Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary Amines and Imines

Article abstract of DOI:10.1021/acs.joc.5b00941

Silylative reduction of nitriles was studied under transition metal-free conditions by using B(C₆F₅)₃ as a catalyst with hydrosilanes as a reductant. Alkyl and (hetero)aryl nitriles were efficiently converted to primary amines or imines under mild conditions. The choice of silanes was found to determine the selectivity: while a full reduction of nitriles was highly facile, the use of sterically bulky silanes allowed for the partial reduction leading to N-silylimines.

Full text of DOI:10.1021/acs.joc.5b00941

Note
pubs.acs.org/joc
Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary
Amines and Imines
Narasimhulu Gandhamsetty,†,‡ Jinseong Jeong,‡,† Juhyeon Park,‡,† Sehoon Park,†,‡ and Sukbok Chang*,†,‡
†Center for Catalytic Hydrocarbon Functionalizations, Institute for Basic Science (IBS), Daejeon 305-701, Korea
‡Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Korea
S
* Supporting Information
ABSTRACT: Silylative reduction of nitriles was studied under
transition metal-free conditions by using B(C6F5)3 as a catalyst with
hydrosilanes as a reductant. Alkyl and (hetero)aryl nitriles were
efficiently converted to primary amines or imines under mild
conditions. The choice of silanes was found to determine the
selectivity: while a full reduction of nitriles was highly facile, the use of
sterically bulky silanes allowed for the partial reduction leading to N-
silylimines.
a
Table 1. Optimization of Hydrosilylation of Benzonitrile
rimary amines and amino group-containing multifunc-
Ptional molecules are widely present in natural products,
biologically active synthetic compounds, and functional
materials,1 also serving as a key building unit in numerous
fine chemicals.2 As a result, synthetic approaches toward
primary amines have actively been pursued in organic synthesis.
Although primary amines can be conventionally produced by
Gabriel synthesis3a or reductive amination,3 substrates are
required to be prepared separately for this approach. In this
regard, the reduction of nitriles would be an important process
to give rise to primary amines. The nitrile reduction is
efficiently performed with stoichiometric amounts of metal
hydrides such as those of borane and aluminum.4 Transition
metal-catalyzed hydrosilylation5 or hydrogenation6 is another
approach with the use of Fe, Ti, Re, Co, Rh, Ru, or other
metals. In recent years, tris(pentafluorophenyl)borane [B-
(C6F5)3] and its analogue have been efficiently utilized in
reduction of imines, ketones, olefins, alkynes, ethers, and N-
heteroaromatics by using hydrosilanes7 or hydrogen8 as the
reducing agents. Beller and co-workers reported a tetra-n-
butylammonium fluoride (TBAF)-catalyzed hydrosilylation of
aryl nitriles using reactive silanes under mild conditions.9 More
recently, Stephan et al. showed that electrophilic phosphonium
salts catalyze the hydrosilylation of ketones, imines, and nitriles
at room temperature.10 Recently, we have developed the
silylative reduction of quinolines and conjugated nitriles to
generate a new sp3 C−Si bond beta to the nitrogen atom of
reduced products.11 In this context, we were curious to study
the hydrosilylation of nitriles under the boron-catalyzed
conditions, and reported herein are our results of this study.
We commenced our study by optimizing boron-catalyzed
hydrosilylation of benzonitrile (Table 1). The reduction was
completed in 10 min at room temperature in CDCl3 when 2.5
equiv of diethylsilane was employed in the presence of 1 mol %
of B(C6F5)3 to afford N,N-disilylated benzylamine as
a
entry
changes from the “standard conditions”
yield (%)
1
none
100
100
<1
2
0.5 mol % of B(C6F5)3 instead of 1 mol % (12 h)
no catalyst
3
4
Toluene-d8 instead of CDCl3 (20 min)
CD2Cl2 instead of CDCl3 (20 min)
C6D5Cl (20 min)
100
100
100
90
5
6
7
Ph2SiH2 (2.5 equiv) instead of Et2SiH2 (12 h)
PhMe2SiH (3 equiv) instead of Et2SiH2 (12 h)
Et3SiH (3 equiv) instead of Et2SiH2 (12 h)
iPr3SiH (3 equiv) instead of Et2SiH2 (12 h)
(EtO)3SiH (3 equiv) instead of Et2SiH2 (12 h)
8
100
21
9
10
11
<1
<1
a
Reactions were carried out in 0.5 mmol scale in a J. Young NMR tube
and yields were determined by H NMR (1,1,2,2-tetrachloroethane:
internal standard).
1
crude reaction mixture with 1 M HCl in ether afforded the
product as hydrochloride salt (1) that can be easily obtained by
filtration. The reduction was still smooth with lower loading of
borane catalyst (entry 2) or in some other solvents as well
(entries 4−6). The reaction did not proceed without catalyst
(entry 3). However, the efficiency of this hydrosilylation was
critically varied depending on the type of silanes employed
(entries 7−9). Notably, triisopropylsilane and triethoxysilane
were totally ineffective for this reaction (entries 10 and 11,
respectively).
