proper conditions for addition, the
hydroboration reaction was further extended to different aldi-
mines and ketimines for the preparation of α-aminoboronic that an adduct consisting of one molecule each of 8, 2, and
MeOH was formed in solution. Therefore, the NMR and MS
esters in MeOH. The results are depicted in Table 2. For ali-
data are consistent with the formation of a MeOH associated
phatic or aromatic aldimines (entries 1–5), the yields were all
above 80% with a dr ratio of 99 : 1 or better. For ketimines NHC-adduct12,15 to diboron 2 or an NHC-adduct with one
MeOH displacing one O–B bond of pinacolatodiboron.14
(entries 6–8), the yields were slightly lower (above 65%) with a
However, based on spectral data alone, one cannot completely
better than those obtained using our one-pot protocol in rule out the formation of a MeO− adduct to 2 that is specially
dr ratio around 70 : 30. These results are comparable to or
associated with a pre-NHC.
toluene.
Regarding the mechanism of NHC-mediated hydroboration
If an NHC-adduct of 2 is responsible for catalysis, one may
of multiple bonds in methanol, activation of diboron through expect varying catalytic efficiencies of pre NHC 4–8 (Table 1)
the formation of an NHC adduct12,15 or a MeO− adduct27,35 is
depending on their acidities. It is known that N-aryl substi-
tution or phenyl ring fusion to the central imidazole ring can
possible. In either case broad peaks in the 11B NMR spectrum
may be observed with very similar chemical shifts at 0–10 ppm lower the acidity of the proton linked to the carbene
center.44–46 1H NMR spectra of 4–8 in d6-DMSO are also con-
sistent with this assumption as an increase in chemical shift
representing a polarized sp3 B species. Indeed, in our catalytic
system in MeOH, formation of a new sp3 B species corres-
ponding to the activation of 2 was observed when both DBU value is observed with increase in acidity of the proton linked
to the carbene center (9.5 ppm for 4, 9.7 ppm for 5, 9.9 ppm
for 6, 10.6 ppm for 7, and 10.8 ppm for 8). Therefore, pre-NHC
and 8 were present (Fig. 1, broad peak at 3 ppm for spectrum
D). The sharp peak at 8 ppm (Fig. 1B and D) caused by base
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Table 3 Catalytic hydroboration of α,β-unsaturated substrates
Table 4 Borylation of alkynes
Entry
R1
R2
Product
Yield (%)
α : β
1
2
3
4
5
6
7
8
9
Ph
4-F-C6H4
n-Butyl
HOCH2-
HO(CH2)2-
Cyclopropyl-
BocNH-CH2-
Me3Si-
H
H
H
H
H
H
H
H
Et-
13a
13b
13c
13d
13e
13f
13g
13h
13i
89
88
76
85
91
86
72
75
84a
<1 : 99
<1 : 99
<1 : 99
2 : 98
3 : 97
<1 : 99
8 : 92
Entry
R1
R2
R3
X
Product
Yield (%)
1
2
3
4
5
H
H
H
CH3
H
H
4-Me-C6H4
Ph
MeO
O
O
O
11a
11b
11c
11d
11e
86
85
87a
91
90
Ph
Ph
CH3
H
H
NS(O)Bu
NS(O)Bu
4-Me-C6H4
<1 : 99
<1 : 99
a Reaction performed at 70 °C.
Ph
a Reaction performed at 70 °C.
8 is the most acidic (least pKa value) among the five precursors
and the easiest to deprotonate to generate a carbene for
catalysis.
and alkyne 12a (1.5 g, 15 mmol) were reacted successfully
with 2 to afford the desired products without any significant
change in the overall yields.
