Expedient trimethylaluminium-promoted one-pot synthesis of functional heteroaromatic and carbocyclic trifluoroethylamines

Article abstract of DOI:10.1002/adsc.201000188

The synthesis of trifluoroethylamines as amide bond mimics is an interesting topic in current research. They are well known tools in pharmaceutical and agrochemical industry. Other methods described in literature are often restricted to few substrates. We herein report a new synthetic approach towards this class of substances. First, the trimethylaluminium- promoted generation of a trifluoromethyl-ketimine from the corresponding trifluoromethyl ketone and an aniline derivative was investigated. Next, the ketimine was converted into the trifluoroethylamines in a one-pot reaction by simple addition of borane-methyl sulfide complex.

Full text of DOI:10.1002/adsc.201000188

FULL PAPERS
DOI: 10.1002/adsc.201000188
Expedient Trimethylaluminium-Promoted One-Pot Synthesis of
Functional Heteroaromatic and Carbocyclic Trifluoroethylamines
Nadine Allendçrfer,a Alexander Sudau,b and Stefan Brꢀsea,*
a
Karlsruhe Institute of Technology (KIT), Institute of Organic Chemistry, Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Fax : (+49)-721-608-8581; phone: (+49)-721-608-2902; e-mail: braese@kit.edu
Bayer CropScience AG, Alfred-Nobel-Str. 50, 40789 Monheim am Rhein, Germany
b
Received: March 10, 2010; Revised: July 23, 2010; Published online: August 20, 2010
Abstract: The synthesis of trifluoroethylamines as yl-ketimine from the corresponding trifluoromethyl
amide bond mimics is an interesting topic in current ketone and an aniline derivative was investigated.
research. They are well known tools in pharmaceuti- Next, the ketimine was converted into the trifluoro-
cal and agrochemical industry. Other methods de-
ACHTUNGTRENeNGNU thylamines in a one-pot reaction by simple addition
scribed in literature are often restricted to few sub- of borane-methyl sulfide complex.
strates. We herein report a new synthetic approach
towards this class of substances. First, the trimethyl- Keywords: amide bond mimics; fluorine; one-pot
aluminium-promoted generation of a trifluorometh- synthesis; trifluoroethylamines
Introduction
themselves as well as new synthetic accesses to this
substance class.[11]
Organofluorine compounds are frequently used as
pharmaceuticals and agrochemicals.[1–4] Among the
large number of marketed pharmaceuticals and agro- Results and Discussion
chemicals 20% to 30% are fluorinated products.[3,5]
These facts underline the great interest in novel fluo- Although there exist several methods to generate tri-
rinated compounds and new methodologies towards fluoroethylamines,[6–13] there is a significant require-
these molecules.
ment on new synthetic approaches. A frequently de-
The unique role of fluorine can be justified by its ployed methodology for the introduction of the tri-
strong electronegativity, small size and the low polar- fluoromethyl group is the addition of Ruppertꢁs re-
isability of the C F bond. Especially amide bond agent to imines.[6,13] This reaction is often restricted to
À
mimics are an interesting topic in current research N-activated substrates. Therefore, we started our
due to the rapid in vivo degradation and low bioavail- route from CF3 ketones, which can be prepared easily
ability of the parent peptides. In particular, a- or which are even commercially available.[14] The
trifluoro
cance[6–9] as amide bond mimics.[10] Since the investiga- were dissolved in various solvents in a sealed vial.
tion of the cathepsin inhibitor Odanacatib Then, trimethylaluminium (1.5 equivalents) was
ACHTUNGTRENNUNGmethylated amines are of ongoing signifi- mentioned ketones 1 and the corresponding anilines 2
K
(Figure 1), which is now in phase III clinical trial, added dropwise under spontaneous heating to start
there is an increased demand for trifluoroethylamines the desired condensation reaction. The in situ formed
CF3-ketimine was subsequently reduced by simple ad-
dition of 3.0 equivalents of borane·methyl sulfide
complex (Scheme 1). After aqueous work-up with
20% NaOH, the amidomimetic trifluoroethylamines 3
could be isolated.
To optimise the reaction conditions, a solvent
screening was carried out. Several solvents like THF,
DMF or cyclohexane were tested. After further ef-
forts dichloromethane was figured out to be the ap-
propriate solvent for this type of reaction. The prod-
uct 3ag could be obtained in an excellent yield of
Figure 1. Odanacatib: a cathepsin K inhibitor in phase III
clinical trials.[12]
Adv. Synth. Catal. 2010, 352, 2815 – 2824
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Table 2. Trifluoroethylamines derived from 2,2,2-trifluoro-
AHCTUNGTREGaNNUN cetophenones 1. Details, see Scheme 1, solvent dichlorome-
thane.
Entry CF3-ketone 1:
Aniline 2:
Amine Yield
3
R1
R2
[%][a,b]
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
H
H
H
3-CF3
4-Br
4-Br
4-Me
4-Me
2-OMe
2-OMe
4-Cl
2-I
3aa[16]
3ab
3ac[16]
3ad
3ae
3af
52
44
37
51
53
86
94
80
18
46
10
13
68
77
81
69
45
26
Scheme 1. One-pot synthesis of trifluoroethylamines 3.
2-OCH3
4-SCF3
4-OCF3
4-t-Bu
3,5-CF3
2,4,6-CH3
2-OH
94%. The use of other solvents led to decreased
yields of 4% to 49% (Table 1).
After optimising the reaction conditions, the scope
and limitations of the developed reaction were ex-
plored. For this purpose, 2,2,2-trifluoroacetophenone
3ag[c]
3ah
3ai
9
10
11
12
13
14
15
16
17
18
2-NH2
2-Py
3aj
5aa
3bg
3cf
3cg
3df
3dg
3ef
3eg
3,5-CF3
4-t-Bu
3,5-CF3
4-t-Bu
3,5-CF3
4-t-Bu
3,5-CF3
Table 1. Solvent screening with trifluoroethylamine 3ag as
model system, details in Scheme 1.
Entry
Solvent
Yield [%][a]
1
2
3
4
5
6
7
THF
MeCN
DMF
toluene
1,2-dichloroethane
cyclohexane
dichloromethane
4[b]
10[b]
14[b]
21[b]
23[b]
49[b]
94[c]
[a]
[b]
[c]
One-pot synthesis.
Isolated yield after column chromatography.
Intermediate imine of amine 3ag has been isolated in
quantitative yield.
[a]
One-pot synthesis.
Yields determined by GC analysis.
Isolated yield after column chromatography.
nopyridine (4a) led to only a 10% yield of the desired
amine 5aa (Scheme 2).
Besides the variation of the aniline derivatives, a
selection of differently substituted 2,2,2-trifluoroace-
[b]
[c]
(1a), as a cost-effective and commercially available tophenones 1 was examined to obtain a broad product
keto compound was chosen as starting material for range. In the case of 2,2,2-trifluoro-3’-(trifluoro-
the substance screening. A variety of differently sub-
ACHTUNGTRENmNGNU ethyl)acetophenone (1b) the formation of the corre-
stituted anilines was utilized as reactant. First, ortho- sponding trifluoroethylamines was not as effective as
and para-substituted derivatives with alkyl, halogen, with unsubstituted acetophenone 1a. Amine 3bg, de-
ether and thioether substituents were transformed rived from 3,5-bis(trifluoromethyl)aniline (2g) could
into the corresponding trifluoroethylamines
(Table 2).
3
be isolated in 13% yield (Table 2). The reaction of tri-
fluoro ketone 1b and alkylated aniline 2f yielded only
Both ortho- and para-monosubstituted anilines traces of the corresponding amine (data not shown).
could be employed in the one-pot synthesis to give Choosing 4-substiuted trifluoroacetophenones like 1c
yields between moderate 37% and excellent 86%. and 1d led to increased yields of the trifluoroethyl-
The tert-butyl group in the 4-position led to the best amines (Table 2, entries 13–16). With a methoxy sub-
result (Table 2, entries 1–6). If the substitution pattern stituent in an ortho-position of the CF3 ketone we
was changed to the 3,5-positions, the trifluoro- were able to obtain the amines 3ef and 3eg in 26–
ACHTUNGTRENNUNGethylamine 3ag was observed in an excellent yield of 45% yield (Table 2, entries 17 and 18).
94% (Table 2, entry 7). Despite its steric demand and
trisubstitution, 2,4,6-trimethylaniline (2h) could be
converted into the corresponding fluorinated amine
3ah in good yield (Table 2, entry 8). Free hydroxy and
amino groups in the ortho-position to the amino func-
tionality were also tolerated during the reaction
(Table 2, entries 9 and 10). The use of aminopyridines
was not as successful as the reaction of anilines. In
case of 2-chloro-3-aminopyridine no product was ob-
Scheme 2. One-pot synthesis of pyridyl trifluoroethylamine
served (data not shown). However, the use of 2-ami- 5aa.
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Adv. Synth. Catal. 2010, 352, 2815 – 2824

Expedient Trimethylaluminium-Promoted One-Pot Synthesis
completely unknown. So, we herein report the first
example for the addition of trialkylaluminium re-
agents to CF3-ketimines to generate a-trisubstituted
amines. This structural feature is of high interest in
medicinal chemistry.[18]
In our studies we first introduced aromatic amines,
but also studied benzylic and aliphatic amines (9a and
10a). Following the protocol described above, we
were able to synthesise two further trifluoromethylat-
ed amines 11aa and 12ea (see Figure 2).
Scheme 3. One-pot synthesis of heterocyclic trifluoroethyl-
ACHTUNGTRENNUNGamines 7.
Both substrates were obtained in excellent yield
The screening of heterocyclic trifluoro ketones was and it was demonstrated that the AlMe3-promoted
performed with pyrrole 6a and imidazole 6b.[15,16] In one-pot synthesis is applicable to a wide range of
most cases, the routine protocol was applicable with- amines and trifluoromethylated ketones.
out change to give the heterocycles 7 in moderate to
very good yields (Scheme 3, Table 3).