With the optimal conditions in hand, we investigated the
scope of aryl nitriles (Table 2). Benzonitrile derivatives bearing
Received: April 27, 2015
1
determined by H NMR analysis (entry 1). Hydrolysis of the
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b00941
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
a
Table 2. Silylative Reduction of (Hetero)aryl Nitriles to Primary Amines
a
Nitrile (0.5 mmol), silane (2.5 equiv), and B(C6F5)3 (1 mol %, 1−15; and 3 mol %, 16−19) in CDCl3 (0.5 mL) at 25 °C under argon atmosphere:
b
c
d
e
f
g
h
isolated yields. PhMe2SiH (2.0 equiv) was used. At 30 °C. Reactions were carried out in 5 mmol scale. 3 mol % B(C6F5)3. At 85 °C. 65 °C. 5
Equiv of Et2SiH2 was used in reaction vial.
a
Table 3. Silylative Reduction of Alkyl Nitriles to Primary Amines
a
b
Nitrile (0.5 mmol), silane (2.5 equiv), and B(C6F5)3 (3 mol %) in CDCl3 (0.5 mL) at 25 °C under argon atmosphere: isolated yields. Reactions
c
d
e
f
were carried out in 5 mmol scale. PhMe2SiH (2.0 equiv) was used. 2 Equiv of Et2SiH2 used. Ph2SiH2 (2.5 equiv). 5 Equiv of Et2SiH2 and 6 mol %
boron were used, at 85 °C.
substituents at the 4-position such as 4-ethyl and 4-phenyl were
quantitatively reduced with diethylsilane to the corresponding
benzylamines (2−3). Benzonitrile substituted at the 2-position
smoothly underwent the hydrosilylation albeit at a longer
reaction time (4). Importantly, an ether bond was compatible
with the present conditions as evidenced by the successful
reduction of methoxy-, phenoxy-, and silyloxy-substituted
benzonitriles (5, 6, and 7, respectively).12 However, the
silylative reduction of substrates bearing the dialkyl ether or
ester functional groups was not compatible to the present
conditions, and failed to give the desired products. High
functional group tolerance was additionally demonstrated in the
reduction of substrates having such diverse groups as halide,
nitro, and trifluoromethyl (8−13). It should be mentioned that
the hydrosilylation was scalable as proven by a successful gram
scale reaction run in a flask in CHCl3 (8). Again, the position of
B
DOI: 10.1021/acs.joc.5b00941
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The Journal of Organic Chemistry
Note
substituents was not critical to the reaction efficiency (12−13).
However, the reaction of 4-nitrobenzonitrile was rather sluggish
to require more demanding conditions (85 °C for 10 min) to
obtain satisfactory product yield (10, 82%). 4-
(Trifluoromethyl)benzonitrile was also hydrosilylated rather
slowly (12 h) to give 80% product yield (11). 2-
Cyanonaphthalene was readily reduced under the optimized
conditions (10 min at 25 °C) in good yield (14).
equiv), benzonitrile and its derivatives were converted to N-
silylimines in excellent yields determined by H NMR analysis
of the crude reaction mixture (Table 4, 32−34). Functional
1
Table 4. Selective Hydrosilylation of Nitriles to Imines
2,4-Dimethylbenzonitrile was converted to the desired
product in good yield (15) and the hydrosilylation of 1,3-
dicyanobenzene was also efficient leading to a diamine product
(HCl salt, 16) with the use of 5 equiv of diethylsilane. Nitriles
of heterocycles such as pyrrole, thiophene, or indole were
smoothly reduced to the corresponding primary amines in
good yields (17−19).13a In particular, 5 mmol scale reaction of
2-cyano-1,5-dimethylpyrrole was also efficient to afford 17
(HCl salt) that was next converted to its tosylate (17a) for the
convenience of isolation. The fact that no reaction was detected
at the heterocyclic rings was noteworthy, considering that
quinoline was readily reduced under the same conditions as
shown in our previous study.11a
We were pleased to further observe that the borane-catalyzed
silylative reduction procedure was readily extended to more
challenging alkyl nitriles (Table 3). Although slightly higher
loading of B(C6F5)3 catalyst (3 mol %) was applied, the
reduction took place smoothly still at room temperature in 10
min to 12 h to give excellent product yields. Acetonitrile
derivatives monosubstituted with phenyl or 1-naphthyl groups
were reacted in high efficiency even on gram scale (20 and 21,
respectively). α,α-Disubstituted acetonitriles were also reactive
in reduction to give the desired β,β-disubstituted primary
alkylamines in quantitative yields (22−23). Reaction of a
sterically more demanding substrate such as pivalonitrile took
place smoothly (24). In addition, caprylonitrile and cyanocy-
clohexane underwent the reduction in high yields even in large
scale (25 and 26, respectively).
Functional group tolerance was maintained high as evidenced
by some representative substrates. For instance, chloro
substituent and isolated double bond were completely
compatible with the present conditions (27 and 28,
respectively).14 In addition, an alkynyl group was tolerated,
and substrates containing either aliphatic or aryl triple bonds15
were reduced highly selectively to afford primary amines
without reacting at the labile acetylenic moiety (29−30) when
diphenylsilane was used in the latter case. Hydrosilylation of
industrially important adipodinitrile proceeded successfully at
85 °C to give hexane-1,6-diamine dihydrochloride in good yield
(92%, 31).
group tolerance was briefly examined by the successful partial
reduction of benzonitriles containing bromo, alkoxy, and
acetylenic groups (35−37). Although reported herein are
crude product yields since N-silylimines were unstable to purify
by column chromatography, purity of the crude products was
high (>95%) indicating that the partial reduction was clean and
highly selective.16
In summary, we have developed the facile B(C6F5)3-catalyzed
hydrosilylation of nitriles to afford primary amines and N-
silylimines depending on the type of silanes employed. The
reaction was highly mild, efficient, and scalable enabling a
convenient synthetic tool to access amines and imines starting
from readily available nitriles including both (hetero)aryl and
alkyl derivatives.