We also investigated the scope and limitations of the
current open-to-air protocol in MeOH with other electrophilic
double bond or triple bond reactants. Hydroboration of several
classes of α,β-unsaturated carbonyl substrates is listed in
Table 3. Not surprisingly, commonly studied α,β-unsaturated
ketones which are highly reactive gave satisfactory results
(entries 1–2). A conjugate addition to ester was also successful
at high temperature (entry 3). Interestingly, α,β-unsaturated
aldimines also gave fairly good results with the final products
isolated in the enamine form (entries 4–5). No product was iso-
lated with alkenes conjugated to a phenyl ring (data not
shown) as the reactivities of these substrates are expected to be
much lower than alkenes conjugated to ketones.27
Conclusions
In summary, a facile metal-free NHC-catalyzed regioselective
hydroboration of multiple bonds has been developed. The
system has several inherent advantages that include simple
operational procedure and wide substrate scope without
requiring a stringent oxygen/moisture free environment.
Experimental
General methods
Examples of hydroboration of non-activated alkynes are
rare. The conjugate addition is usually performed through
metal-assisted catalysis using alkynes linked to a carbonyl
group.47,48 Recently, regioselective hydroboration to non-acti-
vated alkynes was achieved with NHC–Cu(I) catalysis.13 Using
our current protocol, a highly regioselective hydroboration
of terminal alkynes (entries 1–8, Table 4) was conducted.
The initial nucleophilic attack occurred preferentially at the
β-carbon, which was similar to reactions promoted by Cu(II) in
water suspension.49 These results are in contrast to the
carbene–Cu(I) catalyzed system where N-aryl NHC catalysis
favored α-borylation and bulky N-alkyl NHCs favored β-boryl-
ation.13 An example of an internal alkyne was also successful
with β-borylation (entry 9) at higher temperatures.
Chemicals were either purchased from commercial suppliers
or purified by standard techniques. Solvents were used as
purchased (analytical grade) without further purification.
Anhydrous Na2SO4 and MgSO4 were used to dry organic solu-
tions during workups. Reactions were monitored by TLC with
pre-coated silica gel 60 F254 aluminum plates using UV light
as the visualizing agent. Flash column chromatography was
performed with silica gel (0.0035–0.070 mm, 60 Å). 1H NMR,
13C NMR, 19F NMR and 11B NMR spectra were recorded at 400,
100, 376, and 128 MHz respectively. Chemical shifts are given
in δ relative to tetramethylsilane (TMS); the coupling constants
J are given in Hz. Mass spectra were recorded on a time-of-
flight mass spectrometer with an ESI source.
It is noteworthy that the absence of transition metals from
the reaction system was confirmed by inductively coupled
plasma emission spectroscopy. For example, the levels of Cu,
Co, Ni, Pt, Pd, Rh, Ru were all below 50 ppb (μg/L) (most are
below detection limits) in a typical experimental setup of
0.2 mmol scale. In order to further demonstrate the synthetic
utility of the current hydroboration protocol, products 3a, 11c
and 13a were also prepared on a larger scale. The aldimine 1a
(2.8 g, 15 mmol), α,β-unsaturated ester 10c (2.4 g, 15 mmol)
Representative procedure for 3a
Ligand precursor 8 (81 mg, 0.2 mmol) was mixed with DBU
(30 mg, 0.2 mmol), N-tert-butylsulfinyl trimethylacetaldimine
(378 mg, 2.0 mmol) and bis(pinacolato)diboron (559 mg,
2.2 mmol) in 20 mL methanol. The mixture was stirred at
room temperature for 24 h. Then the solution was diluted with
30 mL ethyl acetate and quenched with saturated K2CO3 solu-
tion. After separation and washing the aqueous layer with
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ethyl acetate (2 × 30 mL), the combined organic solution was
Pinacol (R)-1-N-sulfinyl-5-phthalimido-butyl-1-boronate (3d).
dried over anhydrous Na2SO4, and then concentrated. Purifi- Colorless oil; 785 mg (yield 85%); dr = 99 : 1; 19F NMR
cation using water activated silica gel (CH2Cl2–MeOH as (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereo-
eluent) gave 3a as a white solid; 558 mg (yield 88%).
