1-Butyl-3-methylimidazol-2-ylidene Borane: A Readily Available, Liquid N-Heterocyclic Carbene Borane Reagent

Article abstract of DOI:10.1021/acs.joc.7b02730

1-Butyl-3-methylimidazol-2-ylidene borane has been synthesized directly from two inexpensive commercial reagents: 1-butyl-3-methylimidazolium bromide and sodium borohydride. This NHC-borane reagent is a stable, free-flowing liquid that shows promise for use in radical, ionic, and metal-catalyzed reactions.

Full text of DOI:10.1021/acs.joc.7b02730

Subscriber access provided by READING UNIV
Note
1-Butyl-3-methylimidazol-2-ylidene borane. A readily
available, liquid N-heterocyclic carbene borane reagent
Daniel A. Bolt, and Dennis P. Curran
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02730 • Publication Date (Web): 08 Nov 2017
Downloaded from http://pubs.acs.org on November 10, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 6
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1-Butyl-3-methylimidazol-2-ylidene borane. A readily availa-
ble, liquid N-heterocyclic carbene borane reagent
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Daniel A. Bolt and Dennis P. Curran*
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260 USA
ABSTRACT: 1-Butyl-3-methylimidazol-2-ylidene borane has been synthesized directly from two inexpensive commercial reagents: 1-
butyl-3-methylimidazolium bromide and sodium borohydride. This NHC-borane reagent is a stable, free-flowing liquid that shows promise
for use in radical, ionic and metal-catalyzed reactions.
The fundamental chemistry of N-heterocyclic carbene boranes
(NHC-boranes) has been revealed in recent years,1 and NHC-
boranes are now interesting reagents in diverse areas such as main
group chemistry, organic synthesis and polymer chemistry.2 Fol-
lowing its introduction in 2010,3 1,3-dimethylimidazol-2-ylidene
borane 1 has quickly become one of the most important NHC-
boranes (Figure 1). It serves both as a precursor of more complex
NHC-boranes and as a reagent in its own right.4
We first reported NHC-borane 5 in 2015, making it from 1-
butylimidazole, iodomethane and sodium borohydride in a proce-
dure analogous to that in Figure 1a.5a We discovered that 5 is not a
solid, but is instead a low viscosity (free flowing) liquid. We also
learned from very crude experiments that this and related NHC-
boranes are hypergolic.5b,7 Shortly thereafter, a detailed study by
Huang and coworkers showed that 5 and related compounds could
be safer alternatives to hydrazine as fuel components in rocket pro-
pellant.8
Several procedures exist to make 1,3-dimethylimidazol-2-ylidene
borane 1,3 and the most convenient is probably the reaction of 1,3-
dimethylimidazolium iodide 2 with sodium borohydride (Figure
1a).5 Imidazolium salt 2 is made in situ from 1-methylimidazole 3
and methyl iodide. Iodomethane is a costly and reactive methylat-
ing agent, and its safe handling is an issue.
Here we report a simplified synthesis of 1-butyl-3-methyl-
imidazol-2-ylidene borane 5 from 1-butyl-3-methylimidazolium
bromide 4 and sodium borohydride. We also survey some of its
reactions to learn if its reactivity parallels that of 1,3-
dimethylimidazol-2-ylidene borane 1. The ease of synthesis and
favorable reaction profile suggest that 5 could fill an important role
in NHC-borane chemistry, especially in large scale applications
where cost is paramount.
a) Synthesis of 1,3-dimethylimidazol-2-ylidene borane reagent 1
CH3
CH3
N
a) NaBH4,
toluene, reflux
N
N
a) CH3I, MeCN
b) evaporate
N
I–
BH3
The synthesis of 5 is shown in Scheme 1. Imidazolium salt 4 and
sodium borohydride (2 equiv) are mixed, then heated to 125 ˚C.
The imidazolium salt melts at this temperature, and bubbling (H2
gas) occurs for about 45 min. After 6 h, the mixture is cooled and
filtered through a short pad of silica gel, eluting with 50/50 hex-
ane/ethyl acetate. Concentration gives pure 5. This reaction has
been run multiple times on 4–10 mmol scales, and yields center
around 40% ( 5%).
N
b) evaporate
c) recrystallize
N
CH3
CH3
CH3
1, solid
3
2
b) 1-Butyl-3-methylimidazol-2-ylidene borane reagent 5
Bu
Bu
N
N
Br–
BH3
N
N
Bu
Bu
CH3
CH3
N
a) 125 ˚C, 6 h
N
Br–
BH3
+ NaBH4
4
inexpensive precursor
5, liquid
valuable reagent?
