Formation of benzylamines from triazene compounds via a 1,2-proton shift

Article abstract of DOI:10.1016/j.tet.2006.04.063

A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group. The reaction contains the following steps: intramolecular carbon-carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that the reaction proceeds through a 1,2-proton shift.

Full text of DOI:10.1016/j.tet.2006.04.063

Tetrahedron 62 (2006) 7034–7042
Formation of benzylamines from triazene compounds
via a 1,2-proton shift
a,*
a
Keiji Nishiwaki, Takashi Ogawa, Kazumi Shigeta, Koichi Takahashi and Keizo Matsuo
a
b
a,*
a
Department of Pharmaceutical Sciences, School of Pharmacy, Kinki University,
3
-4-1 Kowakae Higashiosaka, Osaka 577-8502, Japan
Department of Informatics, School of Science and Engineering, Kinki University,
-4-1 Kowakae Higashiosaka, Osaka 577-8502, Japan
b
3
Received 5 April 2006; revised 18 April 2006; accepted 19 April 2006
Available online 22 May 2006
Abstract—A new approach to benzylamines using triazene compounds has been developed that is facilitated by the lithiation of aryltriazenes
followed by treatment with an electrophile. The regioselectivity of the reaction can be controlled by means of the substituents in the aryl group.
The reaction contains the following steps: intramolecular carbon–carbon bond formation involving lithiation of an alkyl group on a 3-nitrogen
atom; a 1,2-proton shift; and the subsequent release of nitrogen gas. Through the use of a deuterated triazene, we were able to determine that
the reaction proceeds through a 1,2-proton shift.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
investigations into the transformation of triazenes to benzyl-
amines. In fact, that reaction proceeded via a 1,2-proton
shift. Since a 1,2-proton shift on an aromatic ring has never
been reported, we demonstrated the phenomenon using
NMR, mass spectrometry, and computational chemistry.
Benzylamines are very important intermediates of fine
chemical derivatives such as biologically active compounds
and material chemicals. The methods of forming benzyl-
amines are well-known, for example, the condensation of
benzyl halide with amine derivatives and the reduction of
the benzonitriles etc. In the case of phenols and arylamines
as substrates, functionalized benzylamines were created
using the bimolecular aromatic Mannich reaction with
iminium salt. 1-Aryl-3,3-dialkyltriazenes are also used in
many ways in organic syntheses, including the following:
as protective groups for aniline derivatives; as substrates
of benzyne generation; in diazo coupling; in the
2. Results and discussion
2
.1. Formation of benzylamines
1
2
The alkyltriazenes were prepared from arylamines in good
yields according to the standard conditions (NaNO –HCl,
then the addition of respective amines). And trimethylsilyl-
3
2
4
5
13
6
Sandmeyer–Gattermann reaction; and in the hydroxylation
of positive ion exchange resins. Nicolaou et al. showed that
aryltriazenes are used in the construction of aryl ethers and
applied these results for the synthesis of vancomycin. In
phenyltriazenes were synthesized by way of the halogen–
metal exchange reaction from the corresponding bromophe-
nyltriazenes according to Welch’s procedure. The general
7
3a
8
procedure for the transformation of triazenes into benzyl-
amines is as follows: the alkyltriazenes were treated with
combinatorial chemistry, triazenes are used as linkers in
solid-phase synthesis and as alkylating polymers in solu-
9
ꢀ
n-BuLi (1 equiv) in THF at 0 C for 1 h, followed by the
1
0
tion-phase synthesis. Recently, Haley’s group has reported
the cyclization of 2-alkynylphenyl triazenes.
addition of electrophiles to produce the corresponding
benzylamine derivatives (Eq. 1).
1
1
We have previously reported the preliminary results of
a unique transformation of 3,3-dialkyl-1-aryltriazenes into
benzylamines. We now report the results of our further
R
1
2
N
N
R
E
N
1
2
) n-BuLi (1eq.)/THF
N
R
(1)
) Electrophile
X'
X
R
1-17
Keywords: C–C bond forming; Dearomatization; Nucleophilic addition;
1
*
,2-Proton shift; Triazene.
Corresponding authors. Tel.: +81 6721 2332; fax: +81 6730 1394; e-mail
addresses: k-nishi@phar.kindai.ac.jp; k-matsuo@phar.kindai.ac.jp
The aminoalkyl group of the benzylamines connected to
ortho position of the original triazenyl group was derived
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.04.063

K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
7035
Table 1. Results of transformation reaction of triazenes into benzylamines
In order to explain the interesting results above, we tried to
confirm the place of the first triazene deprotonations. When
3,3-dimethyl-1-phenyltriazene was treated with LDA
Entry
Substrates
Electrophile
Products
Yield
(%)
0
a
X
R
X
E
ꢀ
(1 equiv) at 0 C in the presence of chlorotrimethylsilane
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
Me
–(CH
H
H
H
H
H
H
H
H
H
H
H
H
2
O
n-BuBr
1
2
3
4
5
6
7
8
6
9
H
H
H
H
H
H
57
(1 equiv), 3-monosilylated- and 3,3-disilylated triazenes
18 and 19) were obtained at yields of 16 and 10%, respec-
n-Bu 78
Boc 81
Boc 47
Boc 69
H
H
(
(Boc)
(Boc)
(Boc)
2
2
2
O
O
O
tively (Scheme 1). We did not observe any silylated products
of the phenyl group, which are generated by the neighboring
effects of nitrogen atoms. In the absence of chlorotrimethyl-
silane, the same procedure created benzylmethylamine at
a yield of 48%. These results indicate that deprotonation
of the triazene with LDA occurred at the alkyl group on
H
2 2
) –
o-Me
m-Me
m-Me
p-Me
p-Me
m-MeO
p-MeO
o-F
H
H
2
O
O
m-Me
o,p-Me (2:1)
o,p-Me (2:1) Boc 90
m-Me
m-Me
74
71
2
(Boc)
O
2
O
H
2
H
95
10
11
12
13
14
15
16
17
18
19
20
21
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
(Boc)
2
2
2
2
2
2
2
2
2
2
2
2
O
O
O
O
O
O
O
O
O
O
O
O
Boc 95
Boc 70
Boc 65
Boc Trace
Boc 41
Boc 89
Boc 29
1
4
10 o-MeO
11 m-MeO
12 m-F
13 o-F
12 m-F
14 m-Cl
15 o,p-Cl (1:1) Boc 45
14 m-Cl
16 m-TMS
17 p-TMS
16 m-TMS
the 3-nitrogen atom and that the successive nucleophilic
attack of the carbanion to complete the reaction proceeded
on the aromatic ring.
m-F
p-F
1
5
We should also note that both Katritzky’s group and
o-Cl
m-Cl
p-Cl
o-TMS
m-TMS
p-TMS
1
6
H
H
H
H
Johnson’s group reported that 1-alkylated benzotriazoles
introduced some electrophiles on the 1-alkyl group via de-
protonation with the base (Scheme 2). These reports support
our results.
