Redox-photosensitized amination of alkenes and alkadienes with ammonia and alkylamines

Article abstract of DOI:10.1016/j.tet.2006.10.064

Using 1,2,4-triphenylbenzene as a photosensitizer, the photoamination of alkenes and alkadienes (1), which had no absorption at >300 nm proceeded efficiently in the presence of p-dicyanobenzene to give addition products by incorporating both amino and p-c

Full text of DOI:10.1016/j.tet.2006.10.064

Tetrahedron 63 (2007) 374–380
Redox-photosensitized amination of alkenes and alkadienes
with ammonia and alkylamines
a
b
b
b
Toshiaki Yamashita,a, Junichi Itagawa, Daichi Sakamoto, Yuji Nakagawa, Jin Matsumoto,
*
Tsutomu Shiragamib and Masahide Yasudab,
*
aDepartment of Chemical Science and Engineering, Miyakonojo National College of Technology, Miyakonojo,
Miyazaki 885-8567, Japan
bDepartment of Applied Chemistry, Faculty of Engineering, University of Miyazaki, Gakuen-Kibanadai, Miyazaki 889-2192, Japan
Received 9 August 2006; revised 24 October 2006; accepted 25 October 2006
Available online 15 November 2006
Abstract—Using 1,2,4-triphenylbenzene as a photosensitizer, the photoamination of alkenes and alkadienes (1), which had no absorption at
>300 nm proceeded efficiently in the presence of p-dicyanobenzene to give addition products by incorporating both amino and p-cyanophenyl
groups. The reaction efficiency was discussed in terms of the relationships between 1 and the photosensitizer in their oxidation potentials and
ꢀ
the distribution of positive charge on the reaction site of the cation radical of 1 (1+ ).
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
2.1. Product analysis
Ammonia is the simplest nitrogen source in biological and
industrial syntheses. However, the common direct amination
to C–C double bond using ammonia has been scarcely re-
ported. Photochemical reactions make it possible for direct
amination with ammonia to provide a more convenient
synthetic method.1 We have successfully achieved the direct
amination of arenes and aryl-substituted alkenes by the
nucleophilic addition of ammonia to the cation radicals of
the substrates generated by photoinduced electron trans-
fer.2–7 However, simple alkenes are different from highly
conjugated system such as arenes and aryl-substituted al-
kenes in the photoreactivity, because simple alkenes have
relatively higher oxidation potentials, no aromatic groups
stabilizing their cation radicals, and weak absorption at
near UV region. For the photoinduced nucleophilic addition
of MeOH to simple alkenes, Arnold and his co-workers have
proposed a photo-NOCAS (photochemical nucleophile–
olefin combination, aromatic substitution) reaction by
photosensitization using biphenyl and p-dicyanobenzene
(DCB) system.8 Herein, we will report on the photo-NOCAS
type reaction of simple alkenes and alkadienes using ammo-
nia and alkylamines as nucleophiles.
Redox-photosensitization was applied to the photoamina-
tion of simple alkenes and alkadienes (1), which had no
absorption at >300 nm (Chart 1). The redox-photosensitiza-
ꢀ
tion9 generates a cation radical of 1 (1+ ) by the hole transfer
ꢀ
from the cation radical of a sensitizer (S+ ) generated by the
photoinduced electron transfer, as shown in Scheme 1. In the
present redox-photosensitized amination, 1,2,4-triphenyl-
benzene (TPB) and 2,20-methylenedioxy-1,10-binaphthalene
(BN) were used as sensitizers since TPB and BN have higher
Keywords: Redox-photosensitization; Photoamination; Addition reaction;
Electron-transfer.
* Corresponding authors. Tel./fax: +81 986 47 1314 (T.Y.); tel./fax: +81 985
58 7314 (M.Y.); e-mail addresses: photoya@cc.miyakonojo-nct.ac.jp;
yasuda@cc.miyazaki-u.ac.jp
Chart 1. The alkadienes (1a–f) and alkenes (1g–j) for photoamination. The
values are charge distribution on the carbon atom of the cation radicals of 1
calculated by ab initio method. The values given in bold italics correspond to
the amination sites.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.10.064

T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
375
Table 1. Redox-photosensitized amination of alkadienes and alkenes
(1a–j)a
Entry
1
RNH2
t (h)b Products
(yields, %)c
Recovery (%)
DCB
S
1
1a NH3
1a NH3
1a NH3
1a NH3
1a i-PrNH2
1a i-PrNH2
1a t-BuNH2
1a HO(CH2)2NH2
1a CH2]CHCH2NH2
1b NH3
1b NH3
1b NH3
1c NH3
8
8
8
8
8
8
8
8
8
2a (79)
8
0
94
44
—
99
98
—
99
99
99
94
—
99
99
2d
3e
4f
5
2a (93)
2a (33)
2a (0)
3a (70)
3a (5)
3b (62)
3c (62)
3d (73)
2b (57)
2b (16)
2b (0)
2c0 (42),
2c (16),
2c00 (7)
55
—
12
87
16
5
6
9
47
—
17
6e
7
8
9
10
11e
12f
13
8
24
24
8
Scheme 1. Redox-photosensitization.
ox
1/2
oxidation potentials (E vs Ag/AgNO3) than those of most
of 1 (Scheme 2) and were inert toward the nucleophilic attack
of ammonia and alkylamines.10 p-Dicyanobenzene (DCB)
was used as an electron acceptor for the present photoamina-
tion in order to isolate the photo-NOCAS type products.