N
b) silica filtration
N
CH3
CH3
4
5
~40% yield
Figure 1. Existing and new NHC-borane reagents.
Thanks to ionic liquid chemistry,6 quite a number of imidazoli-
um salts are now commercially available in large quantities. Among
the least expensive is 1-butyl-3-methylimidazolium bromide 4
(Figure 1b). This is not a room temperature ionic liquid itself (mp
~70 ˚C), but it is a precursor to 1-butyl-3-methylimidazolium salts
with other counteranions that are room temperature ionic liquids.
Based on this, we posited that 1-butyl-3-methylimidazol-2-ylidene
borane 5 could be a valuable new NHC-borane reagent.
Scheme 1. Simple synthesis of reagent 5.
Despite the modest 40% yield, this procedure is both more con-
venient and less expensive than standard procedures that start from
imidazolium salts and require strong bases (typically NaN(TMS)2)
and reactive borane sources (typically BH3-THF). It gives about
the same yield as the previous NaBH4 procedure5a but is improved
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 6
because only one reaction is involved (methyl iodide and acetoni-
more practical procedure because benzene is not used and because
the thiol has little smell.
1
2
3
4
5
6
7
8
trile are no longer used) and because that reaction can be run with-
out solvent (the procedure optimized for solid imidazolium salts
calls for a large volume of toluene).
One of the more atypical radical reactions of NHC-boranes is
reductive decyanation,4g and two examples of this type of reaction
with 5 are shown in Figure 2c. The first reaction is designed with
malononitrile 12 as the substrate and 5 as the reagent. Here decy-
anated product 13 was isolated in 83% yield. The second reaction
is designed with NHC-borane 5 as the substrate and readily availa-
ble glutaronitrile as the reagent. This provided stable new boryl
nitrile 14 in 52% yield.
NHC-boranes are good hydride sources,11 and ionic reductions
of three simple aldehydes and ketones are shown in Figure 3. Sev-
eral procedures are available for this transformation,4c,12 and we
chose the method based on silica gel activation.13 Here the carbon-
yl compound and NHC-borane 5 are dissolved in CH2Cl2, silica gel
is added, then the slurry is stirred at rt. Aldehydes 15 and 17 pro-
vided 1˚-alcohols 16 and 18 in 82% and 48% yields. Notice that
reductive debromination does not occur with 15. Ketone 19 pro-
vided 2˚-alcohol 20 in 50% yield.
We next assessed the capabilities of NHC-borane 5 as a synthet-
ic reagent in representative radical, ionic and metal-catalyzed trans-
formations. For comparison purposes, procedures were based on
the analogous transformations with NHC-borane 1. Because 5 is
not a salt, no aqueous workups were used for any of the following
transformations. Isolated yields were obtained by concentration
and automated flash chromatography, unless otherwise indicated.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2 summarizes the results of several radical reactions of 5.
Reductions of sec-xanthates 6a and 6b with 5 and AIBN proceed-
ed smoothly in refluxing benzene over 2 h,9 and the reduction
products 7a and 7b were isolated in 63% and 85% yields (Figure
2a).
(a) Xanthate reductions
S
5, 1 equiv
AIBN, 0.5 equiv
O
SMe
H
O
5, 1 equiv
silica gel
O
O
benzene
80 °C, 2 h
R
R
H
OH
5
5
CH2Cl2,
rt, 2 h
Br
Br
6a, R = Et
6b, R = iPr
7a, 63%
7b, 85%
15
17
19
16, 82%
18, 48%
20, 50%
(b) Halide reductions with thiol catalysis
O
5, 1 equiv
silica gel
I
H
H
OH
5, 1.1 equiv
tBuON=ONtBu, 20%
CH2Cl2,
rt, 2 h
PhSH, 5%
benzene
80 °C, 2 h
8
9, >95%
NMR yield
O
OH
5, 1 equiv
silica gel
R
R
5, 1.1 equiv
H
CH2Cl2,
rt, 2 h
H
tBuON=NOtBu, 20%
H
H
C9H19C(CH3)2SH, 5%
PhCF3
80 °C, 2 h
Br
Figure 3. Carbonyl reductions promoted by silica gel.
10, R = (CH2)3CH(CH3)2
11, 83%
Two examples of rhodium-catalyzed B–H insertion reactions of
diazoesters are shown in Figure 4.14 Reaction of 5 with ethyl diazo-
acetate 21 and Rh2(esp)2 (bis[rhodium(α,α,α′,α′-tetramethyl-1,3-
benzenedipropionic acid)]) provided stable α-NHC-boryl acetate
22 in 40% yield.
