Reductive coupling of N-methoxycarbonyl lactams with benzophenone and 9-fluorenone by low-valent titanium

Article abstract of DOI:10.1016/j.tetlet.2012.02.001

The reductive coupling of N-methoxycarbonyl lactams with benzophenone by Zn-TiCl₄ in THF gave cross-coupled products as cyclic α-diphenylidene-N-methoxycarbonylamines and ring-opening α,α-diphenyl-α-hydroxy-ω-(N-methoxycarbonyl)amino ketones selectively depending on the reduction conditions. The reductive coupling of N-methoxycarbonyl lactams with 9-fluorenone by Zn-TiCl₄ gave cyclic α-(9H-fluoren-9-ylidene)-N-methoxycarbonylamines preferentially irrespective to the conditions.

Full text of DOI:10.1016/j.tetlet.2012.02.001

Tetrahedron Letters 53 (2012) 1940–1945
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Reductive coupling of N-methoxycarbonyl lactams with benzophenone
and 9-fluorenone by low-valent titanium
⇑
Naoki Kise , Yosei Takenaga, Yohei Ishikawa, Yoichi Morikami, Toshihiko Sakurai
Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101, Koyama-cho Minami, Tottori 680-8552, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The reductive coupling of N-methoxycarbonyl lactams with benzophenone by Zn-TiCl4 in THF gave cross-
Received 7 January 2012
Revised 30 January 2012
Accepted 2 February 2012
Available online 9 February 2012
coupled products as cyclic
-hydroxy- -(N-methoxycarbonyl)amino ketones selectively depending on the reduction conditions.
The reductive coupling of N-methoxycarbonyl lactams with 9-fluorenone by Zn-TiCl4 gave cyclic
a-diphenylidene-N-methoxycarbonylamines and ring-opening a,a-diphenyl-
a
x
a
-(9H-fluoren-9-ylidene)-N-methoxycarbonylamines preferentially irrespective to the conditions.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Reductive coupling
Low-valent titanium
McMurry coupling
N-Methoxycarbonyl lactams
Benzophenone
9-Fluorenone
Reductive coupling of carbonyl compounds by low-valent tita-
nium is well known as McMurry coupling.1 To date, not only homo
couplings but also a lot of inter-2 and intramolecular3 cross McMurry
couplings have been reported. In this context, we recently disclosed
that the reductive coupling of uracils with benzophenones by low-
valent titanium gave unusual two-to-one cross-coupled products.4
We report herein the reductive coupling of N-methoxycarbonyl lac-
tams 1 with benzophenone by low-valent titanium generated from
Zn-TiCl4 (Scheme 1). Although it has been reported that the reductive
coupling of N-acyl lactams with ketones by SmI2 gave ring-opening
a,a-diphenyl-a-hydroxy-x-(N-methoxycarbonyl) amino ketones 3
were obtained as the cross-coupled products and the product selec-
tivity depended on the ring size of 1 and the reaction conditions
(Scheme 1). In the cases of five- and six-membered substrates 1
(n = 1 and 2), both products 2 and 3 could be obtained selectively
by tuning the reaction conditions. On the other hand, the reductive
coupling of 1 (n = 1–3) with 9-fluorenone by Zn-TiCl4 afforded
cyclic
a-(9H-fluoren-9-ylidene)-N-methoxycarbonylamines pre-
dominantly or mainly regardless of the ring size of 1 and the reaction
conditions. This reductive coupling provides a synthetic method for
a,a
-dialkyl-
a
-hydroxy-
x
-(N-acyl)amino ketones,5 we expected to
cyclic
a-diarylidene-N-methoxycarbonylamines and ring-opening
obtain cyclic products by the cross McMurry coupling of 1 with
ketones. The reductive coupling of 1 with ketones has been unknown
to date. In addition, N-deprotection of N-methoxycarbonyl lactams 1
is more facile than that of N-acyl lactams. We found that cyclic
a
,
a
-diaryl-
a
-hydroxy- -(N-methoxycarbonyl) amino ketones.
x
The reaction mechanism of the reductive cross coupling is also
discussed.
The results of the reductive cross coupling of methyl 2-oxopyr-
rolidine-1-carboxylate 1a (n = 1) with benzophenone using
a-diphenylidene-N-methoxycarbonylamines
2
and ring-opening
Ph
Ph
Ph
n
Ph
OH
Zn-TiCl4
Ph
n
Ph
+
MeO2CNH
+
N
O
n
N
THF
O
O
CO2Me
CO2Me
3
2
1 n = 1-3
Scheme 1. Reductive coupling of N-methoxycarbonyl lactams 1 with benzophenone by Zn-TiCl4.