In one case, the a-methylated amine 8ba was isolat-
ed (Scheme 4). This by-product 8ba was only ob-
served when the reaction was performed with tri-
fluoro ketone 6b and 4-chloroaniline (2a). In this
case, 2.5 equivalents of AlMe3 were added. With this
large excess of the metal organic species one methyl
group was transferred into the in situ formed CF3-ke-
Figure 2. Benzylic and aliphatic CF3-amines 11aa and 12ea.
timine. In the literature the addition of ZnMe2 to tri-
fluoroketimines is described, even in a catalytic asym- Conclusions
metric manner.[7,17] However, the use of trimethylalu-
minium for the alkylation in this synthetic approach is In conclusion, we have developed a new protocol for
the easy synthesis of aromatic, heterocyclic, benzylic
and aliphatic trifluoroethylamines. With this method
in hands, the design of novel amide bond mimics
should be facilitated which could find an application
Table 3. Trifluoroethylamines derived from heterocyclic CF3
ketones 6.
as pharmaceuticals and agrochemicals.
Entry CF3-ketone 6 Aniline 2: R2 Amine 7 Yield [%][a]
1
2
3
4
5
6a
6a
6b
6b
6b
4-Cl
3,5-CF3
4-Cl
3,5-CF3
3-NO2
7aa
7ag
7ba
7bg
7bj
77
54
41
30
61
Experimental Section
General Remarks
[a]
Isolated yield after column chromatography.
Compounds were purchased from ABCR, Apollo Scientific,
Fluka, Merck, Sigma–Aldrich and Thermo Fisher Scientific
and used without further purification. Solvents were dried
and purified by standard methods. For TLC, aluminium foils
layered with silica gel (silica gel 60 F254) produced by Merck
were used. Column chromatography was performed employ-
ing Merck silica gel Geduran Si 60 under flash conditions
(EtOAc=ethyl acetate, c-Hex=cyclohexane). 1H, 13C and
19F NMR spectra were measured with a Bruker Avance 400
spectrometer (400 MHz/100 MHz/376 MHz, respectively).
CDCl3 was used as solvent and residual CHCl3/CDCl3 as
shift reference:
d
(CHCl3)=7.26 ppm,
d
(CDCl3)=
77.0 ppm. The signals in 13C spectra were characterised as
follows: +=primary or tertiary C atom, Cquart =quaternary
C atom. 19F NMR spectra were recorded with internal soft-
ware calibration. IR spectra were recorded with Bruker FT-
IR device IFS 88. EI-MS, FAB-MS, FAB-HR-MS and EI-
HR-MS: these spectra were measured with a Finnigan MAT
95 instrument; elemental analyses were performed using an
Elementar Vario Micro device.
Scheme 4. Formation of amine 7ba and a-methylated amine
8ba.
Adv. Synth. Catal. 2010, 352, 2815 – 2824
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FULL PAPERS
1073 (w), 1030 (w), 1008 (m), 923 (vw) cmÀ1: MS (70 eV,
General Procedure for the Formation of
Trifluoroethylamines
EI): m/z (%)=379/378/377 (1/14/90) [M+], 310/309/308 (0.5/
+
13/100) [MÀCF3 ], 180 (42) [C13H10N+], 109 (17), 91 (13);
The CF3 ketone (1.00 equiv.) and the corresponding aniline
(1.00 equiv.) were dissolved under argon in dry CH2Cl2
(3.5 mLmmolÀ1) in a vial. To the reaction mixture AlMe3
(1.50–3.00 equiv., 1M in heptane) was added dropwise via
syringe. After a slight exothermal reaction (~408C), the vial
was sealed and the solution was stirred at room temperature
for 15 h. Then, BH3·SMe2 in THF (2.00 equiv„ 2M in THF)
was added dropwise and the mixture was stirred for 2 h. The
reaction was quenched by dropwise addition of 20% aqueos
NaOH and the aqueous layer was extracted with CH2Cl2
(3ꢃ30 mL). The organic layer was dried over Na2SO4, the
solvent removed under reduced pressure and the residue
was purified by column chromatography (silica gel).
EI-HR-MS: m/z=376.9890 (C14H11NIF3), calcd.: 376.9888.
2-Methoxy-N-(2,2,2-trifluoro-1-phenylethyl)aniline (3ac):
According to the general procedure, o-anisidine (2c,
71.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
100 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 19:1, v/v) afforded 3ac as a col-
ourless oil; yield: 60.0 mg (37%); Rf =0.21 (c-Hex/EtOAc,
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=3.84 (s, 3H,
OCH3), 4.97 (q, J=6.8 Hz, 1H, CHCF3), 6.72–6.83 (m, 4H,
Ar-H-3,4,5,6), 7.39–7.48 (m, 5H, Ph-H); 13C NMR
(100 MHz, CDCl3): d=55.4 (+, OCH3), 72.6 (q, J=31.7 Hz,
+, CHCF3), 110.5 (+, C-Ar-6), 115.4 (+, C-Ar-3), 118.9 (+,
4-Chloro-N-(2,2,2-trifluoro-1-phenylethyl)aniline
(3aa):
According to the general procedure, 4-chloroaniline (2a,
73.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
100 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 24:1, v/v) afforded 3aa as a
yellow oil; yield: 85.0 mg (52%); Rf =0.63 (c-Hex/EtOAc,
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=4.35 (bs, 1H,
NH), 4.87 (q, J=6.5 Hz, 1H, CHCF3), 6.55–6.59 (m, 2H,
Ar-H-3,5), 7.09–7.13 (m, 2H, Ar-H-2,6), 7.39–7.47 (m, 5H,
Ph-H); 13C NMR (100 MHz, CDCl3): d=60.7 (q, J=
30.0 Hz, +, CHCF3), 115.1 (+, C-Ar-3,5), 124.0 (Cquart, C-
Ar-1), 124.9 (q, J=281.9 Hz, Cquart, CF3), 127.8 (+, C-Ar-
3’,5’), 129.0 (+, C-Ar-2’,6’), 129.2 (+, C-Ar-2,6), 129.3 (+,
C-Ar-5), 121.0 (+, C-Ar-4), 124.3 (q, J=282.0 Hz, Cquart
,
CF3), 127.4 (+, C-Ar-3’,5’), 128.5 (+, C-Ar-2’,6’), 129.4 (+,
C-Ar-4’), 134.2 (Cquart, C-Ar-2), 135.6 (Cquart, C-Ar-1’), 147.5
(Cquart, C-Ar-1); 19F NMR (376 MHz, CDCl3): d=À74.0 (s,
˜
3F, CHCF3); IR (KBr): n=3394 (w), 2932 (w), 2841 (w),
1616(w), 1505 (m), 1458 (w), 1384 (w), 1353 (w), 1263 (m),
1225 (m), 1206 (w), 1168 (m), 1125 (m), 1066 (w), 1046 (w),
1028 (w) cmÀ1. MS (70 eV, EI): m/z (%)=282/281 (8/49)
+
[M+], 212 (86) [MÀCF3 ], 210 (100), 195 (21), 43 (89); EI-
HR-MS: m/z=281.1031, (C15H14NOF3), calcd.: 281.1027.
N-(2,2,2-Trifluoro-1-phenylethyl)-4-(trifluoromethylthio)-
aniline (3ad): According to the general procedure, 4-(tri-
fluoromethylthio)aniline (2d, 111 mg, 0.575 mmol), 2,2,2-tri-
fluoroacetophenone (1a, 100 mg, 0.575 mmol) and AlMe3 in
heptane (0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2
(2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
24:1, v/v) afforded 3ad as a colourless oil; yield: 104 mg
(51%); Rf =0.42 (c-Hex/EtOAc, 19:1, v/v). 1H NMR
(400 MHz, CDCl3): d=4.65 (d, J=7.1 Hz, 1H, NH), 4.94
(dq, J=7.2 Hz , J=7.2 Hz, 1H, CHCF3), 6.66 (m, 2H, Ar-
H-3,5), 7.40–7.49 (m, 7H, Ar-H-2,2’,3’,4’,5’,6,6’); 13C NMR
(100 MHz, CDCl3): d=60.0 (q, J=30.2 Hz, +, CHCF3),
112.4 (q, J=2.1 Hz, Cquart, C-Ar-1), 114.2 (+, C-Ar-3,5),
124.8 (q, J=282.0 Hz, Cquart, CHCF3), 127.8 (+, C-Ar-3’,5’),
129.1 (+, C-Ar-2,6), 129.5 (+, C-Ar-4’), 129.6 (q, J=
308.3 Hz, Cquart, SCF3), 133.2 (Cquart, C-Ar-1’), 138.2 (+, C-
Ar-2’,6’), 147.7 (Cquart, C-Ar-4); 19F NMR (376 MHz, CDCl3):
C-Ar-4’), 133.6 (Cquart
, C-Ar-1’), 144.0 (Cquart, C-Ar-4);
19F NMR (376 MHz, CDCl3): d=À74.0 (s, 3F, CF3); IR
˜
(KBr): n=3421 (w), 3035 (vw), 2926 (vw), 1601 (m), 1499
(m), 1456 (w), 1404 (vw), 1345 (w), 1313 (m), 1293 (w), 1248
(m), 1178 (m), 1124 (s), 1096 (m), 1031 (vw), 1005 (vw), 891
(vw) cmÀ1; MS (70 eV, EI): m/z (%)=287/286/285 (21/10/63)
+
[M+], 218/217/216 (32/15/100) [M-CF3 ], 138 (11), 109 (13);
EI-HR-MS: m/z=285.0530 (C14H11NClF3), calcd.: 285.0532;
anal. calcd. for C14H11ClF3N: N 4.90, C 58.86, H 3.88; found:
N 4.68, C 59.18, H 3.93.
