Efficient intramolecular hydroamination of aminoalkynes catalyzed by a zirconium(IV) complex

Article abstract of DOI:10.1016/j.tet.2008.01.031

The neutral zirconium(IV) bis(thiophosphinic amidate) complex was demonstrated to be an effective precatalyst for 5-exo-, 6-exo-, and 7-exo-dig intramolecular hydroamination of aminoalkynes, producing the cyclic imines in excellent yields (92-98%).

Full text of DOI:10.1016/j.tet.2008.01.031

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 2525e2529
www.elsevier.com/locate/tet
Efficient intramolecular hydroamination of aminoalkynes
catalyzed by a zirconium(IV) complex
a,
Hyunseok Kim a, Tom Livinghouse b, , Phil Ho Lee
*
*
a National Research Laboratory for Catalytic Organic Reaction, Department of Chemistry and Institute for Basic Science, Kangwon National University,
Chunchon 200-701, Republic of Korea
b Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA
Received 23 November 2007; received in revised form 8 January 2008; accepted 9 January 2008
Available online 12 January 2008
Abstract
The neutral zirconium(IV) bis(thiophosphinic amidate) complex was demonstrated to be an effective precatalyst for 5-exo-, 6-exo-, and
7-exo-dig intramolecular hydroamination of aminoalkynes, producing the cyclic imines in excellent yields (92e98%).
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Aminoalkyne; Catalysis; Cyclization; Hydroamination; Zirconium
1. Introduction
aminoalkenes.2j Very recently, we reported that a neutral zirco-
nium(IV) complex was an effective precatalyst for intramolec-
ular hydroamination of aminoalkenes and aminoallenes to give
cyclic amines in good to excellent yields.4 In continuation of our
studies directed toward the development of efficient group 4
metal-catalyzed-hydroamination of aminoalkynes, we now
report the realization of this goal with zirconium complex
(Scheme 1).
Transition metal-catalyzed intramolecular hydroamination
of aminoalkynes has been recognized as an effective method
for the synthesis of nitrogen-containing heterocyclic com-
pounds.1 A variety of metallocenes as well as nonmetallocene
complexes of the group 3 metals have been developed as effi-
cient catalysts in hydroamination of aminoalkenes, aminoal-
kynes, and aminoallenes.2 Recently, there have been several
reports describing inter- and intramolecular hydroamination
of these compounds with the group 4 metals.3 However, these
procedures suffer from some disadvantages such as inconve-
nient preparation and instability of the catalysts and limited
substrate scope. Therefore, there is still a strong need fora highly
efficient catalytic synthesis of azacycles common to naturally
occurring alkaloids through hydroamination. We have previ-
ously described that chelating bis(thiophosphinic amidate)
complexes of the group 3 metals (particularly Y and Nd) are
powerful catalysts for intramolecular hydroamination of
R1
R1
NH2
N
cat-ZrL4
L= ligand
R2
R2
n
n
Scheme 1. Zirconium-catalyzed intramolecular hydroamination of
aminoalkynes.
2. Results and discussion
The catalytic activity of several group 3 and 4 metal com-
plexes in Scheme 2 was first examined in the hydroamination
of 5-phenyl-4-pentynyl-1-amine (1) and 5-decynyl-1-amine
(2) and the results are summarized in Table 1. TiCl(NMe2)3
gave the desired product in 91% yield (by NMR in benzene-
d6) at 75 ꢀC for 17 h (entry 1). However, Ti(NMe2)4 required
* Corresponding authors. Tel.: þ82 33 250 8493; fax: þ82 33 253 7582
(P.H.L.); tel.: þ1 406 994 5408; fax: þ1 406 994 5407 (T.L.).