mer δ = −68.98, minor diastereomer δ = −69.15; 1H NMR
(400 MHz, DMSO-d6, δ): 7.85 (m, 4H), 4.70 (d, J = 6.0 Hz, 1H),
3.57 (t, J = 6.8 Hz, 2H), 1.56 (m, 4H), 1.27 (m, 2H), 1.10 (d, J =
5.2 Hz, 12H), 1.06 (s, 9H); 13C NMR (100 MHz, DMSO-d6, δ):
Representative procedure for the determination of
diastereomeric ratio of product 3a
The crude product 3a was dissolved in dioxane in an oven- 168.4, 134.8, 132.1, 123.4, 83.7, 55.6, 42.2, 37.8, 32.6, 28.4,
dried vial equipped with a Teflon coated stir bar under nitro- 25.0, 24.7, 24.0, 23.0; MS (ESI-TOF) m/z: 463.2 [M + H]+; HRMS
gen. Freshly distilled MeOH (10 equiv.) was added to the solu- (ESI-TOF) m/z: calcd for C23H36BN2SO5 [M + H]+ 463.2432,
tion, followed by the dropwise addition of 4.0 M HCl in found 463.2430.
dioxane (1 equiv.). The reaction mixture was stirred at room
Pinacol
(R)-1-N-sulfinyl-4-chlorophenyl-1-boronate
(3e).
temperature for 45 min to 1 h before it was directly concen- White solid; 616 mg (yield 83%); mp 85.6–87.5 °C; dr > 99 : 1;
trated under reduced pressure. The resulting amine hydrochlo- 19F NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major
ride salt was triturated with a 2 : 1 mixture of hexanes to Et2O. diastereomer δ = −68.58, minor diastereomer δ = −68.89;
The amine hydrochloride (1.0 equiv.) was then dissolved in 1H NMR (400 MHz, DMSO-d6, δ): 7.36 (m, 4H), 5.56 (d, J =
CH2Cl2 and cooled to 0 °C. DIPEA (4.0 equiv.) was then added 5.6 Hz, 1H), 4.08 (d, J = 5.6 Hz, 1H), 1.12 (m, 21H); 13C NMR
followed by the addition of >99% ee (+) or >99% (−) MTPA (100 MHz, DMSO-d6, δ): 104.7, 131.3, 129.4, 128.5, 84.3, 56.2,
chloride (∼2.0 equiv.), and the resulting mixture was stirred 46.8, 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 372.2 [M + H]+; HRMS
for 1 h at 0 °C. The reaction mixture was diluted with EtOAc (ESI-TOF) m/z: calcd for C17H28BNSClO3 [M + H]+ 372.1566,
and then washed with 1 N sodium bisulfate. The organic layer found 372.1574.
was then washed with 1 N NaHCO3 and brine. The organic
Pinacol (R)-1-N-sulfinyl-4-methoxyphenyl-1-boronate (3f).
layer was dried over Na2SO4 and concentrated. Diastereomeric Colorless oil; 602 mg (yield 82%); dr = 99 : 1; 19F NMR
ratios were determined by 19F NMR of the unpurified material (376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereo-
(376 MHz, DMSO-d6): (R)-MTPA derivative of major diastereo- mer δ = −68.80, minor diastereomer δ = −68.53; 1H NMR
mer δ = −68.00, minor diastereomer δ = −68.16.
(400 MHz, DMSO-d6, δ): 7.23 (d, J = 8.8 Hz, 2H), 6.87 (d, J =
Pinacol (R)-1-N-sulfinyl-tert-butyl-1-boronate (3a). White 8.8 Hz, 2H), 5.27 (d, J = 5.2 Hz, 1H), 3.99 (d, J = 5.2 Hz, 1H),
solid; 558 mg (yield 88%); mp 98.6–100.7 °C; dr > 99 : 1; 19F 3.72 (s, 3H), 1.13 (s, 15H), 1.11 (s, 6H); 13C NMR (100 MHz,
NMR (376 MHz, DMSO-d6): (R)-MTPA derivative of major dia- DMSO-d6, δ): 158.4, 133.1, 128.9, 114.1, 84.0, 56.1, 55.5, 46.8,
stereomer δ = −68.00, minor diastereomer δ = −68.16; 1H NMR 24.9, 24.5, 23.1; MS (ESI-TOF) m/z: 368.2 [M + H]+; HRMS
(400 MHz, DMSO-d6, δ): 4.30 (d, J = 7.6 Hz, 1H), 2.51 (d, J = (ESI-TOF) m/z: calcd for C18H31BNSO4 [M + H]+ 368.2061,