Boc 54
Boc 68
Boc 81
Boc 70
H
a
1
The ratio of diastereomers was determined by H NMR.
Katritzky's work
N
N
from the alkyl group on 3-nitrogen of the triazenyl group.
The results of transformation of the triazenes to benzylamines
are summarized in Table 1. The 3,3-dimethyl-1-phenyltri-
azene was transformed to benzylmethylamine (1) at a 57%
1
) n-BuLi, THF, -78°C
N
N
N
N
2
OMe
) Electrophile
OMe
E
yield, by treating first with n-BuLi and then with H O. The
2
Johnson's work
addition of (Boc) O instead of H O as an electrophile greatly
2
2
N
N
N
increased the isolated yield of 3 (81%) (entries 1 and 3).
When o- and p-methylphenyltriazenes were treated as
above, m-methylbenzylamines (6 and 9) were formed in
both cases, but the yield of the product was superior in the
latter case (entries 6, 9, and 10).
1) LDA, THF, -78°C
2) Electrophile
N
N
N
E
Scheme 2. Deprotonation position of 1-alkylated benzotriazoles.
As mentioned above, m-methoxy- and m-fluorophenyltri-
azenes exclusively created the o-substituted benzylamines
(10 and 13). These results can be accounted for by the
chelation control as shown in Scheme 3.
Other o- and p-substituted triazenes also gave m-substituted
benzylamine derivatives (11, 12, 14, and 16) (entries 12, 13,
1
5, 16, 18, 19, and 21). In entry 13, the desired product was
obtained in trace amount and the most of substrate was
remained. In the case of the m-methyl- and m-chlorophenyl-
triazenes, the mixtures of o- and p-substituted benzylamine
derivatives (7, 8, and 15) were obtained (entries 7, 8, and
N
N
N
N
N
N
CH2
Li
X = MeO, F
1
7). In contrast, m-methoxy- and m-fluorophenyltriazenes
H C
2
X
N
created the o-substituted benzylamines (10 and 13) exclu-
sively in moderate to good yields, and m-trimethylsilyl-
phenyltriazene gave p-trimethylsilylbenzylamine (17) as
the sole product (entries 11, 14, and 20). When o-, m-, and
p-bromophenyltriazenes were treated with n-BuLi (1 equiv)
as above, non-substituted triazene was obtained at yields of
X
X
Li
Li
Scheme 3. Chelation control by substituents on the aromatic ring.
Conversely, the observation that m-trimethylsilylphenyltri-
azene provided p-trimethylsilylbenzylamine (17) was attrib-
uted to the steric bulk of trimethylsilyl group (Scheme 4).
The regioselectivities of the carbon–carbon bond formation
were attributed to the electronic and steric features of the
substituents on the aromatic rings.
6
0, 32, and 41%, respectively. Similarly, trimethylsilyl-
phenyltriazenes were obtained from bromophenyltriazenes,
when chlorotrimethylsilane was used as an electrophile. It
seemed that these reactions proceeded via transmetallation
and then protonation, or trimethylsilylation.
TMS
N
N
LDA/THF
TMS-Cl
N
N
TMS
N
N
TMS
N
N
N
N
+
N
+
N
18
16%
19 10%
22%
Scheme 1. Deprotonation position.

7036
K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
CH3
Li
Li
N
N
C
N
N
CH3
N
H
2
N
N
N
N
CH2
N
Li
H2C
CH3
Li
Si
CH3
Si
CH3
Si
CH3
Si
CH3
3
H C
CH
3
3
H C
CH
3
H C
CH
3
3
H3C
CH3
Scheme 4. Steric control by substituents on the aromatic ring.
When the substituents on the benzene ring were the strongly
electron-withdrawing group like nitro group and trifluoro-
methyl groups, the reactions did not produce good results.
In the case of the nitro and trifluoromethyl groups, the tri-
azene reactions created complex mixtures containing
unidentified polymerized products. On the other hand, the
fluoro- and chlorophenyltriazenes were transformed to the
corresponding benzylamines in good to moderate yields.
Also, silyl substituted benzenes are very important inter-
mediates in organic synthesis, because the benzene nuclei are
easily transformed to various electron-withdrawing groups
1
7
by aromatic electrophilic ipso-desilylation. Consequently,
in order to get benzylamines, which are substituted with
electron-withdrawing groups, the silyl substituted products
(
16 and 17) may become valuable compounds.
2
.2. Proton source
1
Figure 1. H NMR spectrum of the products obtained from 20.
To reveal the proton source of the products, 1-(2,6-dideute-
riophenyl)-3,3-dimethyltriazene (20) was treated with base
1
2.3. Computational studies
(
Scheme 5). The H NMR spectra of the products (21+22)
indicated that the integrated value of peaks of the phenyl
protons is 3.6, while that of the methyl group protons is 3
The 1,2-proton shift on aromatic ring was proposed and veri-
fied by a computational study, because it had not yet been
reported. Semiempirical PM3 optimization, as demonstrated
in the WinMOPAC 2.0 program (Fujitsu Limited), was used
(
Fig. 1). This result indicated that the products involved
one or two deuterium atoms and one deuterium atom was ab-
stracted. The MS spectra of the benzylmethylamine and the
1
8
+
during the preliminary studies. We confirmed the reasonable
reaction coordinates by searching through the transition states
and conducting vibrational frequency analysis (Fig. 3). The
first anion of the molecule was located on the methyl group
ofnearsidetoN1–N2doublebond. Inthecasewheretheanion
stayed on another methyl group, the transition state 1 (TS1)
had no negative frequencies. When the new carbon–carbon
bond formed (I), the configuration of methyl group and the
proton of new ring junction was syn. When the two methyl
groupswereanticonfigured,wecouldnotachievethe required
optimized structure for the TS1. The second transition state
reaction products gave an (M ꢁ1) peak as the standard peak
and the parent peaks did not appear clearly. Therefore, the
amines were treated with acetic anhydride to provide the
amides. The MS spectra of the acetylated compounds
(
23+24) and N-benzyl-N-methylacetamide are shown in
Figure 2. In the former case, the parent peaks appeared at
m/z¼164 and 165, indicating that one or two deuterium
atoms remained in the products. This suggests that the pro-
ton, located on the ipso position of the triazenyl group in
the product, shifted from the o-position of the triazenyl
group and/or was abstracted by the THF of the solvent.
(TS2) contained reasonable coordinates among the intermedi-
ate (I) to the product (P) that possessed only one negative
ꢁ
1
vibrational frequency: ꢁ2303.5 cm
.
D
D
D
N
D
N
n-BuLi/THF
H
D
We performed precise ab initio calculations for the PM3 re-
sults using HyperChem software. We obtained the energies
N
H
N
+
H
N
19
(including electron correlation effects) from single point cal-
culations using second order perturbation theory according
20
21
22
D
D
2
0
to Møller and Plesset 2 (MP2/6-31G*). The nature of
each stationary point was verified by vibrational frequency
analysis. As this reaction was conducted in the hexane solu-
tion, we did not consider the solvent effect. In Figure 4,
the vertical line represents relative energy, and the abscissa
axis is the transition of the reaction. Unexpectedly, the
H
D
Ac
N
+
Ac
N
23
24
m/z: 164
m/z: 165
Scheme 5. Reaction of dideuterated triazene.