2-Iodo-N-(2,2,2-trifluoro-1-phenylethyl)aniline (3ab): Ac-
cording to the general procedure, 2-iodoaniline (2b, 126 mg,
0.575 mmol), 2,2,2-trifluoroacetophenone (1a, 100 mg,
0.575 mmol) and AlMe3 in heptane (0.86 mL, 0.86 mmol)
were reacted in dry CH2Cl2 (2 mL). Addition of BH3·SMe2
in THF (0.58 mL, 1.15 mmol) and column chromatography
(c-Hex/EtOAc, 10:1, v/v) afforded 3ab as a yellow oil; yield:
˜
d=À73.9 (s, 3F, CHCF3), À44.2 (s, 3F, SCF3); IR (KBr): n=
3437 (w), 3069 (vw), 3036 (vw), 2927 (vw), 2301 (vw), 1890
(vw), 1710 (vw), 1598 (m), 1509 (m), 1456 (w), 1409 (w),
1344 (w), 1322 (w), 1297 (w), 1252 (m), 1119 (m), 1089 (m),
1031 (vw), 1006 (vw), 922 (vw) cmÀ1; MS (70 eV, EI): m/z
(%)=353/352/351 (4/11/73) [M+], 284/283/282 (5/15/100)
1
95.0 mg (44%); Rf =0.66 (c-Hex/EtOAc, 10:1, v/v). H NMR
(400 MHz, CDCl3): d=4.96 (m, 1H, CHCF3), 5.02 (d, J=
7.6 Hz, 1H, NH), 6.52 (m, 2H, Ar-H-3,5), 7.13 (dt, J=
7.9 Hz, J=1.4 Hz, 1H, Ar-H-4), 7.39–7.44 (m, 3H, Ar-H-
3ꢄ,4ꢄ,5ꢄ), 7.48 (m, 2H, Ar-H-2ꢄ,6ꢄ), 7.69 (dd, J=8.3 Hz, J=
1.5 Hz, 1H, Ar-H-6); 13C NMR (100 MHz, CDCl3): d=60.8
(q, J=30.1 Hz, +, CHCF3), 86.4 (Cquart, C-Ar-1), 111.9 (+,
+
+
[MÀCF3 ], 159 (18) [C8H6F3 ], 109 (15), 58 (37), 43 (89);
EI-HR-MS: m/z=351.0518 (C15H11NSF6), calcd.: 351.0516.
N-(2,2,2-Trifluoro-1-phenylethyl)-4-(trifluoromethoxy)-
aniline (3ae): According to the general procedure, 4-(tri-
fluoromethoxy)aniline (2e, 102 mg, 0.575 mmol), 2,2,2-tri-
fluoroacetophenone (1a, 100 mg, 0.575 mmol) and AlMe3 in
heptane (0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2
(2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
24:1, v/v) afforded 3ae as a yellow oil; yield: 107 mg (55%);
Rf =0.38 (c-Hex/EtOAc, 24:1, v/v). 1H NMR (400 MHz,
C-Ar-3), 120.5 (+, C-Ar-5), 124.8 (q, J=281.9 Hz, Cquart
,
CF3), 127.9 (+, C-Ar-3’,5’), 129.0 (+, C-Ar-4’,6’), 129.3 (+,
C-Ar-4), 129.4 (+, C-Ar-2’), 133.3 (Cquart, C-Ar-1’), 139.3 (+,
C-Ar-6), 144.8 (Cquart, C-Ar-2); 19F NMR (376 MHz, CDCl3):
˜
d=À74.1 (m, 3F, CF3); IR (KBr): n=3389 (w), 3066 (w),
3034 (w), 2925 (w), 1677 (w), 1590 (m), 1512 (m), 1456 (m),
1433 (m), 1343 (m), 1317 (m), 1252 (s), 1180 (s), 1126 (s),
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Adv. Synth. Catal. 2010, 352, 2815 – 2824

Expedient Trimethylaluminium-Promoted One-Pot Synthesis
CDCl3): d=4.41 (d, J=6.9 Hz, 1H, NH), 4.86 (dq, J=
7.2 Hz, J=7.2 Hz, 1H, CHCF3), 6.59–6.63 (m, 2H, Ar-H-
3,5), 7.01 (m, 2H, Ar-H-2,6), 7.40–7.46 (m, 5H, Ph-H);
13C NMR (100 MHz, CDCl3): d=60.8 (q, J=30.0 Hz,
CHCF3), 120.6 (q, J=255.9 Hz, Cquart, OCF3), 124.9 (q, J=
281.9 Hz, Cquart, CHCF3), 114.4 (+, C-Ar-2,6), 122.5 (+, C-
Ar-3,5), 127.8 (+, C-Ar-3’,5’), 129.0 (+, C-Ar-2’,6’), 129.3
(+, C-Ar-4’), 133.6 (Cquart, C-Ar-1’), 141.7 (Cquart, C-Ar-1),
144.2 (Cquart, C-Ar-4); 19F NMR (376 MHz, CDCl3): d=
˜
1391 (s), 1352 (m), 1279 (s), 1176 (s), 1129 (s), 1076 (m),
1032 (vw), 997 (w) cmÀ1; MS (70 eV, EI): m/z (%)=388/387
+
(31/5) [M+], 320/319/318 (1/16/100) [MÀCF3 ], 214/213 (1/
+
+
17) [C8H3F6 ], 109 (16), 77 (4) [C6H5 ]; EI-HR-MS: m/z=
387.0673 (C16H10F9N), calcd.: 387.0669; anal. calcd. for
C16H10F9N: N 3.62, C 49.63, H 2.60; found: N 3.35, C 49.53,
H 2.49.
À74.0 (s, 3F, CHCF3), À58.4 (s, 3F, OCF3); IR (KBr): n= Intermediate Imine of Amine 3ag
3433 (w), 3039 (vw), 1615 (w), 1516 (m), 1456 (w), 1347 (w),
N-(2,2,2-Trifluoro-1-phenylethylidene)-3,5-bis(trifluorometh-
1248 (s), 1169 (m), 1125 (m), 1031 (vw), 919 (vw) cmÀ1; MS
yl)aniline: Under argon 3,5-bis(trifluoromethyl)aniline (2g,
0.132 g, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
0.100 g, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). After aque-
ous work-up and column chromatography (c-Hex/EtOAc,
14/1) afforded the intermediate imine as a yellow oil; yield:
221 mg (>99%); Rf =0.61 (c-Hex/EtOAc, 10/1). 1H NMR
(400 MHz, CDCl3): d=7.18–7.20 (m, 4H, Ar-H-2,6,2’,6’),
7.35 (t, J=7.5 Hz, 2H, Ar-3’,5’), 7.43 (t, J=7.4 Hz, 1H, Ar-
H-4’), 7.57 (s, 1H, Ar-H-4); 13C NMR (100 MHz, CDCl3):
(70 eV, EI): m/z (%)=337/336/335 (1/19/100) [M+], 268/267/
+
266 (0.4/10/80) [MÀCF3 ], 159 (2) [C8H6F3N+]; EI-HR-MS:
m/z=335.0746 (C15H11F6NO), calcd.: 335.0744.
4-tert-Butyl-N-(2,2,2-trifluoro-1-phenylethyl)aniline (3af):
According to the general procedure, 4-tert-butylaniline (2f,
120 mg, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
100 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 24:1, v/v) afforded 3af as a
yellow oil; yield: 153 mg (86%); Rf =0.52 (c-Hex/EtOAc,
19:1, v/v). 1H NMR (400 MHz, CDCl3): d=1.28 [s, 9H,
d=118.9 (m, +, C-Ar-4), 119.4 (q, J=279.4 Hz, Cquart
CHCF3), 120.9 (+, C-Ar-2,6), 122.8 (q, J=272.8 Hz, Cquart
,
,
ArCF3), 128.4 (+, C-Ar-2’,6’), 128.7 (Cquart, C-Ar-1’), 129.0
(+, C-Ar-3’,5’), 131.2 (+, C-Ar-4’), 132.4 (q, J=33.8 Hz,
Cquart, C-Ar-3,5), 148.4 (Cquart, C-Ar-1), 160.4 (q, J=34.7 Hz,
Cquart, CCF3); 19F NMR (376 MHz, CDCl3): d=À70.3 (s, 3F,
CACHTUNGTRENNUNG(CH3)3], 4.28 (bs, 1H, NH), 4.91 (q, J=7.3 Hz, 1H,
CHCF3), 6.61–6.65 (m, 2H, Ar-H-2,6), 7.20–7.24 (m, 2H,
Ar-H-3,5), 7.39–7.51 (m, 5H, Ph-H); 13C NMR (100 MHz,
CDCl3): d=31.4 [+, CACTHUNRGTNNEGU(CH3)3], 33.9 [Cquart, CCAHTUNGTREN(NGUN CH3)3], 60.8
˜
CHCF3), À63.2 (s, 6F, ArCF3); IR (KBr): n=3440 (vw),
(q, J=29.7 Hz, +, CHCF3), 113.8 (+, C-Ar-2,6), 125.1 (q,
J=281.9 Hz, Cquart, CF3), 126.1 (+, C-Ar-3,5), 127.9 (+, C-
Ar-3’,5’),128.9 (+, C-Ar-2’,6’), 129.0 (+, C-Ar-4’), 134.4
(Cquart, C-Ar-1’), 142.0 (Cquart, C-Ar-4), 143.2 (Cquart, C-Ar-1);
19F NMR (376 MHz, CDCl3): d=À74.0 (s, 3F, CF3); IR
1667 (vw), 1460 (vw), 1374 (m), 1334 (w), 1280 (m), 1168
(m), 1134 (m), 976 (w) cmÀ1; MS (70 eV, EI): m/z (%)=386/
+
385 (5/28) [M+], 317/316 (16/100) [MÀCF3 ], 213 (5)
+
+
[C8H3F6 ], 77 (22) [C6H5 ]; HR-MS: m/z=385.0510
(C16H8F9N), calcd.: 385.0513.
˜
(KBr): n=3419 (w), 3065 (w), 3033 (w), 2962 (s), 2867 (m),
2,4,6-Trimethyl-N-(2,2,2-trifluoro-1-phenylethyl)aniline
(3ah): According to the general procedure, 2,4,6-trimethyl-
AHCTUNGTREGaNNUN niline (2h, 71.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophe-
1881 (vw), 1743 (vw), 1616 (m), 1520 (s), 1493 (m), 1456
(m), 1408 (w), 1394 (w), 1364 (m), 1345 (m), 1319 (m), 1300
(m), 1251 (s), 1173 (s), 1124 (s), 1074 (w), 1030 (w) cmÀ1
;
none (1a, 100 mg, 0.575 mmol) and AlMe3 in heptane
(0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2 (2 mL).