(c) Reductive decyanations
5, 1.2 equiv
tBuOOtBu, 20%
NC CN
H
CN
Ph
Ph
Ph
Ph
tBuOH
120 °C, 16 h
Bu
O
H
O
5, 1 equiv
Rh2(esp)2, 1%
N
12
Bu
13, 83%
BH2 OEt
N2
OEt
N
CH2Cl2,
reflux, 2 h
glutaronitrile, 2 equiv
tBuOOtBu, 40%
Bu
Me
22, 40%
N
N
21, 1.2 equiv
BH3
BH2CN
N
N
PhCF3
120 °C, 2 h
CH3
CH3
14, 52%
Bu
N
Ph
O
5, 1 equiv
Rh2(esp)2, 1%
Ph
N2
O
5
BH2 OMe
OMe
CH2Cl2,
reflux, 4 h
N
Figure 2. Representative radical transformations.
Me
NHC-borane 5 also served in reductive dehalogenations by po-
larity reverse catalysis (Figure 2b).10 In an NMR experiment, thiol-
catalyzed reduction of adamantyl iodide 8 gave adamantane 9 in
>95% yield (di-t-butyl hyponitrite, PhSH, benzene, 80 ˚C). To
obtain an isolated yield, cholesterol bromide 10 was reduced (di-t-
butyl hyponitrite, t-dodecanethiol, benzotrifluoride, 80 ˚C) to
provide reduced cholesterol derivative 11 in 83% yield. This is a
23, 1.2 equiv
24, 97%
Figure 4. Rhodium-catalyzed boron-hydrogen insertion reactions.
A similar reaction with a donor-acceptor diazo precursor—
methyl 2-diazo-2-phenyl acetate 23—provided the corresponding
NHC-boryl ester 24 in 97% yield.
ACS Paragon Plus Environment

Page 3 of 6
The Journal of Organic Chemistry
Proton (1H), carbon (13C), boron (11B), and fluorine (19F) nuclear mag-
netic resonance sepctra (NMR) were performed on 300, 400, or 500 MHz
Finally, Figure 5 shows reactions directed at accessing Suzuki
chemistry starting from 5.15 First, in situ generation of benzyne
from 2-(trimethylsilyl)phenyl trifluoromethanesulfonate 25 and
KF4h provided the hydroboration product, B-phenyl NHC-borane
26, in 46% yield. This was fluorinated by Selectfluor (1-
chloromethyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetra-
fluoroborate)) to give stable B,B-difluoro-B-phenyl NHC-borane
27 in 63% yield.16 Results of direct Suzuki reactions of 27 were
subpar. For example, reaction of 27 with 4-bromobenzonitrile
stopped after about 50% conversion to 4-phenylbenzonitrile. As an
alternative, 26 was converted to the corresponding pinacol borane
28 in 74% yield by treatment with pinacol and HCl.4a Likewise,
several procedures can convert 26 cleanly to phenylboronic acid
(PhB(OH)2).16 These transformations establish a convenient
bridge to Suzuki and related chemistry.
1
2
3
4
5
6
7
8
instruments. Chloroform (δ 7.26 ppm) or TMS (δ 0.00 ppm) was used as
1
an internal standard for H NMR spectra and CDCl3 (δ 77.00 ppm) was
used as an internal standard for 13C NMR spectra. 11B chemical shifts are
relative to Et2O•BF3 and 19F chemical shifts are relative to CFCl3. The
following abbreviations are used to describe coupling: s, d, t, q, quint, sept,
m, and br represent singlet, doublet, triplet, quartet, quintet, septet, multi-
plet, and broad signal respectively. The resonances of hydrogen atoms
1
connected to boron were often difficult to observe in H NMR spectra due
to quadrupole broadening. For the same reason, no resonances of carbon
atoms bonded to the boron atom could be observed by 13C NMR spectros-
copy. MS experiments were conducted with a TOF analyzer.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Preparation of NHC-borane 5
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)trihydroborate
(5):1 1-Butyl-3-methylimidazolium bromide (4 mmol, 0.88 g) was added
to a 250-mL pear-shaped flask fitted with a magnetic stirbar under argon at
room temperature. The flask was fitted with a long reflux condenser and a
gas outlet line. NaBH4 (8 mmol, 0.303 g) was added, and the neat mixture
was heated to 125 °C. After 6 h, the mixture was cooled to room tempera-
ture. The residue was rinsed out with CH2Cl2 and filtered through a silica
plug. Solvent was removed from the filtrate under vacuum, which gave pure
Bu
5, 1 equiv
TMS
N
KF, 2 equiv
BH2Ph
N
OTf
18-crown-6, 2 equiv
THF, rt, 3.5 h
Me
26, 46%
25
26
1
MeBu-Imd-BH3 5 as a colorless liquid (0.26 g, 43% yield): H NMR
Bu
Selectfluor,
2 equiv
(CDCl3, 500 MHz) δ 6.80 (d, J = 2.0 Hz, 1 H), 6.79 (d, J = 1.5 Hz, 1 H),
4.09 (t, J = 7.5 Hz, 2 H), 3.71 (s, 3 H), 1.78-1.71 (m, 2 H), 1.34 (tq, J = 7.5,
7.5 Hz, 2 H), 1.00 (q, JB-H = 86.0 Hz, 3 H), 0.94 (t, J = 7.0 Hz); 13C NMR
(CDCl3, 125 MHz) 171.8 (br m), 112.0, 118.8, 48.6, 35.8, 32.2, 19.7, 13.6;
11B NMR (CDCl3, 160 MHz) δ –37.3 (q, JB-H = 86.5 Hz).