E-mail addresses: livinghouse@chemistry.montana.edu (T. Livinghouse),
phlee@kangwon.ac.kr (P.H. Lee).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.01.031

2526
H. Kim et al. / Tetrahedron 64 (2008) 2525e2529
the direct metalation of several 1,2- or 1,3-diamino proligands
with titanium, zirconium, or yittrium complexes were applied
to intramolecular hydroamination. Of the catalytic systems ex-
amined, the best results were obtained with 5 mol % of catalyst
5 in benzene-d6 at 75 ꢀC for 5.5 h, producing the desired product
in 95% yield (entry 5). Although the use of catalysts 6 and 8 did
not provide the cyclic compound (entries 6, 7, and 9), 5 mol % of
catalyst 7 afforded compound 4 in 73% yield at 75 ꢀC for 43 h
(entry 8). Treatment of 1 with 5 mol % of 5 gave rise to the cyclic
imine 3 in 95% yield through 5-exo-dig intramolecular hydro-
amination (entry 10). The hydroamination of 1 was also exam-
ined using Y[N(TMS)2]3, 9, 10, and 11. When aminoalkyne 1
was treated with 5 mol % of Y[N(TMS)2]3 at 60 ꢀC for 80 h,
the desired product 3 was produced in 96% yield (entry 15).
Although the hydroamination of 1 using catalysts 9, 10, and
11 gave the cyclic imine 3 in 94%, 95% and 91% yields,
P
P
P
P
P
N
N
N
N
N
N
Zr(NMe2)2
S
YN(TMS)2
S
Ti(NMe2)2
S
P
6
5
7
N
N
N
S
YN(TMS)2
Zr(NMe2)2
S
N
8
9
P
P
P
N
N
Table 2
Zirconium-catalyzed intramolecular hydroamination of aminoalkynesa
Ti(NMe2)2
Zr(NMe2)2
N
S
N
R1
R1
P
S
NH2
R2
R2
R2
R2
N
cat-5
R4
R4
10
R3n
11
n
R3
Scheme 2. Representative group 3 and 4 complexes.
Entry
1
Aminoalkyne
Time (h)
Product
Yieldb (%)
95 (91)c
NH2
N
Table 1
Optimization of intramolecular hydroamination of aminoalkynesa
1.5
2.5
Ph
Ph
3
1
NH2
N
catalyst
n
Ph
n
C6D6 (1.0 M)
NH2
Ph
N
2
98
93
1 (n= 1), 2 (n= 2)
3 (n= 1), 4 (n= 2)
17
12
Entry
n
Catalyst
Temp (ꢀC)
Time (h)
Yieldb (%)
NH2
N
1
2
3
4
2
2
2
2
TiCl(NMe2)3
Ti(NMe2)4
Zr(NMe2)4
Zr(NMe2)4
75
75
17
58
24
24
91
87
0
3
4
2.5
18
75
125
13
N
86
NH2
96d
90e
5
6
7
8
9
2
2
2
2
2
5
6
6
7
8
75
75
5.5
21
95
0
11
SiMe3
BnO
R
BnO
14
19 (R: SiMe3) 20 (R: H)
100
75
30
43
0
NH2
73
0
N
125
41
5
6
5.5
95
92
93
10
11
12
13
14
15
a
1
1
1
1
1
1
5
60
60
1.5
9
95
94
0
4
2
9
10
60
9
NH2
N
10
11
125
60
9
95
91
96
10
9
80
Y[N(TMS)2]3
60
21
15
Reactions were carried out in the presence of 5 mol % of catalyst in
benzene-d6.
NH2
N
b
Ph
7f
7
NMR yields based on p-xylene as an internal standard.
Ph
22
a longer reaction time (75 ꢀC, 58 h) to produce the cyclic imine
(4) in 87% yield (entry 2). Although reaction of aminoalkyne 2
with 5 mol % of Zr(NMe2)4 did not proceed at 75 ꢀC for 24 h
(entry 3), compound 4 was obtained in 86% yield at 125 ꢀC after
24 h (entry 4), indicating that reactivity of TiCl(NMe2)3 and
Ti(NMe2)4 in hydroamination is better than Zr(NMe2)4. With
these results, a variety of precatalysts generated in situ from
16
a
Reactions were carried out in the presence of 5 mol % of catalyst 5 in
benzene-d6 at 75 ꢀC.
b
NMR yields based on p-xylene as an internal standard.
c
Isolated yield (3.0 mmol scale). Reaction was carried out at 60 ꢀC.
