Reductive coupling of 1,3-dimethyluracils with benzophenone by low-valent titanium: Unusual two-to-one coupling

Article abstract of DOI:10.1016/j.tetlet.2011.09.154

The reductive coupling of 1,3-dimethyluracil with benzophenone by Zn-TiCl₄ in THF gave unusual two-to-one adduct and its further reduced product. The reductive coupling of 1,3-dimethyl-5-fluorouracil with benzophenone by Zn-TiCl₄ als

Full text of DOI:10.1016/j.tetlet.2011.09.154

Tetrahedron Letters 52 (2011) 6627–6631
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Tetrahedron Letters
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Reductive coupling of 1,3-dimethyluracils with benzophenone
by low-valent titanium: unusual two-to-one coupling
⇑
Naoki Kise , Shinta Akazai, 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 1,3-dimethyluracil with benzophenone by Zn–TiCl4 in THF gave unusual two-
to-one adduct and its further reduced product. The reductive coupling of 1,3-dimethyl-5-fluorouracil
with benzophenone by Zn–TiCl4 also gave two-to-one adduct. 1,3-Dimethylthymine was, however, com-
pletely inert under the same conditions.
Received 6 September 2011
Accepted 30 September 2011
Available online 6 October 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Reductive coupling
Low-valent titanium
McMurry coupling
1,3-Dimethyluracils
Benzophenone
Reductive cross coupling between two different carbonyl
groups is a powerful tool for the synthesis of adjacent difunctional
compounds. For this purpose, cross McMurry coupling is one of the
most useful, convenient, and economical method.1 Recently, a lot
of inter2 and intramolecular3 cross McMurry couplings have been
reported. In the course of our study on the reductive cross coupling
of heterocycles with carbonyl compounds using electroreduction
or metal reducing agents,4 we found that the reduction of 1,3-dim-
ethyluracil (1a) and benzophenone by low-valent titanium gave
unusual two-to-one coupled product 2a and its further reduced
product 3a (Scheme 1). Although uracil is well known as one of
the nucleic-acid bases, the reductive coupling of uracils with car-
bonyl compounds has been hitherto unknown.5 We report herein
the unusual two-to-one reductive coupling of 1a with benzophe-
none by low-valent titanium. Furthermore, it was found that 1,3-
dimethyl-5-fluorouracil (1b) was more reactive than 1a, whereas
1,3-dimethylthymine (1c) was completely inert under the same
conditions. This reductive coupling provides a synthetic method
for new classes of multi-substituted pyrimidin-2(1H)-ones from
uracils and aromatic ketones. The reaction mechanism of the unu-
sual two-to-one reductive coupling is also discussed.
and 4 were low. The major product in these cases was 1,1,2,2-tet-
raphenylethane-1,2-diol, usual pinacol-type coupling product of
benzophenone (60–70% yields based on benzophenone). When
5 mol equiv of benzophenone was employed at 25 °C (run 4),6 al-
most all 1a was consumed and two-to-one coupled product 2a
(53%) was obtained together with one-to-one coupled product 4
(18%). A small amount (<3%) of further reduced product of 2a
(3a) was also detected.7 Therefore, the reaction was carried out
at 25 °C for 2 h and then refluxed for 2 h (run 5). In this case, the
yields of 2a and 4 were decreased to 5% and 8%, respectively,
whereas the yield of 3a significantly increased to 58%. When the
reaction mixture was refluxed for 2 h from the beginning (run 6),
the adduct 3a was obtained in 67% yield. Under reflux conditions
(runs 5 and 6), the major product was 1,2,3,4-tetraphenyethene,
usual McMurry-type coupling product of benzophenone (60–65%
yields based on benzophenone). These results suggest that 3a
was formed from both 2a and 4. In fact, it was confirmed that
Ph
O
N
Y
Ph
NMe
O
The results of the reductive coupling of 1a with benzophenone
using Zn–TiCl4 as a reducing agent in THF are summarized in Table
1. The molar ratio of benzophenone/Zn/TiCl4 was fixed to 1:2:1.
When the reaction was carried out at 25 °C with the ratio of 1a/
Ph2CO as 1:1, 1:2, and 1:3 (runs 1–3), considerable amounts of
1a were recovered and the yields of cross coupling products 2a
X
X
HO
Ph
Ph
Zn-TiCl4
THF
NMe
O
+
O
N
Ph
Me
Me
Ph
1a: X = H
1b: X = F
1c: X = Me
2a: X = H, Y = OH
2b: X = F, Y = OH
3a: X = Y = H
⇑
Corresponding author.
E-mail address: kise@bio.tottori-u.ac.jp (N. Kise).
Scheme 1. Reductive coupling of 1a–c with benzophenone by Zn–TiCl4.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.09.154