N
BF2Ph
CH3CN, rt, 3.5 h
N
Me
27, 63%
Radical reactions
pinacol, 2 equiv
HCl, 2.6 equiv
Octyloxymethyl-benzene (7a): To a solution of MeBu-Imd-BH3 5
(30 mg, 0.2 mmol), and radical precursor 6a (65 mg, 0.2 mmol) in deoxy-
genated benzene (2 mL) was added AIBN (16 mg, 0.1 mmol) in one por-
tion. The colorless solution was refluxed for 2 h. After cooling to room
temperature, the solvent was removed under vacuum, and the residue was
purified by flash column chromatography. Compound 7a1 was isolated
(hexane : ethyl acetate = 98 : 2, 28 mg, 63%) as a colorless liquid.
((7-Methyloctyloxy)methyl)benzene (7b): To a solution of
MeBu-Imd-BH3 5 (30 mg, 0.2 mmol), and radical precursor 6b (66 mg,
0.2 mmol) in deoxygenated benzene (2 mL) was added AIBN (16 mg, 0.1
mmol) in one portion. The colorless solution was refluxed for 2 h. After
cooling to room temperature, the solvent was removed under vacuum, and
the residue was purified by flash column chromatography. Compound 7b1
was isolated (hexane : ethyl acetate = 98 : 2, 39 mg, 85%) as a colorless
liquid.
Adamantane (9): TBHN (3.5 mg, 0.02 mmol) was added to a solu-
tion of MeBu-Imd-BH3 5 (17 mg, 0.11 mmol) and adamantyl iodide 8 (0.1
mmol) in benzene (0.45 mL). Thiophenol (11.0 mg, 0.1 mmol) was dis-
solved in deuterated benzene (0.9 mL). A portion of the diluted solution of
thiophenol (0.1 M in benzene, 50 μL, 0.005 mmol) and 1,3,5-
trimethoxybenzene internal standard (16.8 mg, 0.1 mmol) were added to
the solution of adamantyl iodide and TBHN. The colorless solution was
charged to a sealed tube and heated in oil bath at 80 °C for 2 h. A 1H NMR
spectrum was taken of the mixture, and the NMR yield was estimated to be
>95%.
Cholest-5-ene (11): TBHN (3.5 mg, 0.02 mmol) was added to a so-
lution of MeBu-Imd-BH3 5 (33 mg, 0.22 mmol) and (3β)-3-bromocholest-
5-ene 10 (0.2 mmol) in benzotrifluoride (0.9 mL). tert-Dodecanethiol
(20.2 mg, 0.1 mmol) was dissolved in benzotrifluoride (1 mL). Dilued tert-
dodecanethiol solution (0.1 M in benzotrifluoride, 100 μL, 0.01 mmol) was
added to the solution of 10 and TBHN. The colorless solution was charged
to a sealed tube and heated in oil bath at 80 °C for 2 h. The mixture was
cooled to room temperature, then the solvent was evaporated and the
crude product was purified by flash column chromatography (100% hex-
anes) to yield 113 as a white solid (62 mg, 83% yield).
O
B
O
26
CH3CN, rt, 1.5 h
28, 74%
Figure 5. Bridging reactions to Suzuki and related chemistry.
In summary, 1-butyl-3-methylimidazol-2-ylidene borane 5
shows promise as a valuable new NHC-borane reagent. Like its
forerunner, 1,3-dimethylimidazol-2-ylidene borane 1, it is readily
available, stable, and engages in an assortment of radical, ionic and
organometallic reactions. In the majority of the reactions tested
here, reagent 5 gave comparable yields to the current standard 1
(the only exception being direct Suzuki reaction of 27).