⇑
Corresponding author.
E-mail address: kise@bio.tottori-u.ac.jp (N. Kise).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2012.02.001

N. Kise et al. / Tetrahedron Letters 53 (2012) 1940–1945
1941
Table 1
Table 3
Reductive coupling of 1a with benzophenone by Zn-TiCl4
Reductive coupling of 1d with benzophenone by Zn-TiCl4
Zn-TiCl4
THF
Zn-TiCl4
THF
Ph
Ph
Ph
Ph
MeO2C
+
+
O
O
N
N
O
O
CO2Me
CO2Me
1a (1 mmol)
1d (1 mmol)
Ph
Ph
Ph
Ph
CO2Me
Ph
Ph
Ph
+
MeO2CNH
OH
N
Ph
OH
MeO2C
O
N
+
MeO2CNH
CO2Me
3a
O
CO2Me
2a
3d
a
2d
Run
1a/Ph2CO/TiCl4
Temp (°C)
Time (h)
Yieldb (%)
a
2a
3a
Run
1d/Ph2CO/TiCl4
Temp (°C)
Time (h)
Yieldb (%)
2d 3d
1
2
3
4
5
6
1/1/2
Reflux
Reflux
25
0
0
2
2
6
12
12
24
60
78
48
17
7
Trace
Trace
26
53
76
1/1.5/3
1/1.5/3
1/1.5/3
1/2/2
1
2
3
1/1.5/3
1/1.5/3
1/2/2
Reflux
25
0
2
12
12
76
65
8
—
13
72
1/2/2
ꢀ15
5
52
a
Zn/TiCl4 = 2:1.
Isolated yields based on 1d.
b
a
Zn/TiCl4 = 2:1.
b
Isolated yields based on 1a.
Figure 1. X-ray crystal structures of 2a and 2b.
Table 2
Reductive coupling of 1b,c with benzophenone by Zn-TiCl4
n-1
Ph
Ph
Zn-TiCl4
THF
n-1
N
CO2Me
Ph
Ph
N
+
O
O
CO2Me
2b,c
1b n = 2
1c n = 3
(1 mmol)
Ph
Ph
Ph
Ph
MeO2CNH
MeO2CNH
+
OH
H
+
n-1
n-1
O
O
3b,c
4b,c
Yieldb (%)
a
Run
n
1/Ph2CO/TiCl4
Temp (°C)
Time (h)
2
3
4
1
2
3
4
5
6
2
2
2
3
3
3
1/1.5/3
1/1.5/3
1/2/2
1/1.5/3
1/1.5/3
1/2/2
Reflux
25
0
Reflux
25
0
2
6
12
2
12
12
2b
2b
2b
2c
—
50
56
13
—
—
12
—
—
25
—
3b
3b
12
66
—
14
83
4b
Trace
3c
3c
4c
—
a
Zn/TiCl4 = 2:1.
Isolated yields based on 1b,c.
b

1942
N. Kise et al. / Tetrahedron Letters 53 (2012) 1940–1945
Table 4
Reductive coupling of 1a–c with 9-fluorenone by Zn-TiCl4
Zn-TiCl4
n
+
O
N
THF
CO2Me
O
1a-c (1 mmol)
n
+
N
MeO2CNH
n
OH
CO2Me
O
6a-c
5a-c
a
Run
n
1/9-fluorenone/TiCl4
Temp (°C)
Time (h)
Yieldb (%)
5
6
1
2
3
4
5
6
7
8
9
1
1
1
2
2
2
3
3
3
1/1.5/3
1/1.5/3
1/2/2
1/1.5/3
1/1.5/3
1/2/2
1/1.5/3
1/1.5/3
1/2/2
Reflux
25
0
Reflux
25
0
Reflux
25
0
2
5a
43
60
36
49
70
32
68
67
33
6a
6a
6a
6b
6b
6b
6c
6c
6c
—
—
Trace
—
—
12
—
—
12
24
2
12
24
2
5a
5a
5b
5b
5b
5c
5c
5c
12
24
24
a
Zn/TiCl4 = 2:1.