14
1d NH3
1e NH3
8
8
2d0 (23),
2d (20),
2d00 (11)
2e (7),
43
67
73
82
15g
2e0 (10)
2f (85)h
2g (42),
4a (22)
2g (39),
4a (12)
2g (31),
4a (17)
3e (20),
2g (23),
5 (18), 6 (8)
2h (17),
4b (trace)
2i (43)i
2j (24)
16
17
1f NH3
1g NH3
8
8
9
14
91
94
18g
19d
20g
1g NH3
8
8
8
30
34
34
87
50
78
1g NH3
1g i-PrNH2
21g
1h NH3
20
74
95
22
23
1i NH3
1j NH3
10
20
27
33
100
74
a
Irradiation of an ammonia-saturated MeCN–H2O solution (19:1, 70 mL)
containing 1 (7 mmol), DCB (3.5 mmol), and sensitizer (1 mmol).
Irradiation time.
Isolated yields based on DCB used.
Using BN (1 mmol) as a sensitizer instead of TPB.
In the absence of TPB.
b
c
d
e
f
In the absence of DCB.
In the presence of Et4NBF4 (0.1 mol dmꢁ3).
cis and trans isomers ratio was 1:0.35.
cis and trans isomers ratio was 1:1.18.
g
h
i
(Table 1, entry 1). A similar type of product was formed
by the photoreaction of 1a with MeOH in the presence of
biphenyl and DCB pair.8b Also, the BN-photosensitized
amination of 1a gave 2a in a high yield (93%) (entry 2).
The photoamination of 1a without the sensitizer, however,
was inefficient (33%, entry 3). It was confirmed that the
TPB-photosensitization in the absence of DCB gave no ami-
nated product (entry 4). Scheme 3 summarizes the aminated
products with the optimal yields.
Scheme 2. Relationship between the oxidation potentials of 1a–j and those
of sensitizers.
The TPB-photosensitized amination of 2,4-hexadiene (1b)
with NH3 gave a diastereomeric mixture of 4-(4-amino-1-
methyl-2-pentenyl)benzonitrile (2b) in a 57% yield (entry
10). The regioselectivity was examined for the photoamina-
tion of unsymmetrical 2,4-dimethyl-1,3-pentadiene (1c) and
4-methyl-1,3-pentadiene (1d) with NH3. These photoamina-
tions gave both 1,4-adducts (2c,d and 2c0,d0) and a 1,2-ad-
duct (2c00 and 2d00) (entries 13 and 14). In the case of the
The TPB-photosensitized amination of 2,5-dimethyl-2,4-
hexadiene (1a) with NH3 was carried out by irradiation of
an ammonia-saturated MeCN–H2O solution (v/v, 19:1,
70 mL) containing 1a (7 mmol), DCB (3.5 mmol), and
TPB (1 mmol) by a high-pressure Hg lamp through a Pyrex
filter. (E)-4-(4-Amino-1,1,4-trimethyl-2-pentenyl)benzo-
nitrile (2a) incorporating both amino and p-cyanophenyl
groups into 1,4-positions of 1a was formed in a 79% yield
photoamination of 2,3-dimethyl-1,3-butadiene (1e) whose
ox
1/2
E
(1.64 V) was higher than that of TPB, no aminated

376
T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
typical photo-NOCAS adduct (2g) and unexpected azabi-
cyclo compound (4a) were formed in 42 and 22% yields,
respectively (Scheme 4, entry 17). The structure of 4a was
determined by X-ray crystallographic analysis (Fig. 1).
Arnold has reported that the photo-NOCAS reaction of 1g
with MeOH gave 4-(2-methoxy-1,1,2-trimethylpropyl)-
benzonitrile in a 70% yield as a sole product.8b The photo-
amination of 2-methyl-2-butene (1h) in the presence of
Et4NBF4 gave 4-(2-amino-1,1-dimethylpropyl)benzonitrile
(2h) and azabicyclo compound (4b) in low yields (entry
21). In the cases of 3,4-dihydro-2H-pyran (1i), cis and trans
isomers of 4-(3-amino-tetrahydro-2-pyranyl)benzonitrile
(2i) were obtained in a ratio of 1:1.18 (entry 22). 4-(2-Ami-
no-1-isobutoxyethyl)benzonitrile (2j) was obtained from the
photoamination of isobutyl vinyl ether (1j) (entry 23). In both
adducts, the amino group was incorporated on the b-carbon
of the double bond of these substrates, whereas no adduct in-
corporating the amino group on the a-carbon was obtained.
Scheme 3. Reagents: (i) hn, TPB, DCB, MeCN–H2O (19:1); Ar–¼p-NC–
ꢁ
.
C6H4
product was obtained. The photoamination gave 2e,e0 in low
yields in the presence of Et4NBF4 (0.1 mol dmꢁ3), which
was well known to enhance the efficiency of the electron
transfer (entry 15).10,11 The stereoselectivity was examined
for the photoamination of cyclopentadiene derivative (1f),
which gave an 85% yield of cis and trans isomers of 4-
(4-amino-1,2,3,4-tetramethyl-2-cyclopentenyl)benzonitrile
(2f) in a ratio of 1:0.35 (entry 16). The stereochemistry of
cis-2f was confirmed by X-ray crystallographic analysis of
the acetamide of cis-2f (Fig. 1).
The TPB-photosensitized amination was applied to simple
alkenes. In the case of 2,3-dimethyl-2-butene (1g), the
Scheme 4. Reagents: (i) hn, TPB, DCB, MeCN–H2O (19:1); Ar–¼p-NC–
ꢁ
.
