Nitrogen fixation: Synthesis of heterocycles using molecular nitrogen as a nitrogen source

Article abstract of DOI:10.1246/bcsj.77.1655

Nitrogen fixation using transition metals is a fascinating process. We have already reported on the incorporation of molecular nitrogen into organic compounds using a titanium-nitrogen complex reported by Yamamoto. We developed a novel titanium-catalyzed nitrogenation procedure using TiCl₄ in the presence of an excess amount of Li and TMSCl. In this reaction, a 1 atm pressure of nitrogen gas can be used and the reaction proceeds at room temperature. The procedure is very simple. A THF solution of TiCl₄ or Ti(O ⁱPr)₄ (1 equiv.), Li (10 equiv.), and TMSCl (10 equiv.) was stirred under an atmosphere of nitrogen at room temperature overnight to give titanium-nitrogen complexes. Although the structures of the titanium-nitrogen complexes have not yet been determined, they would consist of N(TMS)₃, X₂TiN(TMS)₂, and XTi=NTMS. Using this procedure, various heterocycles, such as indole, quinoline, pyrrole, pyrrolizine, and indolizine derivatives, could be synthesized from molecular nitrogen in good-to-moderate yields as a stoichiometric reaction based on a titanium complex by a one-pot reaction. Furthermore, monomorine I and pumiliotoxin C were synthesized from molecular nitrogen as a nitrogen source. This procedure was further extended for the syntheses of heterocycles using a catalytic amount of titanium complex; also, indole and pyrrole derivatives were obtained in high yields.

Full text of DOI:10.1246/bcsj.77.1655

Ó 2004 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 77, 1655–1670 (2004) 1655
Nitrogen Fixation: Synthesis of Heterocycles Using
Molecular Nitrogen as a Nitrogen Source
ꢀ
Mayumi Nishida, and Yoshihiro Sato
Miwako Mori, Masaya Akashi, Masanori Hori, Katsutoshi Hori,
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812
Received December 25, 2003; E-mail: mori@pharm.hokudai.ac.jp
Nitrogen fixation using transition metals is a fascinating process. We have already reported on the incorporation of
molecular nitrogen into organic compounds using a titanium–nitrogen complex reported by Yamamoto. We developed a
novel titanium-catalyzed nitrogenation procedure using TiCl4 in the presence of an excess amount of Li and TMSCl. In
this reaction, a 1 atm pressure of nitrogen gas can be used and the reaction proceeds at room temperature. The procedure
is very simple. A THF solution of TiCl4 or Ti(OiPr)4 (1 equiv.), Li (10 equiv.), and TMSCl (10 equiv.) was stirred under
an atmosphere of nitrogen at room temperature overnight to give titanium–nitrogen complexes. Although the structures
of the titanium–nitrogen complexes have not yet been determined, they would consist of N(TMS)3, X2TiN(TMS)2, and
XTi=NTMS. Using this procedure, various heterocycles, such as indole, quinoline, pyrrole, pyrrolizine, and indolizine
derivatives, could be synthesized from molecular nitrogen in good-to-moderate yields as a stoichiometric reaction based
on a titanium complex by a one-pot reaction. Furthermore, monomorine I and pumiliotoxin C were synthesized from
molecular nitrogen as a nitrogen source. This procedure was further extended for the syntheses of heterocycles using
a catalytic amount of titanium complex; also, indole and pyrrole derivatives were obtained in high yields.
Since the discovery by Vol’pin and Shur that molecular ni-
Br(CH2)4Br
trogen could be fixed by transition metals1 and reducing agents
under mild conditions, various systems of nitrogen fixation
have been reported.2 In 1967, Yamamoto reported on the syn-
thesis of a cobalt–nitrogen complex3 and then a titanium–nitro-
gen complex.4 Hidai5 and Bercaw6 later reported on the syn-
thesis of a molybdenum–nitrogen complex and a zirconium–
nitrogen complex, respectively. However, there have been
few reports on the incorporation of molecular nitrogen into or-
ganic compounds. In 1968, Vol’pin reported the synthesis of
aniline from Cp2TiCl2 and phenyllithium under a high pres-
sure of nitrogen (Eq. 1).7 Later, van Tamelen succeeded to ob-
tain diethylamine and banzonitrile from diethyl ketone and
benzoyl chloride, respectively, using Cp2TiCl2 and Mg under
nitrogen (Eq. 2).8 In 1977, Chatt synthesized pyrrolidine and
isopropylamine from 1,4-dibromobutane and acetone, respec-
tively, using a molybdenum– or tungsten–nitrogen complex
(Eqs. 3 and 4).9 Hidai et al. synthesized pyrrole from a tung-
sten–nitrogen complex (Eq. 5).10
trans-[M(N2)2(dppe)2]
[MBr{N2(CH2)4}(dppe)2]Br
hν
(M=Mo or W)
ð3Þ
1. LiAlH4
N
H
2. MeOH
3. HBr
80-87%
HBr
cis-[W(N2)2(PMe2Ph)4]
[WBr2(NNH2)(PMe2Ph)3]
MeOH
ð4Þ
1. LiAlH4
iPrNH2
Me2CO
[WBr2(=N-N=CMe2)(PMe2Ph)3]
2. MeOH
3. HBr
94%
NH2
N
N
M
N
N
N
OMe
O
N
M
F
MeO
HBF4
P
P
P
P
P
P
P
P
N
P
BF4
P
P
BF4
M
P
F
M=Mo, W
LiAlH4
M=W
N
Li
NH2
1. Cp2TiCl2
2. H2O
75%
H
+ N2
ð1Þ
ð5Þ
R
R
(R=H, Me etc.)
3-65%
These results prompted us to utilize molecular nitrogen in
organic synthesis. Yamamoto reported on the synthesis of a
very interesting titanium–nitrogen complex 1 from TiCl4 or
TiCl3 and Mg as a reducing agent (Eq. 6).4 In this reaction,
the nitrogen–nitrogen triple bond was cleaved by a titanium
complex and a reducing agent to give a Ti–N complex. The re-
sult is very attractive for the synthesis of nitrogen heterocycles
from molecular nitrogen because one nitrogen can be intro-
1. Et2CO
2. H2O
Cp2TiCl2 + Mg + N2
Et2CHNH2 + (Et2CH)2NH
25-50%
ð2Þ
Published on the web September 10, 2004; DOI 10.1246/bcsj.77.1655

1656 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
Table 1. Effects of Titanium Complex and Reducing
Agents for Nitrogen Fixation
duced into the molecule. Sobota reported that the reaction of 1
with CO2 gave titanium–isocyanate complex 2 (Eq. 7).11
N N
Mg, N2
THF
TiCl4
or
TiCl3
1. 10% HCl
TiX4
Ti-N complexes
[THF Mg2Cl2 TiN]
ð6Þ
PhCONH2
2. K2CO3
3. PhCOCl
benzene
TMSCl (10 equiv.)
Reducing
Agent (10 equiv.)
1
7
CO2
1
[THF Mg2Cl2O TiNCO]
ð7Þ
Run
TiX4
Reducing agent
PhCONH2/%
2
1
2
3
4
TiCl4
Li
Li
96
46
4
Since the handling of the latter complex 2 was easier than
that of 1, we used 2 as a nitrogenation agent, and succeeded
to synthesize various heterocycles (Eqs. 8 and 9).12a–e Al-
though the synthesis of heterocycles using titanium–nitrogen
complex 2 was achieved, an extension of this reaction to a cat-
alytic reaction based on a transition metal was difficult because
titanium–nitrogen complexes 1 and 2 were used after their iso-
lation. Thus, various attempts were made, and we succeeded to
develop a titanium-catalyzed nitrogen fixation method using
TiX4–TMSCl–Li.12f,g That is, a THF solution of TiCl4 was
stirred in the presence of excess amounts of TMSCl and Li
overnight under an atmosphere of nitrogen to give titanium–ni-
trogen complexes 7a that would contain a titanium–imide
complex, a titanium–amide complex, and N(TMS)3.13 After
the hydrolysis of titanium–nitrogen complexes 7a with 10%
HCl, excess amounts of PhCOCl and K2CO3 were added
and the solution was stirred overnight. After the usual workup,
benzamide was obtained in more than 100% yield based on
TiCl4 (Scheme 1). This means that the reaction proceeds cata-
lytically with regard to TiCl4.
Cp2TiCl2
Ti(OiPr)4
Ti(OiPr)4
iPrMgCl
Li
91
for nitrogen fixation, and it was found that Li gave good re-
sults. In this study, the effects of various titanium complexes
were examined for nitrogen fixation. To measure the amount
of fixed nitrogen, titanium–nitrogen complexes 7 were hydro-
lyzed with aqueous HCl to be converted into NH4Cl, which re-
acted with benzoyl chloride in the presence of K2CO3 to give
benzamide. The amount of nitrogen fixed by this method was
estimated by the yield of benzamide. The results are given in
Table 1.
A THF solution of TiCl4 (1 equiv.), Li (10 equiv.), and
TMSCl (10 equiv.) was stirred under an atmosphere of nitro-
gen overnight to give a black solution of titanium–nitrogen
complexes 7a, which was hydrolyzed with 10% HCl. To this
solution was added a benzene solution of excess amounts of
PhCOCl (10 equiv.) and K2CO3, and the solution was stirred
at room temperature overnight to give benzamide in 96% yield
(Table 1, run 1). When Cp2TiCl2 was used as a titanium com-
plex, nitrogen could be fixed, but the results were not satisfac-
tory. A low-valent titanium complex prepared from Ti(OiPr)4
and Grignard reagent, which was reported by Sato,14 gave only
a small amount of benzamide. It was very interesting that tita-
nium–nitrogen complexes 7b, prepared from Ti(OiPr)4 instead
of TiCl4, gave benzamide in 91% yield (run 4).
Synthesis of Indole and Quinoline Derivatives from 1,3-
Diketone Bearing a Keto–Carbonyl Group in a Tether at
the 2-Position. Since titanium–nitrogen complexes 7 were
easily obtained from TiCl4 or Ti(OiPr)4, TMSCl, and Li under
nitrogen, an experiment was carried out to determine whether
fixed nitrogen can be incorporated into organic compounds.12h
As a model compound, cyclohexenone derivative 9 was chos-
en. To a THF solution of titanium–nitrogen complexes 7a,
which was prepared from TiCl4 (1 equiv.), TMSCl (10 equiv.),
and Li (10 equiv.) in THF under nitrogen, was added enol tri-
flate 9a, and the whole solution was refluxed overnight. After
the usual workup, enaminone 10 was obtained in 35% yield
(Table 2, run 1). This means that fixed nitrogen can be intro-
duced directly into organic compounds. Various cyclohexe-
none derivatives 9 were examined, and enol triflate gave a
good result. When CsF was added to this solution as an addi-
tive, the yields increased (runs 2 and 4). Provably, CsF would
accelerate the cleavage of the nitrogen–silicon bond on titani-
um–nitrogen complexes. To clarify whether N(TMS)3 in tita-
nium–nitrogen complexes 7a is an active species, the reaction
of 9a with N(TMS)3 was carried out in the presence of CsF.
However, no product containing nitrogen was formed, indi-
cating that the nitrogen source of 10 is derived from a titani-
Nirtogenation-Carbonylation
R
O
Pd (0), CO
R
base, 2 (3 equiv.)
NMP, 120 °C, 24 h
55-77%
ð8Þ
ð9Þ
NH
Br
3
O
4
Nitrogenation-Transmetalation
O
O
Pd (0), 2 (3 equiv.)
R
R
N
NMP, 100 °C, 12 h
Br
R
H
OH
R
6
5
73-85%
R=H or Me
Since molecular nitrogen can be fixed by this method and it
is a very simple procedure, it was applied to the synthesis of
heterocyclic compounds as a stoichiometric reaction.
Results and Discussion
Effects of Titanium Complexes and Reducing Agents for
Nitrogen Fixation. We previously examined the effect of
various reducing agents,12f,g such as Mg, Na, K, Zn, and Li,
ClTi=NTMS
Cl2TiN(TMS)2
N2
1. 10% HCl
TiCl4
PhCONH2
2. PhCOCl, K2CO3
(10 equiv.)
Li (50equiv.)
Me3SiCl (50 equiv.)
N(TMS)3
8
250%*
7a
* based on TiCl4
Scheme 1.

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1657
Table 2. Synthesis of Heterocycles
O
O
N2
TiCl4, Li, TMSCl
7a, Additive
R
O
7a, additive
O
O
THF, reflux, 24 h
N
X
H
11
THF, reflux, 24 h
X
12
NH2
9
10
Scheme 3.
Run
X
Additive
YieldaÞ/%
Table 3. Synthesis of Heterocycles
1
2
3
4
5
6
7
8
9
10
OTf
OTf
OMe
OMe
OMs
OCOOMe
OAc
OCOOPh
Cl
OH
9a
9a
9b
9b
9c
9d
9e
9f
—
CsF
—
CsF
CsF
CsF
CsF
CsF
CsF
CsF
35
40
14
29
11
10
8
4
—
6
Run
1
Substrate
X
Additive Product Yielda)/%
O
O
11a OTf
CsF
51
71
86
46
86
57b)
O

N
2
3
4
5
6
11b OH
11b OH
11c OTf
11d OH
11e OH
X
12a H
CsF
CsF
CsF
CsF
9g
9h
O
O
O
a) Based on substrate.
O
N
H
X
12c
N
N
O
O
O
Ph
R
Ph
7
O
N
H
O
X
X
12e
R
N
O
O
O
II
I
7
8
11f OTf
11g OH
CsF
32
32
Scheme 2.
N
X
12f
um–nitride complex or a titanium–amide complex. Thus, we
next attempted to synthesize heterocycles from molecular ni-
trogen as a nitrogen source. Our plan is shown in Scheme 2.
On the basis of the above results, if keto cyclohexenone I bear-
ing a keto–carbonyl group in a tether at the 2-position is treat-
ed with titanium–nitrogen complexes 7a, molecular nitrogen
would be introduced at the 3-position of cyclohexenone, and
then fixed nitrogen would further react with the carbonyl group
in a tether to give cyclized compounds II.
a)
All reactions
were
carried out using a THF
O
solution of titanium-nitrogen complexes 7a,
prepared from TiCl4 (1.25 equiv.), Li (12.5
equiv.), and TMSCl (12.5 equiv.) and to this
solution was added the substrate (1 equiv.)
and the whole solution was refluxed in THF
overnight. b) 2 equiv. of titanium-nitrogen
complexes 7a was used.
N
13
We were very pleased to find that when a THF solution
of 11a and 7a was refluxed overnight, indole derivative 12a
was obtained in 51% yield (Scheme 3, Table 3, run 1). In this
reaction, the addition of CsF gave a good result (runs 2 or 3)
and the hydroxy group was suitable as a leaving group (runs
3 and 5), although the reaction of 9h with 7a did not give a
good result. Various indole derivatives were obtained in high
yields. Elongation of the methylene group in a tether gave di-
hydroquinoline derivative 12f in moderate yield. In this reac-
tion, the spot on the TLC of the reaction mixture was different
from that of the purified product 12f. Presumably, tetrahydro-
quinoline derivative 13 would be formed, and then easily con-
verted into dihydro-derivative 12f by air oxidation. The treat-
ment of triketone 11g in a similar manner afforded 12f in the
same yield.
N
N
R
R'
7
R
N
R'
O O
H
III
IV
Scheme 4.
complexes 7a, pyrrole derivative 15a was obtained in 25%
yield (Table 4, run 1). In a similar manner, various pyrroles
15b–e (runs 2–5) or fuzed-pyrrole derivatives 15f–h (runs 6–
8) could be synthesized in good-to-moderate yields. The ester
group of 14e did not react with 7a (run 5).
Synthesis of Pyrrolizine and Indolizine Derivatives.
Since titanium–nitrogen complexes 7a could react with two
keto–carbonyl groups to give pyrrole derivatives, we next ex-
amined the reaction of titanium–nitrogen complexes 7 with tri-
ketone V. If this reaction proceeds, it would be possible to syn-
thesize pyrrolizine or indolizine derivatives VI in one step
from triketone (Scheme 5).
Synthesis of Pyrrole Derivatives from 1,4-Diketone.
Since it was clear that titanium–nitrogen complexes 7a could
react with the carbonyl group of I, we next tried to synthesize
pyrrole derivative IV from 1,4-diketone III (Scheme 4). If 1,4-
diketone III were treated with titanium–nitrogen complexes 7,
pyrrole derivative IV would be formed.
To a THF solution of 7a was added triketone 16a and CsF,
and the whole solution was refluxed overnight to give a mix-
When compound 14a was treated with titanium–nitrogen