Isolated yields based on 1a–c.
b
Figure 2. X-ray crystal structures of 5a and 5b.
Zn-TiCl4 as a reducing agent in THF are summarized in Table 1. The
molar ratio of Zn/TiCl4 was fixed to 2/1. The reaction at reflux
temperature with the ratio of 1a/Ph2CO/TiCl4 as 1/1/2 gave methyl
2-(diphenylmethylene)pyrrolidine-1-carboxylate 2a in a 60% yield
with 20% recovery of 1a (run 1). When the reaction was carried out
at this temperature with the ratio of 1a/Ph2CO/TiCl4 as 1/1.5/3 for

N. Kise et al. / Tetrahedron Letters 53 (2012) 1940–1945
1943
Table 5
this case, the major by-product was 1,1,2,2-tetraphenyethane-
1,2-diol, usual pinacol-type coupling product of benzophenone
(40% yield based on benzophenone). Since the reaction at ꢀ15 °C
was slow, 25% of 1a was recovered even after 24 h (run 6). These
results showed that 2a and 3a could be prepared selectively by
choosing the reaction conditions in runs 2 and 5. The products
2a and 3a were assigned by spectroscopic analyses7 and the crystal
structure of 2a was determined by X-ray crystallography (Fig. 1).8
The reductive coupling of methyl 2-oxopiperidine-1-carboxyl-
ate 1b (n = 2) with benzophenone was carried out under the same
conditions as runs 2, 3, and 5 in Table 1 (Table 2, runs 1–3). Methyl
2-(diphenylmethylene)piperidine-1-carboxylate 2b was formed as
a sole cross-coupled product in a 50% yield under reflux conditions
(run 1). The cyclic product 2b was obtained in a better yield (56%)
Reductive coupling of 1d with 9-fluorenone by Zn-TiCl4
Zn-TiCl4
+
O
MeO2C
N
THF
CO2Me
O
1d (1 mmol)
CO2Me
MeO2C
N
+
MeO2CNH
OH
CO2Me
O
6d
5d
Yieldb (%)
a
Run
1d/9-fluorenone/TiCl4
Temp (°C)
Time (h)
by the reaction at 25 °C (run 2), although ring-opening a-hydroxy
5d
6d
ketone 3b (12%) and its dehydroxylated ketone 4b (12%) were also
produced. The structure of 2b was confirmed by X-ray crystallogra-
phy (Fig. 1).8 The ring-opening product 3b was selectively obtained
in a 66% yield under the conditions at 0 °C (run 3).
The reaction of methyl 2-oxoazepane-1-carboxylate 1c (n = 3)
with benzophenone was carried out under the same conditions
as above (Table 2, runs 4–6). Under reflux conditions, complex
mixture was formed and a trace amount (<2%) of methyl 2-(diphe-
nylmethylene)azepane-1-carboxylate 2c was detected (run 4). In
1
2
3
1/1.5/3
1/1.5/3
1/2/2
Reflux
25
2
12
24
43
53
28
—
—
24
0
a
Zn/TiCl4 = 2:1.
Isolated yields based on 1d.
b
2 h, almost all 1a was consumed and 2a was exclusively produced
in a 78% yield (run 2).6 In this case, the major by-product was
1,1,2,2-tetraphenyethene, usual McMurry-type coupling product
of benzophenone (35% yield based on benzophenone). With lower-
ing the reaction temperature to 25 °C and 0 °C, the yield of 2a de-
contrast, ring-opening a-hydroxy ketone 3c (13%) and its dehydr-
oxylated ketone 4c (25%) were formed at 25 °C (run 5). It is noted
that 3c was exclusively obtained in a good yield (83%) by the reac-
tion at 0 °C (run 6).