K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
7037
Figure 2. MS spectra of N-benzyl-N-methylacetamide (upper) and the mixture of 23 and 24 (lower).
TS 2
3
2
1
0
0
0
0
N
N
N
TS 1
N
27.67
N
N
N
N
16.36
722.8 cm
N
-2303.5 cm-1
N
anion
H
-1
-
H
-
0
-
-
-
-
-
10
20
30
40
50
N
N
H
N
N
I
N
P
26.61
H
-36.03
Reaction Progress
Figure 3. Potential energy correlation diagram and vibrational frequency analysis of reaction. Energy values are given in kcal/mol relative to isolated reactants.
N
N
N
TS 2'
4.38
N
N
N
6
5
4
3
2
1
0
0
0
0
0
0
0
H
6
N
H
N
N
TS 1'
2
3.07
I'
anion'
0
3
.23
-
-
-
-
-
-
10
20
30
40
50
60
N
N
N
N
N
N
H
H
P'
66.66
-
Reaction Progress
Figure 4. Potential energy surface calculated for the reaction of triazene and base via a mechanism involving 1,2-proton shift. Energy values are given in
kcal/mol relative to isolated reactants.

7038
K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
B
H
N
N
N
N
N
N
N
N
N
N
N
Base
N
N
X
X
X
X
X
H
N
N
path A
N
N
1,2-proton shift
N
N
-N2
H
N
N
N
X
X
X
X
H
H
path B
X
E
H
N
Sol.
H
H
N
H
N
N
N
N
E
N
X
H
Sol.
Scheme 6. The proposed reaction mechanism.
0
13
intermediate (I ) was 3.23 kcal/mol higher than the starting
anion, which suggests that the dearomatized compound
was comparatively stable. Although the second transition
C 125 MHz) spectrometers in CDCl or CD OD with
3 3
TMS as an internal standard. Mass spectra (EI) were re-
corded on a JMS-HX100 spectrometer. Infrared spectra
were recorded on a Shimadzu IR-435 spectrophotometer.
Unless otherwise noted, all materials were obtained from
commercial suppliers and used without further purification.
Tetrahydrofuran (THF) was freshly distilled under nitrogen
from sodium benzophenone ketyl prior to use.
0
state (TS2 ) needs extremely high energy (61.15 kcal/mol)
0
to activate I , it had one negative vibration and the 1,2-shift
of the proton reflected this experimental result. The release
of nitrogen was the driving force of this reaction.
2
.4. Reaction mechanism
4
.2. Preparation of triazenes
Considering the above results, we proposed the reaction
mechanism shown in Scheme 6. Deprotonation occurred on
the a-carbon of the 3-nitrogen. This anion took place in a
nucleophilic attack at the o-position to the triazenyl group
on the aryl group, similar to the Sommelet–Hauser rear-
rangement and formed a dearomatized intermediate like
the Meisenheimer complex. For further reactions, two possi-
ble routes were considered. In path A, a 1,2-proton shift
occurred. In path B, the solvent was involved in the reaction.
The proton that originated from the solvent was incorporated
into the anion. This was followed by the abstraction of the
proton with the anion derived from the solvent. The carban-
ion formed a double bond to reconstruct the benzene nuclei,
which released nitrogen gas continuously.
Most 1-aryl-3,3-dialkyltriazene was synthesized according
1
3
to the method described in the literature. And the tri-
methylsilylphenyltriazenes were synthesized by way of the
halogen–metal exchange reaction from the corresponding
2
1
3
a
bromophenyltriazene according to Welch’s procedure.
4
.2.1. Registry numbers of triazenes.
3
3
1
,3-Dimethyl-1-phenyltriazene
,3-Diethyl-1-phenyltriazene
-(Phenylazo)pyrrolidine
7227-91-0
13056-98-9
36719-71-8
20240-98-6
20241-03-6
7203-89-6
20241-03-6
7203-92-1
52010-51-2
52010-52-3
23456-94-2
20241-00-3
20241-05-8
7203-90-9
52010-61-4
7239-21-6
29878-94-2
3,3-Dimethyl-1-(2-methylphenyl)triazene
3
3
3
,3-Dimethyl-1-(3-methylphenyl)triazene
,3-Dimethyl-1-(4-methylphenyl)triazene
,3-Dimethyl-1-(3-methoxyphenyl)triazene
3. Conclusion
3,3-Dimethyl-1-(4-methoxyphenyl)triazene
1
1
1
1
-(2-Fluorophenyl)-3,3-dimethyltriazene
-(3-Fluorophenyl)-3,3-dimethyltriazene
-(4-Fluorophenyl)-3,3-dimethyltriazene
-(2-Chlorophenyl)-3,3-dimethyltriazene
We discovered a benzylamine forming reaction from 1-aryl-
,3-dialkyltriazene. It contained an intramolecular carbon–
3
carbon bond forming reaction. This reaction was proceeded
by an unusual 1,2-proton shift, which was revealed using the
deuterated triazene. In the case where the aryl group
possessed a strong electron-withdrawing group as nitro or
trifluoromethyl, this reaction was not permitted. These reac-
tions provide an alternative method for the preparation of
benzylamine derivatives and the new cleavage of triazenyl
linkers in the solid-phase synthesis.
1-(3-Chlorophenyl)-3,3-dimethyltriazene
1-(4-Chlorophenyl)-3,3-dimethyltriazene
1
1
1
-(2-Bromophenyl)-3,3-dimethyltriazene
-(4-Bromophenyl)-3,3-dimethyltriazene
-(3-Bromophenyl)-3,3-dimethyltriazene
4
.2.2. 3,3-Dimethyl-1-(2-trimethylsilylphenyl)triazene.