7.6 Hz, 1H), 1.21 (d, J = 2.8 Hz, 12H), 1.09 (s, 9H), 0.92 (s, 9H); found 368.2054.
13C NMR (100 MHz, DMSO-d6, δ): 83.9, 56.2, 54.1, 34.2, 28.1,
Pinacol (R)-1-N-sulfinyl-1-methyl-ethyl-1-boronate (3g). Col-
25.2, 24.9, 22.9; MS (ESI-TOF) m/z: 318.2 [M + H]+; HRMS orless oil; 479 mg (yield 79%); dr = 73 : 27; 19F NMR (376 MHz,
(ESI-TOF) m/z: calcd for C15H33BNSO3 [M + H]+ 318.2269, DMSO-d6): (R)-MTPA derivative of major diastereomer δ =
found 318.2266.
−68.64, minor diastereomer δ = −68.88; 1H NMR (400 MHz,
Pinacol (R)-1-N-sulfinyl-methyl-1-boronate (3b). Colorless DMSO-d6, δ): 4.34 (s, 1H), 1.63 (m, 1H), 1.51 (m, 1H), 1.21 (d,
oil; 468 mg (yield 85%); dr > 99 : 1; 19F NMR (376 MHz, DMSO- J = 3.2 Hz, 12H), 1.13 (m, 12H), 0.84 (t, J = 7.2 Hz, 3H);
d6): (R)-MTPA derivative of major diastereomer δ = −69.14, 13C NMR (100 MHz, DMSO-d6, δ): 84.1, 55.4, 32.7, 25.1, 24.9,
1
minor diastereomer δ = −69.00; H NMR (400 MHz, DMSO-d6, 24.0, 23.0, 22.2; MS (ESI-TOF) m/z: 304.2 [M + H]+; HRMS
δ): 4.75 (d, J = 5.6 Hz, 1H), 2.86 (m, 1H), 1.19 (d, J = 5.6 Hz, (ESI-TOF) m/z: calcd for C14H31BNSO3 [M + H]+ 304.2112,
12H), 1.16 (d, J = 7.2 Hz, 3H), 1.09 (s, 9H); 13C NMR (100 MHz, found 304.2105.
DMSO-d6, δ): 83.7, 55.5, 37.4, 25.1, 24.8, 23.1, 18.7; MS
(ESI-TOF) m/z: 276.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for orless oil; 477 mg (yield 68%); dr = 69 : 31; 19F NMR (376 MHz,
C12H27BNSO3 [M + H]+ 276.1799, found 276.1789.