NMR yield of 19.
d
e
Isolated yield of 20 after quenching with NaOH in methanol.
The reaction was carried out at 100 ꢀC.
f

H. Kim et al. / Tetrahedron 64 (2008) 2525e2529
2527
respectively, a longer reaction time (9 h) was needed at 60 and
125 ꢀC (entries 11e14). These results show that zirconium(IV)
bis(thiophosphinic amidate) complex 5 is the best catalyst for
the hydroamination of both aminoalkynes 1 and 2 in terms of
yield and reaction time.
an argon atmosphere. Organozirconium complexes were ma-
nipulated under an argon atmosphere in a glove box. Benzene
was distilled from sodium. Zirconium(IV) bis(thiophosphinic
amidate) complex (5) was prepared from the reaction of
Zr(NMe2)4 with N,N0-bis(p,p-diisopropylthiophosphinyl)-2,2-
dimethyl-1,3-propanediamine (NPS ligand).4
To demonstrate the efficiency and scope of the present
method, we applied this catalyst 5 to intramolecular hydroami-
nation of a variety of aminoalkynes. The results of this study are
summarized in Table 2. Aminoalkyne 12 bearing a methyl group
at carbon adjacent to nitrogen was smoothly cyclized to give 17
in 98% yield (75 ꢀC, 2.5 h, entry 2). Subjecting 13 to 5 mol % of
5 provided the desired product 18 in 93% yield (75 ꢀC, 2.5 h,
entry 3). Reaction of 14 with 5 mol % of 5 produced compound
19 in 96% NMR yield (75 ꢀC, 11 h, entry 4). The reaction mix-
ture was quenched with methanolic NaOH, producing the proto-
desilylated compound 20 in 90% yield. Under the optimum
conditions, 6-aminoalkyne 15 was readily cyclized to afford
21 in 92% yield through 6-exo-dig intramolecular hydroamina-
tion (entry 6). Encouraged by these results regarding the prepa-
ration of five- and six-membered cyclic imines through
hydroamnation of 5- and 6-aminoalkyne, the intramolecular hy-
droamination of 7-aminoalkynes was subsequently examined.
Exposure of 7-aminoalkyne 16 to catalyst 5 produced the
seven-membered cyclic imine 22 in 93% yield (100 ꢀC, 7 h)
through 7-exo-dig intramolecular hydroamination (entry 7).
Since the aminoalkynes 1 and 2, which do not have substituents
on carbon chain between amino and alkynyl group, gave the de-
sired products 3 and 4 in excellent yields, the present method is
not strongly reliant on the ThorpeeIngold effect.
4.2. Typical procedure for intramolecular hydroaminations
of aminoalkynes using catalyst 5
In an argon-filled glove box, Zr(NMe2)4 (20 ml, 0.02 mmol,
1.0 M solution in benzene-d6) and N,N0-bis(p,p-diisopropyl-
thiophosphinyl)-2,2-dimethyl-1,3-propanediamine (7.97 mg,
0.02 mmol) in benzene-d6 (0.4 mL) were introduced sequen-
tially into a J. Young NMR tube.5 The reaction mixture was
stirred at 25 ꢀC for 10 min until ligand exchange was judged
complete by the disappearance of the Zr(NMe2)4 resonance
in the 1H NMR spectrum with concomitant production of
Me2NH. The appropriate aminoalkyne (0.4 mmol) and p-xy-
lene (10 ml, 0.08 mmol) as an internal standard were added
to the resulting solution and the reaction mixture was subse-
quently heated at 75 or 100 ꢀC in an oil bath to achieve hydro-
amination. The reaction mixture was treated with 10 drops of
methanolic NaOH (5%), stirred for 0.5 h at room temperature,
concentrated in vacuo, and filtered the crude compound
through silica gel to afford pure imines.