1658 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
Table 4. Synthesis of Pyrrole Derivatives 15 Using 7a
O
Ph
Ph
Ph
Run
1
Substrate
Product
Yielda)/%
15a
7a, CsF
O
O
Ph
THF, reflux, 24 h
25
39
54
64
60
23
41
41
Ph
14a
14b
14c
14d
31%
N
H
16a
O
O
O
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2
3
4
15b
15c
15d
15e
15f
Ph
Ph
Ph
O
N
H
+
+
N
N
N
Ph
O
O
N
H
17c
17b
17a
17a:17b:17c = 1:1.8:1
Ph
Ph
PtO2, H2
O
O
N
H
17a, 17b, 17c
17c
EtOH
86%
O
EtO2C
5 EtO C
2
14e
Ph
Ph
N
H
7a, CsF
O
O
17a + 17b + 17c
THF, reflux, 24 h
32%
O
O
O
O
O
17a:17b:17c = 1:1.7:0.9
16b
14f
14g
14h
6
7
8
N
H
O
Scheme 6.
Table 5. Synthesis of Pyrrolizine and Indolizine Derivatives
15g
15h
O
N
H
Run
Triketone
Pyrrolizine or indolizine Yield/%
Ph
O
O
Ph
O
N
1
18
H
19
30
N
O
O
a) All reactions were carried out upon heating in THF for 24 h.
O
H
21a)
23a
23b
23c
23d
2
3
4
5
6
20
N
N
31
N
O
N
R'
7
O
O
R
O
Ph
Ph
R
R'
Ph Ph
O
V
VI
41b)
56b)
30b)
30b)
22a
22b
22c
22d
Scheme 5.
N
O
O
ture of pyrrolizine derivatives (17a, 17b, and 17c) as an insep-
arable mixture in 31% yield, whose ratio was determined to be
1:1.8:1 by a H NMR spectrum (Scheme 6). The hydrogena-
tion of these compounds with PtO2 in EtOH afforded pyrroli-
zine derivative 17c in 86% yield. In a similar manner, 16b
gave the same pyrrolizine derivatives (17a, 17b, and 17c) in
the same ratio in 32% yield.
A treatment of triketone 18 with 7a gave pyrrolizine deriv-
ative 19 in 30% yield (Table 5, run 1). Although the yield was
moderate, it is very interesting that the pyrrolizine derivative
19 could be synthesized from triketone 18 and 7a by a one-step
reaction. Triketone 20 was treated with 7a in a similar manner
to give tricyclic compound 21 as a mixture of two inseparable
isomers in 31% yield (run 2). Subsequently, the synthesis of an
indolizidine derivative was examined. Triketone 22a, whose
one methylene was elongated compared with that of 18, was
treated with 7a to give indolizine derivative 23a in 29% yield.
When 2 equiv. of 7a was used for this reaction, the yield of
23a increased to 41% (run 3). In a similar treatment of 22b,
22c, and 22d with 7a (2 equiv.), indolizine derivatives 23b,
23c, and 23d were formed in 56%, 30%, and 30% yields, re-
spectively (runs 4–6). From 23d, monomorine I and indolizi-
Ph
O
Ph
1
N
O
O
O
O
O
O
N
O
Bu
N
O
Bu
Me
a) 3.4:1 (determined by 1H NMR (500 MHz)). b) 2 equivalents of
7a was used.
dine 195 B could be synthesized by hydrogenation (Fig. 1).12i
Synthesis of Heterocycles from Keto–Alkyne. Next, the
Michael-type addition of titanium–nitrogen complexes 7 to
ꢀ,ꢁ-unsaturated compound was examined. Our plan is shown
in Scheme 7. If keto–alkyne VII reacts with 7, imine complex
should be formed, and it would then react with ꢀ,ꢁ-unsaturat-

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1659
N
N
H
N
H
N
Ti(OiPr)4, Li
R
TMSCl
7, CsF, THF
Bu
O
Me
Bu
Indolizidine 195B
N
H
Me
rt, 50 min
conditions
26
27
R
Monomorine I
Scheme 9.
Fig. 1. Monomorine I and indolizine 195B.
Table 7. Effects of Substituents on the Aromatic Ring
N
N
Run Substrate
R
Conditions Yield/% 26/%
O
7
R
1
2
3
4
5
6
7
26a
26b
26c
26d
26e
26f
26f
p-CH3 reflux, 20 h
p-CO2Me reflux, 20 h
32
42
45
49
31
30
21
14
8
R
R
O
R
N
H
R
R
NX
VII
O
O
VIII
p-CN
p-CF3
p-NO2
reflux, 5 h
reflux, 20 h
reflꢁux, 12 h
Scheme 7.
ed compound to give VIII.12j
—
o-CO2Me 40 C, 20 h
o-CO2Me reflux, 20 h
35aÞ
18bÞ
19
6
A THF solution of keto–alkyne 24a (1 equiv.) and titanium–
nitrogen complexes 7a, which was prepared from TiCl4 (1.2
equiv.), Li (10 equiv.), and TMSCl (10 equiv.) under nitrogen,
was refluxed in the presence of CsF (6 equiv.) for 17 h. Sur-
prisingly, indole derivative 25a was obtained in 90% yield
(Scheme 8, Table 6, run 1). When the reaction was carried
out at room temperature for 24 h, the desired indole derivative
25a was obtained in 59% yield (run 2). On the other hand,
when Ti(OiPr)4 was used for the preparation of titanium–nitro-
gen complexes 7b in a similar manner, the reaction proceeded
at room temperature for only 50 min and 25a was obtained in
82% yield (run 3). In the absence of CsF, the yield slightly
decreased (run 4). Indole derivative 25b, having an acetoxy
group on a six-membered ring, was also synthesized from
keto–alkyne 24b (run 5). Subsequently, the effect of a substitu-
a) 28 was obtained in 3% yield. b) 28 and 280 were obtained in
7% and 5% yields.
N
N
O
O
28
28′
ent on alkyne was examined. In the case of the nitrile group,
the yield was also high (run 6), and 24d or 24e bearing the
amide or keto–carbonyl group on alkyne gave the desired
indole derivative, 25d or 25e, in moderate yields (runs 7 and
8). Although, keto–alkyne 24f having the alkyl group on an
alkyne part gave only a trace amount of the desired product
25f (run 9), keto–alkyne 24g having a phenyl group afforded
indole derivative 25g in moderate yield (runs 9 and 10). These
results indicate that the electron-withdrawing group on the
alkyne gives a good result.
N N
TiX4, Li, TMSCl
R1
R1
7
R2
R2
N
Thus, the substituent effect of the aromatic ring on the
alkyne was examined (Scheme 9). The results are given in
Table 7. The electron-withdrawing group on the aromatic ring
gave good results (runs 2–4), but keto–alkyne 26e having the
CsF, THF
O
H
25
24
Scheme 8.
Table 6. Synthesis of Indole Derivatives
Run
Substrate
X
R1
R2
Temp.
Time/h
YieldaÞ/%
1
2
3
4
5
6
7
8
9
10
24a
24a
24a
24a
24b
24c
24d
24e
24f
Cl
Cl
H
H
H
H
OAc
H
H
H
H
H
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CN
CONEt2
COCH3
Me
reflux
rt
rt
rt
rt
rt
rt
rt
reflux
reflux
17
24
50 (min)
2
50 (min)
12
24
90
59bÞ
82
OiPr
OiPr
OiPr
OiPr
OiPr
OiPr
OiPr
OiPr
77cÞ
62
92
45
1.5
35
20dÞ
20eÞ
3fÞ
24g
Ph
35gÞ
a) 7a or 7b were prepared from TiX4 (1 equiv.), Li (10 equiv.), and TMSCl (10 equiv.). All
reactions were carried out using 24 (1 equiv.), CsF (6 equiv.), and 7a or 7b (1.25 equiv.). b)
24a was recovered in 30% yield. c) In the absence of CsF. d) The solution was stirred at rt
for 2 h and then refluxed. e) The solution was stirred at rt for 70 min and then refluxed. f)
24f was recovered in 45% yield. g) 24g was recovered in 21% yield.

1660 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
Path A
7b, CsF
N(TMS)3
CO2Me
25
+
R
CsF
R
R
N
THF, rt, overnight
N
H
N
CO
2Me
O
O
ii
TMS
i
TMS
30
24
29
O
Ti X
Path B
Scheme 10.
XTi=N-TMS
R
O
TMS
N
Table 8. Synthesis of Heterocycles from Keto–Alkyne
Ti
iii
X
Run
1
Substrate
Product
Yield/%
72
Scheme 11.
CO2Me
CO2Me
O
N
H
H
29a
30a
+
N
H
H2
Cl-
CO2Me
2
3
4
5
6
39
66
34
63
79
O
N
( )-Pumiliotoxin C HCl
CO2Me
H
29b
30b
Fig. 2.
O
N
N N
O
CO2Me
COMe
3H0c
CO2Me
CO2Me
29c
( )
n
( )
R
7
n
N
O
O
H
O
N
H
30d
X
IX
R=Leaving Group
29d
OBn OBn
Scheme 12.
OBn OBn
N(TMS)2], and the complex would react with the carbonyl car-
bon to give imine i via iii.15,16 Then, the Michael addition of
nitrogen gives 25. The mechanism of this reaction is similar
to that in the synthesis of a pyrrole derivative by Arcadi,
who obtained a pyrrole derivative from keto–alkyne and pri-
mary amine.17 The total synthesis of (ꢂ)-pumiliotoxin C was
achieved from 30g (Fig. 2).12l
O
CO2Me
N
H
30e
CO2Me
29e
N
H
O
CO2Me
CO2Me
Synthesis of Lactams from Keto–Carboxylic Acid. Next,
we tried to synthesize lactam X from keto–carboxylic acid IX
and 7 (Scheme 12). At first, a THF solution of acid chloride
31b and 7a, which was prepared using a TiCl4–Li–TMSCl sys-
tem under nitrogen, was refluxed in the presence of CsF to give
lactam 32 in 28% yield (Scheme 13, Table 9, run 1). The use
of titanium–nitrogen complexes 7b, prepared by a Ti(OiPr)4–
Li–TMSCl system, slightly increased the yield of 32 (run 2).
In this reaction, various carboxylic acid derivatives, such as
chloride 31b, mixed anhydrides (31c and 31d, ester 31e),
and even the carboxylic acid 31a, could be used and lactam
32 was produced in good yields (runs 1–7). Various bicyclic
lactams (34, 36, and 38) were obtained in good yields using
this method. In a similar manner, piperidone derivatives 40,
42, and 44 were also obtained in moderate yields from the
corresponding keto–esters (39, 41, and 43).
Investigation of Titanium-Catalyzed Nitrogenation. As
described in Scheme 1, this nitrogenation method was devel-
oped as a catalytic reaction based on a titanium complex. Al-
though the reaction species are not clear, the possible reaction
course is considered as shown in Fig. 3. TiX4 would be re-
duced with Li and converted into TiX2 XI, which would react
with N2 to give XII. This would then be converted into titani-
um–nitride complex XIII by Li and TMSCl and XIII would
30g
29g
nitro group did not give the desire product (run 5). In the case
of keto–alkyne 26f having the methoxycarbonyl group at the
ortho-position on the aromatic ring, small amounts of tetracy-
clic compounds 28 and 280 were obtained (runs 6 and 7). Var-
ious mono- and bicyclic heterocycles were synthesized from
keto–alkyne 29 using 7b (Scheme 10), the results are given
in Table 8. The desired heterocyclic compounds, such as pyr-
roles 30a and 30b, quinolines 30c, and piperidine derivatives
30d and 30e, were obtained in good-to-moderate yields.
The possible reaction course for the formation of heterocy-
clic compounds from keto–alkyne is shown in Scheme 11.
There are two possible pathways. If the reaction of keto–al-
kyne 24 with N(TMS)3 proceeds in the presence of CsF, imine
i would be formed. Then, a Michael addition of nitrogen of
imine would afford ii, which would isomerize to give 25 (path
A). However, when 24a was reacted with N(TMS)3 in the
presence of CsF at room temperature for 16 h, no cyclized
product was formed, indicating that N(TMS)3 in titanium–ni-
trogen complexes 7b is not an active species. Thus, the active
species in this reaction would be a titanium–imide com-
plex [XTi=N(TMS)] or titanium–amide complex [X2Ti–

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1661
(X = OiPr or Cl)
react with TMSCl to give titanium–amide complex XIV. In the
presence of Li, XIV reacts with TMSCl to give N(TMS)3 and
TiX2 XI would be regenerated.
2TiIVX4
4Li
N
N
2N(TMS)3 + 2LiCl
4LiX
Thus, an experiment was carried out to determine whether
nitrogen-heterocycles could be catalytically synthesized based
on TiX4 from molecular nitrogen (Scheme 14). To determine
whether TiCl4 acts as a catalyst, titanium–nitrogen complexes
7a were synthesized from TiCl4 (1 equiv.) in the presence of
excess amounts of Li (50 equiv.) and TMSCl (50 equiv.) under
an atmosphere of nitrogen. To this solution was added a THF
solution of an excess amount of 1,3-diketone derivative 9a (10
equiv.), and the solution was refluxed overnight. After the usu-
al workup, enamide 10 was obtained in 189% yield based on
TiCl4. This means that TiCl4 acts as a catalytic reagent in this
2[TiIIX2]
2TMSCl
2Li
XI
[X2TiIII-N=N-TiIIIX2]
2[X2TiIII-N(TMS)2]
XII
2TMSCl
4Li
XIV
2TMSCl
2[XTiIII=N-TMS]
2LiX + 2LiCl
2TMSCl
XIII
Fig. 3. Possible reaction course.
reaction. It was already reported that the reaction of 9a with
N(TMS)3 did not afford 10. However, in this reaction, the
use of 1 equiv. of TiCl4 in the presence of the excess amounts
of Li and TMSCl afforded 189% yield of 10. Although the rea-
son why TiCl4 acts as a catalytic reagent is not clear, the pos-
sibility for a catalytic reaction is that the titanium species acts
as a Lewis acid in this reaction, or generated titanium-oxide
(
)
( )
COOR
n
n
7
( )
(
)
m
m
O
N
H
O
CsF, THF, reflux
Scheme 13.
Table 9. Synthesis of Lactams
Run
1
Substrate
R
Ti=NX Time/h
Product Yield/%
28
31b
31b
31c
31c
Cl
7a
7b
7a
24
24
24
COR
N
H
O
O
2
3
Cl
31
25
31
32
OCO2Et
OCO2Et
4
5
7b
7b
7b
7b
7b
7b
7b
7b
24
24
24
12
1
55
58
53
50
24
22
38
32
31d OPO(OEt)2
6
31a
31e
33
OH
OEt
7
COR
8
OEt
O
N
O
H
33
34
36
9
COR 35a
OH
24
24
24
24
N
H
O
O
10
11
35d
OPO(OEt)2
OH
35
COR
37a
N
O
O
H
12
13
7b
7b
42
19
37d
38
OPO(OEt)2
OPO(OEt)2
37
CO2Et
O
O
CO2Et
Me
N
COOR
H
39
40
O
COOR
14
15
7b
7b
29
51
OPO(OEt)2
OPO(OEt)2
Me
N
H
O
41
42
O
E
t
t
E
BuO2C CO2 Bu
COOR
Me
43
E = CO2 Bu,
N
O
t
H
44