EXPERIMENTAL SECTION
■
General Methods. All solvent, nitriles, silanes, and reagents were
directly used as purchased without further purification unless
otherwise stated. Analytical thin layer chromatography (TLC) was
performed on precoated silica gel 60 F254 plates. Visualization on
TLC was achieved by the use of UV light (254 nm), exposure to
treatment with acidic anisaldehyde, phosphomolybdic acid, ninhydrin,
or ceric ammonium molydate stain followed by heating. Chemical
shifts were quoted in parts per million (ppm) referenced to the
appropriate solvent peak. 13C{1H} NMR was recorded after broad
band proton decoupling. Infrared (IR) spectra of new products are
given in wave numbers (cm−1), and only selected peaks are reported.
General Procedure of the B(C6F5)3-Catalyzed Reduction of
Nitriles to Primary Amines (Tables 2 and 3). Silane (2.5 equiv)
was added to a solution of B(C6F5)3 (1.0 mol % for aryl nitriles and 3.0
mol % for heteroaryl and aliphatic nitriles) in CDCl3 (0.5 mL) in a J.
Young NMR tube under argon atmosphere, and the solution was
shaken briefly and nitrile (0.50 mmol) [for solids, dissolved in CDCl3]
was then added and the reaction mixture was continued at required
temperature for 10 min ∼12 h. After indicated time, volatiles were
removed by reduced pressure and 1 M HCl solution in ether (3 mL)
was added, stirred it for 1 h at room temperature to give the desired
primary amines as HCl salts as white solid upon filtration washing with
ether.
As shown above, the present hydrosilylation procedure was
convenient to carry out in large scale, and a reaction of
benzonitrile (20 mmol) was performed successfully using 0.5
mol % of B(C6F5)3 to give benzylamine as HCl salt in 92%
yield (1, 2.63 g, TON ∼200) at 25 °C in chloroform (eq 1).
Phenylmethanamine Hydrochloride (Table 2, 1).13a Colorless
1
solid (70 mg, 98%); H NMR (600 MHz, DMSO-d6) δ 8.70 (s, 3H),
7.51 (d, J = 7.3 Hz, 2H), 7.40−7.31 (m, 3H), 3.97 (s, 2H); 13C NMR
(150 MHz, DMSO-d6) δ 134.5, 129.4 (2C), 128.9 (2C), 128.7, 42.5;
HRMS (FAB-TOF): Calculated for C7H10N [M-Cl]+: 108.0813,
Found: 108.0810.
During the course of our study on the silylative reaction of
nitriles, a partial reduction was observed to occur highly
selectively when 1 equiv of bulky trialkylsilanes was employed
as a reducing reagent. In fact, with the use of triethylsilane (1
C
DOI: 10.1021/acs.joc.5b00941
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Note
(4-Ethylphenyl)methanamine Hydrochloride (Table 2, 2).17
Colorless solid (84.6 mg, 99%); H NMR (600 MHz, DMSO-d6) δ
(FAB-TOF): Calculated for C8H9NF3 [M-Cl]+: 176.0687, Found:
176.0689.
1
8.66 (s, 3H), 7.42 (d, J = 7.7 Hz, 2H), 7.19 (d, J = 7.7 Hz, 2H), 3.92
(s, 2H), 2.56 (q, J = 7.6 Hz, 2H), 1.13 (t, J = 7.6 Hz, 3H); 13C NMR
(150 MHz, DMSO-d6) δ 144.4, 131.8, 129.5 (2C), 128.2 (2C), 42.3,
28.3, 16.1; HRMS (FAB-TOF): Calculated for C9H14N [M-Cl]+:
136.1126, Found: 136.1128.
(2-Chlorophenyl)methanamine Hydrochloride (Table 2, 12).
Colorless solid (78 mg, 88%); mp 222−224 °C; 1H NMR (400 MHz,
DMSO-d6) δ 8.81 (s, 3H), 7.81−7.63 (m, 1H), 7.58−7.47 (m, 1H),
7.46−7.30 (m, 2H), 4.10 (d, J = 8.3 Hz, 2H); 13C NMR (100 MHz,
DMSO-d6) δ 133.3, 132.1, 131.1, 130.7, 129.8, 127.9, 40.0; IR (cm−1):
2892, 1598, 1535, 1438, 1381, 1205, 1050, 890, 746; HRMS (FAB-
TOF): Calculated for C7H9ClN [M-Cl]+: 142.0424, Found: 142.0425.
(3-Chlorophenyl)methanamine Hydrochloride (Table 2, 13).
[1,1′-Biphenyl]-4-ylmethanamine Hydrochloride (Table 2,
3).13a Colorless solid (108.4 mg, 99%); 1H NMR (600 MHz, DMSO-
d6) δ 8.75 (s, 3H), 7.75−7.55 (m, 6H), 7.44 (t, J = 7.6 Hz, 2H), 7.35
(t, J = 7.4 Hz, 1H), 4.03 (s, 2H); 13C NMR (150 MHz, DMSO-d6) δ
140.5, 139.9, 133.7, 130.1 (2C), 129.4 (2C), 128.1, 127.1 (2C), 127.1
(2C), 42.2; HRMS (FAB-TOF): Calculated for C13H14N [M-Cl]+:
184.1126, Found: 184.1125.