Since dimethyl (S)-5-oxopyrrolidine-1,2-dicarboxylate 1d pos-
sesses three carbonyl groups, it is interesting as the substrate
for the reductive coupling with benzophenone. As shown in Table
3, the coupling proceeded at the endocyclic carbonyl group in 1d
specifically. Similarly to the reaction of 1a, cyclic product di-
methyl (S)-5-(diphenylmethylene)pyrrolidine-1,2-dicarboxylate
creased and ring-opening
a-hydroxy ketone 3a was formed
increasingly (runs 3 and 4). Nevertheless, 2a was still formed in a
17% yield and 10% of 1a was recovered in run 4. Therefore, 2 M
equivalents of benzophenone and TiCl4 were employed at 0 °C
(run 5). According to our expectations, the desired 3a was obtained
in a good yield (76%) together with a small amount (7%) of 2a. In
Ph
Ph
Ph
O
Ph
O
Ph
Ph
Ti(+X)
Zn-TiCl4
Zn-TiCl4
Ph
Ph
Ph
Ph
Ph
Ph
O
Ph
Ph
O
n
McMurry-type
coupling
pinacol-type
coupling
O
A
Ti
Ti
O
Ph
Ph
O
n
n
A
Zn-TiCl4
O
N
Ph
Ph
N
N
CO2Me
CO2Me
CO2Me
2a-c
1a-c
B
ring-opening
(n = 2,3)
work-up with water
OH
Ph
Ph
Ph
O
Zn-TiCl4
(n = 2,3)
MeO2CN
Ti
Ph
OH
Ph
Ph
n
n
MeO2CN
Ti
O
n
N
Ti
O
Ti
CO2Me
E
D
C
work-up
work-up
with water
with water
ring-opening
Ph
Ph
Ph
H
Ph
OH
MeO2CNH
MeO2CNH
n
n
O
O
4b,c
3a-c
Scheme 2. Reaction mechanism of reductive coupling of 1a-c with benzophenone by Zn-TiCl4.

1944
N. Kise et al. / Tetrahedron Letters 53 (2012) 1940–1945
3. For recent reports, see: (a) Honda, T.; Namiki, H.; Nagase, H.; Mizutani, H.
Tetrahedron Lett. 2003, 44, 3035; (b) Some, S.; Dutta, B.; Ray, J. K. Tetrahedron
Lett. 2006, 47, 1221; (c) Kise, N.; Shiozawa, Y.; Ueda, N. Tetrahedron 2007, 63,
5415; (d) Jones, C. P.; Anderson, K. W.; Buchwald, S. L. J. Org. Chem. 2007, 72,
7968; (e) Buchgraber, P.; Domostoj, M. M.; Scheiper, B.; Wirtz, C.; Mynott, R.;
Rust, J.; Fürstner, A. Tetrahedron 2009, 65, 6519.
2d and ring-opening product 3d could be obtained selectively by
the reaction at reflux temperature and 0 °C, respectively (runs 1
and 3).
Next, we investigated the reductive coupling of 1a–c with 9-flu-
orenone by Zn-TiCl4 and the results are summarized in Table 4. Dif-
ferently from the reaction with benzophenone described above,
the reaction at reflux temperature or 25 °C gave cyclic products
5a–c predominantly even in the reaction of the seven-membered
substrate 1c (runs 1, 2, 4, 5, 7, and 8). In addition, ring-opening
products 6a–c were the minor products even under the conditions
at 0 °C (runs 3, 6 and 9). The stereostructures of 5a and 5b were as-
signed by X-ray crystallography (Fig. 2).8 As shown in Table 5, the
reaction of 1d with 9-fluorenone also afforded cyclic product 5d as
a sole product under the conditions at reflux temperature and
25 °C in 43% and 53% yields, respectively (runs 1 and 2). Ring-
4. Kise, N.; Akazai, S.; Sakurai, T. Tetrahedron Lett. 2011, 52, 6627.
5. Farcas, S.; Namy, J.-L. Tetrahedron Lett. 2000, 41, 7299.
6. Typical procedure for the reductive coupling of 1a with benzophenone by Zn-
TiCl4 (Table 1, run 2) is as follows. To a solution of 1a (143 mg, 1 mmol),
benzophenone (273 mg, 1.5 mmol), and zinc powder (390 mg, 6 mmol) in THF
(10 mL) was added TiCl4 (0.33 mL, 3 mmol) dropwise at 0 °C and then the dark
blue suspension was refluxed for 2 h. To the mixture was added 0.5 M HCl
(20 mL) at 0 °C and the mixture was stirred for 15 min. The mixture was
extracted with ethyl acetate three times. The organic layer was washed with
aqueous NaCl and dried over MgSO4. After the solvent was removed, the residue
was purified by column chromatography on silica gel to give 2a in a 78% yield.