4.2.1. Spectral data
4.2.1.1. 5-Phenyl-4-pentynyl-1-amine (1). 1H NMR (CDCl3,
500 MHz) d 7.38e7.37 (m, 2H, Ph), 7.27e7.26 (m, 3H, Ph),
2.87 (t, J¼6.8 Hz, 2H, CH2NH2), 2.48 (t, J¼7.0 Hz, 2H,
CH2^C), 1.74 (q, J¼6.9 Hz, 2H, CH2CH2CH2), 1.32 (br, 2H,
NH2). 13C NMR (CDCl3, 125 MHz) d 131.7, 128.4, 127.8, 124.1,
89.8, 81.1, 41.5, 32.7, 17.1. IR (film) 3298, 3056, 2938, 2866,
2228, 1598, 1570, 1560, 1490, 1442, 756, 692 cmꢁ1. HRMS
(EI): calcd for C11H13N (Mþ), 159.1048; found, 159.1043.
3. Conclusion
In conclusion, we have demonstrated that the neutral zirco-
nium(IV) bis(thiophosphinic amidate) complex 5 generated in
situ from the direct metalation of NPS ligand with Zr(NMe2)4
is a potent catalyst for intramolecular hydroamination of a
variety of aminoalkynes. 5-exo-, 6-exo- and 7-exo-dig intramo-
lecular hydroamination of aminoalkynes proceeded smoothly
in all cases to produce the cyclic imines in excellent yields.
No endo-cyclized products were formed in these reactions.
4.2.1.2. 5-Decynyl-1-amine (2). 1H NMR (CDCl3, 500 MHz)
d 2.67 (t, 2H, J¼6.5 Hz, CH2NH2), 2.15e2.10 (m, 4H,
CH2C^CCH2), 1.51e1.45 (m, 4H, NH2CH2CH2CH2), 1.45e
1.32 (m, 4H, C^CCH2CH2CH2), 1.08 (br, 2H, NH2), 0.87 (t,
J¼7.0 Hz, 3H, CH2CH3). 13C NMR (CDCl3, 125 MHz)
d 80.6, 79.9, 42.0, 33.2, 31.4, 26.6, 22.1, 18.8, 18.6, 13.8. IR
(film) 3338, 2958, 2934, 2862, 2158, 1570, 1488, 1466, 1434,
1382, 1328 cmꢁ1. HRMS (EI): calcd for C10H19N (Mþ),
153.1517; found, 153.1516.
4. Experimental
4.1. General
Infrared spectra were recorded on a PerkineElmer model
1600 FT-IR. 1H NMR spectra were recorded on a Bruker
AVANCE DPX-300 (300 MHz) or AVANCE DPX-500
(500 MHz) spectrometer. Chemical shifts were reported in parts
per million from TMS with the residual protic solvent resonance
4.2.1.3. 1-Methyl-4-nonynyl-1-amine (12). 1H NMR (CDCl3,
500 MHz) d 3.02 (sex, 1H, J¼6.3 Hz, CHNH2), 2.24e2.21
(m, 2H, CH2C^C), 2.16e2.12 (m, 2H, C^CCH2), 1.56e
1.45 (m, 4H, C^CCH2CH2CH2), 1.43e1.35 (m, 4H, CHCH2,
NH2), 1.08 (d, J¼6.5 Hz, 3H, NH2CHCH3), 0.90 (t, J¼7.5 Hz,
3H, CH2CH3). 13C NMR (CDCl3, 125 MHz) d 80.8, 79.7,
46.3, 39.2, 31.4, 23.9, 22.2, 18.6, 16.1, 13.8. IR (film) 3300,
2950e2850, 1590, 1460, 1370, 825 cmꢁ1. HRMS (EI): calcd
for C10H19N (Mþ), 153.1517; found, 153.1519.
as the internal standard (chloroform: 7.27, benzene: 7.16). 13
C
NMR spectra were recorded on a Bruker AVANCE DPX-300
(75 MHz) or AVANCE DPX-500 (125 MHz) spectrometer.