Being a liquid rather than a solid, 5 is complementary to 1. Es-
pecially on large scale, liquid reagents can be preferred over solids
because they can be transferred by pumping without dissolution.
Further, when dissolution in a reaction solvent is needed, liquids
can often be easier to dissolve. Finally, coming directly from two
common, inexpensive reagents (an imidazolium salt and sodium
borohydride), 5 is now the easiest NHC-borane to prepare.
Experimental Section
General Information
Chemicals were purchased from suppliers and used as received unless
otherwise noted. Toluene and CH2Cl2 were dried by passing through an
activated alumina column. THF was dried by a benzophenone-sodium still.
Reactions were monitored by TLC analysis or 11B NMR spectroscopy.
TLC visualization was accomplished with a 254 mm UV lamp, by staining
with vanillin solution, or by placement in an iodine chamber. Separations
were performed using an automated flash chromatography instrument with
normal phase columns containing 230-400 mesh silica gel. Unless other-
wise noted the experiments were performed under argon in dried glassware.
Phenethyl-4-phenylbutyronitrile
malononitrile (12) (137 mg, 0.5 mmol), MeBu-Imd-BH3 5 (88 mg, 0.60
(13): 2,2-Diphenylethyl-
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 6
mmol), DTBP (15 mg, 0.10 mmol) and t-BuOH (1 mL) were mixed and
23 (106 mg, 0.6 mmol) in dry DCM (2 mL) was added via syringe pump
placed in a pressure‐resistant vial, then the mixture was heated at 120 °C
(bath temperature) for 16 h under argon. The reaction mixture was con-
centrated under reduced pressure. The residue was purified by flash chro-
matography (hexanes : ethyl acetate = 90 : 10) to give product 134 as a
white solid (103 mg, 83% yield).
over a period of 4 h. The color of the solution turned to be orange. After 4
h, the solvent was removed. The mixture was concentrated and purified by
flash chromatography (hexanes : ethyl acetate = 7 : 3) to give the pure
1
2
3
4
5
6
7
8
1
product 24 as a white solid (146 mg, 97% yield). H NMR (CDCl3, 500
MHz) δ 7.28 (dd, J = 1 Hz, 7 Hz, 2 H), 7.14 (td, J = 2 Hz, 6 Hz, 2 H), 7.02
(tt, J = 1.5 Hz, 7.0 Hz, 1 H), 6.81 (d, J = 2 Hz, 1 H), 6.77 (d, J = 2 Hz, 1 H),
3.88-3.78 (m, 2 H), 3.59 (s, 3 H), 3.46 (s, 3 H), 3.24 (br, 1H), 1.65-1.58
(m, 2 H), 1.33-1.25 (m, 2 H), 0.91 (t, J = 7.5 Hz, 3 H); 11B NMR (CDCl3,
160 Hz): –23.2 (t, J = 90.0 Hz); 13C NMR (CDCl3, 100 MHz): 179.8,
145.4, 127.8, 127.6, 123.9, 120.6, 118.8, 50.8, 48.2, 35.6, 32.4, 19.8, 13.6; IR
(film): 2918, 2354, 1703, 1476, 1364 cm-1; HRMS (ESI) calcd for
C32H49O4N4B2 599.3934 [(M+)2 – H], found 599.3942.