Addition of BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and
column chromatography (c-Hex/EtOAc, 24:1–10:1, v/v) af-
forded 3ah as a colourless oil; yield: 135 mg (80%); Rf =
MS (70 eV, EI): m/z (%)=308/307 (2/35) [M+], 293/292 (13/
+
+
100) [MÀCH3 ], 239/238 (1/20) [MÀCF3 ], 159 (24)
+
[C8H6F3 ]; EI-HR-MS: m/z=307.1546 (C18H20F3N), calcd.:
307.1547.
1
N-(2,2,2-Trifluoro-1-phenylethyl)-3,5-bis(trifluoromethyl)-
aniline (3ag): According to the general procedure, 3,5-bis-
ACHTUNGTRENNUNG(trifluoromethyl)aniline (2g, 132 mg, 0.575 mmol), 2,2,2-tri-
0.20 (c-Hex/EtOAc, 10:1, v/v). H NMR (400 MHz, CDCl3):
d=2.16 (s, 6H, 2ꢃo-CH3), 2.22 (s, 3H, p-CH3), 5.01 (q, J=
6.7 Hz, 1H, CHCF3), 6.78 (s, 2H, Ar-H-3,5), 7.40–7.49 (m,
5H, Ph-H); 13C NMR (100 MHz, CDCl3): d=17.6 (+, 2ꢃo-
CH3), 20.3 (+, p-CH3), 72.8 (q, J=31.9 Hz, +, CHCF3),
122.2 (Cquart, C-Ar-2,6), 124.2 (q, J=282.1 Hz, Cquart, CF3),
127.4 (+, C-Ar-3’,5’), 127.5 (Cquart, C-Ar-4), 128.6 (+, C-Ar-
fluoroacetophenone (1a, 100 mg, 0.575 mmol) and AlMe3 in
heptane (0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2
(2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
14:1, v/v) afforded 3ag as a colourless oil; yield: 209 mg
(94%); Rf =0.59 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
(400 MHz, CDCl3): d=4.79 (d, J=7.3 Hz, 1H, NH), 4.97
(dq, J=7.1 Hz, J=7.1 Hz, 1H, CHCF3), 7.03 (s, 2H, Ar-H-
2,6), 7.25 (s, 1H, Ar-H-4), 7.42–7.49 (m, 5H, Ph-H);
13C NMR (100 MHz, CDCl3): d=60.1 (q, J=30.1 Hz, +,
CHCF3), 112.4 (sept, J=3.7 Hz, +, C-Ar-4), 113.1 (q, J=
3.3 Hz, +, Ar-H-2,6), 123.2 (q, J=272.7 Hz, Cquart, 2ꢃCF3),
124.6 (q, J=282.2 Hz, Cquart, CHCF3), 127.8 (+, C-Ar-3’,5’),
129.3 (+, C-Ar-2’,6’), 129.7 (+, C-Ar-4’), 132.5 (Cquart, C-Ar-
1’), 132.7 (q, J=32.8 Hz, Cquart, C-Ar-3,5), 146.3 (Cquart, C-
Ar-1); 19F NMR (376 MHz, CDCl3): d=À73.9 (s, 3F, CF3),
2’,6’), 128.8 (+, C-Ar-3,5), 129.5 (+, C-Ar-4’), 134.0 (Cquart
,
C-Ar-1’), 139.7 (Cquart
,
C-Ar-1); 19F NMR (376 MHz,
˜
CDCl3): d=À78.3 (s, 3F, CHCF3); IR (KBr): n=3406 (vw),
2920 (w), 2861 (w), 1628 (vw), 1606 (vw), 1488 (m), 1455
(w), 1377 (w), 1336 (w), 1303 (w), 1259 (m), 1228 (m), 1168
(m), 1120 (m), 1072 (w), 1030 (w) cmÀ1; MS (70 eV, EI): m/z
+
(%)=294/293 (17/100) [M+], 224 (20) [MÀCF3 ], 134 (60)
[C9H12N+]; EI-HR-MS: m/z=293.1393 (C17H18F3N), calcd.:
293.1391.
2-(2,2,2-Trifluoro-1-phenylethylamino)phenol (3ai): Ac-
cording to the general procedure, 2-aminophenol (2i,
63.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
100 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
˜
À63.3 (s, 6F, 2ꢃCF3); IR (KBr): n=3445 (w), 3040 (vw),
1625 (s), 1527 (m), 1499 (w), 1475 (m), 1458 (w), 1440 (m),
Adv. Synth. Catal. 2010, 352, 2815 – 2824
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2819

Nadine Allendçrfer et al.
FULL PAPERS
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 14:1, v/v) afforded 3ai as a
brown oil; yield: 28.0 mg (18%); Rf =0.81 (c-Hex/EtOAc,
1253 (m), 1188 (m), 1127 (m), 1076 (w), 1033 (w), 933 (w)
cmÀ1; MS (70 eV, EI): m/z (%)=253/252 (2/13) [M+], 183
+
(27) [MÀCF3 ], 78 (31), [C5H4N+], 43 (100); EI-HR-MS:
1
1/1). H NMR (400 MHz, CDCl3): d=4.62 (bs, 1H), 4.84 (m,
m/z=252.0872 (C13H11F3N2), calcd.: 252.0874.
1H, CHCF3), 5.18 (bs, 1H), 6.56–6.59 (m, 1H, Harom), 6.68–
6.78 (m, 3H, Harom), 7.35–7.50 (m, 5H, Harom); 13C NMR
(100 MHz, CDCl3): d=61.2 (q, J=29.9 Hz, +, CHCF3),
114.7 (+, C-Ar-3), 114.7 (+, C-Ar-6), 120.1 (+, C-Ar-5),
121.4 (+, C-Ar-4), 125.1 (q, J=281.8 Hz, Cquart, CF3), 128.0
(+, C-Ar-2’,6’), 128.9 (+, C-Ar-3’,5’), 129.1 (+, C-Ar-4’),
134.0 (Cquart, C-Ar-1’), 134.1 (Cquart, C-Ar-2), 144.6 (Cquart, C-
Ar-1); 19FNMR (376 MHz, CDCl3): d=À74.1 (s, 3F, CF3);
N-{2,2,2-Trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-3,5-
bis(trifluoromethyl)aniline (3bg): According to the general
procedure, 3,5-bis(trifluoromethyl)aniline (2g, 132 mg,
0.575 mmol),
2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]-
AHCTUNGTRENeGNUN thanone (1b, 139 mg, 0.575 mmol) and AlMe3 in heptane
(0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2 (2 mL).
Addition of BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and
column chromatography (c-Hex/EtOAc, 19:1, v/v) afforded
3bg as a colourless oil; yield: 34.0 mg (13%); Rf =0.57 (c-
Hex/EtOAc, 10:1, v/v). 1H NMR (400 MHz, CDCl3): d=
4.81 (d, J=7.3 Hz, 1H, NH), 5.05 (dq, J=6.9 Hz, J=6.9 Hz,
1H, CHCF3), 7.02 (s, 2H, Ar-H-2,6), 7.29 (s, 1H, Ar-H-4),
7.58–7.74 (m, 4H, Ar-H-2’,4’,5’,6’); 13C NMR (100 MHz,
CDCl3): d=59.8 (q, J=30.8 Hz, +, CHCF3), 112.9 (m, +,
C-Ar-4), 113.1 (q, J=3.5 Hz, +, C-Ar-2,6), 123.1 (q, J=
272.8 Hz, Cquart, 2ꢃCF3), 123.6 (q, J=272.4 Hz, Cquart, CF3),
124.4 (q, J=282.3 Hz, Cquart, CHCF3), 124.6 (q, J=3.3 Hz,
+, C-Ar-6’), 126.8 (q, J=3.6 Hz, +, C-Ar-2’), 129.9 (+,
C-Ar-5’), 131.2 (+, C-Ar-4’), 131.9 (q, J=32.9 Hz, Cquart, C-
˜
IR (ATR): n=3420 (w), 2927 (vw), 1611 (w), 1512 (m), 1453
(m), 1341 (w), 1250 (m), 1169 (m), 1119(s), 1042 (w), 889
(w) cmÀ1; MS (70 eV, EI): m/z(%)=269/268/267 (1/15/100)
+
[M+], 199/198 (12/85) [MÀCF3 ], 108 (70) [C6H6NO+]; HR-
MS: m/z=267.0875 (C14H12F3NO), calcd.: 267.0870.
N1-(2,2,2-Trifluoro-1-phenylethyl)benzol-1,2-diamine
(3aj): According to the general procedure, o-phenylenedi-
ACHTUNGTRENNUNGamine (2j, 62.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophe-
none (1a, 100 mg, 0.575 mmol) and AlMe3 in heptane
(0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2 (2 mL).
Addition of BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and
column chromatography (c-Hex/EtOAc, 14:1, v/v) afforded
3aj as a brown oil; yield 70.0 mg (46%); Rf =0.21 (c-Hex/
Ar-1’), 132.9 (q, J=33.3 Hz, Cquart, C-Ar-3,5), 133.7 (Cquart
,
C-Ar-3’), 145.8 (Cquart
,
C-Ar-1); 19F NMR (376 MHz,
1
EtOAc, 10:1, v/v). H NMR (400 MHz, CDCl3): d=3.54 (bs,
CDCl3): d=À73.8 (s, 3F, CHCF3), À63.3 (s, 6F, 2ꢃCF3),
2H, NH2), 4.10 (d, J=7.3 Hz, 1H, NH), 4.87 (dq, J=7.5 Hz,
J=7.5 Hz, 1H, CHCF3), 6.51 (d, J=8.1 Hz, 1H, Ar-H-3),
6.68 (ddd, J=8.9 Hz, J=6.7 Hz, J=3.8 Hz, 1H, Ar-H-4),
6.73–6.79 (m, 2H, Ar-H-5,6), 7.35–7.50 (m, 5H, Ar-H-
2’,3’,4’,5’,6’); 13C NMR (100 MHz, CDCl3): d=60.7 (q, J=
29.4 Hz, +, CHCF3), 115.7 (+, C-Ar-6), 117.1 (+, C-Ar-3),
120.3 (+, C-Ar-4), 121.3 (+, C-Ar-5), 125.2 (q, J=281.5 Hz,
Cquart, CF3), 128.0 (+, C-Ar-2’,6’), 128.8 (+, C-Ar-3’,5’),
129.0 (+, C-Ar-4’), 134.0 (Cquart, C-Ar-1’), 134.2 (Cquart, C-
Ar-2), 136.2 (Cquart, C-Ar-1); 19F NMR (376 MHz, CDCl3):
˜
À62.8 (s, 3F, CF3); IR (KBr): n=3845 (vw), 3447 (w), 2928
(vw), 2286 (vw), 1710 (vw), 1625 (w), 1529 (w), 1475 (w),
1441 (w), 1390 (w), 1331 (w), 1280 (w), 1129 (w), 1076 (w)
cmÀ1; MS (70 eV, EI): m/z (%)=457/456/455 (0.34/4/14)
+
[M+], 388/387/386 (1/14/100) [MÀCF3 ], 317 (0.36)
+
[C15H9F6N+], 240 (8) [C6H3F6 ], 213 (11); EI-HR-MS: m/z=
455.0540 (C17H9NF12), calcd.: 455.0543.