1
Colorless solid (86.7 mg, 98%); mp 307−309 °C; H NMR (600
MHz, DMSO-d6) δ 8.72 (s, 3H), 7.65 (s, 1H), 7.59−7.25 (m, 3H),
4.00 (s, 2H); 13C NMR (150 MHz, DMSO-d6) δ 136.9, 133.4, 130.7,
129.4, 128.6, 128.2, 41.9; IR (cm−1): 2960, 2903, 1598, 1576, 1458,
1216, 1111, 1083, 969, 788; HRMS (FAB-TOF): Calculated for
C7H9ClN [M-Cl]+: 142.0424, Found: 142.0422.
o-Tolylmethanamine Hydrochloride (Table 2, 4).18 Colorless
solid (69.1 mg, 88%); 1H NMR (400 MHz, DMSO-d6) δ 8.58 (s, 3H),
7.43 (d, J = 7.2 Hz, 1H), 7.30−7.16 (m, 3H), 3.98 (s, 2H), 2.35 (s,
3H); 13C NMR (100 MHz, DMSO-d6) δ 137.1, 132.8, 130.7, 129.7,
128.9, 126.5, 39.9, 19.3; HRMS (FAB-TOF): Calculated for C8H12N
[M-Cl]+: 122.0970, Found: 122.0970.
Naphthalen-2-ylmethanamine Hydrochloride (Table 2,
14).4d Colorless solid (88.8 mg, 92%); 1H NMR (400 MHz,
DMSO-d6) δ 8.73 (s, 3H), 8.10−7.81 (m, 4H), 7.77−7.63 (m, 1H),
7.62−7.43 (m, 2H), 4.18 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ
133.0, 132.2, 128.6, 128.4, 128.2, 128.1, 127.1 (2C), 127.0, 127.0
(2C); HRMS (FAB-TOF): Calculated for C11H12N [M-Cl]+:
158.0970, Found: 158.0969.
(4-Methoxyphenyl)methanamine Hydrochloride (Table 2,
5).13a Colorless solid (78.7 mg, 91%); H NMR (600 MHz, DMSO-
1
d6) δ 8.59 (s, 3H), 7.43 (d, J = 8.2 Hz, 2H), 6.91 (d, J = 8.3 Hz, 2H),
3.88 (d, J = 5.8 Hz, 2H), 3.71 (s, 3H); 13C NMR (150 MHz, DMSO-
d6) δ 159.7, 131.0 (2C), 126.4, 114.3 (2C), 55.6, 42.0; HRMS (FAB-
TOF): Calculated for C8H12NO [M-Cl]+: 138.0919, Found: 138.0917.
(4-Phenoxyphenyl)methanamine Hydrochloride (Table 2,
(2,4-Dimethylphenyl)methanamine Hydrochloride (Table 2,
15).20 Colorless solid (83.8 mg, 98%); mp 215−216 °C; H NMR
1
(600 MHz, DMSO-d6) δ 8.57 (s, 3H), 7.30 (d, J = 7.8 Hz, 1H), 7.01
(s, 1H), 7.00 (d, J = 8.5 Hz, 1H), 3.90 (s, 2H), 2.30 (s, 3H), 2.24 (s,
3H); 13C NMR (150 MHz, DMSO-d6) δ 138.1, 136.9, 131.3, 129.8,
129.7, 126.9, 39.6, 21.1, 19.2.
1
6). Colorless solid (96.3 mg, 82%); mp 251−253 °C; H NMR (400
MHz, DMSO-d6) δ 8.59 (s, 3H), 7.54 (d, J = 8.6 Hz, 2H), 7.47−7.31
(m, 2H), 7.23−7.09 (m, 1H), 7.08−6.87 (m, 4H), 4.09−3.88 (m, 2H);
13C NMR (100 MHz, DMSO-d6) δ 157.3, 156.8, 131.5 (2C), 130.6
(2C), 129.6, 124.2, 119.2 (2C), 118.9 (2C), 42.0; IR (cm−1): 2950,
2875, 1588, 1507, 1487, 1250, 1171, 964, 872, 689; HRMS (FAB-
TOF): Calculated for C13H14NO [M-Cl]+: 200.1075, Found:
200.1074.
1,3-Phenylenedimethanamine Dihydrochloride (Table 2,
16).21 Colorless solid (102 mg, 98%); 1H NMR (600 MHz,
DMSO-d6) δ 8.73 (s, 6H), 7.66−7.46 (m, 3H), 7.41 (s, 1H), 3.95
(s, 4H); 13C NMR (150 MHz, DMSO-d6) δ 134.7 (2C), 130.2, 129.2,
129.1 (2C), 42.4 (2C).
(1,5-Dimethyl-1H-pyrrol-2-yl)methanamine Hydrochloride
1
(Table 2, 17). Brown solid; mp 203−205 °C; H NMR (400 MHz,
[4-(Triisopropylsilyloxy)phenyl]methanamine (Table 2, 7).