7. All the products were assigned by 1H NMR and 13C NMR analyses. Compound 2a:
White solid; mp 133–134 °C; 1H NMR (CDCl3) d 1.88–1.97 (m, 2 H), 2.53 (t, 2 H,
J = 7.5 Hz), 3.12 (s, 3 H), 3.67 (t, 2 H, J = 7.3 Hz), 7.08–7.30 (m, 10 H); 13C NMR
(CDCl3) d 21.5 (t), 30.8 (t), 47.3 (t), 51.8 (q), 125.9 (d), 126.0 (s), 126.4 (d), 127.5
(d), 127.8 (d), 128.6 (d), 130.0 (d), 135.8 (s), 142.3 (s), 142.8 (s), 153.2 (s).
Compound 3a: Colorless paste; 1H NMR (CDCl3) d 1.62–1.72 (m, 2 H), 2.64 (t, 2 H,
J = 7.1 Hz), 3.04 (q, 2 H, J = 6.3 Hz), 3.62 (s, 3 H), 4.58 (br s, 1 H), 4.73 (br s, 1 H),
7.32–7.42 (m, 10 H); 13C NMR (CDCl3) d 24.5 (t), 35.2 (t), 40.0 (t), 51.9 (q), 85.6
(s), 127.9 (d), 128.1 (d), 128.4 (d), 141.3 (s), 157.0 (s), 210.8 (s). Compound 2b:
White solid; mp 128–129 °C; 1H NMR (CDCl3) d 1.50–1.89 (m, 4 H), 2.01–2.12
(m, 1 H), 2.51–2.63 (m, 1 H), 2.96–3.07 (m, 1 H), 3.17 (s, 3 H), 4.32–4.42 (m, 1 H),
7.00–7.34 (m, 10 H); 13C NMR (CDCl3) d 25.2 (t), 26.4 (t), 29.7 (t), 47.7 (t), 52.1
(q), 126.5 (d), 126.9 (d), 127.8 (d), 128.0 (d), 128.6 (d), 130.0 (d), 135.0 (s), 135.3
(s), 141.2 (s), 141.5 (s), 154.6 (s). Compound 3b: Colorless paste; 1H NMR (CDCl3)
d 1.30–1.53 (m, 4 H), 2.59 (t, 2 H, J = 7.2 Hz), 2.99–3.08 (m, 2 H), 3.63 (s, 3 H),
4.85 (br s, 1 H), 5.11 (s, 1 H), 7.29–7.40 (m, 10 H); 13C NMR (CDCl3) d 21.2 (t),
29.0 (t), 37.6 (t), 40.3 (t), 51.8 (q), 85.5 (s), 127.9 (d), 128.1 (d), 128.3 (d), 141.4
(s), 156.9 (s), 210.9 (s). Compound 4b: Colorless paste; 1H NMR (CDCl3) d 1.38–
1.47 (m, 2 H), 1.56–1.65 (m, 2 H), 2.55–2.62 (m, 2 H), 3.07–3.14 (m, 2 H), 4.69 (br
s, 1 H), 5.11 (s, 1 H), 7.18–7.42 (m, 10 H); 13C NMR (CDCl3) d 20.7 (t), 29.1 (t),
40.4 (t), 42.1 (t), 51.8 (q), 64.0 (d), 127.1 (d), 128.6 (d), 128.8 (d), 138.2 (s) 157.0
(s), 208.2 (s). Compound 3c: Colorless paste; 1H NMR (CDCl3) d 1.10–1.18 (m, 2
H), 1.31–1.39 (m, 2 H), 1.43–1.51 (m, 2 H), 2.57 (t, 2 H, J = 7.3 Hz), 3.02–3.09 (m,
2 H), 3.62 (s, 3 H), 4.71 (br s, 1 H), 4.88 (s, 1 H), 7.30–7.39 (m, 10 H); 13C NMR
(CDCl3) d 23.9 (t), 25.9 (t), 29.5 (t), 38.1 (t), 40.6 (t), 51.9 (q), 85.5 (s), 128.0 (d),
128.1 (d), 128.3 (d), 141.4 (s), 157.0 (s), 211.0 (s). Compound 2d: Colorless paste;
opening a-hydroxy ketone 6d was also formed as a minor product
(24%) at 0 °C (run 3).