N-[1-(4-Bromophenyl)-2,2,2-trifluoroethyl]-4-tert-butyl-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
˜
d=À74.0 (s, 3F, CF3); IR (KBr): n=3347 (w), 3034 (w),
fluoroacetophenone (1c, 145 mg, 0.575 mmol) and AlMe3 in
heptane (0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2
(2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
49:1, v/v) afforded 3cf as a colourless oil; yield: 151 mg
(68%); Rf =0.63 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
2926(w), 1619 (m), 1509 (m), 1456 (m), 1332 (m), 1255 (s),
1172 (s), 1123 (s), 1066 (w), 1031 (w), 1003 (vw), 922 (w)
cmÀ1; MS (70 eV, EI): m/z (%)=267/266 (11/70) [M+], 197
+
+
(27) [MÀCF3 ], 107 (100) [C6H7N2 ]; EI-HR-MS: m/z=
266.1029 (C14H13F3N2), calcd.: 266.1030.
N-(2,2,2-Trifluoro-1-phenylethyl)pyridine-2-amine (5aa):
According to the general procedure, 2-aminopyridine (4a,
54.0 mg, 0.575 mmol), 2,2,2-trifluoroacetophenone (1a,
100 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 10:1–5:1, v/v) afforded 5aa as a
yellow solid; yield: 15.0 mg (10%); Rf =0.09 (c-Hex/EtOAc,
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=5.05 (m, 1H,
CHCF3), 6.56 (d, J=8.7 Hz, 1H, Ar-H-3), 6.72 (t, J=6.7 Hz,
1H, Ar-H-5), 7.43–7.49 (m, 5H, Ph-H), 7.60 (t, J=7.3 Hz,
1H, Ar-H-4), 8.29 (d, J=5.9 Hz, 1H, Ar-H-6); 13C NMR
(100 MHz, CDCl3): d=59.2 (q, J=31.2 Hz, +, CHCF3),
107.7 (+, C-Ar-3), 113.5 (+, C-Ar-5), 124.1 (q, J=282.2 Hz,
Cquart, CF3), 127.8 (+, C-Ar-3’,5’), 129.2 (+, C-Ar-2’,6’),
129.9 (+, C-Ar-4’), 131.6 (Cquart, C-Ar-1’), 140.5 (+, C-Ar-4),
(400 MHz, CDCl3): d=1.27 [s, 9H, CACHTNUGTRNEUNG(CH3)3], 4.26 (d, J=
6.5 Hz, 1H, NH), 4.87 (dq, J=7.1 Hz, J=7.1 Hz, 1H,
CHCF3), 6.55–6.59 (m, 2H, Ar-H-2’,6’), 7.19–7.23 (m, 2H,
Ar-H-3’,5’), 7.37 (d, J=8.4 Hz, 2H, Ar-H-3,5), 7.53–7.56 (m,
2H, Ar-H-2,6); 13C NMR (100 MHz, CDCl3): d=31.4 [+,
CACHTNURTGNNEG(U CH3)3], 33.9 [Cquart, CCAHTUNTGERN(NUNG CH3)3], 60.3 (q, J=29.9 Hz, +,
CHCF3), 113.6 (+, C-Ar-2’,6’), 123.2 (Cquart, C-Ar-1), 124.7
(q, J=281.8 Hz, Cquart, CF3), 126.2 (+, C-Ar-3’,5’), 129.6 (+,
C-Ar-3,5), 132.1 (+, C-Ar-2,6), 133.3 (Cquart, C-Ar-4), 142.2
(Cquart, C-Ar-4’), 142.7 (Cquart, C-Ar-1’); 19F NMR (376 MHz,
˜
CDCl3): d=À74.1 (s, 3F, CHCF3); IR (KBr): n=3414 (w),
3030 (w), 2963 (m), 2904 (w), 2868 (w), 2296 (vw), 1905
(vw), 1710 (m), 1616 (m), 1521 (m), 1489 (m), 1409 (m),
1363 (m), 1318 (m), 1302 (m), 1250 (m), 1174 (m), 1128 (m),
1095 (m), 1074 (m), 1012 (m) cmÀ1; MS (70 eV, EI): m/z
(%)=387/386/385 (6/2/7) [M+], 372/371/370 (14/3/16)
146.9 (+, C-Ar-6), 153.5 (Cquart
,
C-Ar-2); 19F NMR
+
+
[MÀCH3 ], 318/317/316 (2/1/3) [MÀCF3 ], 237 (2)
[C17H19N+], 58 (35), 43 (100); EI-HR-MS: m/z=385.0650
(C18H19BrF3N), calcd.: 385.0653; anal. calcd. for
˜
(376 MHz, CDCl3): d=À74.2 (s, 3F, CF3); IR (KBr): n=
3350 (w), 2920 (w) , 2850 (w), 2417 (w), 2289 (w), 1630 (m),
1589 (m), 1533 (m), 1497 (w), 1475 (m), 1456 (m), 1361 (w),
2820
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2815 – 2824

Expedient Trimethylaluminium-Promoted One-Pot Synthesis
C18H19BrF3N: N 3.63, C 55.97, H 4.96; found: N 4.15, C
55.47, H 5.08.
N-[1-(4-Bromophenyl)-2,2,2-trifluoroethyl]-3,5-bis-(tri-
fluoromethyl)aniline (3cg): According to the general proce-
CH2Cl2 (2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
29:1, v/v) afforded 3dg as a colourless solid; yield: 159 mg
(69%); Rf =0.66 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
(400 MHz, CDCl3): d=2.38 (s, 3H, CH3), 4.75 (d, J=7.4 Hz,
1H, NH), 4.93 (dq, J=7.1 Hz, J=7.1 Hz, 1H, CHCF3), 7.03
(s, 2H, Ar-H-2,6), 7.23–7.27 (m, 3H, Ar-H-4,3’,5’), 7.35 (d,
J=8.0 Hz, 2H, Ar-H-2’,6’); 13C NMR (100 MHz, CDCl3):
d=21.1 (+, CH3), 59.9 (q, J=30.5 Hz, +, CHCF3), 112.3
(+, C-Ar-4), 113.1 (+, C-Ar-2,6), 123.6 (q, J=272.7 Hz,
Cquart, 2ꢃCF3), 124.7 (q, J=282.1 Hz, Cquart, CHCF3), 127.6
(+, C-Ar-3’,5’), 129.5 (Cquart, C-Ar-1’), 130.0 (+, C-Ar-2’,6’),
132.7 (q, J=33.0 Hz, Cquart, C-Ar-3,5), 139.8 (Cquart, C-Ar-4’),
146.4 (Cquart, C-Ar-1); 19F NMR (376 MHz, CDCl3): d=
dure,
3,5-bis(trifluoromethyl)aniline
(2g,
132 mg,
0.575 mmol),
4’-bromo-2,2,2-trifluoroacetophenone
(1c,
145 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 49:1, v/v) afforded 3cg as a col-
ourless oil; yield: 206 mg (77%); Rf =0.53 (c-Hex/EtOAc,
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=4.77 (d, J=
7.0 Hz, 1H, NH), 4.95 (dq, J=6.9 Hz, J=6.9 Hz, 1H,
CHCF3), 7.00 (s, 2H, Ar-H-2’,6’), 7.28 (s, 1H, Ar-H-4’), 7.35
(d, J=8.1 Hz, Ar-H-3,5), 7.58 (d, J=8.2 Hz, Ar-H-2,6);
13C NMR (100 MHz, CDCl3): d=59.7 (q, J=30.7 Hz, +,
CHCF3), 112.7 (m, +, C-Ar-4’), 113.1 (q, J=3.2 Hz, +, C-
˜
À74.0 (s, 3F, CHCF3), À63.2 (s, 6F, 2ꢃCF3); IR (KBr): n=
3437 (s), 3094 (m), 3034 (m), 2933 (m), 2233 (w), 1913 (w),
1807 (w), 1727 (w), 1625 (s), 1537 (s), 1517 (s), 1477 (s),
1443 (s), 1395 (s), 1347 (s), 1278 (s), 1179 (s), 1114 (s), 1043
(m), 1022 (m), 997 (m) cmÀ1; MS (70 eV, EI): m/z (%)=
403/402/401 (0.4/6/35) [M+], 334/333/332 (1/16/100)
Ar-2’,6’), 123.3 (q, J=272.8 Hz, Cquart, 2ꢃCF3), 124.1 (Cquart
,
C-Ar-1), 124.3 (q, J=282.1 Hz, Cquart, CHCF3), 129.4 (+, C-
Ar-2,6), 131.5 (Cquart, C-Ar-4), 132.5 (+, C-Ar-3,5), 132.8 (q,
+
+
+
J=33.1 Hz, Cquart
,
C-Ar-3’,5’), 145.9 (Cquart
,
C-Ar-1’);
[MÀCF3 ], 213 (13) [C8H3F6 ], 174/173 (3/34) [C9H8F3 ];
EI-HR-MS: m/z=401.0824 (C17H12F9N), calcd.: 401.0826;
anal. calcd. for C17H12F9N: N 3.49, C 50.88, H 3.01; found: N
3.33, C 50.87, H 3.08.