C6H4
Also the photoaminations of 1a and 1g with alkylamines
were carried out by the TPB-photosensitization. Irradiation
was performed for a degassed MeCN–H2O (v/v, 19:1,
70 mL) containing 1 (7 mmol), DCB (3.5 mmol), TPB
(1 mmol), and the amines (70 mmol). The TPB-photosensi-
tized amination of 1a with isopropylamine, tert-butylamine,
ethanolamine, and allylamine gave the corresponding N-
alkyl substituted 2a (3a–d) in relatively good yields (entries
5, 7–9). The TPB-photosensitized amination was much more
effective than the photoamination without TPB (entry 6). In
the case of photoamination with ethanolamine, no product
Figure 1. Crystal structure of the acetamide of cis-2f and 4a.

T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
377
was derived by the attack from the oxygen site of ethanol-
amine to 1a, although MeOH acted as a nucleophile in
photo-NOCAS reaction of 1a.8 The photoamination of 1g
with isopropylamine gave considerable amounts of 5 and 6
along with the formation of aminated products (3e and 2g)
(entry 20).
higher and in the case of 1i and 1j little positive charge
was distributed over the reaction site. Moreover, the ami-
nated products of simple alkenes and alkadienes were en-
tirely photo-NOCAS type products, because their aminated
radicals (7) have no stabilizing groups.
2.2. Mechanism
4. Experimental
4.1. General
It was confirmed that TPB and BN played as redox-photo-
sensitizers in the above photoamination, since the photoami-
nation in the absence of DCB gave no aminated products and
almost incident light was absorbed by the sensitizer under
these reaction conditions. The value of free energy changes
(DG) for the electron transfer from TPB or BN to DCB was
Melting points were measured using open capillary tubes
and are uncorrected. 1H and 13C NMR spectra were recorded
in CDCl3 at 250 and 62.9 MHz, respectively. Chemical shifts
were reported in parts per million relative to TMS as an in-
ternal standard. Mass spectra were operated at an ionization
voltage of 70 eV. GLC analysis was performed using a 25 m
fused-silica capillary column. The ab initio calculation was
performed on a Silicon graphics O2 workstation using the
SPARTAN program.
calculated to be negative (ꢁ40 kJ molꢁ1 and ꢁ7 kJ molꢁ1
)
by the Rehm–Weller equation,12 as previously reported.10
Therefore, an initiation step of this photoamination should
be the electron transfer from the excited singlet states of
the sensitizer to DCB, resulting in the cation radicals of
ꢀ
the sensitizer and the anion radical of DCB (DCBꢁ ). The
hole transfer from the cation radicals of the sensitizer to 1
should be an important step for the efficient photoamination.
The efficient photoamination requires that E of 1 is lower
MeCN was distilled from CaH2. The amines were used as re-
ceived. Commercially available 1 was distilled from sodium
under reduced pressure before use, and TPB14 and BN15
were prepared according to literature method.
ox
1/2
than that of TPB. In fact, the TPB-photosensitized amination
of 1e and 1h whose E was near those of TPB gave the
ox
1/2
ꢀ
aminated products in low yields. The resulting 1+ allowed
4.2. General procedure of photoamination
the nucleophilic addition of RNH2 followed by the radical
ꢀ
coupling of the aminated radicals (7) with DCBꢁ to give
2 according to Scheme 1.
An ammonia-saturated MeCN–H2O solution (v/v, 19:1,
70 mL) of 1a–j (7 mmol), DCB (3.5 mmol), and sensitizer
(1 mmol) was poured into a Pyrex glass tube, sealed with
a rubber septum, and irradiated with a high-pressure mer-
cury lamp for 8–24 h at ambient temperature. In the cases
of photoamination with RNH2, a MeCN–H2O (v/v, 19:1,
70 mL) solution containing 1 (7 mmol), DCB (3.5 mmol),
and TPB (1 mmol) was bubbled with argon gas and then
RNH2 (70 mmol) was added and irradiated for 8 h. In the
photoamination in the presence of Et4NBF4, 7 mmol of
Et4NBF4 was added to the solutions (70 mL).
Moreover, we elucidated that the reaction efficiency and
regiochemistry depend on both the distribution of positive
ꢀ
charge in 1+ and the stability of 7 as previously re-
ported.4,7,10 Chart 1 shows the positive charge distribution
ꢀ
in 1+ calculated by ab initio method. When little positive
charge was distributed over the reaction site in the case of
1i and 1j, the photoaminations were inefficient.
Azabicyclo compounds 4 would be obtained via the ami-
nated anion (8) in competition with the elimination of CNꢁ
from 8 to give 2, as shown in Scheme 1. The photoamination
of 1g with i-PrNH2 gave not only aminated products (3e and
2g) but also 5 and 6. Probably, in competition with the addi-
After irradiation, the photolysates were treated with Ac2O to
protect the amino group of the aminated products, and then
sensitizer, DCB, and the acetamide of aminated products
were isolated by chromatography on silica gel. The struc-
tural determination of the acetamide was performed on the
basis of their spectroscopic and physical properties. In the
case of photoaminations of 1a with RNH2 (entries 5–9),
the photolysates were separated by chromatography on silica
gel without the treatment of Ac2O, because acetylation of
3a–d was unsuccessful. In particular, 3b was easily decom-
posed at room temperature, therefore the peaks of molecular
ion of 3b–d were not obtained in their mass spectra. In
the case of 5 and 6, the structural determination was per-
formed by comparisons of the data with those published in
the literature.16
ꢀ
ꢀ
tion of i-PrNH2 to 1g+ , the deprotonation from 1g+ occurred
to give the radical intermediate, which underwent radical
ꢀ
coupling with DCBꢁ and then followed by the elimination
of CNꢁ to give 5 and 6. However, it is possible that the for-
mation of 5 and 6 proceeds by the radical coupling process
proposed by Arnold in the photoreaction of 1g with DCB
in MeCN.13
3. Conclusions
The photoaminations of simple alkenes and alkadienes (1),
which had no absorption at >300 nm could be accomplished
using the redox-photosensitization. Efficient photoamina-
tions were achieved in the following cases: the oxidation po-
tentials of 1 were sufficiently lower than that of the sensitizer
and the sufficient positive charge distributes over the reac-
4.2.1. (E)-4-(4-Amino-1,1,4-trimethyl-2-pentenyl)benzo-
nitrile (2a). The acetamide; a white solid; mp 135.5–
136.0 ꢂC (from benzene–ethyl acetate); 1H NMR d 1.39 (s,
6H), 1.43 (s, 6H), 1.93 (s, 3H), 5.62 (br s, 1H), 5.63 (d,
J¼16.0 Hz, 1H), 5.73 (d, J¼15.9 Hz, 1H), 7.46–7.48 (m,
2H), 7.56–7.60 (m, 2H); 13C NMR d 24.35, 27.73, 28.58,
40.60, 53.75, 109.54, 119.15, 127.17, 131.98, 133.67,
ꢀ
tion site of 1+ . On the contrary, the photoaminations are in-
ox
1/2
efficient in the case of 1e and 1h whose E was relatively

378
T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
135.49, 154.86, 169.13; IR (CHCl3, cmꢁ1): 3442, 2972,
2229, 1675, 1505. HRMS calcd for C17H22N2O: 270.1732;
found: 270.1680. Calcd for C17H22N2O: C, 75.52; H, 8.20;
N, 10.36%. Found C, 75.43; H, 8.08; N, 10.29%.