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)(cyano)-
dihydroborate (14): Glutaronitrile (94 mg, 1.0 mmol), MeBu-Imd-
BH3 5 (76 mg, 0.50 mmol), DTBP (29 mg, 0.20 mmol) and BTF (2.5 mL)
were mixed and placed in a screw-cap test tube with a stir bar. The cap was
added and the mixture was stirred at 120 °C (bath temperature) for 16 h
under argon. The reaction mixture was concentrated under reduced pres-
sure. The residue was purified by flash chromatography on silica gel (100%
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
ethyl acetate) to give product 14 as a yellow oil (46 mg, 52% yield): H
Bridging reactions to Suzuki chemistry
NMR (CDCl3, 500 MHz) δ 6.93 (s, 2 H), 4.11 (t, J = 7.5 Hz, 2 H), 3.80 (s,
3 H), 1.75 (quart, J = 7.5 Hz, 2 H), 1.34 (tq, J = 7.5, 7.5 Hz, 2 H), 0.93 (t, J
= 7.0 Hz, 3 H); 13C NMR (CDCl3, 125 MHz): 161.8 (br), 134.8 (br),
121.3, 120.0, 48.9, 36.1, 32.3, 19.5, 13.4; 11B NMR (CDCl3, 160 MHz): –
37.7 (t, J = 93.1 Hz); IR (film) 2962, 2391, 2188, 1483, 1379 cm-1; HRMS
(ESI) calcd for C9H17N3B [M+ + H] 178.1510, found 178.1510
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)(phenyl)-
dihydroborate (26): To a stirred solution of aryl trifuoromethanesul-
fonate 25 (0.60 g, 2.0 mmol), MeBu-Imd-BH3 (0.61 g, 2.0 mmol) and 18-
crown-6 ether (1.06 g, 4.0 mmol) in THF (2.0 mL) was added potassium
fluoride (0.23 mg, 4.0 mmol), and the mixture was vigorously stirred at
room temperature for 4 h. The solvent was removed under reduced pres-
sure, and the crude material was purified by silica gel chromatography
(hexanes : ethyl acetate 75 : 25) to give the product 26 as a colorless oil
(0.21 g, 46% yield): 1H NMR (CDCl3, 500 MHz) δ 7.19 (br, 2 H), 7.14 (t,
J = 7.5 Hz, 2 H), 7.02 (t, J = 7.5 Hz, 1 H), 6.88 (d, J = 1.5 Hz, 1 H), 6.85 (d,
J = 2.0 Hz, 1 H), 4.15 (t, J = 7.5 Hz, 2 H), 3.72 (s, 3 H), 2.43 (q, JBH = 83.5
Hz, 2 H), 1.74-1.68 (m, 2 H), 1.32 (dq, J = 7.5, 7.5 Hz, 2 H), 0.91 (t, J = 7.5
Hz); 11B NMR (CDCl3, 160 MHz): –25.2 (t, J = 84.9 Hz); 13C NMR
(CDCl3, 125 MHz): 134.2, 127.1, 123.5, 120.4, 119.0, 48.7, 36.1, 32.6,
19.7, 13.6; IR (film): 3055, 2962, 2304, 1642, 1476 cm-1; HRMS (ESI)
calcd for C14H20N2B [M+ – H] 227.1716, found 227.1714.
Carbonyl reductions
4-Bromobenzyl alcohol (16): To
a
solution of 4-
bromobenzaldehyde 15 (46 mg, 0.25 mmol) in CH2Cl2 (2 mL) were add-
ed MeBu-Imd-BH3 (5) (38 mg, 0.25 mmol) and silica gel (230-400 mesh,
250 mg), and the mixture was stirred at room temperature for 2 h. The
solvent was removed under reduced pressure. The silica gel residue absorb-
ing the crude product was directly placed in a sample loading cartridge, and
an automated flash chromatography was conducted (hexanes : ethyl ace-
tate = 5 : 1), which gave product 16 as a white solid (38 mg, 82% yield).
3-Phenylpropanol (18): To a solution of 3-phenylpropanal 17 (37
mg, 0.25 mmol) in CH2Cl2 (2 mL) were added MeBu-Imd-BH3 (5) (38
mg, 0.25 mmol) and silica gel (230-400 mesh, 250 mg), and the mixture
was stirred at room temperature for 0.5 h. The solvent was removed under
reduced pressure. The silica gel residue absorbing the crude product was
directly placed in a sample loading cartridge, and an automated flash chro-
matography was conducted (hexanes : ethyl acetate = 5 : 1), which gave
product 18 as colorless oil (34 mg, 48% yield).
4-Phenyl-2-butanol (20): To a solution of benzylacetone 19 (74
mg, 0.5 mmol) in CH2Cl2 (2 mL) were added MeBu-Imd-BH3 (5) (76 mg,
0.5 mmol) and silica gel (230-400 mesh, 250 mg), and the mixture was
stirred at room temperature for 5 h. The solvent was removed under re-
duced pressure. The silica gel residue absorbing the crude product was
directly placed in a sample loading cartridge, and an automated flash chro-
matography was conducted (hexanes : ethyl acetate = 5 : 1), which gave
product 20 as colorless oil (34 mg, 48% yield).