1662 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
lization of molecular nitrogen in organic synthesis are exciting.
It is known that various transition metals can fix nitrogen, but
there have been few reports on the incorporation of nitrogen
into organic compounds. We previously reported that the het-
erocycles could be synthesized using the titanium–nitrogen
complex reported by Yamamoto. Next, we considered whether
nitrogen can be catalytically introduced in regard to the metal.
After various attempts had been made, a novel TiCl4 or
Ti(OiPr)4–Li–TMSCl system was developed for nitrogen fixa-
tion, and it was found that the reaction proceeded catalytically
based on TiX4 in the presence of excess amounts of Li and
TMSCl under nitrogen (1 atm). This method was then extend-
ed to the synthesis of heterocycles as a stoichiometric reaction,
and various heterocycles, such as indole, quinoline, pyrrole,
pyrrolizine, indolizine derivatives, and lactams, could be syn-
thesized from molecular nitrogen as a nitrogen source. Further-
more, various heterocycles were obtained by a catalytic
amount of titanium–nitrogen complexes in the presence of ex-
cess amounts of Li and TMSCl. The results mean that titani-
um–nitrogen complexes could be used as nitrogenation re-
agents for the synthesis of nitrogen containing compounds
and heterocycles.
O
O
7a, CsF
THF, reflux, 24 h
OTf
NH2
9a
10
189%
based on TiCl4
Scheme 14.
R1
O
O
R1
R2
7a, CsF
R2
THF, reflux
24 h
O
N
H
X
12
11
Scheme 15.
Table 10. Synthesis of Indole Derivative Using Titanium-
Catalyzed Nitrogenation
Run
SM
R1
R2
X
Product
YieldaÞ/%
1
2
3
4
11a
11b
11d
11e
H
H
Me
Me
Me
Ph
OTf
OH
OH
OH
12a
12a
12d
12e
129
273
369
208
Me
H
Experimental
All manipulations were performed under a nitrogen atmosphere
using standard Schlenk techniques, and all of the reaction solu-
tions were degassed through a freeze–pump–thaw cycle. THF
and TMSCl were distilled under an argon atmosphere from so-
dium diphenylketyl (THF) or CaH2 (TMSCl). All other reagents
and solvents were purified when necessary using standard proce-
dures. Column chromatography was performed on silica gel 60
ꢀ
(70–230 mesh, 60 A), and flash chromatography was performed
ꢀ
on silica gel 60 (230–400 mesh, 60 A) using the indicated solvent.
The melting points are uncorrected.
a) Based on TiCl4.
Table 11. Synthesis of Pyrrole and Indole Derivatives
Using Titanium-Catalyzed Nitrogenation
O
O
R3
R4
( )n
( ) n
R4
R3
N
H
O
N
H
O
14b R3=Ph, R4=Bn
14c R3=H, R4=Bn 14h
14d R3=Ph, R4=Me
15b R3=Ph, R4=Bn
15c R3=H, R4=Bn
15d R3=Ph, R4=Me
n=1
n=2
15g n=1
14g
Typical Procedure for Synthesis of Titanium–Nitrogen
Complexes 7. To a suspension of Li (10 equiv.) in THF was add-
ed TiꢁCl4 or Ti(OiPr)4 (1 equiv.) and TMSCl (10 or 16 equiv.) at
ꢃ78 C, and the solution was degassed by a freeze–pump–thaw
cycle. The atmosphere of the reaction vessel was changed to nitro-
gen, and the solution was stirred at room temperature under nitro-
gen (1 atm) overnight. The resultant black solution was used as
titanium–nitrogen complexes 7.
General Procedure for the Synthesis of Nitrogen
Heterocycles. To a black solution of 7 (1.25 equiv.) were added
a substrate (1 equiv.) and CsF (6 equiv.); the solution was then
stirred at an appropriate temperature. After cooling, water was
added and the solution was stirred at room temperature until the
black precipitate had disappeared. The aqueous solution was made
basic by K2CO3, and the solution was extracted with ethyl acetate.
The organic layer was washed with brine, dried over Na2SO4, and
concentrated. The residue was purified by column chromatogra-
phy on silica gel to give a nitrogen-fixation product.
General Procedure for Titanium-Catalyzed Nitrogen
Fixation. A THF suspension of TiCl4 or Ti(OiPr)4 (1 equiv.),
Li (50 equiv.), and TMSCl (50 equiv.) was stirred at room temper-
ature for 24 h. To the solution were added a substrate (10 equiv.)
and CsF (10 equiv.), and the solution was refluxed for 24 h. After
cooling, water was added and the solution was stirred at room
temperature until the black precipitate had disappeared. The solu-
tion was extracted with ethyl acetate. The organic layer was wash-
ed with brine, dried over Na2SO4, and concentrated. The residue
15h n=2
Run
Substrate
Product
Yielda)/%
1
2
3
4
5
14b
14c
14d
14g
14h
15b
15c
15d
15g
15h
247
354
280
350
335
a) Based on TiCl4.
complexes would be reduced by the reducing agent.
Subsequently, the synthesis of indole derivatives was car-
ried out using a catalytic amount of TiX4 (Scheme 15). The re-
action procedure was similar to that used in the synthesis of 10,
the results are given in Table 10. In a similar manner, pyrrole
derivatives were synthesized using a catalytic amount of TiCl4,
as shown in Table 11. In all cases, indole and pyrrole deriva-
tives were obtained in more than 100% yield. These results
mean that these heterocycles could be synthesized from molec-
ular nitrogen as a nitrogen source using a catalytic amount of
TiX4.
Conclusion
Nitrogen fixation is a very interesting and useful method for
synthetic organic chemistry, and studies concerning for the uti-

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1663
was purified by column chromatography on silica gel to give the
nitrogen-fixation product. The yields were calculated based on the
titanium complex.
7.99–8.01 (m and m, 2H); MS m=z 230 (Mþ), 125, 105, 97, 77.
2-(3-Oxobutyl)-3-trifluoromethylsulfonyloxy-2-cyclohexa-
none (11f): A crude product, which was prepared from triketone
11g (364 mg, 2.0 mmol), pyridine (0.18 mL, 2.2 mmol), and Tf2O
(0.37 mL, 2.2 mmol) in CH2Cl2(20 mL), was purified by column
chromatography on silica gel (hexane/ethyl acetate, 3/1) to give a
colorless oil of 11f (547 mg, 87%). IR (neat) 1717, 1688, 1662,
Synthesis of Heterocycles from Di- and Triketones. Gener-
al Procedure for the Synthesis of Triflates (9 and 11): To a
solution of 1,3-diketone derivatives (1 equiv.) and pyridine (1.1
equiv.) in CH2Cl2 was added trifuloromethylsulfonyloxy anhy-
ꢁ
1
dride (Tf2O, 1.1 equiv.) at ꢃ78 C, and the solution was stirred
1418, 1216 cmꢃ1; H NMR (270 MHz, CDCl3) ꢂ 2.05–2.11 (m,
ꢁ
at 0 C for 2 h. Ether was added and the ether layer was washed
2H), 2.13 (s, 3H), 2.45–2.50 (m, 2H), 2.55–2.60 (m, 4H), 2.73–
2.79 (m, 2H). MS m=z 314 (Mþ), 181, 163, 150, 139, 121, 43
(base peak); Anal. Calcd for for C11H13F3O5S: C, 41.88; H,
4.15; S, 10.26; F, 18.08%. Found: C, 42.03; H, 4.17; S, 10.20;
F, 18.14%.
with a 3% HCl solution, a saturated NaHCO3 solution, and brine,
dried over Na2SO4, and concentrated. The residue was purified by
silica-gel chromatography to give the desired product.
2-Methyl-3-trifuloromethanesulfonyloxy-2-cyclohexenone
(9a): A crude product, which was prepared from 9h (630 mg, 5.0
mmol), pyridine (0.445 mmol, 5.5 mmol), and Tf2O (0.95 mL, 5.5
mmol) in CH2Cl2 (50 mL), was purified by column chromatogra-
phy on silica gel (hexane/ethyl acetate, 3/1) to give a colorless oil
1,3-Diphenylhexane-2,5-dione (14b): To a solution of NH-
(iPr)2 (4.4 mL, 36 mmol) in THF (70 mL) was added BuLi (19
mL, 33 mmol, 1.74 M) at 0 ꢁC; the solution was stirred at the same
temperature for 30 min. To this solution was added dibenzyl ke-
tone (6.3 g, 30 mmol) at ꢃ78 ꢁC. The solution was allowed to re-
main at 0 ꢁC for 1 h. To this solution was added allyl bromide (6.5
mL, 45 mmol) at ꢃ78 ꢁC, and the solution was stirred at 0 ꢁC for 4
h. A saturated NH4Cl solution was added and the aqueous layer
was extracted with Et2O. The organic layer was washed with
brine, dried over Na2SO4, and concentrated. The residue was pu-
rified by column chromatography on silica gel (hexane/ethyl ace-
tate, 15/1) to give a colorless oil of 1,3-diphenyl-5-hexen-2-one
of 9a (778 mg, 60%). IR (neat) 1693, 1668, 1419, 1215 cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.86 (t, J ¼ 2:1 Hz, 3H), 2.02–
2.13 (m, 2H), 2.46–2.51 (m, 2H), 2.71–2.78 (m, 2H); MS m=z
258 (Mþ), 257, 225, 123, 98, 83, 55, 43. Anal. Calcd for
C8H9F3O4S: C, 37.21; H, 3.51; S, 12.42; F, 22.07%. Found: C,
37.10; H, 3.50; S, 12.27; F, 22.23%.
2-(2-Oxypropyl)-3-trifluoromethylsulfonyloxy-2-cyclohexe-
none (11a): A crude product, which prepared from triketone
11b1 (168 mg, 1.0 mmol), pyridine (0.089 mL, 1.1 mmol), and
Tf2O (0.19 mL, 1.1 mmol) in CH2Cl2 (10 mL), was purified by
column chromatography on silica gel (hexane/ethyl acetate,
3/1) to give a colorless oil of 11a (279 mg, 93%). IR (neat)
1724, 1690, 1671, 1420, 1216 cmꢃ1; 1H NMR (270 MHz, CDCl3)
ꢂ 2.09–2.18 (m, 2H), 2.24 (s, 3H), 2.48–2.55 (m, 2H), 2.79–2.86
(m, 2H), 3.50 (s, 2H); MS m=z 300 (Mþ), 258, 167, 150, 125, 109;
HRMS (EI, m=z) for C10H11F3O5S calcd 300.0280, found
300.0274.
1
(5.23 g, 70%). IR (neat) 1714, 1640, 1600 cmꢃ1; H NMR (500
MHz, CDCl3) ꢂ 2.41(ddd, J ¼ 7:4, 7.4, 14.3 Hz, 1H), 2.76
(ddd, J ¼ 7:0, 7.4, 14.3 Hz, 1H), 3.62 (d, J ¼ 2:7 Hz, 2H), 3.79
(dd, J ¼ 7:4, 7.4 Hz, 1H), 4.89 (J ¼ 10:0 Hz, 1H), 4.94 (d, J ¼
17:2 Hz, 1H), 5.99 (dddd, J ¼ 7:0, 7.4, 10.0, 17.2 Hz, 1H),
7.00–7.20 (m, 2H), 7.14–7.16 (m, 2H), 7.19–7.47 (m, 6H); To a
solution of 1,3-diphenyl-5-hexen-2-one (2.5 g, 10 mmol) in
DMF–H2O (10:1, 3.3 mL) was added PdCl2 (328 mg, 2.0 mmol)
and CuCl (2.22 g, 22.4 mmol), and the solution was stirred under
oxygen at room temperature for 26 h. Ether was added and the or-
ganic layer was washed with a 10% HCl solution, a sat. NaHCO3
solution and brine, dried over Na2SO4, and concentrated. The res-
idue was purified by column chromatography on silica gel (hex-
ane/ethyl acetate, 5/1) to give a colorless oil of 14b (1.59 g,
2-(1-Methyl-2-oxopropyl)-3-trifluoromethanesulfonyloxy-2-
cyclohexeneone (11c): A crude product, which was prepared
from triketone 11d1 (364 mg, 2.0 mmol), pyridine (0.18 mL, 2.2
mmol), and Tf2O (0.37 mL, 2.2 mmol) in CH2Cl2 (20 mL), was
purified by column chromatography on silica gel (hexane/ethyl
acetate, 3/1) to give a colorless oil of 11c (534 mg, 85%). IR
60%). IR (neat) 1712, 1702, 1600 cmꢃ1 1H NMR (500 MHz,
;
1
(neat) 1722, 1688, 1654, 1418, 1216 cmꢃ1; H NMR (270 MHz,
CDCl3) ꢂ 2.13 (s, 3H), 2.58 (dd, J ¼ 3:9, 18.0 Hz, 1H), 3.43
(dd, J ¼ 10:3, 18.0 Hz, 1H), 3.71 (d, J ¼ 16:4 Hz, 1H), 3.74 (d,
J ¼ 16:4 Hz, 1H), 4.31 (dd, J ¼ 3:9, 10.3 Hz, 1H), 7.00–7.20
(m, 2H), 7.14–7.16 (m, 2H), 7.19–7.47 (m, 6H); MS m=z 266
(Mþ), 175, 147, 91, 65, 43; HRMS (EI, m=z) for C18H18O2, calcd
266.1307, found 266.1295. Anal. Calcd for C18H18O2: C, 81.13;
H, 6.81%. Found: C, 81.12; H, 6.97%.
CDCl3) ꢂ 1.34 (d, J ¼ 7:0 Hz, 3H), 2.08–2.18 (m, 2H), 2.12 (s,
3H), 2.48–2.53 (m, 2H), 2.81–2.87 (m, 2H), 3.51 (q, J ¼ 7:0
Hz, 1H); MS m=z 314 (Mþ), 299, 271, 181, 139, 123, 93, 69,
43; HRMS m=z for C11H13F3O5S calcd 314.0436, found
314.0430.
2-(2-Oxophenethyl)cyclohexane-1,3-dione (11e): To a solu-
tion of 1,3-cyclohexanedione (1.12 g, 10 mmol) in MeOH (4 mL)
were added an aq. KOH (678.3 mg, 12 mmol, 1 mL) solution and
Ethyl 5,8-dioxo-6-methylnonanoate (14e): IR (neat) 2972,
1734, 1712 cmꢃ1
;
1H NMR (500 MHz, CDCl3) ꢂ 4.13 (q, J ¼
ꢁ
phenacyl bromide (1.855 mg, 12 mmol) at 0 C; the solution was
7:0 Hz, 2H), 2.86–3.05 (m, 2H), 2.64 (t, J ¼ 7:2 Hz, 1H), 2.63
(t, J ¼ 7:2 Hz, 1H), 2.41 (m, 1H), 2.32 (t, J ¼ 7:2 Hz, 2H),
2.13 (s, 3H), 1.90 (tt, J ¼ 7:2, 7.2 Hz, 2H), 1.25 (t, J ¼ 7:0 Hz,
3H), 1.08 (d, J ¼ 6:9 Hz, 3H); 13C NMR (125 MHz, CDCl3) ꢂ
212.6, 207.0, 173.2, 60.2, 46.5, 40.9, 40.0, 33.2, 29.8, 18.8,
16.5, 14.2; MS m=z 228 (Mþ), 183, 143, 115; HRMS calcd for
C12H20O4 228.1362, found 228.1363.
stirred at room temperature for 48 h. KBr was filtered off, and to
the filtrate was added a 10% NaOH solution, and the solvent was
evaporated. The residue was extracted with ethyl ether. The aque-
ous layer was acidified by 10% HCl and extracted with ethyl ace-
tate. The organic layer was washed with brine, dried over Na2SO4,
and concentrated. The residue was purified by column chromatog-
raphy on silica gel (hexane/ethyl acetate, 1/1) to give a colorless
4,6-Disphenylnonane-2,5,8-trione (16a, 16b): A crude prod-
uct that was prepared from 4,6-diphenyl-1,8-nonadiene-5-one (3.2
g, 11.2 mmol), PdCl2 (400 mg, 2.44 mmol), and CuCl (2.22 g,
22.4 mmol) in DMF (5 mL)–H2O (0.3 mL) under oxygen was pu-
rified by column chromatography on silica gel (hexane/ethyl ace-
tate, 4/1) to give 16a (536.7 mg, 15%) and 16b (771.4 mg, 21%).
ꢁ
crystal (836.1 mg, 36%). mp 148–150 C (from Et2O); IR (neat)
3172, 1727, 1688, 1598 cmꢃ1 1H NMR (270 MHz, CDCl3) ꢂ
;
1.85–1.99 (m, 2H), 2.38–2.50 and 2.70–2.79 (m and m, 4H),
3.67–4.02 (d, J ¼ 4:6 Hz, and s, 1H), 3.93 (s and t, J ¼ 4:6
Hz), 7.43–7.92 and 7.58–7.62 (m and m, 3H), 8.17–8.22 and