DMSO-d6): (R)-MTPA derivative of major diastereomer δ =
Pinacol (R)-1-N-sulfinyl-phenyl-methyl-1-boronate (3h). Col-
Pinacol (R)-1-N-sulfinyl-cyclopentyl-1-boronate (3c). Color- −68.80, minor diastereomer δ = −69.16; 1H NMR (400 MHz,
less oil; 592 mg (yield 90%); dr > 99 : 1; 19F NMR (376 MHz, DMSO-d6, δ): 7.40 (m, 2H), 7.31 (m, 2H), 7.18 (m, 1H), 5.18 (s,
DMSO-d6): (R)-MTPA derivative of major diastereomer δ = 0.34H), 5.15 (s, 0.51H), 1.64 (s, 1.22H), 1.58 (s, 1.78H), 1.20 (s,
−68.96, minor diastereomer δ = −69.15; 1H NMR (400 MHz, 9H), 1.16 (s, 12H), 1.13 (s, 6H); 13C NMR (100 MHz, DMSO-d6,
DMSO-d6, δ): 4.58 (d, J = 6.4 Hz, 1H), 2.64 (dd, J1 = 6.4 Hz, J2 = δ): 146.2, 146.1, 128.3, 128.2, 127.2, 126.3, 126.2, 84.4, 84.2,
8.4 Hz, 1H), 2.03 (m, 1H), 1.75 (m, 1H), 1.64 (m, 1H), 1.58 (m, 56.7, 55.8, 25.0, 24.9, 24.9, 24.6, 24.4, 23.4, 23.2; MS (ESI-TOF)
2H), 1.49 (m, 2H), 1.18 (d, J = 5.2 Hz, 12H), 1.08 (s, 9H); m/z: 352.2 [M
13C NMR (100 MHz, DMSO-d6, δ): 83.7, 55.8, 47.0, 42.7, 30.9, C18H31BNSO3 [M + H]+ 352.2112, found 352.2119.
29.6, 25.5, 25.4, 25.2, 25.1, 24.9, 24.8, 23.1; MS (ESI-TOF) m/z: Pinacol (R)-1-N-sulfinyl-(2-phenylethyl)-phenyl-1-boronate (3i).
+
H]+; HRMS (ESI-TOF) m/z: calcd for
330.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd for C16H33BNSO3 Colorless oil; 750 mg (yield 85%); dr = 71 : 29; 19F NMR
[M + H]+ 330.2269, found 330.2260.
(376 MHz, DMSO-d6): (R)-MTPA derivative of major
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diastereomer δ = −69.08, minor diastereomer δ = −69.01; 1H
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-phenyl-ethene
NMR (400 MHz, DMSO-d6, δ): 7.42 (m, 4H), 7.23 (m, 6H), 5.25 (13a). White Solid; 409 mg (yield 89%); mp 31.4–32.4 °C;
(s, 0.63H), 5.05 (s, 0.25H), 2.73 (m, 1H), 2.35 (m, 2H), 2.17 (m, 1H NMR (400 MHz, CDCl3, δ): 7.52 (m, 2H), 7.43 (d, J =
1H), 1.25 (m, 12H), 1.07 (m, 9H); 13C NMR (100 MHz, DMSO- 18.4 Hz, 1H), 7.34 (m, 3H), 6.21 (d, J = 18.4 Hz, 1H), 1.34
d6, δ): 143.3, 143.1, 128.8, 128.8, 128.7, 128.6, 128.5, 128.3, (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 149.5, 137.5, 128.9,
128.0, 127.7, 127.6, 127.5, 126.6, 126.5, 126.3, 126.2, 126.0, 128.6, 127.1, 83.4, 24.8; MS (ESI-TOF) m/z: 231.2 [M + H]+;
84.7, 84.2, 57.0, 56.1, 55.9, 48.9, 31.8, 29.5, 29.2, 25.0, 24.8, HRMS (ESI-TOF) m/z: calcd for C14H20BO2 [M + H]+ 231.1551,
24.6, 24.4, 23.6, 23.3, 23.2, 22.5; MS (ESI-TOF) m/z: 442.2 Found 231.1550.
[M + H]+; HRMS (ESI-TOF) m/z: calcd for C25H37BNSO3
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(4-fluoro-
[M + H]+ 442.2582, Found 442.2575.