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)difluoro-
(phenyl)borate (27): Selectfluor (0.65 g, 2 mmol) was added to a
solution of the MeBu-Imd-BH3 (5) (0.28 g, 1.5 mmol) in acetonitrile (10
mL) under argon at room temperature. After 3 h, the solvent was evapo-
rated. The crude product was purified by flash chromatography (hexanes :
ethyl acetate = 3 : 2) to give product 27 as a colorless oil (152 mg, 63%
yield): 1H NMR (CDCl3, 500 MHz) δ 7.41 (d, J = 7.0 Hz, 2 H), 7.25 (t, J =
7.0 Hz, 2 H), 7.19 (t, J = 7.5 Hz, 1 H), 6.85 (d, J = 1.5 Hz, 1 H), 6.82 (d, J =
2 Hz, 1 H), 4.20 (t, J = 8.0 Hz, 2 H), 3.82 (s, 3.82), 1.71-1.65 (m, 2 H), 1.30
(dq, J = 7.5, 7.5 Hz, 2 H), 0.89 (t, J = 7.5 Hz, 3 H); 13C NMR (CDCl3, 125
MHz): 130.99 (t, J = 3.0 Hz), 127.5, 126.9, 122.0, 120.3, 49.1 (t, JCF = 4.1
Hz), 36.6 (t, JCF = 4.6 Hz), 33.13, 19.72, 13.57; 11B NMR (CDCl3, 160
MHz): 4.63 (br); 19F NMR (CDCl3, 470 MHz): –156.05 (br); IR (film)
3174, 3139, 3005, 2961, 2932, 1433, 1415; HRMS (ESI) calcd for
C14H19N2BF 245.1620 [M+ – F], found 245.1618.
4,4,5,5-Tetramethyl-2-phenyl-1,3,2-dioxaborolane
(28):
Rhodium-catalyzed B–H insertions
To a solution of 26 (56 mg, 0.25 mmol) in CH3CN (5.6 mL) was added 2
M HCl (aq) (320 μL, 0.64 mmol) and pinacol (58 mg, 0.49 mmol). The
reaction mixture was stirred at room temperature. After 1.5 h, solvent was
evaporated. The crude material was purified by flash column chromatog-
raphy (hexanes : ethyl acetate = 5 : 1) to give pinacol boronate ester prod-
uct 28 as a white solid (337 mg, 74% yield).
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)(2-ethoxy-2-
oxoethyl)dihydroborate (22): MeBu-Imd-BH3 (5) (76 mg, 0.5
mmol) and the Rh2(esp)2 (4 mg, 0.005 mmol) were dissolved in dry DCM
(2 mL) under argon. The solution was dark green. The reaction mixture
was heated to reflux. A solution of the ethyl diazoacetate 21 (78 mg, 0.6
mmol) in dry DCM (2 mL) was added via syringe pump over a period of 2
h. The color of the solution turned to be orange. After 2 h, the solvent was
removed. The mixture was concentrated and purified by flash chromatog-
raphy (hexanes : ethyl acetate = 30 : 70) to give the pure product 225 as a
colorless liquid (51 mg, 40% yield). 1H NMR (CDCl3, 500 MHz) δ 6.83 (d,
J = 7.1 Hz, 2 H), 4.08 (t, J = 7.5 Hz, 2 H), 3.91 (q, J = 7 Hz, 2 H), 3.73 (s, 3
H), 1.73 (quint, J = 7.5 Hz, 2 H), 2.39 (br, 2 H), 1.34 (dq, J = 7.0, 7.5 Hz, 2
H) 1.11 (t, J = 7.0 Hz, 3 H), 0.93 (t, J = 7 Hz, 33 H); 11B NMR (CDCl3,
160 MHz): –28.3 (t, J = 89.4 Hz); 13C NMR (CDCl3, 125 MHz): 181.0,
120.4, 118.8, 58.7, 48.4, 35.8, 32.6, 19.8, 14.5, 13.6.
ASSOCIATED CONTENT
Supporting Information
Contains copies of NMR spectra of all reaction products. The Sup-
porting Information is available free of charge on the ACS Publications
website.
Copies of spectra (PDF)
(1-Butyl-3-methyl-1H-imidazol-3-ium-2-yl)(2-methoxy-2-
oxo-1-phenylethyl)dihydroborate (24): MeBu-Imd-BH3 (5) (76
mg, 0.5 mmol) and the Rh2(esp)2 (4 mg, 0.005 mmol) were dissolved in
dry DCM (2 mL) under argon. The solution was dark green. The reaction
mixture was heated to reflux. A solution of the methyl 2-phenyldiazoacetate
AUTHOR INFORMATION
Corresponding Author
* curran@pitt.edu
ACS Paragon Plus Environment

Page 5 of 6
The Journal of Organic Chemistry
Synthesis of Bioactive Heterocycles; Ameta, K. L., Dandia, A., Eds.;
ACKNOWLEDGMENT
We thank the National Science Foundation (CHE-1660927) for fund-
ing this work.