1664 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
16a: mp 77–78 ꢁC (from Et2O); IR (neat) 1718, 1706, 1598 cmꢃ1
;
175, 161, 147, 104, 91, 43; HRMS m=z: for C22H24O3, calcd
336.1725, found 336.1716; Anal. Calcd for C22H24O3: C, 78.54;
H, 7.19%. Found: C, 78.55; H, 7.21%.
1H NMR (500 MHz, CDCl3) ꢂ 2.09 (s, 6H), 2.44 (dd, J ¼ 4:6,
17.6 Hz, 2H), 3.27 (dd, J ¼ 9:6, 17.6 Hz, 2H), 4.12 (dd,
J ¼ 4:6, 9.6 Hz, 2H), 7.09–7.10 (m, 4H), 7.29–7.38 (m, 6H);
13C NMR (67.8 MHz, CDCl3) ꢂ 29.98, 46.00, 51.07, 127.58,
128.73, 129.00, 137.86, 206.20, 207.24; MS m=z: 322 (Mþ),
175, 147, 104, 77, 43; HRMS m=z for C21H22O3, calcd
322.1569, found 322.1541; Anal. Calcd for C21H22O3: C, 78.23;
H, 6.88%. Found: C, 78.23; H, 6.99%. 16b: mp 87–89 ꢁC (recrys-
4-Phenyl-decane-2,5,9-trione (22b):
Compound 22b was
prepared from 4-phenyl-1,9-decadien-5-one (1.5 g, 6.58 mmol),
PdCl2 (233 mg, 1.32 mmol), and CuCl (1.43 g, 14.5 mmol) in
DMF–H2O (10:1, 8.8 mL) under oxygen. The crude product
was purified by column chromatography on silica gel (hexane/
ethyl acetate, 3/1) to give a pale-yellow oil of 22b (783 mg,
1
tallized from Et2O); IR (neat) 1716, 1704, 1600 cmꢃ1; H NMR
46%). IR (neat) 1714, 1712, 1675, 1600 cmꢃ1 1H NMR (500
;
(500 MHz, CDCl3) ꢂ 2.13 (s, 6H), 2.67 (dd, J ¼ 5:2, 17.9 Hz,
2H), 3.34 (dd, J ¼ 8:9, 17.9 Hz, 2H), 4.41 (dd, J ¼ 5:2, 8.9 Hz,
2H), 6.84–6.86 (m, 4H), 7.03–7.08 (m, 6H); 13C NMR (67.8
MHz, CDCl3) ꢂ 29.9, 47.1, 52.9, 126.9, 128.3, 128.4, 137.3,
206.3, 208.8; MS m=z 322 (Mþ), 175, 147, 104, 77, 43; HRMS
m=z for C21H22O3, calcd 322.1569, found 322.1580; Anal. Calcd
for C21H22O3: C, 78.23; H, 6.88%. Found: C, 78.27; H, 6.88%.
4-Phenyl-nonane-2,5,8-trione (18): Compound 18 was pre-
pared from 4-phenyl-1,8-nonadien-5-one (1.28 g, 6.0 mmol),
PdCl2 (213 mg, 1.2 mmol), and CuCl (1.3 g, 13.2 mmol) in
DMF–H2O (10:1, 8.8 mL) under oxygen. The crude product
was purified by column chromatography on silica gel (hexane/
ethyl acetate, 3/1) to give a pale yellow oil of 18 (154.5 mg,
MHz, CDCl3) ꢂ 1.75 (ddddd, J ¼ 6:7, 7.0, 7.0, 7.3, 14.2 Hz,
1H), 1.80 (ddddd, J ¼ 6:7, 7.0, 7.0, 7.3, 14.3 Hz, 1H), 2.03 (s,
3H), 2.16 (s, 3H), 2.29 (ddd, J ¼ 7:0, 7.0, 17.5 Hz, 1H), 2.35
(ddd, J ¼ 7:3, 7.3, 17.5 Hz, 1H), 2.42 (ddd, J ¼ 7:0, 7.0, 17.5
Hz, 1H), 2.55 (ddd, J ¼ 6:7, 6.7, 17.5 Hz, 1H), 2.59 (dd,
J ¼ 3:6, 14.5 Hz, 1H), 3.46 (dd, J ¼ 10:5, 14.5 Hz, 1H), 4.17
(dd, J ¼ 3:6, 14.5 Hz, 1H), 7.17–7.18 (m, 2H), 7.27–7.28 (m,
1H), 7.32–7.33 (m, 2H); MS m=z 260 (Mþ), 243, 199, 184, 171,
159, 148, 113, 104, 85; HRMS m=z for C16H20O3 calcd
260.1413, found 260.1408. Anal. Calcd for C16H2O3: C, 73.82;
H, 7.74%. Found: C, 73.87; H, 7.93%.
2-(3-Oxobutyl)-6-(2-oxopropyl)cyclohexanone (22c): Com-
pound 22c was prepared from 2-(3-oxobutyl)-6-(2-propenyl)cy-
clohexanone (4.16 g, 20 mmol), PdCl2 (354 mg, 2 mmol), and
CuCl (2.2 g, 22 mmol) in DMF–H2O (10:1, 11 mL) under oxygen.
The crude product was purified by column chromatography on
silica gel (hexane/ethyl acetate, 4/1 to 3/1) to give a pale-yellow
10%). IR (neat) 1715, 1712, 1670, 1600 cmꢃ1 1H NMR (500
;
MHz, CDCl3) ꢂ 2.12 (s, 3H), 2.14 (s, 3H), 2.60 (dd, J ¼ 3:9,
18.0 Hz, 1H), 2.63 (dd, J ¼ 6:2, 6.2 Hz, 2H), 2.68 (dt, J ¼ 6:2,
25.4 Hz, 1H), 2.78 (dt, J ¼ 6:2, 25.4 Hz, 1H), 3.42 (dd,
J ¼ 10:0, 18.0 Hz, 1H), 4.23 (dd, J ¼ 3:9, 10.0 Hz, 1H), 7.19–
7.20 (m, 2H), 7.27–2.78 (m, 1H), 7.33–7.34 (m, 2H); MS m=z
246 (Mþ), 228, 185, 148, 99, 91, 77; HRMS m=z for C15H18O3,
calcd 246.1256, found 246.1249. Anal. Calcd for C15H18O3: C,
73.15; H, 7.37%. Found: C, 73.14; H, 7.36%.
oil of 22c (2.8 mg, 63%). IR (neat) 1710, 1702 cmꢃ1 1H NMR
;
(500 MHz, CDCl3) [major product] ꢂ 1.30–1.40 (m, 3H), 1.78–
1.95 (m, 4H), 2.10–2.20 (m, 1H), 2.12 (s, 3H), 2.20 (s, 3H),
2.36–2.45 (m, 3H), 2.89–3.00 (m, 3H); [minor product] ꢂ 1.47–
1.55 (m, 3H), 1.69–1.70 (m, 1H), 1.92–2.02 (m, 1H), 2.04–2.20
(m, 6H), 2.15 (s, 3H), 2.17 (s, 3H), 2.53–2.59 (m, 2H), 3.05–
3.11 (m, 1H); MS m=z 224 (Mþ), 206, 166, 148, 135, 123, 109,
96, 81, 71, 43; HRMS m=z for C13H20O3, calcd 224.1313, found
224.1420; Anal. Calcd for C13H20O3: C, 69.61; H, 8.99%. Found:
C, 69.65; H, 9.08%.
2,6-Bis(2-oxopropyl)cycloheptane-1-one (20):
Compound
16c was prepared from 2,7-di(2-propenyl)cycloheptane-1-one
(1.73 g, 9.0 mmol), PdCl2 (190 mg, 0.9 mmol), and CuCl (1.78
mg, 0.18 mmol) in DMF–H2O (7:1, 7.2 mL) under oxygen. The
crude product was purified by column chromatography on silica
gel (hexane/ethyl acetate, 3/1) to give a pale yellow oil of
Synthesis of Nitrogen Containing Compounds from Di- or
Triketone. 2-Methyl-5-(phenethyl)pyrrole (15a): A crude
product that was prepared from TiCl4 (0.055 mL, 0.5 mmol),
TMSCl (0.63 mL, 5.0 mmol), Li (37 mg, 5.0 mmol), 14a (82
mg, 0.4 mmol), and CsF (369 mg, 2.5 mmol) in THF (7.5 mL)
was purified by column chromatography on silica gel [hexane/
ethyl acetate (10/1) which was contained 3% Et3N] to give 15a
20 (711 mg, 35%). IR (neat) 1714, 1702 cmꢃ1 1H NMR (270
;
MHz, CDCl3) ꢂ 1.23–1.49 (m, 4H), 1.70–1.95 (m, 4H), 2.13 (s,
6H), 2.49 (dd, J ¼ 7:3, 15.4 Hz, 2H), 2.95 (dd, J ¼ 7:3, 21.6
Hz, 2H), 2.96–3.07 (m, 2H); MS m=z 224 (Mþ), 206, 181, 166,
95, 43. HRMS m=z for C13H2O3 calcd 224.1413, found
224.1402. Anal. Calcd for C13H20O3: C, 69.61; H, 8.99%. Found:
C, 69.61; H, 9.12%.
1
(19 mg, 25%). IR (neat) 3372, 1602 cmꢃ1; H NMR (500 MHz,
4,6-Diphenyldecane-2,5,9-trione (22a): Compound 22a was
prepared from 4,6-diphenyl-1,9-decadien-5-one (1.58 g, 5.2
mmol), PdCl2 (177.3 mg, 1 mmol), and CuCl (1.13 g, 11.4 mmol)
in DMF–H2O (10:1, 3.3 mL) under oxygen. The crude product
was purified by column chromatography on silica gel (hexane/
ethyl acetate, 5/1) to give a pale-yellow oil of 22a (786.3 mg,
CDCl3) ꢂ 2.21 (s, 3H), 2.85–2.94 (m, 4H), 5.76 (d, J ¼ 2:0 Hz,
1H), 5.18 (dd, J ¼ 2:0, 2.7 Hz, 1H), 7.18–7.23 (m, 3H), 7.27–
7.31 (m, 2H), 7.47 (brs, 1H); 13C NMR (100 MHz, CDCl3) ꢂ
13.0, 29.7, 36.3, 105.2, 105.7, 126.1, 126.2, 128.4, 130.6, 141.8;
MS m=z 185 (Mþ), 150, 122, 99, 91, 77; HRMS m=z for C13H15N,
calcd 185.1205, found 185.1197.
45%, major/minor = 4). 22a: IR (neat) 1712, 1600 cmꢃ1
;
2-Benzyl-5-methyl-3-phenylpyrrole (15b): A crude product
that was prepared from TiCl4 (0.055 mL, 0.5 mmol), TMSCl (0.63
mL, 5.0 mmol), Li (37 mg, 5.0 mmol), 15a (106 mg, 0.4 mmol),
and CsF (376 mg, 2.5 mmol) in THF (7.5 mL) was purified by col-
umn chromatography on silica gel [hexane/ethyl acetate (10/1),
which was contained 3% Et3N] to give 14b (39 mg, 39%). IR
1H NMR (500 MHz, CDCl3) [major product] ꢂ 1.87–1.92 (m,
1H), 2.05–2.15 (m, 1H), 2.09 (s, 3H), 2.16 (s, 3H), 2.34–2.39
(m, 2H), 2.59 (dd, J ¼ 3:5, 18.1 Hz, 1H), 3.42 (dd, J ¼ 10:7,
18.1 Hz, 1H), 3.93 (dd, J ¼ 6:9, 6.9 Hz, 1H), 4.22 (dd, J ¼ 3:5,
10.7 Hz, 1H), 6.82–6.86 (m, 4H), 7.00–7.08 (m, 6H), [minor prod-
uct] ꢂ 1.87–1.92 (m, 21H), 1.88 (s, 3H), 2.05 (s, 3H), 2.05–2.15
(m, 1H), 2.30–2.35 (m, 2H), 2.54 (dd, J ¼ 5:0, 17.7 Hz, 1H),
3.26 (dd, J ¼ 9:1, 17.7 Hz, 1H), 3.60 (dd, J ¼ 7:2, 7.2 Hz, 1H),
4.16 (dd, J ¼ 5:0, 9.1 Hz, 1H), 7.10–7.16 (m, 4H), 7.28–7.31
(m, 2H), 7.34–7.38 (m, 4H); MS m=z: 336 (Mþ), 318, 260, 189,
1
(neat) 3412, 1600 cmꢃ1; H NMR (500 MHz, CDCl3) ꢂ 2.21 (s,
3H), 4.10 (s, 2H), 6.04 (d, J ¼ 2:5 Hz, 1H), 7.17–7.25 (m, 4H),
7.30–7.34 (m, 4H), 7.40–7.41 (m, 2H), 7.44 (brs, 1H); 13C NMR
(100 MHz, CDCl3) ꢂ 12.7, 32.4, 106.4, 122.0, 124.5, 125.1,
126.3, 126.5, 127.5, 128.3, 128.5, 128.6, 137.0, 139.7; MS m=z