118.94, 123.69, 126.96, 131.99, 140.98, 153.99, 169.80.
HRMS calcd for C15H18N2O: 242.1419; found: 242.1373.
4.2.7. 4-(4-Amino-4-methyl-2-pentenyl)benzonitrile
1
(2d0). The acetamide; a yellow oil; H NMR d 1.42 (s,
4.2.2. (E)-4-(4-Amino-1-methyl-2-pentenyl)benzonitrile
(2b). A yellow oil; IR (neat, cmꢁ1): 3287, 2972, 2228. The
acetamide; a yellow oil; 1H NMR d 1.22 (t, J¼6.8 Hz,
3H), 1.35 (d, J¼7.0 Hz, 3H), 1.96 (s, 3H), 3.45–3.55 (m,
1H), 4.50–4.60 (m, 1H), 5.47 (ddd, J¼15.5, 5.4, 1.2 Hz,
1H), 5.63 (br s, 1H), 5.71 (ddd, J¼15.5, 6.5, 1.3 Hz, 1H),
7.30 (d, J¼8.4 Hz, 2H), 7.58 (d, J¼8.3 Hz, 2H); 13C NMR
d 20.65, 20.70, 20.92, 23.24, 41.69, 46.18, 109.76, 119.00,
128.13, 131.73, 132.24, 133.16, 151.37, 169.41. HRMS
calcd for C15H18N2O: 242.1417; found: 242.1408.
6H), 1.93 (s, 3H), 3.42 (d, J¼6.6 Hz, 2H), 5.46 (br s, 1H),
5.60 (dt, J¼15.6, 6.7 Hz, 1H), 5.81 (dt, J¼15.6, 1.3 Hz,
1H), 7.30 (d, J¼8.3 Hz, 2H), 7.57 (d, J¼8.3 Hz, 2H); 13C
NMR d 27.55, 38.54, 53.77, 109.90, 119.00, 124.46,
129.29, 132.18, 138.67, 146.17, 169.15. HRMS calcd for
C15H18N2O: 242.1419; found: 242.1468.
4.2.8. 4-(1-Aminomethyl-3-methyl-2-butenyl)benzo-
nitrile (2d00). The acetamide; a yellow oil; 1H NMR d 1.66
(d, J¼1.1 Hz, 3H), 1.75 (d, J¼1.0 Hz, 3H), 1.93 (s, 3H),
3.30–3.42 (m, 1H), 3.49–3.60 (m, 1H), 3.77–3.87 (m, 1H),
5.20–5.27 (m, 1H), 5.58 (br s, 1H), 7.34 (d, J¼8.2 Hz,
2H), 7.60 (d, J¼8.4 Hz, 2H); 13C NMR d 18.24,
23.14, 25.82, 44.18, 44.65, 110.23, 118.78, 123.69,
128.35, 132.34, 136.15, 148.43, 170.07. HRMS calcd for
C15H18N2O: 242.1419; found: 242.1376.
4.2.3. 4-(4-Amino-1,1,3-trimethyl-2-butenyl)benzonitrile
(2c). The acetamide of E-isomer; a colorless oil; H NMR
1
d 1.13 (d, J¼1.1 Hz, 3H), 1.42 (s, 6H), 2.02 (s, 3H), 3.57
(d, J¼5.9 Hz, 2H), 5.61 (d, J¼1.3 Hz, 1H), 6.11 (br s, 1H),
7.46 (d, J¼8.6 Hz, 2H), 7.57 (d, J¼8.6 Hz, 2H); 13C NMR
d 15.80, 23.22, 31.00, 39.87, 47.53, 109.13, 119.13,
127.04, 132.04, 133.83, 135.35, 156.18, 170.17; IR (neat,
cmꢁ1): 3448, 3019, 2229, 1667. HRMS calcd for
C16H20N2O: 256.1575; found: 256.1566. The acetamide of
4.2.9. (E)-4-(4-Amino-2,3-dimethyl-2-butenyl)benzo-
nitrile (2e). The acetamide; a yellow oil; H NMR d 1.61
1
(d, J¼0.8 Hz, 3H), 1.77 (d, J¼0.8 Hz, 3H), 1.98 (s, 3H),
3.55 (s, 2H), 3.95 (d, J¼5.5 Hz, 2H), 5.56 (br s, 1H), 7.25
(d, J¼8.3 Hz, 2H), 7.58 (d, J¼8.3 Hz, 2H); 13C NMR
d 17.37, 19.00, 23.30, 40.00, 48.33, 110.62, 119.11,
128.02, 129.27, 130.38, 132.32, 146.12, 170.12. HRMS
calcd for C15H18N2O: 242.1419; found: 242.1376.