phenyl)-ethene (13b). White solid; 436 mg (yield 88%); mp
1
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-(4-methyl- 63.9–65.4 °C; H NMR (400 MHz, CDCl3, δ): 7.48 (m, 2H), 7.38
phenyl)-butane-2-one (11a). White solid; 471 mg (yield 86%); (d, J = 18.4 Hz, 1H), 7.05 (t, J = 8.8 Hz, 2H), 6.10 (d, J = 18.4 Hz,
1
mp 47.8–49.0 °C; H NMR (400 MHz, DMSO-d6, δ): 7.84 (d, J = 1H), 1.34 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 163.2, 148.2,
8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 3.07 (m, 2H), 2.37 (s, 3H), 133.7, 128.7, 128.7, 115.7, 115.4, 83.4, 24.8; 19F NMR
1.16 (s, 12H), 0.87 (t, J = 6.8 Hz, 2H); 13C NMR (100 MHz, (376 MHz, CDCl3, δ): −112.4; MS (ESI-TOF) m/z: 249.2
DMSO-d6, δ): 200.2, 143.7, 134.5, 129.6, 128.3, 83.0, 33.6, 25.3, [M + H]+; HRMS (ESI-TOF) m/z: calcd for C14H19BFO2 [M + H]+
25.0, 21.6, 5.4; MS (ESI-TOF) m/z: 275.2 [M + H]+; HRMS 249.1457, Found 249.1455.
(ESI-TOF) m/z: calcd for C16H23BO3Na [M + Na]+ 297.1632,
Found 297.1630.
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-hexene (13c).
Colorless oil; 319 mg (yield 76%); H NMR (400 MHz, DMSO-
1
4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-phenyl-1-phenyl- d6, δ): 6.05 (dt, J1 = 17.6 Hz, J2 = 6.4 Hz, 1H), 5.30 (m, 1H), 2.11
butane-2-one (11b). White solid; 571 mg (yield 85%); mp (m, 2H), 1.35 (m, 2H), 1.25 (m, 2H), 1.18 (s, 12H), 0.88 (t, J =
78.6–79.7 °C; 1H NMR (400 MHz, CDCl3, δ): 8.00 (d, J = 7.2 Hz, 6.8 Hz, 3H); 13C NMR (100 MHz, DMSO-d6, δ): 154.7, 118.5,
2H), 7.57 (m, 1H), 7.46 (m, 2H), 7.33 (m, 4H), 7.22 (m, 1H), 83.1, 35.3, 30.3, 25.1, 22.2, 14.2; MS (ESI-TOF) m/z: 211.2[M +
3.59 (dd, J1 = 10.8 Hz, J2 = 18.0 Hz, 1H), 3.45 (dd, J1 = 5.2 Hz, H]+; HRMS (ESI-TOF) m/z: calcd for C12H24BO2 [M + H]+
J2 = 18.4 Hz, 1H), 2.83 (dd, J1 = 5.2 Hz, J2 = 10.8 Hz, 1H), 1.28 211.1864, Found 211.1869.
(s, 6H), 1.20 (s, 6H); 13C NMR (100 MHz, CDCl3, δ): 199.7,
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-3-hydroxy-
142.0, 136.8, 132.9, 128.5, 128.4, 128.1, 125.6, 83.4, 43.3, 24.6, 1-propene (13d). Colorless oil; 313 mg (yield 85%); 1H NMR
24.5; MS (ESI-TOF) m/z: 337.2 [M + H]+; HRMS (ESI-TOF) m/z: (400 MHz, CDCl3, δ): 6.76 (dd, J1 = 18.4 Hz, J2 = 4 Hz, 1H), 5.73
calcd for C21H25BO3Na [M + Na]+ 359.1789, Found 359.1778.
(d, J = 18.4 Hz, 1H), 4.26 (d, J = 2.4 Hz, 2H), 1.62 (s, 1H), 1.30
Methyl-3-(4,4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-phenyl (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 151.7, 83.3, 64.6, 24.8;
propionate (11c). White solid; 505 mg (yield 87%); mp MS (ESI-TOF) m/z: 185.1 [M + H]+; HRMS (ESI-TOF) m/z: calcd
1
67.6–68.5 °C; H NMR (400 MHz, CDCl3, δ): 7.27 (m, 4H), 7.17 for C9H18BO3 [M + H]+ 185.1344, Found 185.1348.