To a solution of 1-(2-bromophenyl)-3,3-dimethyltriazene
3.68 g, 16.1 mmol) in dry THF (16 mL) was added drop-
wise a solution of n-BuLi (10.0 mL, 1.72 mmol, 1.72 M in
(
4. Experimental
ꢀ
hexane) at ꢁ84 C. After stirring for 5 min, chlorotrimethyl-
4
.1. General methods
silane (2.08 mL, 16.4 mmol) was added dropwise, and the
mixture was stirred for 30 min at room temperature. The
reaction was quenched with water. Extractive work-up and
subsequent flash silica gel chromatography (hexane)
1
NMR spectra were recorded on JEOL GSX-270 ( H
2
1
3
1
70 MHz, C 67.5 MHz) or JEOL GX-500 ( H 500 MHz,

K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
7039
1
afforded the title compound as an oil (1.78 g, 8.03 mmol,
4.3.1. Benzylmethylamine (1). Oil, 57%; H NMR (CDCl )
3
1
13
5
7
1
0
1
0%); H NMR (CDCl ) d: 7.48 (dd, J¼7.0, 1.5 Hz, 1H),
d: 7.26 (m, 5H), 4.42 (s, 2H), 2.82 (s, 3H); C NMR
(CDCl ) d: 139.90, 127.97, 127.76, 126.52, 55.72, 35.65;
IR (neat) cm : 3500 (m), 3000 (m), 1680 (s), 1440 (m),
1380 (m), 1250 (m), 1140 (m), 870 (m), 680 (m); Low-MS
(EI) (m/z, %): 121 (M , 86), 120 (100), 104 (5.0), 91 (69),
3
.43 (dd, J¼8.0, 1.0 Hz, 1H), 7.32 (ddd, J¼8.0, 7.0,
3
ꢁ
1
.5 Hz, 1H), 7.12 (dd, J¼7.0, 1.0 Hz, 1H), 3.35 (br s, 6H),
1
3
.31 (s, 9H); C NMR (CDCl ) d: 155.59, 134.38, 129.90,
3
ꢁ
1
+
24.82, 115.46, 41.26, 39.39, ꢁ0.22; IR (neat) cm : 2900
(
(
s), 1580 (m), 1460 (s), 1400 (m), 1320 (s), 1250 (s), 1060
s), 830 (s), 750 (s); Low-MS (EI) (m/z, %): 221 (M , 27),
77 (11), 65 (18), 51 (11), 41 (61); HRMS: 121.0897
(Calcd for C H N, 121.0892).
+
8
11
2
1
2
06 (21), 178 (5), 163 (16), 149 (100), 135 (9), 121 (78),
05 (5.0), 91 (5.1), 73 (7.0), 59 (3.0), 43 (8.1); HRMS:
21.1354 (Calcd for C H N Si, 221.1349).
1
4.3.2. N-Benzyl-N-n-butylmethylamine (2). Oil, 78%; H
NMR (CDCl ) d: 7.33–7.19 (m, 5H), 3.48 (s, 2H), 2.36 (t,
1
1
19
3
3
J¼7.5 Hz, 2H), 2.18 (s, 3H), 1.50 (m, 2H), 1.33 (m, 3H),
1
3
0
.90 (t, J¼7.5 Hz, 3H); C NMR (CDCl ) d: 139.20,
3
4
.2.3. 3,3-Dimethyl-1-(3-trimethylsilylphenyl)triazene.
1
29.05, 128.18, 62.69, 57.27, 42.20, 29.54, 20.60, 14.05;
To a solution of 1-(3-bromophenyl)-3,3-dimethyltriazene
3.75 g, 16.4 mmol) in dry THF (16 mL) was added drop-
wise a solution of n-BuLi (10.0 mL, 1.72 mmol, 1.72 M in
ꢁ
1
IR (neat) cm : 2950 (s), 2920 (s), 2850 (s), 1640 (br m),
475 (br m), 1380 (m), 1260 (m); Low-MS (EI) (m/z, %):
(
1
+
ꢀ
177 (M , 8.8), 134 (84), 91 (100), 65 (6.3), 42 (5.0);
HRMS: 177.1508 (Calcd for C H N, 177.1517).
hexane) at ꢁ84 C. After stirring for 5 min, chlorotrimethyl-
1
2 19
silane (2.10 mL, 16.6 mmol) was added dropwise, and the
mixture was stirred for 30 min at room temperature. The
reaction was quenched with water. Extractive work-up and
subsequent flash silica gel chromatography (hexane/
4.3.3. N-Benzyl-N-(t-butoxycarbonyl)methylamine (3).
Oil, 81%; H NMR (CDCl ) d: 7.38–7.18 (m, 5H), 4.42 (s,
1
3
1
3
2H), 2.82 (s, 3H), 1.48 (s, 9H); C NMR (CDCl ) d:
155.87, 138.08, 128.47, 127.14, 79.62, 52.26, 33.86,
3
EtOAc¼19/1 as eluents) afforded the title compound as an
1
oil (3.04 g, 13.7 mmol, 84%); H NMR (CDCl ) d: 7.55
3
ꢁ
1
28.42; IR (neat) cm : 3000 (m), 1680 (s), 1440 (m), 1380
(m), 1250 (m), 1140 (m), 870 (m), 680 (m); Low-MS (EI)
m/z, %): 221 (M , 0.38), 165 (100), 140 (6.3), 120 (48),
(
(
m, 1H), 7.40 (m, 1H), 7.34 (dd, J¼7.0, 0.8 Hz, 1H), 7.30
1
3
dt, J¼3.0, 1.0 Hz, 1H), 3.34 (s, 6H), 0.28 (s, 9H);
C
+
(
NMR (CDCl ) d: 150.13, 141.09, 130.42, 128.27, 126.00,
3
ꢁ
1
91 (57), 77 (2.8), 65 (5.6), 57 (57), 51 (1.9), 41 (11);
HRMS: 221.1443 (Calcd for C H NO , 221.1416).
1
20.33, 39.09, ꢁ1.08; IR (neat) cm : 2900 (m), 1570
1
3
19
2
(
(
(
(
w), 1440 (s), 1380 (s), 1300 (s), 1240 (s), 1070 (s), 820
s), 740 (s); Low-MS (EI) (m/z, %): 221 (M , 26), 206
10), 177 (5), 149 (100), 135 (5), 121 (28), 105 (3.0), 88
5.0), 73 (45), 67 (3.0), 45 (4.0); HRMS: 221.1367 (Calcd
+
4.3.4. N-(t-Butoxycarbonyl)-N-methyl(a-methylbenzyl)-
amine (4). Oil, 47%; H NMR (CDCl ) d: 7.48–7.28 (m,
1
3
5
1
3
1
2
7
2
H), 5.42 (br s, 1H), 3.10 (br m, 1H), 2.93 (br m, 1H),
.52 (d, J¼2.0 Hz, 3H), 1.46 (s, 9H), 0.98 (t, J¼2.0 Hz,
for C H N Si, 221.1349).
11 19 3
1
3
H); C NMR (CDCl ) d: 155.80, 142.18, 128.21, 127.04,
3
4
.2.4. 3,3-Dimethyl-1-(4-trimethylsilylphenyl)triazene.