The reaction mechanism of the reductive coupling of 1a–c with
benzophenone by Zn-TiCl4 can be speculated as depicted in
Scheme 2. The reduction of benzophenone by low-valent titanium
forms dianion intermediate A. The nucleophlic attack of A on 1a–c
produces adduct B. At reflux temperature, the reductive b-elimina-
tion of B (n = 1 and 2) by low-valent titanium rapidly proceeds to
give cyclic products 2a,b. The work-up of B with water and
subsequent ring-opening of resulting diols C leads to
a-hydroxy
ketones 3a–c. Since the further reduction of B is slow at 0 °C, 3a–
c were obtained as major (n = 1 and 2) or predominant (n = 3)
products. Alternatively, the ring-opening of B (n = 2 and 3) takes
place at 25 °C and following work-up of resulting D with water af-
fords 3b,c. The deoxylation of D caused by low-valent titanium at
25 °C gives E, which is transformed to dehydroxylated ketones
4b,c by subsequent work-up with water. On the other hand, cyclic
products 5a–c were predominant or major products in the reduc-
tive coupling of 1a–c with 9-fluorenone. For this reason, it seems
that the reductive elimination of the adducts produced by the addi-
tion of A to 9-fluorenone are more rapid than that of B, since the
resulting alkenes 5a–c are more stable than 2a–c. The X-ray crystal
structures of 5a and 5b (Fig. 2) clearly show that the newly formed
carbon–carbon double bond and two benzene rings are coplanar.
Therefore, it is likely that the double bond is well stabilized by
the conjugation with the two benzene rings. In contrast, the newly
formed double bond and two benzene rings are not coplanar in 2a
and 2b as shown in Fig. 1.
½
a 2D0
ꢁ
ꢀ252.4 (c 1.08, CHCl3); 1H NMR (CDCl3) d 1.84–1.93 (m, 1 H), 2.32–2.40 (m,
1 H), 2.51–2.66 (m, 2 H), 3.10 (br s, 3 H), 3.82 (s, 3 H), 4.57 (t, 1 H, J = 8.4 Hz),
7.12–7.39 (m, 10 H); 13C NMR (CDCl3) d 27.1 (t), 30.6 (t), 52.26 (q), 52.34 (q),
60.3 (d), 126.2 (d), 126.68 (s), 126.74 (d), 127.7 (d), 127.9 (d), 129.0 (d), 130.2
(d), 134.8 (s), 142.4 (s), 142.5 (s), 153.0 (s), 173.2 (s). Compound 3d: Colorless
paste; 1H NMR (CDCl3) d 1.76–1.85 (m, 1 H), 2.03–2.13 (m, 1 H), 2.59–2.67 (m, 1
H), 2.72–2.82 (m, 1 H), 3.64 (s, 3 H), 3.68 (s, 3 H), 4.28 (br s, 1 H), 4.56 (s, 1 H),
5.12–5.20 (m, 1 H), 7.31–7.40 (m, 10 H); 13C NMR (CDCl3) d 27.1 (t), 34.0 (t), 52.4
(q), 52.5 (d), 53.1 (q), 85.6 (s), 127.8 (d), 127.9 (d), 128.2 (d), 128.4 (d), 128.5 (d),
141.3 (s), 141.4 (s), 156.6 (s), 172.3 (s), 210.3 (s). Compound 5a: Yellow solid; mp
153–154 °C; 1H NMR (CDCl3) d 1.91–2.06 (m, 1 H), 2.13–2.26 (m, 1 H), 3.00–3.16
(m, 1 H), 3.24–3.37 (m, 1 H), 3.48–3.89 (m, 4 H), 3.96–4.14 (m, 1 H), 7.23–7.48
(m, 5 H), 7.58–7.66 (m, 1 H), 7.72–7.80 (m, 2 H); 13C NMR (CDCl3) d 21.1 (t), 31.5
(t), 48.6 (t), 53.1 (q), 119.2 (d), 119.5 (d), 122.4 (s), 123.4 (d), 124.0 (d), 126.2 (d),
126.3 (d), 126.5 (d), 126.7 (d), 137.3 (s), 138.6 (s), 138.8 (s), 139.1 (s), 140.8 (s),
154.6 (s). Compound 5b: Yellow solid; mp 196–198 °C; 1H NMR (CDCl3) d
1.69–1.92 (m, 3 H), 2.01–2.09 (m, 1 H), 2.56–2.67 (m, 1 H), 3.13–3.23 (m, 1 H),
3.45–3.58 (m, 4 H), 4.48–4.57 (m, 1 H), 7.20–7.38 (m, 4 H), 7.58–7.62 (m, 1 H),
7.68–7.79 (m, 2 H), 7.83–7.89 (m, 1 H); 13C NMR (CDCl3) d 24.5 (t), 25.4 (t), 30.8
(t), 46.9 (t), 53.1 (q), 119.3 (d), 119.7 (d), 123.6 (d), 124.7 (d), 126.8 (d), 127.49
(d), 127.52 (d), 127.7 (d), 131.0 (s), 137.5 (s), 137.6 (s), 139.0 (s), 140.6 (s), 140.8
(s), 155.7 (s). Compound 6b: Colorless paste; 1H NMR (CDCl3) d 1.07–1.19 (m, 2
H), 1.32–1.41 (m, 2 H), 1.85 (t, 2 H, J = 7.2 Hz), 2.84–2.94 (m, 2 H), 3.61 (s, 3 H),
4.51 (br s, 1 H), 5.13 (s, 1 H), 7.25–7.36 (m, 4 H), 7.43–7.49 (m, 2 H), 7.72–7.77
(m, 2 H); 13C NMR (CDCl3) d 21.0 (t), 28.7 (t), 34.0 (t), 40.2 (t), 51.8 (q), 88.0 (s),
120.5 (d), 123.8 (d), 128.3 (d), 129.8 (d), 141.4 (s), 144.1 (s), 156.8 (s), 209.1 (s).