Chemical shifts were reported in parts per million from TMS
with the solvent as an internal standard (CDCl3: 77.23). High-
resolution mass spectra were recorded on an Autospec M363
series (Micromass). All experiments were carried out under

2528
H. Kim et al. / Tetrahedron 64 (2008) 2525e2529
1
4.2.1.4. 3-Methyl-4-nonynyl-1-amine (13). H NMR (CDCl3,
500 MHz) d 2.83e2.76 (m, CH2NH2), 2.49e2.45 (m, 1H,
CHC^C), 2.15 (td, J¼6.87, 2.07 Hz, 2H, C^CCH2), 1.53e
1.46 (m, 4H, NH2CH2CH2, NH2), 1.45e1.33 (m, 4H, C^
CCH2CH2CH2), 1.15 (d, J¼6.89 Hz, 3H, CHCH3), 0.90 (t,
J¼7.11 Hz, 3H, CH2CH3). 13C NMR (CDCl3, 125 MHz) d 84.1,
80.8, 41.2, 40.4, 31.3, 23.6, 21.9, 21.7, 18.4, 13.6. IR (film) 3353,
2958, 2934, 2859, 2158, 1488, 1382 cmꢁ1. HRMS(EI):calcdfor
C10H19N (Mþ), 153.1517; found, 153.1515.
4.2.1.9. 2-Methyl-5-pentyl-3,4-dihydro-2H-pyrrole (17). 1H
NMR (CDCl3, 500 MHz) d 4.04e3.99 (m, 1H, CHN), 2.57e
2.50 (m, 1H, CH2C]N), 2.45e2.40 (m, 1H, CH2C]N), 2.30
(t, J¼7.75 Hz, N]CCH2), 2.10e2.03 (m, 1H, NCHCH2),
1,60e1.54 (m, 2H, CCH2CH2CH2), 1.39e1.28 (m, 5H,
CCH2CH2CH2CH2, NCHCH2), 1.27 (d, J¼7.0 Hz, 3H,
CHCH3), 0.89 (t, J¼7.0 Hz, 3H, CH2CH3). 13C NMR (CDCl3,
125 MHz) d 177.4, 67.8, 37.5, 34.1, 31.9, 30.9, 26.5, 22.7,
22.3, 14.2. IR (film) 2950, 2920, 2860, 1620, 1425, 1410,
1360 cmꢁ1. HRMS (EI): calcd for C10H19N (Mþ), 153.1517;
found, 153.1516.
4.2.1.5. 3-Benzyloxy-2,2-dimethyl-5-trimethylsilyl-4-pentynyl-
1-amine (14). H NMR (CDCl3, 500 MHz) d 7.35 (d, J¼
1
4.5 Hz, 4H, Ph), 7.31e7.28 (m, 1H, Ph), 4.83 (d, J¼12.0 Hz,
1H, CH2Ph), 4.47 (d, J¼12.0 Hz, 1H, CH2Ph), 3.87 (s, 1H,
CHOCH2), 2.89 (d, J¼13.0 Hz, 1H, CHHNH2), 2.67 (d, J¼
13.0 Hz, 1H, CHHNH2), 1.63 (br, 1H, NH2), 1.03 (s, 3H,
(CH3)2C), 1.01 (s, 3H, (CH3)2C), 0.21 (s, 9H, Si(CH3)3). 13C
NMR (CDCl3, 125 MHz) d 138.3, 128.5, 128.2, 127.8, 103.4,
92.5, 75.6, 71.0, 50.1, 39.6, 22.2, 21.5, 0.2. IR (film) 3396,
3064, 2957, 2887, 2167, 1652, 1608, 1496, 1454, 1386, 1249,
1069, 840, 759, 697 cmꢁ1. HRMS (EI): calcd for C17H27NOSi
(Mþ), 289.1862; found, 289.1864.