19F NMR (376 MHz, CDCl3): d=À73.9 (s, 3F, CHCF3),
˜
À63.2 (6F, 2ꢃCF3); IR (KBr): n=3443 (w), 3090 (vw), 2238
(vw), 1711 (w), 1625 (m), 1528 (m), 1492 (m), 1476 (m),
1441 (w), 1391 (m), 1352 (m), 1320 (w), 1292 (m), 1127 (m),
1092 (m), 1012 (m), 997 (w) cmÀ1; MS (70 eV, EI): m/z
(%)=467/466/465 (34/7/37) [M+], 398/397/396 (91/13/100)
4-tert-Butyl-N-[2,2,2-trifluoro-1-(2-methoxyphenyl)ethyl]-
aniline (3ef): According to the general procedure, 4-tert-bu-
tylaniline (2f, 86.0 mg, 0.575 mmol), 2,2,2-trifluoro-1-(2-me-
thoxyphenyl)ethanone (1e, 118 mg, 0.575 mmol) and AlMe3
in heptane (0.86 mL, 0.86 mmol) were reacted in dry CH2Cl2
(2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
14:1, v/v) afforded 3ef as a colourless solid; yield: 88.0 mg
(45%); Rf =0.54 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
+
+
[MÀCF3 ], 317 (8) [C15H9F6N+], 240 (23) [C6H3F6 ]; HR-
MS: m/z=464.9778 (C16H9BrF9N), calcd.: 464.9774; anal.
calcd. for C16H9BrF9N: N 3.00, C 41.23, H 1.95; found: N
2.88, C 41.27, H 1.92.
4-tert-Butyl-N-(2,2,2-trifluoro-1-p-tolylethyl)aniline (3df):
According to the general procedure, 4-tert-butylaniline (2f,
86.0 mg, 0.575 mmol), 2,2,2-trifluoro-1-p-tolylethanone (1d,
108 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 49:1, v/v) afforded 3df as a col-
ourless oil; yield: 150 mg (81%); Rf =0.69 (c-Hex/EtOAc,
(400 MHz, CDCl3): d=1.25 [s, 9H, CACHTNUGTRNEUNG(CH3)3], 3.91 (s, 3H,
OCH3), 4.41 (d, J=8.5 Hz, 1H, NH), 5.52 (dq, J=7.7 Hz,
J=7.7 Hz, 1H, CHCF3), 6.62 (m, 2H, Ar-H-2,6), 6.97 (m,
2H, Ar-H-3’,4’), 7.19 (m, 2H, Ar-H-3,5), 7.33 (ddd, J=
8.3 Hz, J=7.5 Hz, J=1.7 Hz, 1H, Ar-H-5’), 7.41 (d, J=
7.6 Hz, 1H, Ar-H-6’); 13C NMR (100 MHz, CDCl3): d=31.4
1
10:1, v/v). H NMR (400 MHz, CDCl3): d=1.26 (s, 9H, C-
[+, CACTHGNUTRENNU(G CH3)3], 33.9 [Cquart, CACHTUGNTRENUN(GN CH3)3], 53.5 (q, J=30.5 Hz, +,
A
CHCF3), 55.8 (+, OCH3), 111.1 (+, C-Ar-3ꢄ), 113.3 (+, C-
Ar-2,6), 121.0 (+, C-Ar-5ꢄ), 122.9 (Cquart, C-Ar-1ꢄ), 125.5 (q,
J=282.3 Hz, Cquart, CF3), 126.1 (+, C-Ar-3,5), 128.2 (+, C-
Ar-4’), 130.0 (+, C-Ar-6’), 141.6 (Cquart, C-Ar-4), 143.4
(Cquart, C-Ar-1), 157.5 (Cquart, C-Ar-2’); 19F NMR (376 MHz,
6.61 (d, J=8.6 Hz, 2H, Ar-H-2,6), 7.18–7.23 (m, 4H, Ar-H-
3,5,3’,5’), 7.36 (d, J=7.8 Hz, 2H, Ar-H-2’,6’); 13C NMR
(100 MHz, CDCl3): d=21.2 (+, CH3), 31.4 [+, C
33.9 [Cquart, C(CH3)3], 60.5 (q, J=29.8 Hz, 1H, CHCF3),
˜
113.6 (+, C-Ar-2,6), 125.2 (q, J=281.8 Hz, Cquart, CF3), 126.1
(+, C-Ar-3,5), 127.8 (+, C-Ar-3’,5’), 129.6 (+, C-Ar-2’,6’),
131.3 (Cquart, C-Ar-1’), 138.9 (Cquart, C-Ar-4’), 141.9 (Cquart, C-
Ar-4), 143.2 (Cquart, C-Ar-1); 19F NMR (376 MHz, CDCl3):
CDCl3): d=À74.1 (s, 3F, CF3); IR (KBr): n=3419 (m), 2963
(s), 2905 (m), 2868 (m), 2842 (m), 1615 (s), 1521 (vs), 1493
(s), 1465 (s), 1440 (s), 1394 (m), 1364 (s), 1320 (s), 1300 (s),
1248 (vs), 1171 (vs), 1125 (vs), 1086 (m), 1051 (m), 1028 (s),
897 (m) cmÀ1; MS (70 eV, EI): m/z (%)=337 (64) [M+], 322
˜
d=À74.1 (s, 3F, CHCF3); IR (KBr): n=3420 (w), 3029 (w),
+
+
2963 (w), 2868 (w), 1907 (vw), 1729 (vw), 1617 (w), 1521
(w), 1483 (w), 1410 (w), 1363 (w), 1251 (w), 1122 (w), 1022
(vw), 898 (vw) cmÀ1; MS (70 eV, EI): m/z (%)=323/322/321
(100) [MÀCH3 ], 268 (92) [MÀCF3 ], 189 (14) [C9H8F3O+],
109 (19) [C6H5N+], 77 (8) [C6H5 ]; HR-MS: m/z=337.1656
+
(C19H22NOF3), calcd.: 337.1653.
+
(1/10/54) [M+], 308/307/306 (1/16/100) [MÀCH3 ], 252 (21)
N-[2,2,2-Trifluoro-1-(2-methoxyphenyl)ethyl]-3,5-bis(tri-
fluoromethyl)aniline (3eg): According to the general proce-
+
+
[MÀCF3 ], 173 (7) [C9H8F3 ]; EI-HR-MS: m/z=321.1701
(C19H22F3N), calcd.: 321.1704; anal. calcd. for C19H22F3N: N
4.36, C 71.01, H 6.90; found: N 4.12, C 71.09, H 6.96.
dure,
3,5-bis(trifluoromethyl)aniline
(2f,
132 mg,
0.575 mmol), 2,2,2-trifluoro-1-(2-methoxyphenyl)ethanone
(1e, 118 mg, 0.575 mmol) and AlMe3 in heptane (0.86 mL,
0.86 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.58 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 14:1, v/v) afforded 3eg as a col-
ourless solid; yield: 62.0 mg (26%); Rf =0.52 (c-Hex/EtOAc,
N-(2,2,2-Trifluoro-1-p-tolylethyl)-3,5-bis(trifluoromethyl)-
aniline (3dg): According to the general procedure, 3,5-bis-
ACHTUNGTRENNUNG(trifluoromethyl)aniline (2g, 86.0 mg, 0.575 mmol), 2,2,2-tri-
fluoro-1-p-tolylethanone (1d, 108 mg, 0.575 mmol) and
AlMe3 in heptane (0.86 mL, 0.86 mmol) were reacted in dry
Adv. Synth. Catal. 2010, 352, 2815 – 2824
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2821

Nadine Allendçrfer et al.
FULL PAPERS
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=3.94 (s, 3H,
CH3), 4.99 (d, J=8.9 Hz, 1H, NH), 5.59 (m, 1H, CHCF3),
7.01 (dd, J=14.7 Hz, J=7.8 Hz, 2H, Ar-H-3’,4’), 7.08 (s, 2H,
Ar-H-3,5), 7.23 (s, 1H, Ar-H-4), 7.35–7.42 (m, 2H, Ar-H-
5’,6’); 13C NMR (100 MHz, CDCl3): d=53.1 (q, J=31.4 Hz,
+, CHCF3), 55.7 (+, CH3), 111.2 (+, C-Ar-3’), 112.0 (m, +,
C-Ar-4), 113.0 (q, J=3.3 Hz, +, C-Ar-2,6), 121.1 (Cquart, C-
Ar-1’), 121.3 (+, C-Ar-5’), 123.4 (q, J=272.6 Hz, Cquart, 2ꢃ
CF3), 125.0 (q, J=282.1 Hz, Cquart, CHCF3), 128.0 (+, C-Ar-
4’), 130.8 (+, C-Ar-6’), 132.6 (q, J=32.9 Hz, C-Ar-3,5),
Ar-H-4); 13C NMR (100 MHz, CDCl3): d=34.1 (+, CH3),
52.7 (q, J=32.5 Hz, +, CHCF3), 107.6 (+, C-pyrrole-3),
109.0 (+, C-pyrrole-4), 112.4 (m, +, C-Ar-2,4,6), 123.3 (q,
J=272.7 Hz, Cquart, CHCF3), 123.6 (Cquart, C-pyrrole-2), 124.5
(+, C-pyrrole-5), 124.8 (q, J=282.8 Hz, Cquart, 2ꢃAr-CF3),
132.8 (q, J=33.0 Hz, Cquart, C-Ar-3,5), 146.4 (Cquart, C-Ar-6);
19F NMR (376 MHz, CDCl3): d=À73.4 (s, 3F, CHCF3),
˜
À63.2 (s, 6F, 2ꢃAr-CF3); IR (KBr): n=3446 (w), 3397 (m),
3061 (w), 2954 (w), 2924 (w), 2854 (w), 2824 (w), 2675 (vw),
2527 (vw), 2236 (vw), 2122 (vw), 2025 (vw), 1969 (vw), 1743
(w), 1620 (w), 1526 (w), 1475 (m), 1441 (w), 1389 (w), 1352
146.6 (Cquart
, C-Ar-1), 157.5 (Cquart,
C-Ar-2’); 19F NMR
(376 MHz, CDCl3): d=À63.3 (s, 6F, 2ꢃArCF3), À73.6 (s,
(w), 1267 (m), 1170 (m), 1090 (m), 1064 (w), 996 (w) cmÀ1
;
3F, CHCF3); IR (ATR): n=3457 (vw), 2850 (vw), 1625 (w),
MS (70 eV, EI): m/z (%)=391/390 (2/14) [M+], 322/321 (1/
˜
+
1604 (w), 1531 (vw), 1492 (w), 1467 (w), 1443 (w), 1396 (m),
1359 (w), 1274 (m), 1245 (m), 1166 (m), 1117 (m), 1084 (m),
1050 (w), 1025 (m), 995 (w) cmÀ1; MS (70 eV, EI): m/z
(%)=419/418/417 (0.3/5/18) [M+], 350/349/348 (1/12/100)
6) [MÀCF3 ], 163/162 (8/100) [C7H7F3N+]; EI-HR-MS: m/
z=390.0777 (C15H11N2F9), calcd.: 390.0778; anal. calcd. for
C15H11F9N2: N 7.18, C 46.17, H 2.84; found: N 7.04, C 46.39,
H 2.81.