1
Z-isomer; a colorless oil; H NMR d 1.14 (d, J¼1.2 Hz,
3H), 1.44 (s, 3H), 1.45 (s, 3H), 1.93 (s, 3H), 3.40–3.57 (m,
2H), 5.47 (d, J¼1.2 Hz, 1H), 5.55 (br t, 1H), 7.48 (d,
J¼8.3 Hz, 2H), 7.61 (d, J¼8.3 Hz, 2H); 13C NMR d 19.86,
23.31, 24.97, 26.70, 44.43, 50.61, 109.85, 118.90, 127.78,
129.44, 132.15, 136.25, 152.68, 170.24. HRMS calcd for
C16H20N2O: 256.1575; found: 256.1564.
4.2.10. 4-(1-Aminomethyl-1,2-dimethylallyl)benzonitrile
1
(2e0). The acetamide; a yellow oil; H NMR d 1.40 (s,
4.2.4. 4-(4-Amino-2,4-dimethyl-2-pentenyl)benzonitrile
(2c0). The product was obtained as a mixture of E and Z iso-
mers. The acetamide of E-isomer; a colorless oil; 1H NMR
d 1.50 (s, 6H), 1.57 (d, J¼1.2 Hz, 3H), 1.80 (s, 3H), 3.65
(s, 2H), 5.65 (br s, 1H), 5.86 (br s, 1H), 7.30 (d, J¼8.1 Hz,
2H), 7.57 (d, J¼8.1 Hz, 2H); 13C NMR d 23.96, 24.16,
28.69, 38.04, 52.89, 109.83, 119.02, 129.42, 132.13,
132.23, 134.76, 145.35, 168.92; the acetamide of Z-isomer;
1H NMR d 1.48 (s, 6H), 1.61 (d, J¼1.2 Hz, 3H), 1.93 (s, 3H),
3.32 (s, 2H), 5.54 (br s, 1H), 5.79 (br s, 1H), 7.30 (d,
J¼8.1 Hz, 2H), 7.57 (d, J¼8.1 Hz, 2H); 13C NMR d 16.54,
23.86, 28.53, 47.35, 52.89, 109.83, 119.20, 129.63,
132.13, 132.99, 134.57, 145.97, 168.70. HRMS calcd for
C16H20N2O: 256.1575; found: 256.1575.
3H), 1.52 (d, J¼0.9 Hz, 3H), 1.97 (s, 3H), 3.64 (dd,
J¼13.2, 5.0 Hz, 1H), 3.78 (dd, J¼13.2, 6.5 Hz, 1H), 5.06
(s, 1H), 5.16–5.17 (m, 1H), 5.33 (br s, 1H), 7.40 (d,
J¼8.4 Hz, 2H), 7.64 (d, J¼8.4 Hz, 2H); 13C NMR d 20.19,
23.46, 23.90, 42.52, 45.78, 110.62, 113.82, 118.80,
127.45, 132.42, 147.68, 150.47, 170.33. HRMS calcd for
C15H18N2O: 242.1419; found: 242.1376.
4.2.11. 4-(4-Amino-1,2,3,4-tetramethyl-2-cyclopentenyl)-
benzonitrile (2f). The acetamide of cis-isomer; a white
1
solid; mp 141.5–142.0 ꢂC (from benzene); H NMR d 1.35
(s, 3H), 1.42 (s, 3H), 1.47 (s, 3H), 1.63 (s, 3H), 1.90 (s,
3H), 2.02 (d, J¼13.5 Hz, 1H), 2.67 (d, J¼13.5 Hz, 1H),
6.03 (s, 1H), 7.57 (d, J¼8.5 Hz, 2H), 7.63 (d, J¼8.5 Hz,
2H); 13C NMR d 9.79, 10.86, 23.79, 24.29, 26.86, 52.76,
54.32, 65.90, 108.99, 119.36, 127.93, 131.79, 135.84,
138.29, 155.22, 169.63; IR (CHCl3, cmꢁ1): 3442, 2973,
2227, 1673, 1506. HRMS calcd for C18H22N2O: 282.1731;
found: 282.1765. The acetamide of trans-isomer; a yellow
4.2.5. 4-(1-Aminomethyl-1,3-dimethyl-2-butenyl)benzo-
nitrile (2c00). The acetamide; a colorless oil; 1H NMR
d 1.70 (s, 3H), 1.75 (s, 6H), 1.85 (s, 3H), 3.33 (d, J¼
5.3 Hz, 2H), 5.20 (br s, 1H), 5.72 (br s, 1H), 7.48 (d,
J¼8.4 Hz, 2H), 7.59 (d, J¼8.4 Hz, 2H); 13C NMR d 22.11,
23.02, 28.69, 31.62, 40.04, 40.37, 109.47, 118.90, 127.03,
129.63, 133.52, 138.14, 156.66, 169.86. HRMS calcd for
C16H20N2O: 256.1575; found: 256.1525.
1
oil; H NMR d 1.30 (s, 3H), 1.47 (s, 3H), 1.52 (s, 3H),
1.69 (s, 3H), 1.95 (s, 3H), 2.01 (d, J¼13.8 Hz, 1H), 2.69
(d, J¼13.7 Hz, 1H), 6.07 (s, 1H), 7.31 (d, J¼8.4 Hz, 2H),
7.59 (d, J¼8.4 Hz, 2H); 13C NMR d 9.79, 11.13, 23.99,
25.16, 25.53, 53.32, 54.04, 65.84, 109.22, 119.10, 127.26,
132.04, 136.39, 138.41, 155.22, 169.75; IR (CHCl3,
cmꢁ1): 3449, 3019, 2229, 1667, 1517. HRMS calcd for
C18H22N2O: 282.1731; found: 282.1740.