4.2.1.10. 4-Methyl-5-pentyl-3,4-dihydro-2H-pyrrole (18). 1H
NMR (CDCl3, 400 MHz) d 3.82e3.76 (m, 1H, CH2N), 3.66e
3.59 (m, 1H, CH2N), 2.78e2.68 (m, 1H, CHC]N), 2.35e
2.18 (m, 2H, N]CCH2), 2.15e2.07 (m, 1H, NCH2CH2),
1.67e1.56 (m, 2H, NCHCH2), 1.48e1.41 (m, 1H, NCH2CH2),
1.32 (br m, 2H, CCH2CH2CH2CH2), 1.22 (td, J¼5.02, 1.09 Hz,
2H, CCH2CH2CH2CH2), 1.17 (td, J¼5.58, 1.03 Hz, 2H,
CCH2CH2CH2CH2), 1.11 (dd, J¼7.13, 1.34 Hz, 3H, CHCH3),
0.89 (t, J¼6.10 Hz, 3H, CH2CH3). 13C NMR (CDCl3,
100 MHz) d 182.3, 58.8, 44.4, 32.2, 32.1, 31.69, 26.3, 22.9,
17.8, 14.4. IR (film) 2950, 2928, 2860, 1622 cmꢁ1. HRMS
(EI): calcd for C10H19N (Mþ), 153.1517; found, 153.1515.
4.2.1.6. 4-Methyl-5-decynyl-1-amine (15). 1H NMR (CDCl3,
500 MHz) d 2.67e2.60 (m, 2H, CH2NH2), 2.34e2.31
(m, 1H, C^CCHCH3), 2.09 (td, J¼6.5, 2.0 Hz, 2H,
CHC^CCH2), 1.57e1.48 (m, 1H, CH2CHCH3), 1.48e1.46
(m, 1H, CH2CHCH3), 1.44e1.29 (m, 6H, NH2CH2CH2,
C^CCH2CH2CH2), 1.24 (br, 1H, NH2), 1.08 (d, J¼7.0 Hz,
CH3CHC^C), 0.84 (t, J¼7.0 Hz, 3H, CH2CH2CH3). 13C
NMR (CDCl3, 125 MHz) d 84.6, 80.6, 42.2, 34.7, 31.8,
31.4, 26.0, 22.0, 21.7, 18.5, 13.7. IR (film) 3366, 3296, 2933,
4.2.1.11. 4-Benzyloxy-3,3,5-trimethyl-3,4-dihydro-2H-pyrrole
1
(20). H NMR (CDCl3, 500 MHz) d 7.38 (d, 2H, J¼4.0 Hz,
Ph), 7.34e7.31 (m, 1H, Ph), 4.75 (d, J¼12.0 Hz, 1H, CH2Ph),
4.60 (d, J¼12.0 Hz, 1H, CH2Ph), 3.98 (s, 1H, CHOBn), 3.55
(d, J¼14.5 Hz, 1H, CH2N), 3.37 (d, J¼14.5 Hz, 1H, CH2N), 2.03
(s, 3H, CCH3), 1.17 (s, 3H, C(CH3)2), 1.03 (s, 3H, C(CH3)2). 13
C
NMR (CDCl3, 125 MHz) d 176.2, 138.3, 128.7, 128.1, 128.1,
92.8, 73.8, 71.9, 42.8, 26.7, 21.6, 18.0. IR (film) 3334, 2981,
2361, 1626, 1481, 1377, 1309, 754, 730 cmꢁ1. HRMS (CI): calcd
for C14H20NO (Mþ1), 218.1544; found, 218.1534.