Springer India: 2014, p 201-230; (c) Ionic Liquids in Synthesis;
Wasserscheid, P.; Welton, T., Eds.; Wiley-VCH: Weinheim, 2007.
7. A hypergolic compound ignites spontaneously when a strong oxidant
like white fuming nitric acid is added.
8. Huang, S.; Qi, X.; Liu, T.; Wang, K.; Zhang, W.; Li, J.; Zhang, Q.
Chem. Eur. J. 2016, 22, 10187-10193.
9. Ueng, S.-H.; Fensterbank, L.; Lacôte, E.; Malacria, M.; Curran, D. P.
Org. Lett. 2010, 12, 3002-3005.
10. Pan, X.; Lacôte, E.; Lalevée, J.; Curran, D. P. J. Am. Chem. Soc.
2012, 134, 5669-5675.
11. Horn, M.; Mayr, H.; Lacôte, E.; Merling, E.; Deaner, J.; Wells, S.;
McFadden, T.; Curran, D. P. Org. Lett. 2012, 14, 82-85.
12. (a) Chu, Q.; Makhlouf Brahmi, M.; Solovyev, A.; Ueng, S.-H.;
Curran, D.; Malacria, M.; Fensterbank, L.; Lacôte, E. Chem. Eur. J. 2009,
15, 12937-12940; (b) Lindsay, D. M.; McArthur, D. Chem. Commun.
2010, 46, 2474-2476.
13. Lamm, V.; Pan, X.; Taniguchi, T.; Curran, D. P. Beilstein J. Org.
Chem. 2013, 9, 675-680.
14. Li, X.; Curran, D. P. J. Am. Chem. Soc. 2013, 135, 12076-12081.
15. (a) Valente, C.; Organ, M. G. In Boronic Acids: Preparation and
Applications in Organic Synthesis, Medicine and Materials (Volume 1 and
2), Second Edition; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2011, p 213-
262; (b) Suzuki, A. Heterocycles 2010, 80, 15-43.
1
2
3
4
5
6
7
8
REFERENCES
1. Curran, D. P.; Solovyev, A.; Makhlouf Brahmi, M.; Fensterbank, L.;
Malacria, M.; Lacôte, E. Angew. Chem. Int. Ed. 2011, 50, 10294-10317.
2. Lacôte, E.; Curran, D. P.; Lalevée, J. Chimia 2012, 66, 382-385.
3. (a) Walton, J. C.; Makhlouf Brahmi, M.; Fensterbank, L.; Lacôte, E.;
Malacria, M.; Chu, Q.; Ueng, S.-H.; Solovyev, A.; Curran, D. P. J. Am.
Chem. Soc. 2010, 132, 2350-2358; (b) Bissinger, P.; Braunschweig, H.;
Kupfer, T.; Radacki, K. Organometallics 2010, 29, 3987-3990.
4. (a) Ingleson, M.; McGough, J.; Cid, J. Chem. Eur. J. 2017, 23, 8180-
8184. (b) Ren, S.-C.; Zhang, F.-L.; Qi, J.; Huang, Y.-S.; Xu, A.-Q.; Yan, H.-
Y.; Wang, Y.-F. J. Am. Chem. Soc. 2017, 139, 6050-6053; (c) Wang, M.-
H.; Chen, L.-Y. Tetrahedron Lett. 2017, 58, 732-735; (d) Tambutet, G.;
Guindon, Y. J. Org. Chem. 2016, 81, 11427-11431; (e) Kawamoto, T.;
Geib, S. J.; Curran, D. P. J. Am. Chem. Soc. 2015, 137, 8617-8622; (f)
Taniguchi, T.; Curran, D. P. Angew. Chem. Int. Ed. 2014, 53, 13150-
13154.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5. (a) Gardner, S.; Kawamoto, T.; Curran, D. P. J. Org. Chem. 2015, 80,
9794-9797; (b) Gardner, S.; Kawamoto, T.; Curran, D. P. Org. Synth.
2015, 92, 342-355.
6. (a) Kelley, S. P.; Rogers, R. D. Aldrichimica Acta 2015, 48, e1-e2; (b)
Dake, S. A.; Sarda, S. R.; Marathe, R. P.; Nawale, R. B. In Green Chemistry:
16. Nerkar, S.; Curran, D. P. Org. Lett. 2015, 17, 3394-3397.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 6
TOC GRAPHIC
1
2
Bu
3
4
5
• readily available from inexpensive reagents
BH3 • air-, water-stable; free-flowing liqiud
• undergoes typical radical and ionic reactions
N
N
CH3
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6
ACS Paragon Plus Environment