4.2.6. 4-(4-Amino-1,1-dimethyl-2-butenyl)benzonitrile
(2d). The acetamide; a yellow oil; 1H NMR d 1.40 (s, 6H),
2.00 (s, 3H), 3.89 (dt, J¼5.9, 1.2 Hz, 2H), 5.49 (dt,
J¼15.6, 5.6 Hz, 1H), 5.70 (br s, 1H), 5.75 (dt, J¼15.6,
1.2 Hz, 1H), 7.42 (d, J¼8.4 Hz, 2H), 7.58 (d, J¼8.6 Hz,
2H); 13C NMR d 23.24, 28.33, 40.76, 41.36, 109.73,
4.2.12. 4-(2-Amino-1,1,2-trimethylpropyl)benzonitrile
(2g). The acetamide; a white solid; mp 133.0–133.5 ꢂC

T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
379
(from MeOH). 1H NMR d 1.34 (s, 6H), 1.46 (s, 6H), 1.90 (s,
3H), 4.94 (br s, 1H), 7.53 (d, J¼8.6 Hz, 2H), 7.62 (d,
J¼8.6 Hz, 2H), 13C NMR d 24.13, 24.58, 25.04, 46.39,
59.30, 110.19, 116.71, 128.84, 131.27, 151.63, 169.30; IR
(CHCl3, cmꢁ1): 3434, 2994, 2230, 1677, 1515. Calcd for
C15H20N2O: C, 73.74; H, 8.25; N, 11.47%. Found C,
73.27; H, 8.06; N, 11.41%.
4.2.18. (E)-4-[4-(2-Hydroxy-ethylamino)-1,1,4-tri-
methyl-2-pentenyl]benzonitrile (3c). A white solid; mp
76.5–78.0 ꢂC (from benzene); 1H NMR d 1.21 (s, 6H),
1.41 (s, 6H), 2.61–2.66 (m, 2H), 2.99 (br s, 2H), 3.62–3.66
(m, 2H), 5.45 (d, J¼16.1 Hz, 1H), 5.64 (d, J¼16.1 Hz,
1H), 7.42–7.46 (m, 2H), 7.57–7.60 (m, 2H); 13C NMR
d 27.44, 28.68, 40.68, 44.55, 53.59, 61.53, 109.55, 119.02,
127.04, 131.97, 135.15, 136.66, 154.73; IR (neat, cmꢁ1):
2970, 2229.
4.2.13. 4-(2-Amino-1,1-dimethylpropyl)benzonitrile (2h).
The acetamide; a yellow oil; 1H NMR d 0.90 (d, J¼6.8 Hz,
3H), 1.32 (s, 3H), 1.33 (s, 3H), 1.94 (s, 3H), 4.39 (dq, J¼9.8,
3.4 Hz, 1H), 5.16 (d, J¼10.4 Hz, 1H), 7.49 (d, J¼8.6 Hz,
2H), 7.62 (d, J¼8.5 Hz, 2H), 13C NMR d 16.79, 23.38,
23.65, 25.97, 42.65, 52.39, 110.34, 118.70, 127.41,
132.16, 152.50, 169.56. HRMS calcd for C14H18N2O:
230.1419; found: 230.1403.
4.2.19. (E)-4-(4-Allylamino-1,1,4-trimethyl-2-pentenyl)-
benzonitrile (3d). A yellow oil; H NMR d 1.21 (s, 6H),
1
1.42 (s, 6H), 3.12 (d, J¼6.1 Hz, 2H), 5.05 (dd, J¼10.1,
1.6 Hz, 1H), 5.15 (dd, J¼17.1, 1.6 Hz, 1H), 5.45 (d,
J¼16.1 Hz, 1H), 5.64 (d, J¼16.1 Hz, 1H), 5.92 (ddt,
J¼17.1, 10.1, 6.1 Hz, 1H), 7.42–7.46 (m, 2H), 7.56–7.59
(m, 2H); 13C NMR d 27.57, 28.70, 40.65, 46.06, 53.74,
109.58, 115.38, 118.95, 127.06, 131.91, 135.38, 136.41,
137.50, 154.73; IR (neat, cmꢁ1): 2969, 2227.
4.2.14. 4-(3-Amino-tetrahydro-2-pyranyl)benzonitrile
(2i). The acetamide of trans-isomer; a white solid; mp
208.0–209.0 ꢂC (from benzene–ethyl acetate); 1H NMR
d 1.51–1.69 (m, 1H), 1.76 (s, 3H), 1.80–2.01 (m, 2H), 2.12–
2.18 (m, 1H), 3.53 (dt, J¼3.0, 11.5 Hz, 1H), 3.91–4.12 (m,
2H), 4.12 (d, J¼9.8 Hz, 1H), 5.69 (d, J¼9.3 Hz, 1H), 7.49
(d, J¼8.3 Hz, 2H), 7.61 (d, J¼8.3 Hz, 2H); 13C NMR
d 23.16, 25.58, 30.87, 50.61, 68.25, 83.13, 111.79, 118.82,
128.17, 131.95, 144.89, 169.06; IR (CHCl3, cmꢁ1): 3435,
3011, 2230, 1672, 1512. HRMS calcd for C14H16N2O2:
244.1212; found: 244.1206. The acetamide of cis-isomer;
4.2.20. 4-(2-Isopropylamino-1,1,2-trimethylpropyl)-
benzonitrile (3e). A colorless oil; 1H NMR d 0.97 (d,
J¼6.3 Hz, 6H), 0.99 (s, 6H), 1.36 (s, 6H), 2.86 (sept,
J¼6.3 Hz, 1H), 3.23 (br s, 1H), 7.55 (d, J¼8.6 Hz, 2H),
7.61 (d, J¼8.6 Hz, 2H); 13C NMR d 22.69, 24.19, 26.29,
43.09, 45.85, 57.99, 109.22, 119.23, 129.63, 130.56,
153.18; IR (neat, cmꢁ1): 2973, 2226. HRMS (CI) calcd for
C16H25N2 (MH+): 245.2018; found: 245.2013.