+
[MÀCF3 ], 190/189 (1/7) [C9H8F3O+]; HR-MS: m/z=
4-Chloro-N-[2,2,2-trifluoro-1-(1-methyl-1H-imidazole-2-
yl)ethyl]aniline (7ba): According to the general procedure,
4-chloroaniline (2a, 214 mg, 1.68 mmol), CF3 ketone 6b
(300 mg, 1.68 mmol) and AlMe3 in heptane (5.05 mL,
5.05 mmol) were reacted in dry CH2Cl2 (10 mL). Addition
of BH3·SMe2 in THF (1.68 mL, 3.36 mmol) and column
chromatography (c-Hex/EtOAc, 10:1, v/v) afforded 7ba as a
yellow solid; yield: 198 mg (41%); Rf =0.11 (c-Hex/EtOAc,
10:1, v/v). 1H NMR (400 MHz, CDCl3): d=3.70 (s, 3H,
CH3), 4.93 (m, 1H, CHCF3), 5.14 (d, J=7.9 Hz, 1H, NH),
6.68–6.72 (m, 2H, Ar-H-3,5), 6.91 (d, J=1.0 Hz, 1H, imida-
zole-H-4), 7.07 (d, J=1.1 Hz, 1H, imidazole-H-5), 7.14–7.18
(m, 2H, Ar-H-2,6); 13C NMR (100 MHz, CDCl3): d=33.1
(+, CH3), 53.6 (q, J=32.6 Hz, +, CHCF3), 115.3 (+,C-Ar-
3,5), 122.7 (+, C-imidazole-4), 128.4 (+, C-imidazole-5),
124.4 (Cquart, C-Ar-1), 124.4 (q, J=283.8 Hz, Cquart, CF3),
129.3 (+, C-Ar-2,6), 140.3 (Cquart, C-Ar-4), 144.3 (Cquart, C-
imidazole-2); 19F NMR (376 MHz, CDCl3): d=À73.9 (s, 3F,
417.0777 (C17H12F9NO), calcd.: 417.0775.
4-Chloro-N-[2,2,2-trifluoro-1-(1-methyl-1H-pyrrole-2-yl)-
ethyl]aniline (7aa): According to the general procedure, 4-
chloroaniline (2a, 426 mg, 3.34 mmol), CF3 ketone 6a
(581 mg, 3.34 mmol) and AlMe3 in heptane (8.5 mL,
8.5 mmol) were reacted in dry CH2Cl2 (30 mL). Addition of
BH3·SMe2 in THF (7.1 mL, 14.1 mmol) and column chroma-
tography (c-Hex/EtOAc, 25:1, v/v) afforded 7aa as a yellow
solid; yield: 963 mg (77%); Rf =0.42 (c-Hex/EtOAc, 40/1, v/
1
v). H NMR (400 MHz, CDCl3): d=3.54 (s, 3H, CH3), 3.95
(d, J=7.8 Hz, 1H, NH), 4.97 (m, 1H, CHCF3), 6.14 (dd, J=
3.7 Hz, J=2.8 Hz, 1H, pyrrole-H-4), 6.33 (m, 1H, pyrrole-
H-5), 6.64 (t, J=2.1 Hz, 1H, Ar-H-5), 6.66 (t, J=1.9 Hz,
1H, Ar-H-3), 6.67 (m, 1H, pyrrole-H-3), 7.15 (t, J=3.3 Hz,
1H, Ar-H-6), 7.18 (t, J=3.3 Hz, Ar-H-2); 13C NMR
(100 MHz, CDCl3): d=34.2 (+, CH3), 53.5 (q, J=32.1 Hz,
+, CH-CF3), 107.5 (+, pyrrole-C-3), 108.5 (+, pyrrole-C-4),
114.5 (+, C-Ar-3,5), 124.0 (Cquart, C-pyrrole-2), 124.0 (+, C-
˜
CF3); IR (KBr): n=3391 (w), 3254 (w), 3175 (w), 3108 (w),
pyrrole-5), 124.7 (Cquart, CCl), 125.0 (q, J=282.8 Hz, Cquart
,
3035 (w), 2926 (w), 1871 (vw), 1601 (m), 1494 (m), 1420 (w),
1402 (w), 1345 (m), 1315 (m), 1269 (m), 1135 (m), 1093 (m),
1006 (w), 935 (w) cmÀ1; MS (70 eV, EI): m/z (%)=291/290/
CF3), 129.3 (+, C-Ar-2,6), 144.3 (Cquart, CNH); 19F NMR
˜
(376 MHz, CDCl3): d=À73.5 (s, 3F, CF3); IR (KBr): n=
+
3410 (m), 3107 (w), 3034 (w), 2977 (w), 2748 (w), 2819 (w),
2726 (vw), 2549 (vw), 1859 (w), 1751 (w), 1673 (w), 1597
(m), 1508 (m), 1421 (m), 1404 (m), 1355 (m), 1312 (m), 1294
(m), 1266 (m), 1239 (m), 1169 (s), 1130 (m), 1105 (m), 1090
(m), 1064 (m), 1003 (w), 914 (w) cmÀ1; MS (70 eV, EI): m/z
289 (15/7/46) [M+], 222/221/220 (32/13/100) [MÀCF3 ], 164/
+
163 (3/14) [C6H6F3N2 ], 83 (37), 58 (25), 43 (81); EI-HR-
MS: m/z=289.0596 (C12H11ClF3N3), calcd.: 289.0593.
N-[2,2,2-Trifluoro-1-(1-methyl-1H-imidazole-2-yl)ethyl]-
3,5-bis(trifluoromethyl)aniline (7bg): According to the gen-
eral procedure, 3,5-bis(trifluoromethyl)aniline (2g, 123 mg,
0.561 mmol), CF3 ketone 6b (100 mg, 0.561 mmol) and
AlMe3 in heptane (0.84 mL, 0.84 mmol) were reacted in dry
CH2Cl2 (2 mL). Addition of BH3·SMe2 in THF (0.56 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
10:1, v/v) afforded 7bg as a yellow oil; yield: 66.0 mg
(30%); Rf =0.06 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
(400 MHz, CDCl3): d=3.76 (s, 3H, CH3), 5.03 (dq, J=
7.6 Hz, J=5.7 Hz, 1H, CHCF3), 5.83 (d, J=7.6 Hz, 1H,
NH), 6.97 (d, J=1.1 Hz, 1H, imidazole-H-5), 7.10 (d, J=
1.1 Hz, 1H, imidazole-H-4), 7.13 (s, 2H, Ar-H-2,6), 7.28 (s,
1H, Ar-H-4); 13C NMR (100 MHz, CDCl3): d=33.2 (+,
CH3), 52.5 (q, J=33.2 Hz, +, CHCF3), 112.5 (m, +, C-Ar-
4), 113.1 (m, +, C-Ar-2,6), 123.1 (+, C-imidazole-5), 123.2
+
(%)=290/289/288 (5/2/15) [M+], 219 (1) [MÀCF3 ], 162
(100)
[C7H7F3N+];
EI-HR-MS:
m/z=288.0639
(C13H12ClN2F3), calcd.: 288.0641; anal. calcd. for
C13H12ClF3N2: N 9.70, C 54.08, H 4.19; found: N 9.39, C
54.37, H 4.51.
N-[2,2,2-Trifluoro-1-(1-methyl-1H-pyrrole-2-yl)ethyl]-3,5-
bis(trifluoromethyl)aniline (7ag): According to the general
procedure, 3,5-bis(trifluoromethyl)aniline (2g, 123 mg,
0.565 mmol), CF3 ketone 6a (100 mg, 0.565 mmol) and
AlMe3 in heptane (0.85 mL, 0.85 mmol) were reacted in dry
CH2Cl2 (2 mL). Addition of BH3·SMe2 in THF (0.56 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
10:1, v/v) afforded 7ag as a yellow solid; yield: 118 mg
(54%); Rf =0.39 (c-Hex/EtOAc, 10:1, v/v). 1H NMR
(400 MHz, CDCl3): d=3.60 (s, 3H, CH3), 4.43 (d, J=7.9 Hz,
1H, NH), 5.07 (m, 1H, CHCF3), 6.17 (dd, J=3.7 Hz, J=
2.8 Hz, 1H, pyrrole-H-4), 6.39 (m, 1H, pyrrole-H-3), 6.70
(m, 1H, pyrrole-H-5), 7.09 (s, 2H, Ar-H-2,6), 7.31 (s, 1H,
(q, J=272.6 Hz, Cquart, CHCF3), 124.1 (q, J=283.1 Hz, Cquart
,
2 ꢃ Ar-CF3), 128.5 (+, C-imidazole-4), 132.7 (q, J=33.1 Hz,
Cquart, C-Ar-3,5), 139.2 (Cquart, C-Ar-1), 146.5 (Cquart, C-imida-
zole-2); 19F NMR (376 MHz, CDCl3): d=À73.8 (m, 3F,
2822
asc.wiley-vch.de
ꢂ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 2815 – 2824

Expedient Trimethylaluminium-Promoted One-Pot Synthesis
˜
CHCF3), À63.3 (m, 6F, 2ꢃCF3); IR (KBr): n=3228 (w),
were reacted in dry CH2Cl2 (2 mL). Addition of BH3·SMe2
in THF (0.58 mL, 1.15 mmol) and column chromatography
(c-Hex/EtOAc, 19:1, v/v) afforded 11aa as a colourless oil;
yield: 144 mg (94%); Rf =0.72 (c-Hex/EtOAc, 10/1).