2862, 2152, 1608, 1587, 1455, 1388, 1095, 845, 784 cmꢁ1
HRMS (EI): calcd for C11H21N (Mþ), 167.1674; found,
167.1675.
.
1
1
4.2.1.7. 2,2-Dimethyl-7-phenyl-6-heptynyl-1-amine (16). H
4.2.1.12. 5-Methyl-6-pentyl-2,3,4,5-tetrahydropyridine (21). H
NMR (CDCl3, 500 MHz) d 7.41 (dd, J¼7.75, 2.0 Hz, 2H, Ph),
7.30e7.25 (m, 3H, Ph), 2.46 (s, 2H, CH2NH2), 2.39 (t, J¼
7.0 Hz, 2H, CH2^C), 1.59e1.53 (m, 2H, CH2CH2), 1.37e1.33
(m, 2H, CH2CH2), 1.18 (br, 2H, NH2), 0.87 (s, 6H, (CH3)2C).
13C NMR (CDCl3, 125 MHz) d 131.5, 128.1, 127.4, 124.0,
90.2, 80.7, 52.7, 38.7, 34.3, 24.7, 23.6, 20.2. IR (film) 3346,
3067, 2936, 2864, 2232, 1560, 1542, 1490, 756 cmꢁ1. HRMS
(EI): calcd for C15H21N (Mþ), 215.1674; found, 215.1671.
NMR (CDCl3, 500 MHz) d 3.58e3.50 (m, 2H, CH2N), 2.26e
2.16 (m, 3H, CH2C]N, N]CCHCH3), 1.80e1.74 (m, 1H,
CH2CHC]N), 1.66e1.59 (m, 1H, CH2CHeC]N), 1.56e
1.46 (m, 3H, CH2CH2C]N, NCH2CH2), 1.45e1.40 (m, 1H,
NCH2CH2), 1.35e1.25 (m, 4H, CH2CH2CH3), 1.13 (d, J¼
7.5 Hz, CHCH3), 0.89 (t, J¼7.0 Hz, 3H, CH2CH3). 13C NMR
(CDCl3, 125 MHz) d 49.6, 38.4, 32.9, 32.0, 28.3, 26.6, 22.7,
20.0, 18.8, 14.1. IR (film) 2955, 2930, 2864, 1663 cmꢁ1
.
HRMS (EI): calcd for C11H21N (Mþ), 167.1674; found,
167.1676.
4.2.1.8. 6-Pentyl-2,3,4,5-tetrahydropyridine (4). Subjecting
5-decynyl-1-amine (61.3 mg, 0.4 mmol) to 5 mol % 5 under the
general procedure provided the cyclic imine 4 (58.2 mg, 95%).
1H NMR (CDCl3, 500 MHz) d 3.48 (t, J¼6.5 Hz, 2H, CH2N),
2.08e2.03 (m, 4H, CH2C]N, N]CCH2), 1.62e1.57 (m, 2H,
CH2CH2C]N), 1.51e1.43 (m, 4H, CH2CH2N, CCH2CH2),
1.28e1.21 (m, 4H, CH2CH2CH3), 0.87 (t, J¼6.75 Hz, 3H,
CH2CH3). 13C NMR (CDCl3, 125 MHz)d 171.3, 49.2, 41.2, 31.8,
29.1, 26.3, 22.6, 22.0, 19.7, 14.1. IR (film) 2958, 2934, 2860,
1660 cmꢁ1. HRMS (EI): calcd for C10H19N (Mþ), 153.1517;
found, 153.1519.