1
a colorless oil; H NMR d 1.53–1.65 (m, 1H), 1.78 (s, 3H),
4.2.21. 3,3,4,4-Tetramethyl-2-azabicyclo[3.3.1]non-7-
ene-5,8-dicarbonitrile (4a). A white solid; mp 176.5–
1.81–2.09 (m, 3H), 3.63–3.74 (m, 1H), 4.16–4.28 (m, 1H),
4.42–4.54 (m, 1H), 4.63 (s, 1H), 6.06 (d, J¼9.0 Hz, 1H),
7.44 (d, J¼8.3 Hz, 2H), 7.61 (d, J¼8.3 Hz, 2H); 13C NMR
d 20.56, 22.99, 28.66, 47.15, 69.09, 79.46, 111.00, 118.84,
126.16, 131.92, 144.98, 169.49; MS m/z 244 (M+).
1
178.5 ꢂC (from MeOH); H NMR d 1.01 (s, 3H), 1.15 (s,
6H), 1.39 (s, 3H), 1.56 (br s, 1H), 1.86 (dd, J¼12.7,
2.6 Hz, 1H); 2.54 (ddd, J¼12.7, 3.6, 1.3 Hz, 1H), 2.86 (dd,
J¼21.0, 3.2 Hz, 1H), 3.12 (ddd, J¼21.0, 4.3, 1.3 Hz, 1H),
3.62 (dd, J¼3.6, 2.6 Hz, 1H), 6.58 (dd, J¼4.3, 3.2 Hz, 1H);
13C NMR d 20.99, 24.53, 27.67, 31.04, 31.92, 34.25,
40.03, 40.24, 46.98, 54.84, 118.00, 118.50, 123.88, 143.63;
IR (CHCl3, cmꢁ1): 2989, 2235, 2218; MS m/z 229 (M+).
4.2.15. 4-(2-Amino-1-isobutoxyethyl)benzonitrile (2j).
The acetamide; a yellow oil; 1H NMR d 0.91 (d,
J¼6.7 Hz, 3H), 0.92 (d, J¼6.6 Hz, 3H), 1.86–1.99 (m,
1H), 2.00 (s, 3H), 3.11 (d, J¼6.5 Hz, 2H), 3.14–3.25 (m,
1H), 3.60–3.70 (m, 1H), 4.44 (dd, J¼8.4, 3.9 Hz, 1H),
6.32 (br t, 1H), 7.46 (d, J¼8.3 Hz, 2H), 7.66 (d, J¼8.2 Hz,
2H); 13C NMR d 19.03, 19.13, 22.92, 28.33, 45.31, 76.16,
79.87, 111.39, 118.47, 127.12, 132.12, 145.42, 120.08.
HRMS calcd for C15H20N2O2: 260.1525; found: 260.1540.
4.2.22. 3,4,4-Trimethyl-2-azabicyclo[3.3.1]non-7-ene-5,8-
dicarbonitrile (4b). The acetamide; a white solid; mp
165.0–167.0 ꢂC (from benzene–ethyl acetate); 1H NMR
d 1.10 (s, 3H), 1.24 (s, 3H), 1.53 (d, J¼7.1 Hz, 3H), 1.94
(dd, J¼13.3, 2.5 Hz, 1H), 2.23 (s, 3H), 2.46 (dd, J¼13.4,
3.4 Hz, 1H), 2.75 (dd, J¼20.7, 3.2 Hz, 1H), 2.94 (dd,
J¼20.7, 4.3 Hz, 1H), 3.40 (q, J¼7.1 Hz, 1H), 1.92 (br t,
1H), 6.97 (dd, J¼4.3, 3.2 Hz, 1H); 13C NMR d 15.00,
16.20, 23.12, 24.78, 31.35, 32.66, 39.86, 40.96, 49.51,
54.24, 110.86, 116.75, 121.77, 147.10, 170.80; IR (CHCl3,
cmꢁ1): 3022, 2238, 2223, 1668. HRMS calcd for
C15H19N3O: 257.1528; found: 257.1520.
4.2.16. (E)-4-(4-Isopropylamino-1,1,4-trimethyl-2-pente-
nyl)benzonitrile (3a). A yellow oil; H NMR d 1.03 (d,
1
J¼6.4 Hz, 6H), 1.19 (s, 6H), 1.41 (s, 6H), 1.45 (br s, 1H),
2.82 (sept, J¼6.4 Hz, 1H), 5.45 (d, J¼16.1 Hz, 1H), 5.58
(d, J¼16.1 Hz, 1H), 7.41–7.45 (m, 2H), 7.56–7.60 (m,
2H); 13C NMR d 26.00, 28.34, 28.69, 40.6, 43.50, 54.18,
109.63, 119.03, 127.03, 131.95, 135.48, 136.62, 154.86;
IR (neat, cmꢁ1): 2967, 2227. HRMS calcd for C18H26N2:
270.2096; found: 270.2141.