Compound 5c: Yellow solid; mp 125–127 °C; 1H NMR (CDCl3) d 1.40–1.54 (m, 1
H), 1.57–1.97 (m, 5 H), 3.00–3.14 (m, 2 H), 3.18–3.28 (m, 1 H), 3.61 (s, 3 H),
4.25–4.32 (m, 1 H), 7.23–7.41 (m, 4 H), 7.60–7.80 (m, 4 H); 13C NMR (CDCl3) d
25.2 (t), 27.0 (t), 28.0 (t), 35.6 (t), 48.8 (t), 53.0 (q), 119.4 (d), 119.6 (d), 124.1 (d),
125.4 (d), 127.0 (d), 127.83 (d), 127.85 (d), 128.0 (d), 133.2 (s), 137.0 (s), 137.1
In summary, the reduction of five- and six-membered N-
methoxycarbonyl lactams 1a,b,d with benzophenone by Zn-TiCl4
in THF gave cyclic
a-diphenylidene-N-methoxycarbonylamines
2a,b,d, and ring-opening
a,a
-diphenyl- -hydroxy ketones 3a,b,d
a
selectively depending on the reaction conditions. In the reaction
of seven-membered N-methoxycarbonyl lactam 1c, ring-opening
product 3c was exclusively obtained in a good yield under the con-
ditions at 0 °C. On the other hand, the reductive coupling of 1a–d
with 9-fluorenone under the same conditions afforded cyclic
a-(9H-fluoren-9-ylidene)-N-methoxycarbonylamines 5a–d pre-
dominantly or mainly irrespective of the ring size of 1a–d and
the reaction conditions.
(s), 139.4 (s), 140.6 (s), 142.0 (s), 155.5 (s). Compound 5d: Yellow paste; ½a D20
ꢁ
References and notes
ꢀ83.7 (c 1.22, CHCl3); 1H NMR (CDCl3) d 2.04–2.14 (m, 1 H), 2.58–2.68 (m, 1 H),
3.03–3.14 (m, 1 H), 3.32–3.44 (m, 1 H), 3.66 (br s, 3 H), 3.78 (s, 3 H), 4.92 (t, 1 H,
J = 8.3 Hz), 7.22–7.35 (m, 4 H), 7.56–7.81 (m, 4 H); 13C NMR (CDCl3) d 25.7 (t),
30.8 (t), 52.5 (q), 53.4 (q), 60.7 (d), 119.1 (d), 119.6 (d), 123.3 (d), 126.5 (d), 126.6
(d), 126.7 (d), 126.9 (d), 129.0 (d), 137.2 (s), 138.4 (s), 138.5 (s), 138.8 (s), 139.5
(s), 140.5 (s), 154.7 (s), 172.1 (s). Compound 6d: Colorless paste; 1H NMR (CDCl3)
d 1.55–1.77 (m, 2 H), 1.82–2.02 (m, 2 H), 3.59 (s, 3 H), 3.60 (s, 3 H), 4.03–4.10 (m,
1 H), 4.89–4.95 (m, 1 H), 5.04 (br s, 1 H), 7.27–7.34 (m, 4 H), 7.42–7.48 (m, 2 H),
7.68–7.75 (m, 2 H); 13C NMR (CDCl3) d 26.3 (t), 30.3 (t), 52.1 (q), 52.2 (q), 52.6
(d), 87.9 (s), 120.5 (d), 123.7 (d), 123.8 (d), 128.2 (d), 128.3 (d), 129.8 (d), 141.17
(s), 141.20 (s), 143.98 (s), 144.01 (s), 156.2 (s), 172.0 (s), 208.4 (s).