To a solution of 1-(4-bromophenyl)-3,3-dimethyltriazene
3.66 g, 16.0 mmol) in dry THF (16 mL) was added drop-
ꢁ1
26.93, 53.10, 38.13, 28.51, 17.49, 15.24; IR (neat) cm
950 (m), 1680 (s), 1450 (s), 1400 (s), 1280 (s), 1130 (m),
:
(
+
60 (m), 700 (m); Low-MS (EI) (m/z, %): 249 (M , 0.63),
34 (0.44), 193 (100), 178 (75), 164 (10), 148 (14), 134
wise a solution of n-BuLi (10.0 mL, 1.72 mmol, 1.72 M in
ꢀ
hexane) at ꢁ84 C. After stirring for 5 min, chlorotrimethyl-
(
5
72), 120 (7.5), 105 (87), 91 (5), 77 (15), 72 (6), 57 (78),
(3.5), 41 (16); HRMS: 249.1715 (Calcd for
C H NO , 249.1729).
silane (2.10 mL, 16.6 mmol) was added dropwise, and the
mixture was stirred for 30 min at room temperature. The
reaction was quenched with water. Extractive work-up and
subsequent flash silica gel chromatography (hexane/
1
1
5
23
2
4
6
4
1
1
4
.3.5. 1-(t-Butoxycarbonyl)-2-phenylpyrrolidine (5). Oil,
9%; H NMR (CDCl ) d: 7.12–7.34 (m, 5H), 4.95 and
CHCl ¼4/1 as eluents) afforded the title compound as an
1
3
3
1
oil (2.68 g, 12.1 mmol, 76%); H NMR (CDCl ) d: 7.48
3
.75 (br s, 1H), 3.61 (d, 3H), 2.30 (br s, 1H), 1.87 (m, 3H),
.45 (s, 3H), 1.18 (s, 6H); C NMR (CDCl ) d: 160.95,
(
3
1
dd, J¼8.0, 3.0 Hz, 2H), 7.39 (dd, J¼8.0, 3.0 Hz, 2H),
13
3
1
3
.34 (br s, 6H), 0.26 (s, 9H); C NMR (CDCl ) d: 151.39,
3
52.44, 137.77, 131.16, 125.96, 121.09, 81.66, 63.96,
0.11, 33.69, 28.24, 26.93, 16.54; IR (neat) cm : 2950
36.93, 133.95, 119.86, 41.29, 37.36, ꢁ1.00; IR (neat)
ꢁ1
ꢁ
1
cm : 2950 (s), 1590 (s), 1450 (s), 1410 (s), 1380 (s),
1
(m), 1680 (s), 1600 (w), 1480 (m), 1450 (m), 1380 (s),
320 (s), 1250 (s), 1070 (s), 820 (s), 750 (s); Low-MS (EI)
1
%
250 (m), 1150 (m), 900 (m), 730 (m); Low-MS (EI) (m/z,
): 247 (M , 0.23), 191 (100), 174 (27.5), 163 (4.4), 146
+
(
1
m/z, %): 221 (M , 28), 206 (10), 178 (5.1), 149 (100),
35 (3.0), 121 (28), 73 (15); HRMS: 221.1357 (Calcd for
C H N Si, 221.1349).
+
(
(
(
85), 131 (24), 119 (37), 104 (12), 91 (23), 77 (88), 70
21), 65 (2.5), 57 (72), 51 (3.1), 41 (20); HRMS: 247.1589
Calcd for C H NO , 247.1572).
1
1 19 3
1
5
21
2
4.3. General procedure for transformation of triazenes
into benzylamines
4.3.6. Methyl(m-methylbenzyl)amine (6). Oil, 74% from
o-methylphenyltriazene, 95% from m-methylphenyltri-
1
To a solution (0.5–1 M) of triazene in dry THF was added
ꢀ
azene; H NMR (CDCl ) d: 7.05–7.24 (m, 4H), 3.71 (s,
3
13
dropwise a solution of n-BuLi/hexane (1.0 equiv) at 0 C.
2H), 2.45 (s, 3H), 2.35 (s, 3H); C NMR (CDCl ) d:
3
After stirring for 1 h, the reaction mixture was quenched
with water or each electrophile (1.5 equiv). Extractive
work-up and the subsequent purification afforded benzyl-
amine derivatives.
158.21, 156.21, 147.15, 146.46, 145.89, 143.40, 74.24,
54.22, 39.55; IR (neat) cm : 3315 (m), 2923 (s), 2790 (s),
ꢁ
1
1608 (s), 1444 (s), 1379 (w), 1351 (w); Low-MS (EI) (m/z,
%): 135 (M , 31), 134 (58), 120 (25), 106 (19), 91 (36), 77
+

7040
K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
(
1
31), 44 (100); HRMS: 135.1039 (Calcd for C H N,
9
35.1048).
4.3.11. N-(t-Butoxycarbonyl)-N-methyl(m-methoxy-
benzyl)amine (11). Oil, 96%; H NMR (CDCl ) d: 7.24 (t,
13
1
3
J¼7.8 Hz, 1H), 7.24 (m, 3H), 4.40 (s, 2H), 3.80 (s, 3H),
1
3
4
.3.7. A mixture of methyl(o-methylbenzyl)amine and
2.82 (br s, 3H), 1.48 (s, 9H); C NMR (CDCl ) d: 159.82,
3
methyl(p-methylbenzyl)amine (7). Oil, o/p¼2/1, 71%;
139.75, 129.47, 119.59, 112.94, 112.56, 79.62, 55.13,
52.48, 33.88, 28.43; IR (neat) cm : 2900 (m), 1680 (s),
1
3
ꢁ1
mixture: C NMR (CDCl ) d: 137.95, 136.78, 136.60,
3
1
5
3
1
36.21, 130.23, 129.06, 128.36, 128.17, 126.97, 125.88,
5.65, 53.55, 36.30, 35.80, 21.06, 18.89; IR (neat) cm
318 (m), 3019 (m), 2934 (s), 2789 (s), 1513 (w), 1460 (s),
379 (w), 1354 (w), 1131 (w), 1096 (m), 804 (m), 743 (s).
1600 (s), 1420 (br s), 1280 (br s), 1040 (m), 870 (m), 760
(m); Low-MS (EI) (m/z, %): 251 (M , 5.0), 195 (100), 170
ꢁ
1
+
:
(6.3), 150 (35), 136 (5.0), 122 (58), 107 (2.5), 91 (10), 78
(63), 57 (44), 41 (10); HRMS: 251.1503 (Calcd for
C H NO , 251.1521).
1
4
21
3
1
Major product (o-isomer): H NMR (CDCl ) d: 7.27–7.30
3
(
m, 1H), 7.15–7.18 (m, 3H), 3.74 (s, 2H), 2.50 (s, 3H),
.35 (s, 3H), 1.87 (br s, 1H); IR (neat) cm : 3318 (m),
019 (m), 2934 (s), 2789 (s), 1513 (w), 1460 (s), 1379 (w),
4.3.12. N-(t-Butoxycarbonyl)-N-methyl(m-fluorobenzyl)-
amine (12). Oil, trace from o-fluorophenyltriazene, from
89% p-fluorophenyltriazene; H NMR (CDCl ) d: 7.29 (dt,
3
ꢁ
1
2
3
1
1
354 (w), 1131 (w), 1096 (m), 804 (m), 743 (s); Low-MS
J¼6.0, 7.8 Hz, 1H), 6.89–7.03 (m, 3H), 4.41 (br s, 2H),
+
13
(
EI) (m/z, %): 135 (M , 36), 134 (14), 120 (11), 104 (100),
2.83 (br s, 3H), 1.48 (s, 9H); C NMR (CDCl ) d: 163.26
3
9
(
1 (19), 77 (28), 51 (17), 44 (67); HRMS: 135.1053
Calcd for C H N, 135.1048).