The general procedure was applied and the product was isolated by
flash column chromatography on silica gel (ethyl acetate/n-hexane,
3:7): colorless liquid (126.4 mg, 94%); 1H NMR (600 MHz, CDCl3) δ
7.13 (d, J = 9.0 Hz, 2H), 6.83 (d, J = 6.5 Hz, 2H), 3.76 (s, 2H), 2.02−
1.70 (m, 2H), 1.29−1.20 (m, 3H), 1.09 (d, J = 7.6 Hz, 18H); 13C
NMR (150 MHz, CDCl3) δ 154.9, 135.6, 128.1 (2C), 119.8 (2C),
45.9, 17.9 (6C), 12.6 (3C); 29Si NMR (120 MHz, CDCl3) δ 14.9; IR
(cm−1): 3331, 3228, 2943, 2865, 1669, 1607, 1508, 1460, 1261, 1167,
1071, 911, 672; HRMS (ESI-TOF): Calculated for C16H29NOSiNa
[M + Na]+: 302.1916, Found: 302.1890.
DMSO-d6) δ 8.41 (s, 3H), 6.18−5.90 (d, J = 2.8 Hz, 1H), 5.75 (d, J =
3.5 Hz, 1H), 3.95 (d, J = 5.6 Hz, 2H), 3.48 (s, 3H), 2.16 (s, 3H); 13C
NMR (100 MHz, DMSO-d6) δ 130.2, 124.3, 109.4, 105.9, 34.4, 30.8,
12.7; IR (cm−1): 2972, 1603, 1466, 1412, 1385, 1315, 1109, 1079, 990,
754.
N-[(1,5-Dimethyl-1H-pyrrol-2-yl)methyl]-4-methylbenzene-
sulfonamide (Table 2, 17a). To a flame-dried 50 mL round-bottom
flask were added B(C6F5)3 (77 mg, 0.3 mmol, 3 mol %), diethylsilane
(1.62 mL, 12.5 mmol, 2.5 equiv), and chloroform (5 mL) under argon
atmosphere. Benzonitrile (0.60 g, 5 mmol) was then added and the
reaction mixture was stirred at room temperature for 6 h. After
removing volatiles by rotary evaporator, 1 M HCl solution in ether (30
mL) was added and the reaction mixture stirred for 1 h at room
temperature to form the desired product 17 (HCl salt) as brown solid.
To a flame-dried round-bottom flask were added 17/HCl (5 mmol)
and dichloromethane (25 mL). After the dropwise addition of
triethylamine (2.1 mL, 15 mmol) at 0 °C, it was stirred for 15 min at 0
°C. p-Toluenesulfonyl chloride (1.14 g, 6 mmol) was added and the
reaction mixture was stirred at room temperature for 12 h. Water was
added and the reaction mixture was extracted with dichloromethane
(15 mL × 3). The combined organic layers were dried over Na2SO4,
evaporated under reduced pressure, and purified by flash column
chromatography on silica gel (ethyl acetate/n-hexane, 3:7) to afford
the corresponding product 17a (1.08 g, 78% over two steps): Brown
(4-Bromophenyl)methanamine Hydrochloride (Table 2,
8).13a Colorless solid (1.08 g/5 mmol, 98%); H NMR (600 MHz,
1
DMSO-d6) δ 8.70 (s, 3H), 7.57 (d, J = 8.1 Hz, 2H), 7.48 (d, J = 8.1
Hz, 2H), 3.96 (s, 2H); 13C NMR (150 MHz, DMSO-d6) δ 133.9,
131.8 (2C), 131.7 (2C), 122.1, 41.8; HRMS (FAB-TOF): Calculated
for C7H9BrN [M-Cl]+: 185.9918, Found: 185.9921.
(4-Iodophenyl)methanamine Hydrochloride (Table 2, 9).19
1
Colorless solid (126.4 mg, 94%); H NMR (400 MHz, DMSO-d6) δ
8.69 (s, 3H), 7.76 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3 Hz, 2H), 3.96
(s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 137.7 (2C), 134.3, 131.8
(2C), 95.3, 42.0.
(4-Nitrophenyl)methanamine Hydrochloride (Table 2, 10).4c
Brown solid (77.1 mg, 82%); 1H NMR (400 MHz, DMSO-d6) δ 8.81
(s, 3H), 8.27 (d, J = 8.5 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 4.17 (d, J =
5.7 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 147.8, 142.2, 130.7
(2C), 123.9 (2C), 41.8; HRMS (FAB-TOF): Calculated for
C7H9N2O2 [M-Cl]+: 153.0664, Found: 153.0660.
1
solid (1.08 g/5 mmol, 78%); mp 107−108 °C; H NMR (600 MHz,
CDCl3) δ 7.74 (d, J = 8.2 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 5.83 (d, J
= 3.4 Hz, 1H), 5.73 (d, J = 3.3 Hz 1H), 4.45 (t, J = 5.8 Hz, 1H), 4.03
(d, J = 5.8 Hz, 2H), 3.42 (s, 3H), 2.45 (s, 3H), 2.16 (s, 3H); 13C NMR
(150 MHz, CDCl3) δ 143.5, 136.5, 130.8 (2C), 129.7, 127.1 (2C),
125.1, 108.2, 105.3, 39.9, 30.3, 21.5, 12.3; IR (cm−1): 3270, 2924,
1685, 1584, 1511, 1433, 1324, 1305, 1157, 1091, 1034, 832, 667;
HRMS (ESI-TOF): Calculated for C14H18N2NaO2S [M + Na]+:
301.0987, Found: 301.0983.