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1665
247 (Mþ), 232, 202, 170, 154, 128; HRMS m=z for C18H17N,
calcd 247.1361, found 247.1345.
0.5 mmol), TMSCl (0.63 mL, 5.0 mmol), Li (37 mg, 5.0 mmol),
14h (67 mg, 0.4 mmol), and CsF (378 mg, 2.5 mmol) in THF (7.5
mL), was purified by column chromatography on silica gel [hex-
ane/ethyl acetate (10/1) that contained 3% Et3N] to give 15h (25
2-Benzyl-5-methylpyrrole (15c): A crude product, which
was prepared from TiCl4 (0.055 mL, 0.5 mmol), TMSCl (0.63
mL, 5.2 mmol), Li (37 mg, 5.0 mmol), 14c (76 mg, 0.4 mmol),
and CsF (378 mg, 2.5 mmol) in THF (7.5 mL), was purified by
column chromatography on silica gel [hexane/ethyl acetate
(10/1) which was contained 3% Et3N] to give 15c (37 mg,
mg, 41%). IR (neat) 3364, 1602 cmꢃ1 1H NMR (500 MHz,
;
CDCl3) ꢂ 1.64–1.70 (m, 4H), 1.76–1.79 (m, 2H), 2.19 (s, 3H),
2.49–2.55 (m, 2H), 2.57–2.63 (m, 2H), 5.63 (d, J ¼ 2:2 Hz,
1H), 7.38 (brs, 1H); 13C NMR (100 MHz, CDCl3) ꢂ 12.7, 28.2,
28.3, 29.2, 29.4, 31.9, 108.0, 121.5, 123.2, 128.7; MS (EI, m=z)
149 (Mþ), 134, 120, 107, 94, 91, 79, 67; HRMS m=z for C10H15N,
calcd 149.1204, found 149.1178.
54%). IR (neat) 3366, 1592 cmꢃ1 1H NMR (500 MHz, CDCl3)
;
ꢂ 2.28 (d, J ¼ 3:1 Hz, 3H), 4.02 (s, 2H), 5.87 (d, J ¼ 2:1 Hz,
1H), 5.94 (d, J ¼ 2:1 Hz, 1H), 7.31–7.33 (m, 3H), 7.37–7.42
(m, 2H), 7.58 (brs, 1H); 13C NMR (100 MHz, CDCl3) ꢂ 13.0,
34.2, 105.8, 106.5, 127.0, 128.6, 128.7, 129.2, 139.8; MS m=z
171 (Mþ), 156, 128, 115, 102, 94, 91, 85, 77, 65, 51; HRMS
(EI, m=z) for C12H13N, calcd 171.1048, found 171.1038.
3,5-Dimethyl-1,7-diphenyl-1H-, -3H-, and -1H-2,3-dihydro-
pyrrolizines (17a, 17b, and 17c): A crude product, which was
prepared from TiCl4 (0.055 mL, 0.5 mmol), TMSCl (0.63 mL,
5.0 mmol), Li (37 mg, 5.0 mmol), triketone 16a (67 mg, 0.4 mmol),
and CsF (378 mg, 2.5 mmol) in THF (7.5 mL), was purified by col-
umn chromatography on silica gel [hexane/ethyl acetate (10/1)
that contained 3% Et3N] to give 17 (35.4 mg, 31%, ratio of
2,5-Dimethyl-3-phenyl-1H-pyrrole (15d): A crude product,
which was prepared from TiCl4 (0.055 mL, 0.5 mmol), TMSCl
(0.63 mL, 5.2 mmol), Li (36.9 mg, 5.0 mmol), 14d (76.4 mg,
0.4 mmol), and CsF (377.9 mg, 2.5 mmol) in THF (7.5 mL),
was purified by column chromatography on silica gel [hexane/
ethyl acetate (10/1) that was contained 3% Et3N] to give 15d
17a:17b:17c = 1:1.8:1). 17a: IR (neat) 1602 cmꢃ1 1H NMR
;
(500 MHz, CDCl3) ꢂ 2.30 (t, J ¼ 1:3 Hz, 3H), 2.47 (s, 3H), 4.80
(d, J ¼ 1:3 Hz, 1H), 5.47 (d, J ¼ 1:3 Hz, 1H), 6.11 (s, 1H),
6.91–7.25 (m, 10H); MS m=z 322 (Mþ) 270, 254, 228, 208, 194,
165, 143, 115, 104, 91, 77; HRMS m=z: for C21H22N, calcd
(44.1 mg, 64%). IR (neat) 3366, 1602 cmꢃ1 1H NMR (500
;
MHz, CDCl3) ꢂ 2.25 (s, 3H), 2.35 (s, 3H), 6.00 (d, J ¼ 2:5 Hz,
1H), 7.30–7.40 (m, 5H); 13C NMR (100 MHz, CDCl3) ꢂ 12.5,
12.9, 106.3, 120.9, 122.4, 124.8, 125.7, 127.4, 128.3, 137.2; MS
m=z 171 (Mþ), 170, 156, 128, 115, 102, 94, 77, 63, 43; HRMS
m=z for C12H13N, calcd 171.1048, found 171.1030.
285.1518, found 285.1514. 17b: IR (neat) 1602 cmꢃ1 1H NMR
;
(500 MHz, CDCl3) ꢂ 1.57 (d, J ¼ 6:8 Hz, 3H), 2.40 (s, 3H),
4.77 (dt, J ¼ 6:8, 6.8 Hz, 1H), 6.12 (d, J ¼ 6:8 Hz, 1H), 6.12 (s,
1H), 6.91–7.25 (m, 10H); MS m=z 285 (Mþ), 270, 254, 208,
165, 143, 115, 104, 91, 77; HRMS m=z for C21H22N, calcd
2-(3-Ethoxycarbonylpropyl)-3,5-dimethylpyrrole (15e): IR
(neat) 3386, 3086, 2928, 1718, 1636 cmꢃ1; H NMR (270 MHz,
1
285.1518, found 285.1514. 17c: IR (neat) 1608 cmꢃ1 1H NMR
;
CDCl3) ꢂ 7.98 (d, J ¼ 2:6 Hz, 1H), 7.57 (brs, 1H), 4.15 (q, J ¼
7:1 Hz, 2H), 2.54 (t, J ¼ 7:3 Hz, 2H), 2.31 (t, J ¼ 7:3 Hz, 2H),
2.20 (d, J ¼ 2:6 Hz, 3H), 1.96 (s, 3H), 1.85 (tt, J ¼ 7:3, 7.3 Hz,
2H), 1.26 (t, J ¼ 7:1 Hz, 3H); 13C NMR (100 MHz, C6D6) ꢂ
173.1, 125.1, 124.6, 114.4, 108.4, 60.2, 33.5, 26.2, 25.1, 14.4,
13.2, 11.4; MS m=z 209 (Mþ), 164, 108; HRMS calcd for
C12H19NO2 209.1416, found 209.1417.
(500 MHz, CDCl3) [major product] ꢂ 1.31 (d, J ¼ 6:5 Hz, 3H),
2.18 (ddd, J ¼ 3:2, 6.5, 12.8 Hz, 1H), 2.31 (s, 3H), 3.31 (ddd,
J ¼ 4:2, 9.3, 12.8 Hz, 1H), 4.30 (ddt, J ¼ 4:2, 6.5, 6.5 Hz, 1H),
4.57 (dd, J ¼ 3:2, 9.3 Hz, 1H), 6.32 (s, 1H), 6.95–7.24 (m, 10H),
[minor project] ꢂ 1.47 (d, J ¼ 6:3 Hz, 3H), 2.34 (s, 3H), 2.56
(ddd, J ¼ 5:3, 6.8, 12.5 Hz, 1H), 2.64 (ddd, J ¼ 6:8, 8.0, 12.5
Hz, 1H), 4.40 (ddt, J ¼ 6:3, 6.8, 6.8 Hz, 1H), 4.61 (dd, J ¼ 5:3,
8.0 Hz, 1H), 6.28 (s, 1H), 6.95–7.24 (m, 10H); 13C NMR (100
MHz, CDCl3) [major product] ꢂ 12.1, 22.3, 43.2, 46.9, 52.2,
108.5, 115.6, 123.8, 124.1, 125.3, 126.3, 127.6, 128.2, 128.5,
133.0, 136.0, 144.6, [minor product] ꢂ 12.5, 20.8, 29.7, 48.4,
51.9, 108.9, 124.6, 126.4, 127.3, 128.0, 133.7, 143.9, 149.0; MS
m=z 287 (Mþ) 272, 256, 244, 230, 210, 194, 180, 167, 144, 115,
102; HRMS m=z for C21H22N, calcd 287.1674, found 287.1652.
2-Methyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole (15f):
A
crude product, which was prepared from TiCl4 (0.055 mL, 0.5
mmol), TMSCl (0.63 mL, 5.0 mmol), Li (37 mg, 5.0 mmol),
14f (56 mg, 0.4 mmol), and CsF (379 mg, 2.5 mmol) in THF
(7.5 mL), was purified by column chromatography on silica gel
[hexane/ethyl acetate (10/1) that was contained 3% Et3N] to
give 15f (11 mg, 23%). IR (neat) 3362, 1613 cmꢃ1 1H NMR
;
(500 MHz, CDCl3) ꢂ 2.25 (s, 3H), 2.32–2.43 (m, 2H), 2.57–
2.60 (m, 2H), 2.65–2.69 (m, 2H), 5.78 (s, 1H), 7.53 (brs, 1H);
13C NMR (100 MHz, CDCl3) ꢂ 13.6, 25.4, 25.6, 29.0, 101.7,
126.6, 130.6, 134.7; MS m=z 121 (Mþ), 120, 106, 93, 91, 79,
67; HRMS m=z for C8H11N, calcd 121.0891, found 121.0897.
2-Methyl-4,5,6,7-tetrahydro-1H-indole (15g): A crude prod-
uct, which was prepared from TiCl4 (0.055 mL, 0.5 mmol),
TMSCl (0.63 mL, 5.0 mmol), Li (37 mg, 5.0 mmol), 14g (62
mg, 0.4 mmol), and CsF (376 mg, 2.5 mmol) in THF (7.5 mL),
was purified by column chromatography on silica gel [hexane/
ethyl acetate (10/1) which was contained 3% Et3N] to give 15g
3,5-Dimethyl-7-phenyl-2,3-dihydro-1H-pyrrolizine (19): A
crude product, which was prepared from TiCl4 (0.055 mL, 0.5
mmol), TMSCl (0.63 mL, 5.0 mmol), Li (37 mg, 5.0 mmol), 18
(98 mg, 0.4 mmol), and CsF (375 mg, 2.5 mmol) in THF (7.5
mL), was purified by column chromatography on silica gel [hex-
ane/ethyl acetate (10/1) that contained 3% Et3N] to give 19 (26
1
mg, 30%). IR (neat) 1602 cmꢃ1; H NMR (500 MHz, CDCl3) ꢂ
1.39 (d, J ¼ 6:5 Hz, 3H), 2.13–2.18 (m, 1H), 2.27 (s, 3H),
2.70–2.75 (m, 1H), 2.96–3.01 (m, 1H), 3.08–3.14 (m, 1H),
4.30–4.33 (m, 1H), 6.20 (s, 1H), 7.06–7.09 (m, 1H), 7.28–7.30
(m, 3H), 7.42–7.43 (m, 1H); 13C NMR (100 MHz, CDCl3) ꢂ
12.1, 21.1, 24.3, 36.2, 52.6, 107.8, 114.0, 123.6, 124.1, 124.9,
128.4, 132.1, 136.9; MS m=z 211 (Mþ), 196, 180, 168, 154,
141, 134, 128, 115, 105, 90, 77; HRMS m=z for C15H17N, calcd
211.1361, found 211.1352.
2,3-Dimethyl-5,5a,6,7,8,9-hexahydro-4H-3-azacyclopenta-
[cd]azulene (21): A crude product, which was prepared from
TiCl4 (0.055 mL, 0.5 mmol), TMSCl (0.63 mL, 5.0 mmol), Li
(37 mg, 5.0 mmol), 20 (90 mg, 0.4 mmol), and CsF (379 mg,
1
(22 mg, 41%). IR (neat) 3362, 1606 cmꢃ1; H NMR (500 MHz,
CDCl3) ꢂ 1.70–1.84 (m, 4H), 2.22 (s, 3H), 2.43–2.55 (m, 4H),
5.63 (d, J ¼ 1:4 Hz, 1H), 7.38 (brs, 1H); 13C NMR (100 MHz,
CDCl3) ꢂ 13.0, 22.7, 22.9, 23.6, 23.9, 105.1, 117.0, 125.4,
125.8; MS m=z 135 (Mþ), 117, 107, 94, 91, 77; HRMS m=z for
C9H13N, calcd 135.1048, found 135.1049.
2-Methyl-1,4,5,6,7,8-hexahydrocyclopenta[b]pyrrole (15h):
A crude product, which was prepared from TiCl4 (0.055 mL,

1666 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
2.5 mmol) in THF (7.5 mL), was purified by column chromatog-
raphy on silica gel [hexane/ethyl acetate (10/1) that contained 3%
187.1334.
Synthesis of Heterocycles from 7 and Keto–Alkyne. Methyl
4-(2-Oxocyclohexyl)-2-butynoate (24a): IR (neat) 2940, 2862,
2238, 1714, 1436, 1260, 1078 cmꢃ1; 1H NMR (500 MHz, CDCl3)
ꢂ 1.42 (dddd, J ¼ 12:8, 12.8, 12.8, 3.7 Hz, 1H), 1.68 (m, 1H), 1.93
(m, 1H), 2.11 (m, 1H), 2.3 1 (m, 1H), 2.33 (dd, J ¼ 17:5, 8.5 Hz,
1H), 2.37–2.46 (m, 2H), 2.54–2.60 (m, 2H), 2.77 (dd, J ¼ 17:5,
4.6 Hz, 1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3) ꢂ
209.6, 153.8, 87.6, 73.7, 52.4, 48.7, 41.6, 33.2, 27.5, 24.8, 18.9;
EIMS m=z 194 (Mþ), 179; HRMS calcd for C11H14O3
194.0943, found 194.0938.
1
Et3N] to give 21 (23 mg, 31%). IR (neat) 1608 cmꢃ1; H NMR
(500 MHz, CDCl3) [major product] ꢂ 1.15–1.25 (m, 1H), 1.44–
1.53 (m, 2H), 1.49 (d, J ¼ 6:5 Hz, 3H), 1.64–1.70 (m, 1H),
1.95–2.02 (m, 2H), 2.09–2.12 (m, 1H), 2.21 (s, 3H), 2.39–2.46
(m, 1H), 2.51 (dd, J ¼ 3:7, 15.7 Hz, 1H), 2.63–2.68 (m, 1H),
2.93 (dddd, J ¼ 5:2, 10.7, 17.5, 21.7 Hz, 1H), 4.18–4.25 (m,
1H), 5.68 (s, 1H), [minor product] ꢂ 0.88–0.92 (m, 1H), 1.31 (d,
J ¼ 6:5 Hz, 3H), 1.39–1.45 (m, 2H), 1.64–1.70 (m, 1H), 1.95–
2.02 (m, 2H), 2.16–2.25 (m, 1H), 2.17 (s, 3H), 2.39–2.46 (m,
1H), 2.50–2.53 (m, 1H), 2.63–2.67 (m, 1H), 3.19 (dddd,
J ¼ 5:1, 10.4, 14.3, 22.2 Hz, 1H), 4.28–4.33 (m, 1H), 5.66 (s,
1H); 13C NMR (100 MHz, CDCl3) [major product] ꢂ 12.6, 20.8,
27.7, 30.3, 30.5, 34.7, 39.0, 45.9, 54.9, 109.8, 114.6, 121.9,
138.5, [minor product] ꢂ 11.5, 21.3, 27.7, 30.2, 30.7, 34.7, 38.1,
44.1, 52.9, 108.9, 113.1, 121.0, 136.9; MS m=z 189 (Mþ) 174,
160, 146, 118, 105, 91; HRMS m=z for C13H19N, calcd
189.1517, found 189.1537.
Methyl 4-(5-Acetoxy-2-oxocyclohexyl)-2-butynoate (24b):
IR (neat) 2238, 1714 cmꢃ1 1H NMR (500 MHz, CDCl3) ꢂ
;
1.58–1.95 (m, 2H), 2.04 (s, 33/13H), 2.12 (s, 6/13H), 2.57–2.97
(m, 7H), 3.72 (s, 3H), 5.17 (dddd, J ¼ 4:4, 4.4, 11.0, 11.0 Hz,
11/13H), 5.23 (m, 2/13H); 13C NMR (68 MHz, CDCl3) [major
product] ꢂ 207.0, 170.2, 153.8, 86.5, 74.3, 69.6, 52.5, 45.0,
37.8, 36.4, 31.1, 21.1, 18.8. LRMS m=z 252 (Mþ), 237, 43; HRMS
calcd for C13H16O5 252.0997, found 252.0991.
3,5-Dimethyl-1,8-diphenyl-7,8-dihydroindolizine (23a):
A
4-(2-Oxocyclohexyl)-2-butynenitrile (24c): IR (neat) 2318,
1
crude product, which was prepared from TiCl4 (0.11 mL, 1.0
mmol), TMSCl (1.26 mL, 10.0 mmol), Li (73.1 mg, 10.0 mmol),
22a (168.0 mg, 0.5 mmol), and CsF (377 mg, 2.5 mmol) in THF
(7.5 mL), was purified by column chromatography on silica gel
[hexane/ethyl acetate (10/1) that contained 3% Et3N] to give
2264, 1712 cmꢃ1; H NMR (270 MHz, CDCl3) ꢂ 1.44 (m, 1H),
1.58–1.80 (m, 2H), 1.94 (m, 1H), 2.12 (m, 1H), 2.23–2.50 (m,
4H), 2.57 (m, 1H), 2.72 (dd, J ¼ 17:8, 5.3 Hz, 1H); 13C NMR
(68 MHz, CDCl3) ꢂ 19.4, 24.9, 27.5, 33.4, 41.7, 48.4, 56.2,
85.6, 105.1, 209.0; LRMS m=z 161 (Mþ), 133, 97, 77; HRMS
calcd for C10H11NO 161.0892, found 161.0831.
1
23a (60.8 mg, 41%); IR (neat) 1666, 1602 cmꢃ1; H NMR (500
MHz, CDCl3) ꢂ 2.28 (s, 3H), (ddd, J ¼ 6:0, 6.2, 16.2 Hz, 1H),
2.51 (s, 3H), 2.65 (ddd, J ¼ 6:0, 6.2, 16.2 Hz, 1H), 4.36 (dd,
J ¼ 6:0, 6.2 Hz, 1H), 4.95 (dd, J ¼ 6:2, 6.2 Hz, 1H), 6.16 (s,
1H), 7.05–7.29 (m, 10H); 13C NMR (100 MHz, CDCl3) ꢂ 16.3,
20.9, 30.4, 108.7, 109.3, 120.2, 125.3, 126.1, 127.5, 127.6,
128.2, 129.0, 134.7, 136.1, 144.2; MS m=z 299 (Mþ), 284, 268,
222, 207, 194, 180, 165, 141, 128, 115, 102, 91; HRMS m=z for
C22H22N, calcd 299.1674, found 299.1673.
N,N-Diethyl-4-(2-oxocyclohexyl)-2-butynamide (24d): IR
(neat) 2226, 1710, 1622 cmꢃ1 1H NMR (270 MHz, CDCl3) ꢂ
;
1.12 (t, J ¼ 7:2 Hz, 3H), 1.91 (t, J ¼ 7:2 Hz, 3H), 1.44 (m,
1H), 1.54–1.79 (m, 2H), 1.92 (m, 1H), 2.12 (m, 1H), 2.24–2.49
(m, 3H), 2.35 (dd, J ¼ 17:1, 8.1 Hz, 1H), 2.56 (m, 1H), 2.75
(dd, J ¼ 17:1, 4.7 Hz, 1H), 3.40 (q, J ¼ 7:2 Hz, 2H), 3.55 (q, J ¼
7:2 Hz, 2H); 13C NMR (68 MHz, CDCl3) ꢂ 209.5, 153.3, 89.1,
74.9, 48.5, 43.0, 41.3, 38.6, 33.0, 27.2, 24.5, 18.8, 13.9, 12.3;
EIMS m=z 235 (Mþ), 135; HRMS calcd for C14H21NO
235.1583, found 235.1569.
3,5-Dimethyl-1-phenyl-7,8-dihydroindolizine (23b):
A
crude product, which was prepared from TiCl4 (0.11 mL, 1.0
mmol), TMSCl (1.26 mL, 10.0 mmol), Li (73.7 mg, 10.0 mmol),
22b (130.0 mg, 0.5 mmol), and CsF (376 mg, 2.5 mmol) in THF
(7.5 mL), was purified by column chromatography on silica gel
[hexane/ethyl acetate (5/1) which was contained 3% Et3N] to
5-(2-Oxocyclohexyl)-3-pentyne-2-one (24e): IR (neat) 2210,
1712, 1676 cmꢃ1 1H NMR (270 MHz, CDCl3) ꢂ 1.42 (dddd,
;
J ¼ 12:6, 12.6, 3.6 Hz, 1H), 1.60–1.80 (m, 2H), 1.95 (m, 1H),
2.11 (m, 1H), 2.25–2.50 (m, 4H), 2.31 (s, 3H), 2.56 (m, 1H),
2.78 (dd, J ¼ 17:6, 4.6 Hz, 1H); 13C NMR (68 MHz, CDCl3) ꢂ
209.9, 184.6, 91.9, 82.2, 48.8, 41.7, 33.3, 32.6, 27.6, 24.9, 19.3;
LRMS m=z 178 (Mþ), 163, 135, 43; HRMS calcd for C11H14O2
178.0993, found 178.1006.
1
give 23b (62.3 mg, 56%). IR (neat) 1664, 1604 cmꢃ1; H NMR
(500 MHz, CDCl3) ꢂ 2.07–2.12 (m, 2H), 2.24 (s, 3H), 2.41 (s,
3H), 2.84 (t, J ¼ 7:2 Hz, 2H), 5.18 (t, J ¼ 4:8 Hz, 1H), 6.04 (s,
1H), 7.15–7.17 (m, 2H), 7.31–7.33 (m, 3H); 13C NMR (100
MHz, CDCl3) ꢂ 16.2, 21.1, 21.5, 21.6, 108.9, 110.9, 119.1,
125.2, 126.7, 127.0, 127.8, 128.3, 134.6, 136.5; MS m=z 223
(Mþ), 208, 193, 167, 152, 141, 128, 121, 115, 102, 91, 77; HRMS
m=z for C16H17N, calcd 223.1361, found 223.1362.
2-(2-Butynyl)cyclohexanone (24f): IR (neat) 1710 cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.38 (m, 1H), 1.53–1.80 (m,
3H), 1.77 (dd, J ¼ 2:5, 2.5 Hz, 3H), 1.80–1.97 (m, 1H), 2.00–
2.18 (m, 2H), 2.21–2.48 (m, 3H), 2.56 (ddq, J ¼ 16:4, 5.0, 2.5
Hz, 1H); 13C NMR (68 MHz, C6D6) ꢂ 3.3, 19.5, 25.1, 27.7,
33.3, 41.7, 49.9, 76.6, 77.7, 208.8; LRMS m=z 150 (Mþ), 149,
135; HRMS calcd for C10H14O 150.1045, found 150.1036.
2,4-Dimethyl-6a,7,8,9-tetrahydro-6H-pyrolo[3,2,1-ij]quino-
line (23c): A crude product, which was prepared from TiCl4
(0.11 mL, 1.0 mmol), TMSCl (1.26 mL, 10.0 mmol), Li (72.9
mg, 10.0 mmol), 22c (112.1 mg, 0.5 mmol), and CsF (376 mg,
2.5 mmol) in THF (7.5 mL), was purified by column chromatog-
raphy on silica gel [hexane/ethyl acetate (5/1) that contained 3%
2-(3-Phenyl-2-propynyl)cyclohexanone (24g):
(from hexane); IR (nujol) 2220, 1702, 1490 cmꢃ1
mp 48 ꢁC
;
1H NMR
(270 MHz, CDCl3) ꢂ 1.47 (m, 1H), 1.62–1.78 (m, 2H), 1.94 (m,
1H), 2.11 (m, 1H), 2.26–2.66 (m, 4H), 2.40 (dd, J ¼ 16:9, 8.6
Hz, 1H), 2.85 (dd, J ¼ 16:9, 4.1 Hz, 1H), 7.24–7.30 (m, 3H),
7.34–7.42 (m, 2H); 13C NMR (68 MHz, CDCl3) ꢂ 19.6, 24.9,
27.6, 32.2, 41.7, 49.6, 81.6, 88.0, 123.6, 127.4, 128.0, 131.4,
210.7; EI-LRMS m=z 212 (Mþ), 183, 135; EI-HRMS calcd for
C15H16O 212.1202, found 212.1208; Anal. Calcd for C15H16O:
C, 84.87; H, 7.60%. Found: C, 85.08; H, 7.73%.
Et3N] to give 23c (28.4 mg, 30%). IR (neat) 1654, 1604 cmꢃ1
;
1H NMR (500 MHz, CDCl3) ꢂ 1.23–1.31 (m, 1H), 1.65–1.82
(m, 2H), 1.93–2.01 (m, 2H), 2.10–2.17 (m, 1H), 2.19 (s, 3H),
2.37 (s, 3H), 2.46–2.50 (m, 2H), 2.68–2.73 (m, 1H), 5.02 (d, J ¼
7:0 Hz, 1H), 5.68 (s, 1H); 13C NMR (100 MHz, CDCl3) ꢂ 15.6,
20.6, 22.4, 24.0, 28.5, 303, 31.1, 107.9, 108.9, 114.4, 126.3,
134.2, 165.2; MS m=z 187 (Mþ), 172, 158, 147, 134, 117, 105,
91, 77, 73; HRMS m=z for C13H17N, calcd 187.1361, found
2-[3-(p-Methylphenyl)-2-propynyl]cyclohexanone
(26a):