1H NMR (400 MHz, CDCl3): d=3.67 (d, J=13.4 Hz, 1H,
CH2), 3.83 (d, J=13.4 Hz, 1H, CH2), 4.14 (q, J=7.5 Hz, 1H,
CHCF3), 7.28–7.36 (m, 5H, Harom), 7.39–7.44 (m, 5H, Harom);
13C NMR (100 MHz, CDCl3): d=51.0 (-, CH2), 63.4 (q, J=
28.6 Hz, +, CHCF3), 125.4 (q, J=281.3 Hz, Cquart, CF3),
127.4 (+, C-Ar-4), 128.2 (+, Carom), 128.5 (+, Carom), 128.6
3076 (w), 2923 (w), 2852 (w), 2372 (vw), 2098 (vw), 1741
(vw), 1625 (w), 1570 (w), 1526 (w), 1475 (w), 1398 (w), 1353
(w), 1325 (vw), 1278 (w), 1171 (w), 1140 (w) cmÀ1; MS
(70 eV, EI): m/z (%)=392/391 (5/29) [M+], 324/323/322
+
+
(1/12/89) [MÀCF3 ], 164/163 (1/7) [C6H6F3N2 ], 83 (21), 58
(28), 43 (100); HR-MS: m/z=391.0729 (C14H10F9N3), calcd.:
391.0730.
3-Nitro-N-[2,2,2-trifluoro-1-(1-methyl-1-imidazole-2-yl)-
ethyl]aniline (7bj): According to the general procedure, 3-
nitroaniline (2j, 77.0 mg, 0.561 mmol), CF3 ketone 6b
(100 mg, 0.561 mmol) and AlMe3 in heptane (0.84 mL,
0.84 mmol) were reacted in dry CH2Cl2 (2 mL). Addition of
BH3·SMe2 in THF (0.56 mL, 1.15 mmol) and column chro-
matography (c-Hex/EtOAc, 5:1, v/v) afforded 7bj as a
yellow oil; yield: 168 mg (61%); Rf =0.48 (c-Hex/EtOAc,
(+, Carom), 128.7 (+, Carom), 129.0 (+, C-Ar-4’), 134.2 (Cquart
,
C-Ar-1), 139.0 (Cquart
,
C-Ar-1’); 19F NMR (376 MHz,
˜
CDCl3): d=À73.9 (s, 3F, CF3); IR (KBr): n=3346 (w), 3065
(m), 3032 (m), 2853 (w), 1955 (vw), 1605 (w), 1495 (m),
1455 (m), 1375 (m), 1263 (s), 1169 (s), 1124 (s), 1078 (m),
1029 (m), 973 (w) cmÀ1; MS (70 eV, EI): m/z (%)=265 (45)
+
+
[M+], 196 (100) [MÀCF3 ], 159 (58) [C8H6F3 ], 109 (53), 91
1
1:1, v/v). H NMR (400 MHz, CDCl3): d=3.76 (s, 3H, CH3),
+
+
(83) [C7H7 ], 77 (15) [C6H5 ]; HR-MS: m/z=265.1078
(C15H14NF3), calcd.: 265.1078.
5.07 (qd, J=5.9 Hz, J=7.9 Hz, 1H, CHCF3), 5.68 (d, J=
8.0 Hz, 1H, NH), 6.95 (d, J=1.1 Hz, 1H, imidazole-H-5),
7.07 (dd, J=8.2 Hz, J=2.4 Hz, 1H, Ar-H-4ꢄ), 7.09 (d, J=
1.2 Hz, 1H, imidazole-H-4), 7.33 (t, J=8.1 Hz, 1H, Ar-H-
5’), 7.58 (t, J=2.2 Hz, 1H, Ar-H-2’), 7.64 (ddd, J=8.1 Hz,
J=2.0 Hz, J=0.7 Hz, 1H, Ar-H-6’); 13C NMR (100 MHz,
CDCl3): d=29.7 (+, CH3), 52.6 (q, J=32.9, +, CHCF3),
107.1 (+, C-Ar-2), 114.1 (+, C-imidazole-5), 120.4 (+, C-
Ar-4’), 122.9 (+, C-Ar-6’), 124.2 (q, J=283.6 Hz, Cquart, CF3),
128.5 (C-Ar-5’), 130.1 (+, C-imidazole-4), 139.7 (Cquart, C-
Ar-1’), 146.6 (Cquart, C-Ar-3’), 149.3 (Cquart, C-imidazole-2);
19F NMR (376 MHz, CDCl3): d=À73.8 (s, 3F, CF3); IR
2,2,2-Trifluoro-1-(2-methoxyphenyl)-N-methylethanamine
(12ea): According to the general procedure, methylamine
(10a, 0.58 mL, 1.15 mmol, 2M in THF), 2,2,2-trifluoro-1-(2-
methoxyphenyl)ethanone (1e, 118 mg, 0.575 mmol) and
AlMe3 in heptane (0.86 mL, 0.86 mmol) were reacted in dry
CH2Cl2 (2 mL). Addition of BH3·SMe2 in THF (0.58 mL,
1.15 mmol) and column chromatography (c-Hex/EtOAc,
14:1, v/v) afforded 12ea as a colourless oil; yield: 94.0 mg
1
(74%); Rf =0.32 (c-Hex/EtOAc, 10/1). H NMR (400 MHz,
CDCl3): d=2.41 (s, 3H, CH3), 3.85 (s, 3H, OCH3), 4.64 (q,
J=7.8 Hz, 1H, CHCF3), 6.93 (d, J=8.3 Hz, 1H, Ar-H-3),
7.01 (td, J=7.6 Hz, J=0.9 Hz, 1H, Ar-H-4), 7.33 (ddd, J=
8.3 Hz, J=7.6 Hz, J=1.7 Hz, 1H, Ar-H-5), 7.38 (d, J=
8.3 Hz, 1H, Ar-H-6); 13C NMR (100 MHz, CDCl3): d=34.6
(+, CH3), 55.7 (+, OCH3), 58.6 (q, J=29.2 Hz, +, CHCF3),
111.0 (+, C-Ar-3), 120.9 (+, C-Ar-5), 122.8 (Cquart, C-Ar-1),
125.7 (q, J=281.8 Hz, Cquart, CF3), 128.2 (+, C-Ar-6), 129.8
(+, C-Ar-4), 158.0 (Cquart, C-Ar-2); 19F NMR (376 MHz,
˜
(KBr): n=3260 (m), 3148 (w), 3091 (w), 2924 (w), 2853 (w),
1950 (vw), 1620 (m), 1525 (m), 1495 (m), 1480 (m), 1438
(w), 1340 (m), 1264 (m), 1191 (m), 1162 (m), 1137 (m), 1114
(m), 995 (w) cmÀ1; MS (70 eV, EI): m/z (%)=301/300 (3/21)
[M+], 233/232/231 (0.6/6/46) [MÀCF3 ], 163 (4)
+
+
[C6H6F3N2 ], 58 (36), 43 (100); EI-HR-MS: m/z=300.0836
(C12H11O2F3N4), calcd.: 300.0834.
4-Chloro-N-[1,1,1-trifluoro-2-(1-methyl-1H-imidazole-2-
yl)propan-2-yl]aniline (8ba): For preparation see general
procedure and details for 7ba. Rf =0.20 (c-Hex/EtOAc, 10:1,
v/v). 1H NMR (400 MHz, CDCl3): d=1.95 (s, 3H, CH3),
3.69 (s, 3H, NCH3), 4.21 (bs, 1H, NH), 6.14 (m, 2H, Ar-H-
3,5), 6.87 (m, 1H, imidazole-H-5), 7.02 (m, 2H, Ar-H-2,6),
7.09 (m, 1H, imidazole-H-4); 13C NMR (100 MHz, CDCl3):
d=19.6 (+, CH3), 34.8 (+, NCH3), 61.5 (q, J=27.8 Hz,
˜
CDCl3): d=À73.5 (s, 3F, CF3); IR (KBr) n=3347 (w), 2945
(m), 2843 (w), 2807 (w), 1604 (m), 1590 (m), 1494 (m), 1466
(m), 1441 (m), 1363 (m), 1247 (s), 1162 (s), 1131 (s), 1052
(m), 1029 (m), 989 (w) cmÀ1; MS (70 eV, EI): m/z (%)=219
+
+
(2) [M+], 189 (2) [MÀNHCH3 ], 150 (100) [MÀCF3 ], 107
(14) [C7H7NO+], 77 (11) [C6H5 ]; HR-MS: m/z=219.0869
+
(C10H12NOF3), calcd.: 219.0870.
C
quart, CCF3), 116.4 (+, C-Ar-3,5), 124.7 (Cquart, C-Ar-1),
124.8 (+, C-imidazole-5), 125.7 (q, J=286.0 Hz, Cquart, CF3),
Acknowledgements
127.8 (+, C-imidazole-4), 129.3 (+, C-Ar-2,6), 141.1 (Cquart
,
C-Ar-4), 142.1 (Cquart, C-imidazole-2); 19F NMR (376 MHz,
We thank Bayer CropScience for funding this work.
˜
CDCl3): d=À77.5 (s, 3F, CF3); IR (KBr): n=3256 (s), 3178
(m), 3099 (m), 3033 (m), 2957 (w), 1876 (w), 1754 (w), 1706
(w), 1601 (s), 1522 (m), 1495 (s), 1400 (m), 1383 (m), 1347
(m), 1318 (m), 1277 (s), 1186 (s), 1169 (s), 1140 (s), 1093 (s),
1006 (m), 958 (m) cmÀ1; MS (70 eV, EI): m/z (%)=305/304/
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303 (28/13/80) [M+], 290/289/288 (3/3/9) [MÀCH3 ], 236/
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Adv. Synth. Catal. 2010, 352, 2815 – 2824