[4-(Trifluoromethyl)phenyl]methanamine Hydrochloride
(Table 2, 11).13a Colorless solid (84.4 mg, 80%); H NMR (400
1
MHz, DMSO-d6) δ 8.68 (s, 3H), 7.80 (d, J = 8.2 Hz, 2H), 7.75 (d, J =
8.2 Hz, 2H), 4.12 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 139.3,
130.3 (2C), 129.3 (q, J = 32 Hz), 125.7 (q, J = 3.8 Hz, 2C), 124.6 (q, J
= 272.7 Hz), 42.0; 19F NMR (376 MHz, DMSO-d6) δ −61.5; HRMS
D
DOI: 10.1021/acs.joc.5b00941
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The Journal of Organic Chemistry
Note
Thiophen-2-ylmethanamine Hydrochloride (Table 2, 18).
White solid (60.3 mg, 81%); mp 292−294 °C; H NMR (400 MHz,
Hex-5-yn-1-amine Hydrochloride (Table 3, 29).26 Brown solid
(64 mg, 96%); H NMR (600 MHz, DMSO-d6) δ 8.19 (s, 3H), 2.78
1
1
(s, 1H), 2.72 (q, J = 6.7 Hz, 2H), 2.21−2.08 (m, 2H), 1.68−1.56 (m,
2H), 1.53−1.39 (m, 2H); 13C NMR (150 MHz, DMSO-d6) δ 84.4,
71.9, 38.6, 26.5, 25.3, 17.7; HRMS (FAB-TOF): Calculated for
C6H12N [M-Cl]+: 98.0970, Found: 98.0971.
DMSO-d6) δ 8.71 (s, 3H), 7.56 (dd, J = 5.1, 1.3 Hz, 1H), 7.30 (dd, J =
3.4, 1.3 Hz, 1H), 7.06 (dd, J = 5.1, 3.5 Hz, 1H), 4.20 (s, 2H); 13C
NMR (100 MHz, DMSO-d6) δ 135.8, 129.6, 127.7 (2C), 37.0; IR
(cm−1): 3339, 3082, 2910, 1617, 1589, 1508, 1275, 1241, 958, 719;
HRMS (FAB-TOF): Calculated for C5H8NS [M-Cl]+: 114.0377,
Found: 114.0378.
(4-Ethynylphenyl)methanamine Hydrochloride (Table 3,
30).27 Brown solid (74.3 mg, 89%); H NMR (400 MHz, DMSO-
1
(1H-Indol-5-yl)methanamine Hydrochloride (Table 2, 19).22
Brown solid (80.1 mg, 88%); 1H NMR (400 MHz, DMSO-d6) δ 11.31
(s, 1H), 8.44 (s, 3H), 7.65 (s, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.37 (t, J
= 2.8 Hz, 1H), 7.21 (dd, J = 8.4, 1.7 Hz, 1H), 6.45−6.41 (m, 1H), 4.03
(q, J = 5.8 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ 136.1, 128.0,
126.7, 124.7, 122.5, 121.4, 111.9, 101.5, 43.4; HRMS (FAB-TOF):
Calculated for C9H11N2 [M-Cl]+: 147.0922, Found: 147.0925.
2-Phenylethan-1-amine Hydrochloride (Table 3, 20).13
d6) δ 8.70 (s, 3H), 7.54 (d, J = 8.4 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H),
4.27 (s, 1H), 4.01 (s, 2H); 13C NMR (100 MHz, DMSO-d6) δ 135.4,
132.2 (2C), 129.7 (2C), 122.1, 83.5, 81.8, 42.2; HRMS (FAB-TOF):
Calculated for C9H10N [M-Cl]+: 132.0813, Found: 132.0813.
Hexane-1,6-diamine Dihydrochloride (Table 3, 31).13a Color-
less solid (86.5 mg, 92%); 1H NMR (600 MHz, DMSO-d6) δ 8.20 (s,
6H), 2.69 (q, J = 7.2, 6.7 Hz, 4H), 1.63−1.40 (m, 4H), 1.27 (t, J = 5.5
Hz, 4H); 13C NMR (150 MHz, DMSO-d6) δ 38.9, 27.1, 25.8.
Synthetic Applications (eq 1): Gram Scale Reduction of
Benzonitrile. To a flame-dried 50 mL round-bottom flask were added
1
Colorless solid (77 mg, 98%); H NMR (600 MHz, DMSO-d6) δ
8.37 (s, 3H), 7.54−6.90 (m, 5H), 3.20−2.60 (m, 4H); 13C NMR (150
MHz, DMSO-d6) δ 137.9, 129.0 (4C), 127.1, 40.3, 33.3; HRMS (FAB-
TOF): Calculated for C8H12N [M-Cl]+: 122.0970, Found: 122.0967.
2-(Naphthalen-1-yl)ethan-1-amine Hydrochloride (Table 3,
21).23 Colorless solid (1.01 g/5 mmol, 98%); H NMR (400 MHz,
1
DMSO-d6) δ 8.39 (s, 3H), 8.21 (dd, J = 8.5, 1.2 Hz, 1H), 7.95 (dd, J =
8.3, 1.3 Hz, 1H), 7.84 (dd, J = 7.6, 1.9 Hz, 1H), 7.62−7.51 (m, 2H),
7.49−7.41 (m, 2H), 3.49−3.38 (m, 2H), 3.12−3.04 (m, 2H); 13C
NMR (100 MHz, DMSO-d6) δ 134.0, 133.9, 131.8, 129.2, 127.9,
127.4, 126.8, 126.3, 126.1, 124.0, 40.0, 30.6; HRMS (FAB-TOF):
Calculated for C12H14N [M-Cl]+: 172.1126, Found: 172.1128.