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1667
mp 46 ꢁC (from hexane); IR (nujol) 2230, 1705, 1518 cmꢃ1
;
1718 cmꢃ1; 1H NMR (270 MHz, CDCl3) ꢂ 2.16 (s, 3H), 2.52–2.61
(m, 2H), 2.68–2.77 (m, 2H), 3.75 (s, 3H); 13C NMR (68 MHz,
CDCl3) ꢂ 12.8, 29.5, 40.8, 52.3, 72.8, 87.9, 153.8, 205.0; LRMS
m=z 155 (Mþ + H), 139, 111; HRMS calcd for C8H11O3 (Mþ
+ H) 155.0708, found 155.0698.
1H NMR (400 MHz, CDCl3) ꢂ 1.45 (m, 1H), 1.60–1.80 (m,
2H), 1.95 (m, 1H), 2.12 (m, 1H), 2.30–2.62 (m, 5H), 2.54 (s,
3H), 2.84 (dd, J ¼ 17:1, 4.3 Hz, 1H), 7.05–7.12 (m, 2H), 7.25–
7.30 (m, 2H); 13C NMR (100 MHz, CDCl3) ꢂ 210.4, 137.2,
131.1, 128.6, 120.4, 87.1, 81.5, 49.5, 41.7, 33.2, 27.6, 24.9,
21.1, 19.5; LRMS m=z 226 (Mþ), 211; HRMS calcd for C16H18O
226.1358, found 226.1347; Anal. Calcd for C16H18O: C, 84.91; H,
8.02%. Found: C, 85.08; H, 8.11%.
5-(2-Oxocyclohexyl)-2-pentynoic Acid Methyl Ester (29c):
IR (neat) 1714 cmꢃ1 1H NMR (270 MHz, CDCl3) ꢂ 1.28–1.58
;
(m, 3H), 1.58–1.82 (m, 2H), 1.84–1.94 (m, 1H), 1.99–2.18 (m,
3H), 2.26–2.51 (m, 2H), 2.42 (t, J ¼ 7:1 Hz, 2H), 3.75 (s, 3H);
13C NMR (125 MHz, CDCl3) ꢂ 16.0, 24.7, 27.1, 27.6, 33.6,
41.7, 48.6, 52.0, 72.7, 88.7, 153.5, 211.4; LRMS m=z 208 (Mþ),
176, 111, 98; HRMS calcd for C12H16O3 208.1099, found
208.1105; Anal. Calcd for C12H16O3: C, 69.21; H, 7.74%. Found:
C, 69.20; H, 7.83%.
Methyl p-[3-(2-Oxocyclohexyl)-2propynyl]benzoate (26b):
ꢁ
mp 69–70 C (from MeOH); IR (nujol) 2220, 1714, 1702, 1606
cmꢃ1 1H NMR (270 MHz, CDCl3) ꢂ 1.50 (m, 1H), 1.60–1.82
;
(m, 2H), 1.95 (m, 1H), 2.11 (m, 1H), 2.28–2.67 (m, 5H), 2.87
(dd, J ¼ 17:1, 4.4 Hz, 1H), 3.91 (m, 3H), 7.41–7.48 (m, 2H),
7.93–7.99 (m, 2H); 13C NMR (68 MHz, CDCl3) ꢂ 210.5, 166.4,
131.3, 129.1, 128.8, 128.4, 91.6, 81.1, 52.0, 49.5, 41.8, 33.3,
27.7, 25.0, 19.7; EIMS m=z 270 (Mþ), 255, 241; HRMS calcd
for C17H18O3 270.2156, found 270.2154; Anal. Calcd for
C17H18O3: C, 75.53; H, 6.71%. Found: C, 75.49; H, 6.76%.
2-[3-(p-Cyanophenyl)-2-propynyl]cyclohexanone (26c): mp
5-(2-Oxocyclopentyl)-2-pentynoic Acid Methyl Ester (29d):
IR (neat) 1744, 1712 cmꢃ1 1H NMR (400 MHz, CDCl3) ꢂ
;
1.43–1.58 (m, 2H), 1.78 (m, 1H), 1.94–2.53 (m, 8H), 3.73 (s,
3H); 13C NMR (125 MHz, CDCl3) ꢂ 16.6, 20.3, 27.3, 29.2,
37.6, 47.6, 52.2, 73.0, 88.4, 153.7, 219.6; MS m=z 194 (Mþ),
162, 111; HRMS calcd for C11H14O3 194.0943, found
194.0949; Anal. Calcd for C11H14O3: C, 68.02; H, 7.27%. Found:
C, 67.95; H, 7.27%.
97–98 ꢁC (from MeOH); IR (nujol) 2224, 1698, 1604 cmꢃ1
;
1H NMR (400 MHz, CDCl3) ꢂ 1.47 (ddd, J ¼ 12:7, 12.7, 3.4
Hz, 1H), 1.60–1.79 (m, 2H), 1.94 (m, 1H), 2.12 (m, 1H), 2.39–
2.49 (m, 4H), 2.59 (m, 1H), 2.84 (dd, J ¼ 17:3, 4.6 Hz, 1H),
7.44 (d, J ¼ 8:3 Hz, 2H), 7.55 (d, J ¼ 8:3 Hz, 2H); 13C NMR
(100 MHz, CDCl3) ꢂ 210.2, 131.8, 131.6, 128.6, 118.3, 110.7,
93.3, 80.3, 49.4, 41.8, 33.3, 27.7, 25.0, 19.8; LRMS m=z 237
(Mþ), 135, 55; HRMS calcd for C16H15NO 237.1153, found
237.1158; Anal. Calcd for C16H15NO: C, 80.98; H, 6.37; N,
5.90%. Found: C, 81.10; H, 6.51; N, 5.88%.
5,5-Bis(benzyloxymethyl)-7-oxo-2-octynoic Acid Methyl
1
Ester (29e): IR (neat) 2234, 1714 cmꢃ1; H NMR (400 MHz,
CDCl3) ꢂ 2.10 (s, 3H), 2.60 (s, 2H), 2.69 (s, 2H), 3.53 (s, 4H),
3.75 (s, 3H), 4.46 (s, 4H), 7.24–7.35 (m, 10H); 13C NMR (125
MHz, CDCl3) ꢂ 22.6, 31.7, 42.0, 43.7, 52.4, 71.3, 73.2, 74.8,
86.7, 127.4, 127.5, 128.2, 138.2, 153.9, 207.5; LRMS m=z 408
(Mþ); HRMS calcd for C25H28O5 408.1947, found 408.1926;
Anal. Calcd for C25H28O5: C, 73.51; H, 6.91%. Found: C,
73.43; H, 7.11%.
2-[3-(p-Trifluolomethylphenyl)-2-propynyl]cyclohexanone
(26d): mp 45–46 ꢁC (from hexane); IR (nujol) 2240, 1734, 1614
cmꢃ1; 1H NMR (400 MHz, CDCl3) ꢂ 1.50 (m, 1H), 1.64–1.80 (m,
2H), 1.95 (m, 1H), 2.13 (m, 1H), 2.30–2.50 (m, 4H), 2.60 (m, 1H),
2.86 (dd, J ¼ 17:0, 4.5 Hz, 1H), 7.47 (d, J ¼ 8:5 Hz, 2H), 7.53 (d,
J ¼ 8:5 Hz, 2H); 13C NMR (68 MHz, CDCl3) ꢂ 210.7, 131.9,
129.4 (q, JC{F ¼ 33 Hz), 127.0, 125.1, 124.1 (q, JC{F ¼ 272
Hz), 91.2, 80.7, 49.7, 42.0, 33.5, 27.9, 25.2, 19.9; MS m=z 280
(Mþ), 261, 183; HRMS calcd for C16H15F3O 280.175, found
280.171; Anal. Calcd for C16H15F3O: C, 68.56; H, 5.39%. Found:
C, 68.62; H, 5.49%.
Synthesis of Indole and Quinoline Derivatives Using Mi-
chael-Type Reaction. Typical Procedure for the Synthesis
of Tetrahydroindole Derivative—Synthesis of Methoxycar-
bonylmethyl)-4,5,6,7-Tetrahydroindole (25a): To a solution
of CsF (379 mg, 2.50 mmol) and 1a (78.4.1mg, 0.404 mmol) in
THF (3.0 mL) was added a THF solution of titanium–nitrogen
complexes, prepared from Ti(OiPr)4 (0.15 mL, 0.504 mol),
TMSCl (1.00 mL, 7.88 mmol), and Li (36.1 mg, 5.20 mmol) in
THF (7.5 mL), and the solutionꢁwas stirred at rt for 50 min. Water
was added to the solution at 0 C, and the solution was stirred at
room temperature for 2 h. The aqueous layer was extracted with
ethyl acetate. The organic layer was washed with brine, dried over
Na2SO4, and concentrated. The residue was purified by column
chromatgraphy on silica gel (hexane:EtOAc = 4:1 containing
1% Et3N) to give 25a (64.4 mg, 82%) as a pale-yellow oil: IR
Methyl o-[3-(2-Oxocyclohexyl)-2-propynyl]benzoate (26f):
IR (neat) 2245, 1735, 1720 cmꢃ1 1H NMR (500 MHz, CDCl3)
;
ꢂ 1.50 (ddd, J ¼ 12:6, 12.6, 3.5 Hz, 1H), 1.65–1.79 (m, 2H),
1.95 (m, 1H), 2.11 (m, 1H), 2.35 (ddd, J ¼ 13:0, 13.0, 6.0 Hz,
1H), 2.41–2.51 (m, 2H), 2.55 (m, 1H), 2.63 (m, 1H), 2.91 (dd,
J ¼ 17:2, 4.3 Hz, 1H), 3.91 (s, 3H), 7.30 (dd, J ¼ 7:6, 7.6 Hz,
1H), 7.41 (dd, J ¼ 7:6, 7.6 Hz, 1H), 7.50 (d, J ¼ 7:9 Hz, 1H),
7.87 (d, J ¼ 7:6 Hz, 1H); 13C NMR (125 MHz, CDCl3) ꢂ 210.4,
166.4, 133.8, 131.7, 131.1, 129.8, 127.0, 123.8, 93.5, 80.0, 51.7,
49.4, 41.6, 33.0, 27.5, 24.8, 19.8; EIMS m=z 270 (Mþ), 255, 55;
HRMS calcd for C17H18O3 270.1256, found 270.1252.
1
(neat) 3384, 2924, 2850, 1734, 1604 cmꢃ1; H NMR (500 MHz,
CDCl3) ꢂ 1.73 (tt, J ¼ 6:1, 6.1 Hz, 2H), 1.81 (tt, J ¼ 6:1, 6.1
Hz, 2H), 2.47 (t, J ¼ 6:1 Hz, 2H), 2.56 (t, J ¼ 6:1 Hz, 2H),
3.62 (s, 2H), 3.72 (s, 3H), 5.77 (brs, 1H), 8.09 (brs, 1H); 13C NMR
(125 MHz, CDCl3) ꢂ 171.7, 127.1, 121.1, 116.9, 106.3, 52.1, 33.3,
23.8, 23.4, 22.8, 22.7; MS m=z 193 (Mþ), 134; HRMS calcd for
C11H15NO2 193.1102, found 193.1086.
4-(2-Oxo-cycloheptyl)-2-butynoic Acid Methyl Ester (29a):
IR (neat) 2930, 2236, 1714 cmꢃ1
;
1H NMR (500 MHz, CDCl3)
5-Acetoxy-2-(methoxycarbonylmethyl)-4,5,6,7-tetrahydro-
indole (25b): IR (neat) 3378, 2950, 2850, 1732, 1606 cmꢃ1
;
ꢂ 1.35 (m, 1H), 1.42–1.60 (m, 2H), 1.68 (m, 1H), 1.80–1.95 (m,
3H), 2.00 (m, 1H), 2.40 (dd, J ¼ 17:6, 8.7 Hz, 1H), 2.47 (m,
1H), 2.59 (m, 1H), 2.68 (dd, J ¼ 17:6, 5.1 Hz, 1H), 2.82 (m,
1H), 3.75 (s, 3H); 13C NMR (68 MHz, CDCl3) ꢂ 20.9, 23.6,
28.6, 29.2, 30.4, 43.1, 49.8, 52.4, 73.6, 87.9, 153.9, 217.7; LRMS
m=z 208 (Mþ); HRMS calcd for C12H16O3 208.1099, found
208.1087.
1H NMR (500 MHz, CDCl3) ꢂ 1.90–2.10 (m, 2H), 2.04 (s, 3H),
2.57 (dd, J ¼ 15:5, 6.7 Hz, 1H), 2.68 (m, 2H), 2.84 (dd,
J ¼ 15:5, 5.1 Hz, 1H), 3.61 (s, 2H), 3.75 (s, 3H), 5.16 (m, 1H),
5.76 (brs, 1H), 8.20 (brs, 1H); 13C NMR (125 MHz, CDCl3) ꢂ
171.7, 170.8, 125.5, 122.2, 113.8, 106.7, 70.6, 52.1, 33.2, 28.7,
27.9, 21.4, 20.0; MS m=z 251 (Mþ), 191, 132; HRMS calced
for C13H17NO4 251.1160, found 251.1174.
6-Oxo-2-heptynoic Acid Methyl Ester (29b): IR (neat) 2240,