(d, J ¼246 Hz), 155.70, 146.80, 140.82 (d, J ¼7.2 Hz),
CF
CF
129.96 (d, J ¼8.3 Hz), 122.89 (d, J ¼20.8 Hz), 114.02
9
13
CF
CF
(
d, J ¼20.8 Hz), 79.84, 52.24, 52.17, 34.02, 28.36; IR
CF
1
ꢁ1
Minor product (p-isomer): H NMR (CDCl ) d: 7.20 (d,
3
(neat) cm : 3020 (m), 2930 (m), 1690 (s), 1620 (w), 1590
(m), 1490 (m), 1450 (m), 1390 (s), 1370 (m), 1295 (w),
1250 (m), 1170 (m), 1145 (m), 1070 (m), 980 (w), 870
(w); Low-MS (EI) (m/z, %): 239 (M , 0.57), 183 (98), 166
(8.6), 138 (43), 109 (80), 83 (14), 57 (100), 41 (41);
HRMS: 239.1331 (Calcd for C H FNO , 239.1322).
J¼8.0 Hz, 2H), 7.13 (d, J¼8.0 Hz, 2H), 3.71 (s, 2H), 2.44
(
s, 3H), 2.33 (s, 3H), 1.87 (br s, 1H); Low-MS (EI) (m/z,
+
+
%
): 135 (M , 35), 134 (56), 120 (27), 105 (56), 91 (36), 77
33), 51 (25), 44 (86), 42 (100); HRMS: 135.1032 (Calcd
for C H N, 135.1048).
(
9
13
13 18
2
4
(
.3.8. A mixture of N-(t-butoxycarbonyl)-N-methyl
o-methylbenzyl)amine and N-(t-butoxycarbonyl)-N-
4.3.13. N-(t-Butoxycarbonyl)-N-methyl(o-fluorobenzyl)-
amine (13). Oil, 41%; H NMR (CDCl ) d: 7.24 (m, 1H),
1
3
1
methyl(p-methylbenzyl)amine (8). Oil, o/p¼2/1, 90%; H
7.12 (dd, J¼7.5, 1.5 Hz, 1H), 6.99–7.09 (m, 2H), 4.48 (br
1
3
NMR (CDCl ) d (major product): 7.14 (m, 4H), 4.44 (2H),
3
s, 2H), 2.87 (br s, 3H), 1.47 (s, 9H); C NMR (CDCl ) d:
3
2
7
.79 (br s, 3H), 2.28 (2H), 1.53 (s, 9H); (minor product):
.14 (m, 4H), 3.38 (2H), 2.79 (br s, 3H), 2.34 (2H), 1.48
160.67 (d, J ¼246 Hz), 155.80, 129.48 (d, J ¼32.2 Hz),
CF
CF
128.77 (d, J ¼8.3 Hz), 124.94 (d, J ¼15.6 Hz), 124.11,
CF
CF
1
3
(
s, 9H); C NMR (CDCl ) d: 155.91, 136.77, 135.00,
3
115.21 (d, J ¼21.8 Hz), 79.71, 46.18, 45.33, 34.13,
CF
ꢁ
1
129.16, 127.10, 125.96, 79.59, 49.84, 28.45, 28.41, 27.40,
18.98; IR (neat) cm : 2950 (m), 1780 (br s), 1690 (s),
1460 (s), 1370 (s), 1280 (s), 1250 (s), 840 (m), 760 (m).
28.35; IR (neat) cm : 2990 (m), 2930 (m), 1710 (s), 1690
(s), 1620 (w), 1590 (m), 1490 (m), 1445 (m), 1395 (m),
1370 (m), 1250 (m), 1225 (m), 1175 (m), 1145 (m), 1050
ꢁ1
(
w), 1025 (w), 875 (w), 830 (w), 750 (m); Low-MS (EI)
+
4.3.9. N-(t-Butoxycarbonyl)-N-methyl(m-methylbenzyl)-
amine (9). Oil, 95%; H NMR (CDCl ) d: 7.22 (t,
(m/z, %): 239 (M , 0.28), 183 (98), 166 (6.0), 138 (57),
109 (86), 83 (13), 57 (100), 41 (37); HRMS: 239.1346
(Calcd for C H FNO , 239.1322).
1
3
J¼8.0 Hz, 1H), 7.10–6.97 (m, 3H), 4.39 (br s, 2H), 2.81
1
3
18
2
1
3
(
br s, 3H), 2.34 (s, 3H), 1.48 (s, 9H); C NMR (CDCl ) d:
3
1
5
1
55.98, 138.08, 137.98, 128.36, 127.86, 124.34, 79.55,
2.47, 33.83, 28.42, 21.38; IR (neat) cm : 2900 (m),
680 (s), 1650 (m), 1380 (br s), 1250 (s), 1120 (br s), 870
4.3.14. N-(t-Butoxycarbonyl)-N-methyl(m-chlorophenyl-
methyl)amine (14). Oil, 29% from o-chlorophenyltriazene;
ꢁ1
1
54% from p-chlorophenyltriazene; H NMR (CDCl ) d: 7.22
3
13
+
(
m), 760 (m), 730 (m); Low-MS (EI) (m/z, %): 235 (M ,
(m, 4H), 4.40 (s, 2H), 2.86 (s, 3H), 1.48 (s, 9H); C NMR
1
1
.3), 179 (100), 164 (7.5), 146 (3.0), 134 (46), 120 (15),
05 (75), 91 (11), 77 (13), 65 (5.0), 57 (74), 51 (2.5), 41
(CDCl ) d: 155.62, 140.21, 134.36, 129.74, 128.43,
3
127.31, 125.28, 79.87, 52.09, 34.02, 28.35; IR (neat)
ꢁ
1
(
20); HRMS: 235.1581 (Calcd for C H NO , 235.1572).
1
cm : 2900 (m), 1680 (s), 1600 (m), 1580 (m), 1420 (br
m), 1250 (s), 1140 (s), 880 (m), 780 (m), 680 (m); Low-
MS (EI) (m/z, %): 255 (M , 0.23), 199 (82), 182 (8.8), 164
4
21
2
+
4.3.10. N-(t-Butoxycarbonyl)-N-methyl(o-methoxy-
benzyl)amine (10). Oil, 70%; H NMR (CDCl ) d: 7.23
1
(5.0), 154 (33), 125 (70), 111 (3.1), 99 (5.0), 89 (15), 77
(3.5), 57 (100), 51 (2.5), 41 (26); HRMS: 255.1031 (Calcd
for C H ClNO , 255.1026).