2-Methylpropan-1-amine Hydrochloride (Table 3, 22).24
B(C6F5)3 (51 mg, 0.5 mol %), diethylsilane (6.5 mL, 2.5 equiv), and
chloroform (20 mL) under argon atmosphere. Benzonitrile (2.06 g, 20
mmol) was then added and the reaction mixture was stirred at room
temperature for 12 h. Volatiles were removed by reduced pressure and
1 M HCl solution in ether (120 mL) was added, and the mixture
stirred for 1 h at room temperature to give the desired primary amine
as HCl salt form as a white solid (1, 92%, 2.63 g) upon filtration
washing with ether.
1
Colorless solid (53.4 mg, 98%); H NMR (600 MHz, DMSO-d6) δ
8.17 (s, 3H), 2.55 (d, J = 7.0 Hz, 2H), 1.93−1.80 (m, 1H), 0.88 (d, J =
6.8 Hz, 6H); 13C NMR (150 MHz, DMSO-d6) δ 46.1, 26.7, 20.3
(2C); HRMS (FAB-TOF): Calculated for C4H12N [M-Cl]+: 74.0970,
Found: 74.0971.
B(C6F5)3-Catalyzed Silylative Reduction of Nitriles to Imines
(Table 4). Triethylsilane (1.0 equiv) was added to a solution of
B(C6F5)3 (3.0 mol %) in CDCl3 (0.5 mL) in a J. Young NMR tube,
and the solution was shaken briefly followed by the addition of the
corresponding nitrile (0.5 mmol) and dibromomethane (0.5 equiv:
internal standard) under argon atmosphere. After 1 h, the reaction
mixture was subjected to 1H NMR spectroscopy and crude NMR
yields were measured on the basis of an internal standard.
2,2-Diphenylethan-1-amine Hydrochloride (Table 3, 23).18
1
Colorless solid (108.3 mg, 93%); H NMR (600 MHz, DMSO-d6) δ
8.28 (s, 3H), 7.62−6.81 (m, 10H), 4.42 (s, 1H), 3.49 (s, 2H); 13C
NMR (150 MHz, DMSO-d6) δ 141.6 (2C), 129.2 (4C), 128.3 (4C),
127.4 (2C), 48.8, 42.8; HRMS (FAB-TOF): Calculated for C14H16N
[M-Cl]+: 198.1283, Found: 198.1280.
1-Phenyl-N-(triethylsilyl)methanimine (Table 4, 32).28 1H
NMR (600 MHz, CDCl3) δ 9.09 (s, 1H), 7.93−7.78 (m, 2H), 7.50−
7.43 (m, 3H), 1.05 (t, J = 8.0 Hz, 9H), 0.81 (q, J = 7.9 Hz, 6H); 13C
NMR (150 MHz, CDCl3) δ 168.7, 139.1, 131.1, 128.5 (2C), 128.4
(2C), 7.0 (3C), 3.6 (3C).
2,2-Dimethylpropan-1-amine Hydrochloride (Table 3, 24).18
1
Colorless solid (59.6 mg, 97%); H NMR (600 MHz, DMSO-d6) δ
8.17 (s, 3H), 2.54 (s, 2H), 0.92 (s, 9H); 13C NMR (150 MHz, DMSO-
d6) δ 50.1, 30.6, 27.4 (3C); HRMS (FAB-TOF): Calculated for
C5H14N [M-Cl]+: 88.1126, Found: 88.1125.
n-Octan-1-amine Hydrochloride (Table 3, 25).24 Colorless
solid (81.7 mg, 99%); 1H NMR (600 MHz, DMSO-d6) δ 8.17 (s, 3H),
2.79−2.57 (m, 2H), 1.53 (t, J = 7.5 Hz, 2H), 1.37−1.05 (m, 10H),
0.82 (t, J = 6.7 Hz, 3H); 13C NMR (150 MHz, DMSO-d6) δ 39.1,
31.6, 28.9, 28.9, 27.3, 26.4, 22.5, 14.3; HRMS (FAB-TOF): Calculated
for C8H20N [M-Cl]+: 130.1596, Found: 130.1595.
1-(4-Ethylphenyl)-N-(triethylsilyl)methanimine (Table 4, 33).
1H NMR (600 MHz, CDCl3) δ 9.06 (s, 1H), 7.77 (d, J = 8.0 Hz, 2H),
7.29 (d, J = 7.8 Hz, 2H), 2.71 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.7 Hz,
3H), 1.04 (t, J = 8.0 Hz, 9H), 0.80 (q, J = 7.9 Hz, 6H); 13C NMR (150
MHz, CDCl3) δ 168.7, 147.8, 137.0, 128.5 (2C), 128.0 (2C), 28.9,
15.5, 7.0 (3C), 3.7 (3C).
Cyclohexylmethanamine Hydrochloride (Table 3, 26).13a
Colorless solid (0.71 g/5 mmol, 95%); 1H NMR (600 MHz,
DMSO-d6) δ 8.19 (s, 3H), 2.56 (s, 2H), 1.87−1.34 (m, 6H), 1.11
(m, 3H), 0.87 (q, J = 12.1, 11.6 Hz, 2H); 13C NMR (150 MHz,
DMSO-d6) δ 44.8, 35.7, 30.3 (2C), 26.1, 25.5 (2C); HRMS (FAB-
TOF): Calculated for C7H16N [M-Cl]+: 114.1283, Found: 114.1284.