(m, 1H), 3.67 (s, 3H), 2.92 (dd, J1 = 15.6 Hz, J2 = 10.0 Hz, 1H),
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-hydroxy-
2.76 (dd, J1 = 10.0 Hz, J2 = 6.0 Hz, 1H), 2.69 (dd, J1 = 15.6 Hz, J2 1-butene (13e). Colorless oil; 360 mg (yield 91%); 1H NMR
= 6.0 Hz, 1H), 1.22 (d, J = 18.0 Hz, 12H); 13C NMR (100 MHz, (400 MHz, CDCl3, δ): 6.60 (dt, J1 = 18 Hz, J2 = 6.4 Hz, 1H), 5.54
CDCl3, δ): 173.8, 141.3, 128.5, 128.2, 125.7, 83.6, 51.6, (d, J = 18 Hz, 1H), 3.71 (t, J = 6.4 Hz, 2H), 2.42 (m, 2H), 1.88 (s,
37.1, 24.6, 24.5; MS (ESI-TOF) m/z: 291.2 [M + H]+; HRMS 1H), 1.26 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 150.1, 121.9,
(ESI-TOF) m/z: calcd for C16H24BO4 [M + H]+ 291.1762, Found 83.2, 61.2, 39.1, 24.8; MS (ESI-TOF) m/z: 199.2 [M + H]+; HRMS
291.1768.
(R)-1-N-Sulfinyl-3-methyl-3-(4,4,5,5-tetramethyl-1,3,2-diox- 199.1500.
(ESI-TOF) m/z: calcd for C10H20BO3 [M + H]+ 199.1505, Found
aborolan-2-yl)-1-butene (11d). Colorless oil; 573 mg (yield
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-cyclopyl-ethene
91%); 1H NMR (400 MHz, CDCl3, δ): 5.98 (dd, J1 = 10.4 Hz, J2 = (13f). Colorless oil; 334 mg (yield 86%); 1H NMR (400 MHz,
14.0 Hz, 1H), 5.14 (d, J = 14.0 Hz, 1H), 5.01 (d, J = 10.0 Hz, 1H), CDCl3, δ): 6.09 (dd, J1 = 18 Hz, J2 = 4 Hz, 1H), 5.50 (d, J1
=
1.24 (s, 9H), 1.23 (s, 12H), 1.05 (s, 6H); 13C NMR (100 MHz, 18 Hz, 1H), 1.53 (m, 1H), 1.26 (s, 12H), 0.81 (m, 2H), 0.54 (m,
CDCl3, δ): 125.3, 120.5, 83.2, 56.2, 24.9, 24.6, 24.5, 24.4, 22.5; 2H); 13C NMR (100 MHz, CDCl3, δ): 158.5, 115.3, 82.9, 24.7,
MS (ESI-TOF) m/z: 316.2 [M + H]+; HRMS (ESI-TOF) m/z: calcd 17.0, 7.9; MS (ESI-TOF) m/z: 195.2 [M + H]+; HRMS (ESI-TOF)
for C15H30BNSO3Na [M + Na]+ 338.1932, Found 338.1913.
(R)-1-N-Sulfinyl-1-(4-methylphenyl)-3-(4,4,5,5-tetramethyl-
m/z: calcd for C11H20BO2 [M + H]+ 195.1551, Found 195.1557.
1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-N-Boc-3-amino-
1,3,2-dioxaborolan-2-yl)-1-propene (11e). Colorless oil; 643 mg 1-propene (13g). White solid; 407 mg (yield 72%); mp
1
(yield 90%); H NMR (400 MHz, CDCl3, δ): 7.35 (d, J = 8.0 Hz, 61.6–62.8 °C; 1H NMR (400 MHz, CDCl3, δ): 6.59 (dt, J1
=
2H), 7.18 (d, J = 8.0 Hz, 2H), 5.44 (t, J = 8.0 Hz, 1H), 4.86 (s, 18 Hz, J2 = 4 Hz, 1H), 5.59 (dt, J1 = 18 Hz, J2 = 6 Hz, 1H), 4.67
1H), 2.37 (s, 3H), 1.71 (dd, J1 = 4.8 Hz, J2 = 8.0 Hz, 2H), 1.27 (s, (s, 1H), 3.85 (m, 2H), 1.45 (s, 9H), 1.27 (s, 12H); 13C
9H), 1.24 (s, 12H); 13C NMR (100 MHz, CDCl3, δ): 138.0, 137.9, NMR (100 MHz, CDCl3, δ): 155.7, 149.4, 118.3, 83.3, 79.4, 44.0,
133.3, 129.5, 129.0, 110.4, 83.3, 55.9, 24.8, 24.8, 22.7, 21.3; MS 28.4, 24.8; MS (ESI-TOF) m/z: 284.2 [M
+
H]+; HRMS
(ESI-TOF) m/z: 358.3 [M + H]+; HRMS (ESI-TOF) m/z: calcd for (ESI-TOF) m/z: calcd for C14H27BNO4 [M + H]+ 284.2024, Found
C21H32BNSO3Na [M + Na]+ 400.2088, Found 400.2061.