4.2.1.13. 7-Benzyl-3,3-dimethyl-3,4,5,6-tetrahydro-2H-azepine
1
(22). H NMR (CDCl3, 500 MHz) d 7.30e7.25 (m, 4H, Ph),
7.22e7.20 (m, 1H, Ph), 3.55 (s, 2H, CH2Ph), 3.40 (s, 2H,
CH2N), 2.24 (t, J¼5.75 Hz, 2H, CH2C]N), 1.40 (t, J¼6.0 Hz,
2H, (CH3)2CCH2), 1.20e1.14 (m, 2H, CH2CH2CH2), 0.88 (s,
6H, (CH3)2C). 13C NMR (CDCl3, 125 MHz) d 176.8, 137.1,
129.4, 128.6, 126.9, 61.9, 49.7, 44.4, 32.1, 27.3, 19.5, 16.3. IR
(film) 3100e2860, 1680, 1485 cmꢁ1. HRMS (EI): calcd for
C15H21N (Mþ), 215.1674; found, 215.1668.

H. Kim et al. / Tetrahedron 64 (2008) 2525e2529
2529
T. E.; Grosche, M.; Herdtweck, E.; Pleier, A.-K.; Walter, E.; Yan, Y.-K.
Organometallics 2000, 19, 170; (d) Vasen, D.; Salzer, A.; Gerhards, F.;
4.3. Preparative synthesis of 3,4-dihydro-5-benzyl-2H-
pyrrole (3)
Gais, H.-J.; Sturmer, R.; Bieler, N. H.; Togni, A. Organometallics 2000,
¨
19, 539; (e) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000, 122,
9546; (f) Haak, E.; Siebeneicher, H.; Doye, S. Org. Lett. 2000, 2, 1935;
(g) Johnson, J. S.; Bergman, R. G. J. Am. Chem. Soc. 2001, 123, 2923;
(h) Pohlki, F.; Doye, S. Chem. Soc. Rev. 2003, 32, 104; (i) Bytschkov, I.;
Doye, S. Eur. J. Org. Chem. 2003, 935; (j) Alonso, F.; Beletskaya, I. P.;
Yus, M. Chem. Rev. 2004, 104, 3079.
Zr(NMe2)4 (150.0 ml, 0.15 mmol, 1.0 M solution in benz-
ene-d6) was added to a solution of N,N0-bis(p,p-diisopropyl-
thiophosphinyl)-2,2-dimethyl-1,3-propanediamine (59.79 mg,
0.15 mmol) in benzene (3 mL) under an argon atmosphere.
The homogeneous reaction mixture was stirred at 25 ꢀC for
10 min. After 5-phenyl-4-pentynyl-1-amine (1) (477.7 mg,
3.0 mmol) was added to the reaction mixture, it was heated to
75 ꢀC for 1.5 h to complete hydroamination. The reaction mix-
ture was cooled and treated with 10 drops of methanolic NaOH
(5%), and then stirred for 0.5 h at room temperature and concen-
trated in vacuo. The residue was subjected to flash chromatogra-
phy on silica gel using MeOH/CH2Cl2¼1:15 to furnish the title
compound (406.0 mg, 85%) as a colorless oil. 1H NMR (CDCl3,
500 MHz) d 7.33e7.30 (m, 2H, Ph), 7.25e7.22 (m, 3H, Ph),
3.84 (t, J¼6.0 Hz, 2H, CH2NH2), 3.69 (s, 2H, CH2Ph), 2.40 (t,
J¼8.0 Hz, 2H, CH2CH2CH2), 1.84 (quintet, J¼8.0 Hz, 2H,
CH2CH2CH2). 13C NMR (CDCl3, 125 MHz) d 177.1, 137.2,
129.2, 128.8, 126.8, 61.1, 40.9, 36.7, 22.8. IR (film) 3100e
2850, 1604, 1496 cmꢁ1. HRMS (EI): calcd for C11H13N
(Mþ), 159.1048; found, 159.1046.
´
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Acknowledgements
This work was supported by the Korea Science and
Engineering Foundation (KOSEF, F01-2006-000-10157-0)
and by KOSEF through the National Research Lab. Program
funded by the Ministry of Science and Technology (No.
M10600000203-06J0000-20310). The NMR and mass data
were obtained from the central instrumental facility in Kang-
won National University.
References and notes
5. J. Young NMR tubes purchased from Aldrich or J. Young Ltd were used
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