1668 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
dole (27f): IR (neat) 3400, 1720, 1600 cmꢃ1 1H NMR (400
2-(Cyanomethyl)-4,5,6,7-tetrahydroindole (25c): IR (neat)
3366, 2254, 1604 cmꢃ1
;
;
1H NMR (400 MHz, CDCl3) ꢂ 1.67–
MHz, C6D6) ꢂ 1.56–1.70 (m, 4H), 2.26 (dd, J ¼ 5:8, 5.8 Hz,
2H), 2.61 (dd, J ¼ 5:7, 5.7 Hz, 2H), 3.42 (s, 3H), 4.17 (s, 2H),
5.94 (d, J ¼ 2:4 Hz, 1H), 6.88 (ddd, J ¼ 7:3, 7.3, 1.5 Hz, 1H),
7.01 (ddd, J ¼ 7:3, 7.3, 1.5 Hz, 1H), 7.13–7.21 (m, 1H), 7.77
(dd, J ¼ 7:3, 1.5 Hz, 1H), 8.09 (brs, 1H); 13C NMR (100 MHz,
C6D6) ꢂ 168.7, 143.4, 132.3, 131.7, 130.4, 129.5, 129.1, 126.0,
125.8, 116.7, 106.0, 51.9, 33.1, 24.8, 24.3, 23.9, 23.4; MS m=z
269 (Mþ), 254, 241; HRMS calcd for C17H19NO2 269.1414,
found 269.1416.
1.74 (m, 2H), 1.74–1.82 (m, 2H), 2.43 (t, J ¼ 6:0 Hz, 2H), 2.52
(t, J ¼ 6:0 Hz, 2H), 3.69 (s, 2H), 5.84 (brs, 1H), 7.72 (brs, 1H);
13C NMR (100 MHz, CDCl3) ꢂ 16.9, 22.5, 22.7, 23.2, 23.6,
107.2, 116.4, 117.2, 117.5, 128.0; LRMS m=z 160 (Mþ), 120;
HRMS calcd for C10H12N2 160.1000, found 160.1028.
2-(N,N-Diethylcarbamoylmethyl)-4,5,6,7-tetrahydroindole
(25d): IR (nujol) 3272, 1626 cmꢃ1; 1H NMR (400 MHz, CDCl3)
ꢂ 1.12 (t, J ¼ 6:8 Hz, 3H), 1.20 (t, J ¼ 6:8 Hz, 3H), 1.68–1.81 (m,
4H), 2.40–2.55 (m, 4H), 3.37 (q, J ¼ 6:8 Hz, 4H), 3.62 (s, 2H),
5.68 (brs, 1H), 8.66 (brs, 1H); 13C NMR (100 MHz, CDCl3) ꢂ
170.0, 126.7, 122.7, 116.2, 105.4, 42.8, 40.7, 31.9, 23.9, 23.5,
22.9, 22.7, 14.6, 13.1; MS m=z 234 (Mþ), 134; HRMS calcd for
C14H22N2O 234.1732, found 234.1746.
2-(2-Oxypropyl)-4,5,6,7-tetrahydroindole (25e): IR (neat)
;
3372, 1706, 1604 cmꢃ1 1H NMR (500 MHz, CDCl3) ꢂ 1.70–
1.82 (m, 4H), 2.21 (s, 3H), 2.45–2.58 (m, 4H), 3.67 (s, 2H),
5.74 (brs, 1H), 8.05 (brs, 1H); 13C NMR (100 MHz, CDCl3) ꢂ
206.6, 127.1, 121.6, 116.9, 106.6, 42.4, 29.6, 23.8, 23.4, 22.8,
22.7; MS m=z 177 (Mþ), 134, 43; HRMS calcd for C11H15NO
177.1154, found 177.1147.
1,2,3,4,4a,6-Hexahydroindolo[1,2-b]isoquinolin-6-one (28):
IR (CCl4) 1734, 1660, 1636, 1622 cmꢃ1 1H NMR (500 MHz,
;
CDCl3) ꢂ 1.05 (m, 1H), 1.33 (ddddd, J ¼ 13:6, 13.6, 13.6, 4.1,
4.1 Hz, 1H), 1.59 (ddddd, J ¼ 13:6, 13.6, 13.6, 3.4, 3.4 Hz,
1H), 1.90 (m, 1H), 2.20 (m, 1H), 2.36 (ddd, J ¼ 13:6, 13.6, 5.5
Hz, 1H), 2.79 (ddd, J ¼ 13:6, 2.2, 2.2 Hz, 1H), 3.36 (m, 1H),
4.45 (dd, J ¼ 11:1, 5.6 Hz, 1H), 6.16 (s, 1H), 6.44 (s, 1H), 7.39
(dd, J ¼ 7:4, 7.4 Hz, 1H), 7.49 (d, J ¼ 8:0 Hz, 1H), 7.59 (m,
1H), 8.40 (d, J ¼ 7:4 Hz, 1H); 13C NMR (125 MHz, CDCl3) ꢂ
161.1, 152.6, 145.6, 138.2, 131.8, 127.3, 125.7, 125.3, 123.8,
116.3, 98.0, 66.1, 32.0, 28.7, 27.5, 23.5; MS m=z 237 (Mþ),
209; HRMS calcd for C16H15NO 237.1154, found 237.1153.
1,2,3,6,12,12a-Hexahydroindolo[1,2-b]isoquinolin-6-one
2-Benzyl-4,5,6,7-tetrahydroindole (25g):
IR (neat) 3424,
1
1
3364, 1602 cmꢃ1; H NMR (400 MHz, CDCl3) ꢂ 1.68–1.82 (m,
4H), 2.45–2.52 (m, 4H), 3.91 (s, 2H), 5.70 (brs, 1H), 7.20–7.30
(m, 6H); 13C NMR (100 MHz, CDCl3) ꢂ 22.7, 22.8, 23.4, 23.8,
34.3, 105.4, 116.7, 126.0, 126.1, 128.4, 128.6, 128.7, 139.5; MS
m=z 211 (Mþ), 183, 134, 120; HRMS calcd for C15H17N
211.1361, found 211.1375.
(280): IR (CCl4) 1692, 1672, 1634, 1604 cmꢃ1; H NMR (400
MHz, CDCl3) ꢂ 1.41 (m, 1H), 1.61 (m, 1H), 1.92 (m, 1H),
2.14–2.28 (m, 2H), 2.42 (m, 1H), 2.62 (dddd, J ¼ 15:1, 11.7,
1.7 Hz, 1H), 2.79 (m, 1H), 3.09 (dd, J ¼ 13:6, 13.6, 13.6, 3.4,
3.4 Hz, 1H), 6.40 (d, J ¼ 1:7 Hz, 1H), 6.89 (m, 1H), 7.38–7.45
(m, 2H), 7.58 (m, 1H), 8.41 (m, 1H); 13C NMR (125 MHz, CDCl3)
ꢂ 21.6, 23.9, 28.5, 35.4, 37.1, 101.1, 112.6, 125.4, 125.8, 125.9,
127.8, 132.1, 136.8, 140.2, 142.5, 161.1; LRMS m=z 237 (Mþ),
209; HRMS calcd for C16H15NO 237.1154, found 237.1156.
(5,6,7,8-Tetrahydro-4H-cyclohepta[b]pyrrol-2-yl)acetic
Acid Methyl Ester (30a): A crude product, which was synthe-
sized from titanium–nitrogen complexes 7b, prepared from
Ti(OiPr)4 (0.15 mL, 0.504 mmol), TMSCl (1.00 mL, 7.88 mmol),
and Li (36.4 mg, 5.24 mmol) in THF (7.5 mL) under nitrogen, 29a
(83.7 mg, 0.40 mmol), and CsF (382 mg, 2.51 mmol) in THF (3.0
mL), was purified by column chromatogrphy on silica gel (hex-
ane–ethyl acetate containing 3% NEt3, 5/1) to give 30a (59.8
2-[(p-Methylphenyl)methyl]-4,5,6,7-tetrahydroindole (27a):
IR (CCl4) 3470, 1604 cmꢃ1 1H NMR (400 MHz, CDCl3) ꢂ
;
1.70–1.82 (m, 4H), 2.36 (s, 3H), 2.40–2.53 (m, 4H), 3.87 (s,
2H), 5.68 (brs, 1H), 7.05–7.35 (m, 5H); 13C NMR (100 MHz,
CDCl3) ꢂ 136.5, 135.7, 129.2, 129.1, 129.0, 126.0, 116.8, 105.3,
33.9, 23.9, 23.5, 22.9, 22.7, 21.1; MS m=z 225 (Mþ), 210, 197,
134, 120; HRMS calcd for C16H19N 225.1518, found 225.1496.
2-[(p-Methoxycarbonylphenyl)methyl]-4,5,6,7-tetrahydro-
indole (27b): IR (CCl4) 3470, 1726, 1610 cmꢃ1; H NMR (400
1
MHz, CDCl3) ꢂ 1.68–1.82 (m, 4H), 2.45–2.53 (m, 4H), 3.91 (s,
2H), 3.96 (s, 3H), 5.70 (brs, 1H), 7.20–7.35 (m, 3H), 7.92–8.10
(m, 2H); 13C NMR (100 MHz, CDCl3) ꢂ 166.8, 145.0, 129.7,
128.6, 128.1, 127.6, 126.4, 116.8, 105.8, 52.0, 34.3, 23.8, 23.4,
22.8, 22.6; EIMS m=z 269 (Mþ), 241, 210, 134, 120; HRMS calcd
for C17H19NO2 269.1416, found 269.1408.
mg, 72%) as a colorless oil. IR (neat) 3384, 1732, 1436 cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.58–1.81 (m, 6H), 2.94 (dd,
J ¼ 5:9, 5.9 Hz, 2H), 2.62 (dd, J ¼ 5:9, 5.9 Hz, 2H), 3.56 (s,
2H), 3.69 (s, 3H), 5.73 (d, J ¼ 2:8 Hz, 1H), 8.07 (brs, 1H);
13C NMR (68 MHz, CDCl3) ꢂ 28.0, 28.3, 29.2, 29.3, 31.9, 33.0,
52.0, 109.5, 118.5, 121.4, 130.6, 171.8; MS m=z 207 (Mþ), 148;
HRMS calcd for C12H17NO2 207.1260, found 207.1277.
2-[(p-Cyanophenyl)methyl]-4,5,6,7-tetrahydroindole (27c):
1
IR (CCl4) 3474, 2230, 1606 cmꢃ1; H NMR (400 MHz, CDCl3)
ꢂ 1.68–1.83 (m, 4H), 2.42–2.53 (m, 4H), 3.96 (s, 2H), 5.68 (d, J ¼
2:4 Hz, 1H), 7.27–7.38 (brs, 1H), 7.33 (d, J ¼ 8:1 Hz, 2H), 7.59
(d, J ¼ 8:1 Hz, 2H); 13C NMR (100 MHz, CDCl3) ꢂ 145.5,
132.2, 129.3, 126.8, 126.7, 118.9, 117.0, 110.0, 106.3, 34.4,
23.8, 23.4, 22.8, 22.7; MS m=z 236 (Mþ), 208, 134; HRMS calcd
for C16H16N2 236.1313, found 236.1314.
(5-Methylpyrrol-2-yl)acetic Acid Methyl Ester (30b):
A
crude product, which was synthesized from titanium–nitrogen
complexes 7b, prepared from Ti(OiPr)4 (0.15 mL, 0.504 mmol),
TMSCl (1.00 mL, 7.88 mmol), Li (36.7 mg, 5.29 mmol) in
THF (7.5 mL) under nitrogen, 29b (61.9 mg, 0.402 mmol), and
CsF (61.9 mg, 0.402 mmol) in THF (3.0 mL), was purified by col-
umn chromatography on silica gel (hexane–ether containing 3%
NEt3, 1/0 to 2/1) to give 30b (24.0 mg, 39%) as a colorless oil.
2-[(p-Trifluoromethylphenyl)methyl]-4,5,6,7-tetrahydroin-
dole (27d): IR (CCl4) 3470, 1618 cmꢃ1 1H NMR (400 MHz,
;
CDCl3) ꢂ 1.69–1.82 (m, 4H), 2.44–2.51 (m, 4H), 3.96 (s, 2H),
5.69 (d, J ¼ 2:8 Hz, 1H), 7.35 (d, J ¼ 8:2 Hz, 2H), 7.35 (brs,
1H), 7.55 (d, J ¼ 8:2 Hz, 2H); 13C NMR (100 MHz, CDCl3) ꢂ
143.9, 128.9, 128.3 (q, JC{F ¼ 32 Hz), 127.6, 126.5, 125.4 (q,
JC{F ¼ 4:1 Hz), 124.2 (q, JC{F ¼ 272 Hz), 117.0, 106.0, 34.2,
23.8, 23.4, 22.9, 22.7; MS m=z 279 (Mþ), 251; HRMS calcd for
C16H16F3N 279.1235, found 279.1219.
1
IR (neat) 3380, 1734 cmꢃ1; H NMR (270 MHz, CDCl3) ꢂ 2.24
(s, 3H), 3.16 (s, 2H), 3.70 (s, 3H), 5.77 (m, 1H), 5.85 (m, 1H),
8.26 (brs, 1H); 13C NMR (68 MHz, CDCl3) ꢂ 13.0, 33.2, 52.1,
105.8, 107.5, 121.6, 127.8, 171.8; LRMS m=z 153 (Mþ), 94;
HRMS calcd for C8H11NO2 153.0790, found 153.0794.
(Z)-(1,2,3,4,5,6,7,8-Octahydroquinolin-2-ylidene)acetic Acid
Methyl Ester (30c): A crude product, which was synthesized
2-[(o-Methoxycarbonylphenyl)methyl]-4,5,6,7-tetrahydroin-