284.2028.
6354 | Org. Biomol. Chem., 2013, 11, 6350–6356
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1-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-trimethylsilyl- 15 C. Kleeberg, A. G. Crawford, A. S. Batsanov, P. Hodgkinson,
ethene (13h). Colorless oil; 340 mg (yield 75%); 1H NMR
(400 MHz, CDCl3, δ): 7.14 (d, J = 22 Hz, 1H), 6.26 (d, J = 22 Hz,
D. C. Apperley, M. S. Cheung, Z. Lin and T. B. Marder,
J. Org. Chem., 2012, 77, 785.
1H), 1.30 (s, 12H), 0.1 (s, 9H); 13C NMR (100 MHz, CDCl3, δ): 16 J. K. Park, B. A. Ondrusek and D. T. McQuade, Org. Lett.,
157.9, 83.4, 24.8, 1.9; MS (ESI-TOF) m/z: 227.2 [M + H]+; HRMS
(ESI-TOF) m/z: calcd for C11H24BO2Si [M + H]+ 227.1633, 17 L. Zhao, Y. Ma, F. He, W. Duan, J. Chen and C. Song, J. Org.
Found 227.1638. Chem., 2013, 78, 1677.
1-Phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-butene 18 K. Wen, H. Wang, J. Chen, H. Zhang, X. Cui, C. Wei, E. Fan
(13i). Colorless oil; 433 mg (yield 84%); 1H NMR (400 MHz,
and Z. Sun, J. Org. Chem., 2013, 78, 3405.
CDCl3, δ): 7.36 (m, 4H), 7.28 (m, 2H), 2.46 (q, J = 7.6 Hz, 2H), 19 S.-S. Zhang, Y.-S. Zhao, P. Tian and G.-Q. Lin, Synlett, 2013,
1.36 (s, 12H), 1.16 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
24, 437–442.
2012, 14, 4790.
CDCl3, δ): 141.4, 137.9, 129.0, 128.1, 127.1, 83.4, 24.8, 22.7, 20 L. Dang, Z. Lin and T. B. Marder, Organometallics, 2008, 27,
14.7; MS (ESI-TOF) m/z: 259.2 [M + H]+; HRMS (ESI-TOF) m/z:
4443.
calcd for C16H24BO2Si [M + H]+ 259.1864, Found 259.1868.
21 H. Zhao, L. Dang, T. B. Marder and Z. Lin, J. Am. Chem.
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22 L. Dang, H. Zhao, Z. Lin and T. B. Marder, Organometallics,
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23 B. Liu, M. Gao, L. Dang, H. Zhao, T. B. Marder and Z. Lin,
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Acknowledgements
Financial support of this work was provided by Shanghai Saijia 24 M. Gao, S. B. Thorpe and W. L. Santos, Org. Lett., 2009, 11,
Chemicals Ltd., Shanghai Municipal Science and Technology 3478.
Commission (Project no. 12430501300), and the Innovation 25 M. Gao, S. B. Thorpe, C. Kleeberg, C. Slebodnick,
Team Building Project of Pharmaceutical Engineering in
Shanghai (XKZZ1205).
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