1. For reviews, see: (a) McMurry, J. E. Chem. Rev. 1989, 89, 1513; (b) Fürstner, A.;
´
Bogdanovic, B. Angew. Chem. Int. Ed. 1996, 35, 2442.
2. For recent reports, see: (a) Sabelle, S.; Hydrio, J.; Leclerc, E.; Mioskowski, C.;
Renard, P.-Y. Tetrahedron Lett. 2002, 43, 3645; (b) Top, S.; Vessières, A.; Leclercq,
G.; Quivy, J.; Tang, J.; Vaissermann, J.; Huché, M.; Jaouen, G. Chem. Eur. J. 2003, 9,
5223; (c) Pigeon, P.; Top, S.; Vessières, A.; Huché, M.; Hillard, E. A.; Salomon, E.;
Jaouen, G. J. Med. Chem. 2005, 48, 2814; (d) Duan, X.-F.; Zeng, J.; Lü, J.-W.; Zhang,
Z.-B. J. Org. Chem. 2006, 71, 9873; (e) Duan, X.-F.; Zeng, J.; Zhang, Z.-B.; Zi, G.-F. J.
Org. Chem. 2007, 72, 10283; (f) Seo, J. W.; Kim, H. J.; Lee, B. S.; Katzenellenbogen,
J. A.; Chi, D. Y. J. Org. Chem. 2008, 73, 715.

N. Kise et al. / Tetrahedron Letters 53 (2012) 1940–1945
1945
8. All measurements of X-ray crystallographic analysis were made on a Rigaku
RAXIS imaging plate area detector with graphite monochromated Mo
1.030. Compound 2b (CCDC 860619): C20H21NO2, FW = 307.38, mp 128–129 °C,
triclinic, P-1 (No. 2), colorless block, a = 7.7071(10) Å, b = 9.9824(17) Å, c =
K
a
radiation. The structure was solved by direct methods with SIR-97 and refined
with SHELXL-97. The non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were refined isotropically. All calculations were performed
using the YADOKARI-XG software package. Crystal data for 2a,b and 5a,b are as
follows: CCDC 860618-860621 contain the supplementary crystallographic data.
These data can be obtained free of charge from The Cambridge Crystallographic
Data Center via www.ccdc.cam.ac.uk/data_request/cif. Compound 2a (CCDC
860618): C19H19NO2, FW = 293.35, mp 133–134 °C, monoclinic, P21/a (No. 14),
colorless block, a = 10.268(2) Å, b = 15.241(3) Å, c = 10.826(2) Å, b = 110.048(2),
11.142(2) Å,
a
= 96.752(5), b = 94.662(6),
c
= 95.521(7),V = 843.6(2) Å3, T =
298 K, Z = 2, Dcalcd = 1.210 g/cm3,
l
= 0.78 cmꢀ1
, GOF = 1.046. Compound 5a
(CCDC 860620): C19H17NO2, FW = 291.34, mp 153–154 °C, orthorhombic, Pca21
(No. 29), yellow block, a = 19.481(9) Å, b = 9.441(3) Å, c = 7.964(3) Å, V =
1464.8(9) Å3, T = 298 K, Z = 4, Dcalcd = 1.321 g/cm3,
l
= 0.86 cmꢀ1, GOF = 1.040.
Compound 5b (CCDC 860621):
monoclinic, Cc (No. 9), colorless block, a = 10.613(4) Å, b = 20.157(10) Å, c =
8.162(3) Å, b = 115.693(17), V = 1573.5 (11) Å3, T = 298 K, Z = 4, Dcalcd
1.289 g/cm3, = 0.83 cmꢀ1, GOF = 1.127.
C20H19NO2, FW = 305.36, mp 196–198 °C,
=
l
V = 1591.5(6) Å3, T = 298 K, Z = 4, Dcalcd = 1.224 g/cm3,
l , GOF =
= 0.79 cmꢀ1