4.3. The X-ray crystallographic analysis
X-ray crystallographic analysis of acetamide of cis-2f and 4a
was performed on an Enraf-Nonius CAD-4 system using
4.2.17. (E)-4-(4-tert-Butylamino-1,1,4-trimethyl-2-pente-
nyl)benzonitrile (3b). A colorless oil; H NMR d 1.16 (s,
1
˚
Mo Ka irradiation (l¼0.71069 A). The molecular structures
9H), 1.29 (s, 6H), 1.41 (s, 6H), 5.51 (d, J¼16.2 Hz, 1H),
5.67 (d, J¼16.2 Hz, 1H), 7.41–7.44 (m, 2H), 7.56–7.59
(m, 2H); IR (neat, cmꢁ1): 2971, 2229; 13C NMR d 28.31,
30.90, 32.42, 40.43, 52.61, 54.90, 109.55, 118.92, 126.95,
131.89, 133.42, 138.83, 154.87.
were drawn using Chem3D based on X-ray crystallographic
data, as shown in Figure 1.
4.3.1. The crystal data of the acetamide of cis-2f. M¼
˚
˚
82.39, monoclinic. P21, a¼9.961(13) A, b¼11.350(4) A,

380
T. Yamashita et al. / Tetrahedron 63 (2007) 374–380
3
ꢂ
˚
˚
7. Kojima, R.; Yamashita, T.; Tanabe, K.; Shiragami, T.; Yasuda,
M.; Shima, K. J. Chem. Soc., Perkin Trans. 1 1997, 217–222.
8. (a) Arnold, D. R.; Mcmanus, K. A.; Du, X. Can. J. Chem. 1994,
72, 415–429; (b) Mcmanus, K. A.; Arnold, D. R. Can. J. Chem.
1994, 72, 2291–2304.
9. Majima, T.; Pac, C.; Nakasone, A.; Sakurai, H. J. Am. Chem.
Soc. 1981, 103, 4499–4508.
10. Yasuda, M.; Kojima, R.; Tsutsui, H.; Utsunomiya, D.; Ishii, K.;
Jinnouchi, K.; Shiragami, T.; Yamashita, T. J. Org. Chem.
2003, 68, 7618–7624.
c¼14.871(14) A, b¼100.673(7) , V¼1652.31 A , Z¼4,
Dm¼1.14 g cmꢁ3, Dcalcd¼1.19 g cmꢁ3, Rw¼0.038, R¼
0.044, unique reflection¼1429.
4.3.2. The crystal data of 4a. M¼229.32, monoclinic. P1,
˚
˚
˚
a¼11.860(13) A, b¼7.832(4) A, c¼14.772(14) A, b¼
109.27(7) , V¼1295.23 A , Z¼4, Dm¼1.19 g cmꢁ3, Dcalcd
¼
3
ꢂ
˚
1.17 g cmꢁ3, Rw¼0.080, R¼0.078, unique reflection¼3060.
11. (a) Mizuno, K.; Ichinose, N.; Otsuji, Y. Chem. Lett. 1985, 455–
458; (b) Santamaria, J. Photoinduced Electron Transfer; Fox,
M. A., Chanon, M., Eds.; Elsevier: Amsterdam, 1988; Part B,
pp 483–540; (c) Yasuda, M.; Matsuzaki, Y.; Shima, K. Chem.
Lett. 1989, 551–554; (d) Mizuno, K.; Ichinose, N.; Otsuji, Y.
J. Org. Chem. 1992, 57, 1855–1860; (e) Yamashita, T.;
Tsurusako, T.; Nakamura, N.; Yasuda, M.; Shima, K. Bull.
Chem. Soc. Jpn. 1993, 66, 857–862; (f) Mizuno, K.;
Ichinose, N.; Yoshimi, Y. J. Photochem. Photobiol., C, Photo-
chem. Rev. 2000, 1, 167–193.
12. Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 259–271.
13. Borg, R. M.; Arnold, D. R.; Cameron, T. S. Can. J. Chem. 1984,
62, 1785–1802.
14. Doss, R. C.; Solomon, P. W. J. Org. Chem. 1964, 29, 1567–
1574.
References and notes
1. (a) Mariano, P. S.; Stavinoha, J. L. Synthetic Organic
Photochemistry; Horspool, W. M., Ed.; Plenum: New York,
NY, 1984; pp 145–257; (b) Lewis, F. D. Photo-induced
Electron Transfer; Fox, M. A., Chanon, M., Eds.; Elsevier:
Amsterdam, 1988; Part C, pp 1–69.
2. Yasuda, M.; Shiragami, T.; Matsumoto, J.; Yamashita, T.;
Shima, K. Organic Photochemistry and Photophysics;
Ramamurthy, V., Schanze, K., Eds.; CRC: New York, NY,
2006; pp 207–253.
3. Yasuda, M.; Yamashita, T.; Shima, K.; Pac, C. J. Org. Chem.
1987, 54, 753–759.
4. Yamashita, T.; Shiomori, K.; Yasuda, M.; Shima, K. Bull.
Chem. Soc. Jpn. 1991, 64, 366–374.
15. Deussen, H.-D.; Hendrickx, E.; Boutton, C.; Krog, D.; Clays,
K.; Bechgaard, K.; Persoons, A.; Bjørnholm, T. J. Am. Chem.
Soc. 1996, 118, 6841–6852.
5. Yasuda, M.; Isami, T.; Kubo, J.; Mizutani, M.; Yamashita, T.;
Shima, K. J. Org. Chem. 1992, 57, 1351–1354.
6. Yamashita, T.; Yasuda, M.; Isami, T.; Tanabe, K.; Shima, K.
Tetrahedron 1994, 50, 9275–9286.
16. Arnold, D. R.; Wong, P. C.; Marouris, A. J.; Cameron, T. S.
Pure Appl. Chem. 1980, 52, 2609–2619.