M. Mori et al.
Bull. Chem. Soc. Jpn., 77, No. 9 (2004) 1669
from titanium–nitrogen complexes 7b, prepared from Ti(OiPr)4
(0.15 mL, 0.504 mmol), TMSCl (1.00 mL, 7.88 mmol), Li (35.9
mg, 5.17 mmol) in THF (7.5 mL) under nitrogen, 29c (83.9 mg,
0.403 mmol), and CsF (383 mg, 2.52 mmol) in THF (3.0 mL),
was purified by column chromatography on silica gel (hexane con-
taining 3% NEt3) to give 30c (55.1 mg, 66%) as a colorless oil. IR
MHz, CDCl3) ꢂ 1.43 (s, 18H), 2.16 (s, 3H), 3.11 (s, 2H), 3.26
(s, 2H); 13C NMR (67.5 MHz, CDCl3) ꢂ 27.6, 30.2, 37.1,
45.9, 54.3, 82.4, 168.2, 176.7, 205.6; MS m=z 274 (Mþꢃ
CH3C(CH3)=CH2), 259, 218, 201, 156, 113, 57; HRMS m=z
calcd for C12H18O7 (Mþ ꢃ CH3C(CH3)=CH2) 274.1052, found
274.1036.
(neat) 3284, 1660, 1612 cmꢃ1
;
1H NMR (400 MHz, CDCl3) ꢂ
Synthesis of Lactams. Methyl 6-Methyl-1,2,3,4-tetrahydro-
2-oxo-3-pyridinecarboxylate (40): A compound 39 was pre-
pared from carboxylic acid (74.6 mg, 0.37 mmol), ClPO(OEt)2
(0.068 mL, 0.47 mmol), and NEt3 (0.07 mL, 0.50 mmol). A crude
product, which was synthesized from titanium–nitrogen com-
plexes 7b, prepared from Li (34.7 mg, 5.0 mmol), Ti(OiPr)4
(0.15 mL, 0.55 mmol), TMSCl (0.65 mL, 5.1 mmol) under nitro-
gen, crude 40, and CsF (383 mg, 2.52 mmol) in THF (7.5 mL),
was purified by column chromatography on silica gel (hexane/
ethyl acetate, 2/1)ꢁ to give 40 (13.0 mg, 19%) as a colorless
1.54–1.70 (m, 4H), 1.91–2.05 (m, 6H), 2.44 (dd, J ¼ 7:3, 7.3
Hz, 2H), 3.61 (s, 3H), 4.47 (s, 1H), 9.25 (brs, 1H); 13C NMR
(100 MHz, CDCl3) ꢂ 22.6, 22.9, 24.7, 26.6, 28.4, 28.8, 50.2,
82.3, 109.3, 127.9, 156.6, 170.5; LRMS m=z 207 (Mþ), 175,
147; HRMS calcd for C12H17NO2 207.1260, found 207.1257.
(Z)-(2,3,4,5,6,7-Hexahydro-1H-cyclopenta[b]pyrindin-5-yli-
dene)acetic Acid Methyl Ester (30d): A crude product, which
was synthesized from titanium–nitrogen complexes 7b, prepared
from Ti(OiPr)4 (0.15 mL, 0.504 mmol), TMSCl (1.00 mL, 7.88
mmol), Li (36.2 mg, 5.22 mmol) in THF (7.5 mL) under nitrogen,
29d (78.5 mg, 0.404 mmol), and CsF (78.5 mg, 0.404 mmol) in
THF (3.0 mL), was purified by column chromatography on silica
gel (hexane containing 3% NEt3) to give 30d (33.8 mg, 34%) as a
crystal. mp 87–88 C; IR (nujol) 3226, 1742, 1700, 1676 cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.28 (t, J ¼ 7:3 Hz, 3H), 1.80
(d, J ¼ 1:5 Hz, 3H), 2.47 (m, 1H), 2.71 (m, 1H), 3.40 (dd,
J ¼ 8:6, 7.3 Hz, 1H), 4.12–4.31 (m, 2H), 4.82 (m, 1H), 7.08
(brs, 1H); 13C NMR (125 MHz, CDCl3) ꢂ 14.1, 18.8, 23.9, 47.1,
61.4, 99.2, 133.0, 167.6, 169.8; MS m=z 183 (Mþ), 138, 110,
92, 80, 67, 42; HRMS calcd for C9H13NO3 183.0896, found
183.0899.
colorless oil. IR (neat) 3926, 1666, 1614 cmꢃ1 1H NMR (500
;
MHz, CDCl3) ꢂ 1.88–1.93 (m, 2H), 2.08–2.14 (m, 2H), 2.26–
2.31 (m, 2H), 2.33–2.39 (m, 2H), 2.52 (dd, J ¼ 7:4, 7.4 Hz,
2H), 3.63 (s, 3H), 4.60 (s, 1H), 9.46 (brs, 1H); 13C NMR (125
MHz, CDCl3) ꢂ 21.0, 21.3, 29.2, 31.0, 32.9, 50.2, 84.2, 112.6,
133.5, 156.9, 170.5; MS m=z 193 (Mþ), 161, 133; HRMS calcd
for C11H15NO2 193.1103, found 193.1115.
6-Methyl-1,2,3,4-tetrahydro-2-pyridone (42): A compound
41 was prepared from carboxylic acid (100.8 mg, 0.775 mmol),
ClPO(OEt)2 (0.14 mL, 0.969 mmol) and NEt3 (0.13 mL, 0.933
mmol). A crude product, which was synthesized from titanium–ni-
trogen complexes 7b, prepared from Li (69.5 mg, 10.0 mmol),
Ti(OiPr)4 (0.30 mL, 1.01 mmol), TMSCl (1.3 mL, 10.2 mmol) un-
der nitrogen, crude 41, and CsF (782 mg, 5.15 mmol) in THF (15
mL), was purified by column chromatography on silica gel (hex-
ane/ethyl acetate, 2/1) to give 42 (26.2 mg, 29%) as a colorless
crystal. mp 112–114 ꢁC; IR (nujol) 3198, 3104, 1696, 1674
(Z)-[4,4-Bis(benzyloxymethyl)-6-methyl-1,2,3,4-tetrahydro-
pyridin-2-ylidene]acetic Acid Methyl Ester (30e): A crude
product, which was synthesized from titanium–nitrogen com-
plexes 7b, prepared from Ti(OiPr)4 (0.075 mL, 0.252 mmol),
TMSCl (0.50 mL, 3.94 mmol), Li (17.4 mg, 2.51 mmol) in
THF (3.8 mL) under nitrogen, 29e (82.3 mg, 0.201 mmol), and
CsF (187 mg, 1.23 mmol) in THF (1.5 mL), was purified by col-
umn chromatography on silica gel (hexane–ethyl acetate contain-
ing 3% NEt3, 1/0 to 5/1) to give 30e (55.1 mg, 66%) as a color-
cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.79 (d, J ¼ 1:5 Hz, 3H),
2.20–2.31 (m, 2H), 2.41 (ddd, J ¼ 8:1, 8.1, 1.5 Hz, 2H), 4.77
(m, 1H), 7.89 (brs, 1H); 13C NMR (125 MHz, CDCl3) ꢂ 18.8,
20.1, 30.2, 100.2, 132.9, 172.3; MS m=z 111 (Mþ), 96, 83, 68,
54, 42; HRMS calcd for C6H9NO 111.0685, found 111.0684.
Di-t-butyl 6-Methyl-1,2,3,4-tetrahydro-2-oxo-4,4-pyridine-
dicarboxylate (44) and Di-t-butyl 6-Methylene-2-oxo-2,3,4,5-
less oil. IR (neat) 3308, 1662, 1610 cmꢃ1 1H NMR (400 MHz,
;
CDCl3) ꢂ 1.80 (s, 3H), 2.42 (s, 2H), 3.25 (d, J ¼ 9:0 Hz, 2H),
3.34 (d, J ¼ 9:0 Hz, 2H), 3.64 (s, 3H), 4.47 (s, 4H), 4.58 (s,
1H), 4.61 (s, 1H), 7.21–7.35 (m, 10H), 9.36 (brs, 1H); 13C NMR
(125 MHz, CDCl3) ꢂ 19.5, 33.5, 38.9, 50.3, 72.3, 73.3, 85.9,
102.7, 127.4, 127.4, 128.3, 133.2, 138.5, 155.6, 170.3; MS m=z
407 (Mþ); HRMS calcd for C25H29NO4 407.2096, found
407.2085.
Synthesis of Lactams from Keto–Carboxylic Acid. 2-Eth-
oxycarbonyl-5-oxohexanoate (39, R = H): A solution of ethyl
2-ethoxycarbonyl-5-oxohexanate (2.47 g, 10.7 mmmol) in an
EtOH (80 mL) and 10% NaOH solution (7.0 mL, 10.6 mmol)
was stirred at room temperature for 2.5 h. The solvent was evapo-
rated and the residue was dissolved in water. The aqueous layer
was extracted with Et2O and acidified with 10% HCl. The aqueous
layer was extracted with ethyl acetate. The organic layer was
washed with brine, dried over Na2SO4, and concentrated to give
a colorless oil of 39 (1.72 g, 80%). IR (neat) 3200, 1718, 1448
tetrahydro-1H-4,4-piperidinedicarboxylate (440):
A com-
pound 43 was prepared from carboxylic acid (100 mg, 0.303
mmol), ClPO(OEt)2 (0.052 mL, 0.360 mmol), and NEt3 (0.050
mL, 0.359 mmol). A crude product, which was synthesized from
titanium–nitrogen complexes 7b, prepared from Li (25.3 mg, 3.64
mmol), Ti(OiPr)4 (0.11 mL, 0.370 mmol), TMSCl (0.47 mL, 3.70
mmol) under nitrogen, crude 43, and CsF (277 mg, 1.82 mmol) in
THF (6 mL), was purified by column chromatography on silica gel
(hexane/ethyl acetate, 2/1) to give 44 (50.6 mg, 51%) as a color-
less crystal. 44: mp 146–149 ꢁC; IR (nujol) 3216, 3162, 3112,
1
1732, 1698, 1676 cmꢃ1; H NMR (270 MHz, CDCl3) ꢂ 1.45 (s,
18H), 1.86 (d, J ¼ 1:1 Hz, 3H), 2.84 (s, 2H), 5.03 (brt, 1H),
6.74 (brs, 1H); 13C NMR (125 MHz, CDCl3) ꢂ 19.1, 36.8, 55.0,
82.2, 98.2, 135.4, 168.6, 169.3, 277.7; MS m=z 311 (Mþ), 256,
210, 154, 126, 57; HRMS calcd for C16H25O5N 311.1733, found
311.1710. 440: mp 126–129 ꢁC; IR (nujol) 3198, 1726, 1682, 1654
cmꢃ1
;
1H NMR (270 MHz, CDCl3) ꢂ 1.28 (t, J ¼ 7:2 Hz, 3H),
2.15 (s, 3H), 2.16 (q, J ¼ 7:2 Hz, 2H), 2.58 (t, J ¼ 7:2 Hz, 2H),
3.44 (t, J ¼ 7:2 Hz, 1H), 4.21 (q, J ¼ 7:2 Hz, 2H), 7.64 (brs,
1H); 13C NMR (125 MHz, CDCl3) ꢂ 13.9, 22.4, 29.8, 40.3,
50.2, 61.8, 169.0, 174.1, 207.8; MS m=z 202 (Mþ), 184, 157,
132, 86, 43; HRMS calcd for C9H14O5 202.0855, found 202.0837.
3,3-Bis(t-butoxycarbonyl)-5-oxohexanoic Acid (43, R = H):
1
cmꢃ1; H NMR (270 MHz, CDCl3) ꢂ 1.44 (s, 18H), 2.75 (s, 2H),
2.82 (s, 2H), 4.17 (s, 1H), 4.29 (s, 1H), 7.58 (brs, 1H); 13C NMR
(125 MHz, CDCl3) ꢂ 27.7, 35.5, 36.7, 53.1, 82.5, 92.9, 137.7,
168.3, 168.4; MS m=z 311 (Mþ), 210, 199, 182, 154, 126, 110,
57; HRMS calcd for C16H25NO5 311.1733, found 311.1726.
mp 91–92 C; IR (nujol) 3286, 1742, 1700 cmꢃ1; H NMR (270
ꢁ
1

1670 Bull. Chem. Soc. Jpn., 77, No. 9 (2004)
Nitrogen Fixation Using Titanium Complexes
12 a) Y. Uozumi, N. Kawasaki, E. Mori, M. Mori, and M.
Shibasaki, J. Am. Chem. Soc., 111, 3275 (1989). b) M. Mori, Y.
Uozumi, and M. Shibasaki, J. Organomet. Chem., 395, 225
(1990). c) Y. Uozumi, E. Mori, M. Mori, and M. Shibasaki, J.
Organomet. Chem., 399, 93 (1990). d) Y. Uozumi, M. Mori,
and M. Shibasaki, J. Chem. Soc., Chem. Commun., 1991, 81. e)
M. Mori, Y. Uozumi, and M. Shibasaki, Heterocycles, 33, 819
(1992). f) M. Kawaguchi, S. Hamaoka, and M. Mori, Tetrahedron
Lett., 34, 6907 (1993). g) M. Mori, M. Kawaguchi, M. Hori, and S.
Hamaoka, Heterocycles, 39, 729 (1994). h) M. Hori and M. Mori,
J. Org. Chem., 60, 1480 (1995). i) M. Mori, M. Hori, and Y. Sato,
J. Org. Chem., 63, 4832 (1998). j) M. Akashi, M. Nishida, and M.
Mori, Chem. Lett., 1999, 465. k) M. Mori, K. Hori, M. Akashi, M.
Hori, Y. Sato, and M. Nishida, Angew. Chem., Int. Ed., 37, 636
(1998). l) M. Akashi, Y. Sato, and M. Mori, J. Org. Chem., 66,
7873 (2001).
13 a) Shiina reported the reductive silylation of molecular
nitrogen via fixation to N(TMS)3. He described that using CrCl3
for the transition metal in the presence of reducing agent afforded
5.4 equiv. of N(TMS)3 but TiCl4 afforded only 0.8 equiv. of
N(TMS)3. See: K. Shiina, J. Am. Chem. Soc., 94, 9266 (1972).
b) Catalytic conversion of molecular nitrogen into silylamide
using molybdenum– and tungsten–dinitrogen complexes was
achieved. K. Komori, H. Oshita, Y. Mizobe, and M. Hidai, J.
Am. Chem. Soc., 111, 1939 (1989).
We thank the Mitsubishi Foundation for support in this
work and we also thank the Japan Society for the Promotion
of Science (JSPS) Research Fellowships for Young Scientists
(to M. A.).
References
1
a) M. E. Vol’pin and V. B. Shur, Dokl. Akad. Nauk SSSR,
156, 1102 (1964); Chem. Abstr., 61, 8933a (1964). b) M. E.
Vol’pin and V. B. Shur, Nature, 209, 1236 (1966).
2
3
M. Hidai and Y. Mizobe, Chem. Rev., 95, 1115 (1995).
A. Yamamoto, S. Kitazume, and S. Ikeda, J. Chem. Soc.,
Chem. Commun., 1976, 79.
4
a) A. Yamamoto, M. Ookawa, and S. Ikeda, J. Chem. Soc.,
Chem. Commun., 1969, 841. b) A. Yamamoto, S. Go, M. Ookawa,
M. Takahashi, S. Ikeda, and T. Keii, Bull. Chem. Soc. Jpn., 45,
3110 (1972).
5
a) M. Hidai, U. Tominari, Y. Uchida, and A. Misono,
J. Chem. Soc., Chem. Commun., 1969, 1392. b) M. Hidai, K.
Tominari, and Y. Uchida, J. Am. Chem. Soc., 94, 110 (1972).
6
a) J. M. Manriquez and J. E. Bercaw, J. Am. Chem. Soc.,
96, 6229 (1974). b) J. M. Manriquez, R. D. Sanner, R. E. Marsh,
and J. E. Bercaw, J. Am. Chem. Soc., 98, 8351 (1976).
7
M. E. Vol’pin, V. B. Shur, R. V. Kudryavtsev, and L. A.
Prodayko, J. Chem. Soc., Chem. Commun., 1968, 1038.
E. E. van Tamelen and H. Rudler, J. Am. Chem. Soc., 92,
5253 (1970).
8
14 A. Kasatkin, T. Nakagawa, S. Okamoto, and F. Sato, J.
Am. Chem. Soc., 177, 3881 (1995).
9
a) P. C. Bevan, J. Chatt, G. J. Leigh, and E. G. Leelamani,
15 [2 + 2] Cycloaddition of a carbonyl group and metal–
imide has been reported. See: S. M. Rocklage and R. R. Schrock,
J. Am. Chem. Soc., 102, 7808 (1980).
16 [2 + 2] Cycloaddition of an alkyne and imide complex
has been reported. See: a) P. L. McGrane, M. Jensen, and T.
Livinghouse, J. Am. Chem. Soc., 114, 5459 (1992). b) D. Duncan
and T. Livinghouse, Organometallics, 18, 4421 (1999).
17 a) A. Arcadi and E. Rossi, Synlett, 1997, 667. b) A. Arcadi
and E. Rossi, Tetrahedron, 54, 15253 (1998).
J. Organomet. Chem., 139, C59 (1977). b) H. Seino, Y. Ishii,
T. Sasagawa, and M. Hidai, J. Am. Chem. Soc., 117, 12181
(1995). c) M. Hidai and Y. Ishii, Bull. Chem. Soc. Jpn., 69, 819
(1996), and references are therein.
10 a) H. Seino, Y. Ishii, and M. Hidai, J. Am. Chem. Soc., 116,
7433 (1994). b) H. Seino, Y. Ishii, T. Sasagawa, and M. Hidai,
J. Am. Chem. Soc., 117, 12181 (1995).
11 P. Sobota, J. Trzebiantowska, and Z. Janas, J. Organomet.
Chem., 118, 253 (1976).