4-Chlorobutylamine Hydrochloride (Table 3, 27).25 Colorless
solid (68 mg, 95%); 1H NMR (600 MHz, CDCl3) δ 8.11 (s, 3H), 3.57
(t, J = 5.4 Hz, 2H), 3.22−2.86 (m, 2H), 2.06−1.75 (m, 4H); 13C NMR
(150 MHz, CDCl3) δ 44.3, 39.5, 29.4, 24.9.
1-[(1,1′-Biphenyl)-4-yl]-N-(triethylsilyl)methanimine (Table
1
4, 34). H NMR (600 MHz, CDCl3) δ 9.19 (s, 1H), 7.97 (d, J =
8.1 Hz, 2H), 7.74 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 7.6 Hz, 2H), 7.54−
7.50 (m, 2H), 7.44 (t, J = 7.4 Hz, 1H), 1.13 (t, J = 8.0 Hz, 9H), 0.89
(q, J = 8.0 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 168.4, 144.0,
140.6, 138.1, 128.9 (2C), 128.9 (2C), 127.8, 127.3 (2C), 127.3 (2C),
7.1 (3C), 3.8 (3C).
1-(4-Bromophenyl)-N-(triethylsilyl)methanimine (Table 4,
1
35). H NMR (600 MHz, CDCl3) δ 8.99 (s, 1H), 7.68 (d, J = 8.2
Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H), 1.02 (t, J = 8.0 Hz, 9H), 0.77 (q, J =
8.0 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 167.1, 137.8, 131.7
(2C), 129.7 (2C), 125.7, 7.0 (3C), 3.6 (3C).
1-(4-Methoxyphenyl)-N-(triethylsilyl)methanimine (Table 4,
36). 1H NMR (600 MHz, CDCl3) δ 9.00 (s, 1H), 7.78 (d, J = 8.6 Hz,
2H), 6.95 (d, J = 8.6 Hz, 2H), 3.84 (s, 3H), 1.03 (t, J = 8.1 Hz, 9H),
0.77 (q, J = 8.0 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 167.9, 162.1,
132.5, 130.0 (2C), 113.8 (2C), 55.3, 7.0 (3C), 3.7 (3C).
2-(Cyclopent-1-en-1-yl)ethan-1-amine Hydrochloride (Table
3, 28). Brown solid (63.2 mg, 86%); mp 220−222 °C: 1H NMR (600
MHz, DMSO-d6) δ 8.22 (s, 3H), 5.40 (s, 1H), 2.83 (d, J = 11.3 Hz,
2H), 2.46−2.28 (m, 2H), 2.29−2.08 (m, 4H), 1.94−1.60 (m, 2H); 13C
NMR (150 MHz, DMSO-d6) δ 140.2, 125.6, 37.5, 35.0, 32.5, 28.9,
23.1; IR (cm−1): 3299, 2954, 1595, 1477, 1336, 1217, 1075, 1009, 837;
HRMS (FAB-TOF): Calculated for C7H14N [M-Cl]+: 112.1126,
Found: 112.1124.
1-(4-Ethynylphenyl)-N-(triethylsilyl)methanimine (Table 4,
1
37). H NMR (600 MHz, CDCl3) δ 9.02 (s, 1H), 7.76 (d, J = 8.1
E
DOI: 10.1021/acs.joc.5b00941
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
Hz, 2H), 7.55 (d, J = 8.0 Hz, 2H), 3.19 (s, 1H), 1.00 (t, J = 8.0 Hz,
9H), 0.76 (q, J = 8.0 Hz, 6H); 13C NMR (150 MHz, CDCl3) δ 167.6,
138.9, 132.3 (2C), 128.1 (2C), 124.7, 83.4, 79.0, 6.9 (3C), 3.6 (3C).
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ASSOCIATED CONTENT
■
S
* Supporting Information
1
Copies of H, 13C, 19F, and 29Si NMR spectra data for all
compounds. The Supporting Information is available free of
charge on the ACS Publications website at DOI: 10.1021/
acs.joc.5b00941.
AUTHOR INFORMATION
Corresponding Author
*E-mail: sbchang@kaist.ac.kr.
■
Mansikkamaki, A.; Piers, W. E.; Tuononen, H. M. Nat. Chem. 2014, 6,
̈
Notes
983. (o) Oestreich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev. 2015, 44,
2202. (p) Chadwick, R. C.; Kardelis, V.; Lim, P.; Adronov, A. J. Org.
Chem. 2014, 79, 7728.
The authors declare no competing financial interest.
(8) (a) Spies, P.; Schwendemann, S.; Lange, S.; Kehr, G.; Frohlich,
ACKNOWLEDGMENTS
This research was supported by the Institute for Basic Science
(IBS-R010-D1).
̈
■
R.; Erker, G. Angew. Chem., Int. Ed. 2008, 47, 7543. (b) Ero
Mehdi, H.; Papai, I.; Rokob, T. A.; Kiraly, P.; Tarkanyi, G.; Soos
Angew. Chem., Int. Ed. 2010, 49, 6559. (c) Farrell, J. M.; Hatnean, J. A.;
̋
s, G.;
́
́
́
́
́
, T.
Stephan, D. W. J. Am. Chem. Soc. 2012, 134, 15728. (d) Greb, L.; Ona-
Burgos, P.; Schirmer, B.; Grimme, S.; Stephan, D. W.; Paradies, J.
̃
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