3
(
br t, J¼7.9 Hz, 1H), 7.14 (br d, J¼7.0 Hz, 1H), 6.93 (dt,
J¼1.0, 8.0 Hz, 1H), 6.88 (d, J¼8.0 Hz, 1H), 4.44 (s, 2H),
1
3
18
2
1
3
3
(
.82 (s, 3H), 2.85 (br s, 3H), 1.45 (s, 9H); C NMR
CDCl ) d: 157.30, 156.17, 128.05, 126.16, 120.43,
4.3.15. A mixture of N-(t-butoxycarbonyl)-N-methyl
(o-chlorobenzyl)amine and N-(t-butoxycarbonyl)-N-
3
1
(
13.87, 110.14, 79.34, 55.19, 47.34, 34.30, 28.43; IR
neat) cm : 2950 (m), 1690 (s), 1600 (m), 1460 (s), 139
ꢁ1
methyl(p-chlorobenzyl)amine (15). Oil, o/p¼1/1, 45%;
13
1
(s), 1250 (s), 1140 (s), 1020 (m), 880 (m), 750 (m); Low-
MS (EI) (m/z, %): 251 (M , 2.5), 195 (61), 180 (1.9), 150
H NMR (CDCl ) d: 7.27 (m, 4H), 4.55 (d, 2H), 2.87 (d,
3
+
3H), 1.46 (m, 9H); C NMR (CDCl ) d: 155.95, 135.44,
129.50, 128.47, 128.23, 127.75, 126.91, 79.82, 50.18, 34.38,
3
(
(
100), 136 (39), 121 (58), 108 (3.1), 91 (40), 78 (8.1), 65
8.8), 57 (56), 51 (3.8), 41 (11); HRMS: 251.1506 (Calcd
ꢁ1
28.36; IR (neat) cm : 2950 (m), 1680 (s), 1480 (br s),
1390 (s), 1250 (s), 1140 (br s), 1040 (m), 880 (m), 740 (m).
for C H NO , 251.1521).
4
1
21
3

K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
7041
4.3.16. N-(t-Butoxycarbonyl)-N-methyl(m-trimethylsilyl-
benzyl)amine (16). Oil, 67% from o-trimethylsilylphenyl-
dropwise a solution of n-BuLi (3.50 mL, 5.10 mmol, 1.45 M
ꢀ
in hexane) at ꢁ80 C. After stirring for an additional 1 h,
1
triazene, 70% from p-trimethylsilylphenyltriazene;
NMR (CDCl ) d: 7.31 (m, 4H), 4.42 (br s, 2H), 2.81 (br s,
H
MeOD (0.29 mL, 7.00 mmol) was added and the mixture
was stirred for 30 min at room temperature. The reaction
was quenched with water and extracted with ether. The
extracts were dried over sodium sulfate, filtered, and con-
centrated in vacuo. To a solution of the residue in dry THF
(2.9 mL) was added dropwise a solution of n-BuLi
3
1
3
3
1
3
1
H), 1.48 (s, 9H), 0.26 (s, 9H); C NMR (CDCl ) d:
3
55.82, 140.78, 137.21, 132.17, 127.86, 79.63, 52.79,
3.91, 28.45, ꢁ1.15; IR (neat) cm : 2950 (m), 1690 (s),
ꢁ
1
460 (s), 1390 (s), 1250 (s), 1150 (s), 820 (s), 750 (s);
+
ꢀ
Low-MS (EI) (m/z, %): 293 (M , 0.13), 237 (100), 222
(3.50 mL, 5.10 mmol, 1.45 M in hexane) at ꢁ80 C. After
(
(
(
48), 206 (3.5), 192 (28), 178 (23), 163 (39), 149 (13), 135
5.0), 120 (37), 103 (13), 91 (3.8), 86 (9.4), 73 (21), 57
68), 41 (10); HRMS: 293.1817 (Calcd for C H NO Si,
stirring for an additional 1 h, MeOD (0.29 mL, 7.00 mmol)
was added and the mixture was stirred for 30 min at room
temperature. The reaction was quenched with water.
Extractive work-up and subsequent flash silica gel chroma-
1
6
27
2
2
93.1811).
tography (hexane/EtOAc¼19/1 as eluents) afforded 20
13
1
4.3.17. N-(t-Butoxycarbonyl)-N-methyl(p-trimethylsilyl-
benzyl)amine (17). Oil, 81%; H NMR (CDCl ) d: 7.49
(0.312 g, 59%); H NMR (CDCl ) d: 7.33 (d, J¼7.2 Hz,
3
1
2H), 7.105–7.165 (t, J¼7.2 Hz, 1H), 3.33 (br s, 6H); C
NMR (CDCl ) d: 150.81, 128.77, 128.67, 125.34, 120.5,
3
(
2
d, J¼7.5 Hz, 2H), 7.21 (d, J¼7.5 Hz, 2H), 4.42 (s, 2H),
3
1
3
ꢁ1
.82 (br s, 3H), 1.48 (s, 9H), 0.26 (s, 9H); C NMR
CDCl ) d: 155.91, 139.20, 138.63, 133.54, 79.63, 52.54
120.20 (t, JCD¼23.9 Hz), 120.0, 41.13; IR (neat) cm
:
760 (s), 640 (w), 610 (m), 560 (w); Low-MS (EI) (m/z,
(
(
1
3
ꢁ
1
+
d), 33.91, 28.45, 28.07, ꢁ1.13; IR (neat) cm : 2950 (m),
%): 151 (M , 28), 107 (50), 79 (100), 52 (10), 42 (4);
HRMS: 151.1050 (Calcd for C H N D , 151.1076).
690 (s), 1470 (s), 1350 (s), 1130 (m), 830 (s), 750 (m);
8
9 3 2
+
Low-MS (EI) (m/z, %): 293 (M , 0.44), 237 (97), 222
100), 206 (2.5), 192 (25), 178 (28), 163 (31), 147 (12),
35 (15), 120 (27), 103 (7.5), 91 (3.5), 73 (14), 57 (51), 41
8.8); HRMS: 293.1806 (Calcd for C H NO Si,
(
1
(
4.3.20. N-Benzyl-N-methylacetamide. To a solution of
N-methylbenzylamine (0.121 g, 1.00 mmol) in Et N
3
(1 mL) was added dropwise Ac O (0.15 mL, 2.00 mmol)
2
1
6
27
2
ꢀ
with water. Extractive work-up and subsequent flash silica
2
93.1811).
at 0 C. After stirring for 1 h, the reaction was quenched
4.3.18. 3-Methyl-1-phenyl-3-(trimethylsilylmethyl)tri-
azene (18) and 1-phenyl-3,3-bis-(trimethylsilylmethyl)-
triazene (19). To a solution of lithium diisopropylamide
[prepared from diisopropylamine (0.14 mL, 1.00 mmol)
and n-BuLi (0.64 mL, 1.01 mmol, 1.58 M in hexane)] in
dry THF (1 mL) was added chlorotrimethylsilane (0.13 mL,
gel chromatography (hexane/EtOAc¼3/2 as eluents) af-
1
forded the title compound (0.123 g, 76%); H NMR
(500 MHz; CD OD) d: 7.19–7.37 (m, 5H), 4.61 and 4.57
3
1
3
(2H), 2.97 and 2.97 (3H), 2.16 and 2.15 (3H); C NMR
(125 MHz; CDCl ) d: 170.92, 170.61, 137.15, 136.36,
3
128.78, 128.41, 127.83, 127.46, 127.17, 126.13, 54.06,
50.41, 35.35, 33.56, 21.63, 21.25; Low-MS (EI) (m/z, %):
1
0
0
.03 mmol). 3,3-Dimethyl-1-phenyltriazene (0.147 mg,
.99 mmol) was added dropwise to the above solution at
C. The mixture was stirred for 30 min and warmed up
+
163 (M , 100), 148 (5), 120 (43), 106 (53), 91 (40), 79 (5),
72 (8), 65 (10), 51 (5), 43 (20).
ꢀ
to room temperature. The reaction was quenched with water.
Extractive work-up and subsequent flash silica gel chroma-
tography (hexane/EtOAc¼99/1 as eluents) afforded 18
4.3.21. A mixture of N-methyl-(3-deuteriobenzyl)amine
(21) and N-methyl-(2,3-dideuteriobenzyl)amine (22).
To a solution of 1-(2,6-dideuteriophenyl)-3,3-dimethyltri-
azene (20) (0.324 g, 2.14 mmol) in dry THF (2.1 mL) was
added dropwise a solution of n-BuLi (1.47 mL, 2.14 mmol,
(
0.034 g, 16%) and 19 (0.029 g, 10%).
1
1
8: H NMR (CDCl ) d: 7.32–7.15 (m, 4H), 7.00 (tt, J¼8.2,
3
1
3
ꢀ
1.8 Hz, 1H), 3.00–3.50 (envelope, 5H), 0.04 (s, 9H);
NMR (CDCl ) d: 151.09, 128.77, 124.70, 120.28, 39.97,
C
1.45 M in hexane) at 0 C. After stirring for 1 h, the reaction
was quenched with water. Extractive work-up and sub-
sequent short path distillation (0.77 mmHg) afforded the
mixture of title compounds (0.099 g); H NMR (500 MHz;
3
ꢁ1
1
1
%
7
1.7, ꢁ1.05; IR (neat) cm : 2952 (s), 1594 (s), 1457 (s),
1
436 (s), 1387 (s), 1346 (s), 852 (s); Low-MS (EI) (m/z,
+
): 221 (M , 6.1), 153 (6.9), 135 (8.3), 105 (40), 77 (100),
3 (93), 59 (15), 51 (23), 43 (31); HRMS: 221.1330
CD OD) d: 7.34–7.21 (m, 4H), 3.68 (s, 2H), 2.36 (s, 3H);
3
+
Low-MS (EI) (m/z, %): 124 (12.5), 123 (M , 37), 122
(100), 105 (5), 93 (34), 92 (55), 78 (10), 66 (10), 51 (8),
(
Calcd for C H N Si, 221.1348).
11 19 3
4
4 (58); HRMS: 123.1025 (Calcd for C H ND , 123.1025).
8 9 2
1
1
3
9: H NMR (CDCl ) d: 7.31–6.95 (m, 5H), 3.24 (s, 2H),
3
1
3
.10 (s, 2H), 0.11 (s, 9H), 0.01 (s, 9H); C NMR (CDCl3)
4.3.22. A mixture of N-(3-deuteriobenzyl)-N-methyl-
acetamide (23) and N-(2,3-dideuteriobenzyl)-N-methyl-
acetamide (24). To a solution of a mixture of N-methyl
(3-deuteriobenzyl)amine and N-methyl(2,3-dideuterio-
benzyl)amine (0.220 g) in Et N (1.78 mL) was added drop-
3
wise Ac O (0.19 mL, 2.00 mmol) at 0 C. After stirring for
2
d: 151.22, 128.75, 124.06, 120.09, 49.13, 44.96, ꢁ0.52,
ꢁ
1
ꢁ
1.29; IR (neat) cm : 3065 (s), 2897 (m), 1595 (m),
482 (m), 1455 (s), 1415 (s), 1388 (s), 1358 (s), 1248 (s),
1
1
2
4
2
+
183 (s), 853 (s); Low-MS (EI) (m/z, %): 293 (M , 0.4),
ꢀ
78 (0.9), 188 (18), 105 (27), 73 (100), 69 (25), 59 (28),
5 (29); HRMS: 293.1730 (Calcd for C H N Si ,
93.1776).
1 h, the reaction was quenched with water. Extractive work-
up and subsequent flash silica gel chromatography (hexane/
1
4
27
3
2
EtOAc¼3/2 as eluents) afforded the title compounds
1
4
.3.19. 1-(2,6-Dideuteriophenyl)-3,3-dimethyltriazene
20). To a solution of 1-(2,6-dibromophenyl)-3,3-dimethyl-
(0.065 g); H NMR (500 MHz; CD OD) d: 7.20–7.40 (m,
3
(
triazene (1.08 g, 3.50 mmol) in dry THF (2.9 mL) was added
4H), 4.59 and 4.53 (s, 2H), 2.95 and 2.92 (s, 3H), 2.163
and 2.158 (s, 3H); C NMR (125 MHz; CDCl ) d: 170.92,
1
3
3

7042
K. Nishiwaki et al. / Tetrahedron 62 (2006) 7034–7042
1
1
1
3
1
1
70.62, 137.23, 137.16, 136.44, 136.35, 128.82, 128.53,
3413; (d) Br a¨ se, S.; Schroen, M. Angew. Chem., Int. Ed.
1999, 38, 1071; (e) Br a¨ se, S.; K o¨ bberling, J.; Enders, D.;
Lazny, R.; Wang, M.; Brandtner, S. Tetrahedron Lett. 1999,
40, 2105; (f) Br a¨ se, S.; Dahmen, S.; Heuts, J. Tetrahedron
Lett. 1999, 40, 6201; (g) Dahmen, S.; Br a¨ se, S. Angew.
Chem., Int. Ed. 2000, 39, 3681; (h) Br a¨ se, S.; Dahmen, S.;
Pfefferkorn, M. J. Comb. Chem. 2000, 2, 710; (i) Enders, D.;
Rijksen, C.; Bremus-K o¨ bberling, E.; Gillner, A.; K o¨ bberling,
J. Tetrahedron Lett. 2005, 45, 2839.
28.45, 128.34, 128.17, 127.88, 127.76, 127.41, 127.21,
27.11, 126.19, 126.08, 54.14, 54.09, 50.46, 50.42, 35.40,
3.60, 24.03, 21.70, 21.31, 13.56; Low-MS (%) 167 (3.5),
+
+
66 (22), 165 (M , 100), 164 (M , 98), 163 (16), 150 (5),
22 (38), 121 (43), 108 (50), 107 (54), 93 (39), 92 (41), 79
(
5), 72 (10), 52 (5), 43 (27).
Acknowledgements
10. Rademann, J.; Smerdka, J.; Jung, G.; Grosche, P.; Schmid, D.
Angew. Chem., Int. Ed. 2001, 40, 381.
Thanks are due to Professor M. Morita, JRC Kinki
University, for the mass spectral analyses. This research
was supported in part by Grant-in-Aid for Encouragement
for Young Scientists, Japan Society for the Promotion of
Science.
11. Kimball, D. B.; Weakley, T. R.; Haley, M. M. J. Org. Chem.
2002, 67, 6395.
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2002, 41, 484.
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4. (a) Seebach, D.; Enders, D. Chem. Ber. 1975, 108, 1293; (b)
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