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N. Kise et al. / Tetrahedron Letters 52 (2011) 6627–6631
Table 1
Ph
Reductive coupling of 1a with benzophenone by Zn–TiCl4
Ph
Ph
Ph
HO
Ph
Ph
NMe
O
O
Zn-TiCl4
NMe
O
Me
O
Ph
Ph
Zn-TiCl4
THF
HO
Ph
HO
Ph
N
+
THF
reflux, 2 h
N
N
O
+
Me
Me
2a
N
Me
1a (1 mmol)
3a 80%
Ph
Scheme 2. Reduction of 2a to 3a by Zn–TiCl4.
Ph
Ph
Ph
Ph
Ph
NMe
HO
Ph
NMe
O
NMe
O
+
Ph
Ph
HO
Ph
HO
Ph
Ph
Ph
N
N
N
O
Me
Me
O
NMe
O
Zn-TiCl4
THF
Me
Ph
NMe
O
HO
Ph
+
Ph
3a
Ph
4
2a
N
N
Me
Ph
3a 63%
(3 equiv) 25 °C, 12 h
Me
Run
1a/Ph2COa
Temperature (°C)
Time (h)
Yieldb (%)
4
4
2a
3a
1a
Scheme 3. Reductive coupling of 4 with benzophenone by Zn–TiCl4.
1
2
3
4
5
1/1
1/2
1/3
1/5
1/5
25
25
25
25
25
Reflux
Reflux
4
4
6
6
2
2
2
5
9
12
18
8
15
26
34
53
5
–
–
–
<3
58
65
42
21
<3
–
Scheme 4. The reduction of benzophenone by low-valent titanium
generates dianion intermediate A. Two molecules of A successively
attack 4- and 6-positions of 1a to give two-to-one adduct D
through one-to-one 1,2-adduct B and 1,4-adduct C. The reductive
b-elimination of the 1,2-adduct B affords 4. Incidentally, the reduc-
tive coupling of 5,6-dihydro-1,3-dimethyluracil (5) and benzophe-
none with Zn–TiCl4 produced McMurry-type product 6, which was
formed by the attack of A at 4-position of 5 and subsequent
reductive elimination of 1,2-adduct (Scheme 5). The two-to-one
adduct D is transformed to E by b-elimination and subsequently
the work-up of E with water gives 2a. At reflux temperature of
6
1/5
–
<3
67
–
a
Ph2CO/Zn/TiCl4 = 1:2:1.
Isolated yields based on 1a.
b
the reduction of 2a as well as that of 4 with benzophenone by
Zn–TiCl4 gave 3a (Schemes 2 and 3).
The reaction mechanism of the unusual reductive coupling of 1a
with benzophenone by Zn–TiCl4 can be presumed as illustrated in
Ph
Ph
Ph Ph
Ph
Ph
Ti(+X)
Zn-TiCl4
Zn-TiCl4
Ph
Ph
Ph
Ph
Ph
Ph
O
Ph
Ph
O
O
O
McMurry-type
coupling
pinacol-type
coupling
O
A
Ti
Ph
Ph
Ph
Ti
O
Ph
Ph
Ph
Ph
O
Ti
O
H2O
4
A
A
Zn-TiCl4
NMe
O
NMe
O
5
NMe
O
NMe
3a
O
6N
6
6N
O
work-up
N
1,4-addition
(slow)
1,2-addition
N
Ph
Me
Me
Me
Me
1a
G
4
B
A
1,4-addition
A
1,4-addition
Ti
Ph
Ph
Ph
Ti
O
O
Ph
Ti
TiO
Ph
O
4
A
H2O
NMe
O
Zn-TiCl4
(slow)
NMe
O
Ti
Ph
O
TiO
Ph
3a
4
NMe
O
NMe
O
5
TiO
Ph
N
work-up
O
N
1,2-addition
Ph
Me
Me
N
N
Ph
Ph
Ph
Me
Me
C
Ph
Ph
F
E
D
work-up
H2O
2a
Scheme 4. Reaction mechanism of reductive coupling of 1a with benzophenone by Zn–TiCl4.

N. Kise et al. / Tetrahedron Letters 52 (2011) 6627–6631
6629
group at 5-position of 1a strictly restrains the addition of A at
the 4- and 6-positions. On the contrary, the methyl substitution
at 6-position of 1a does not restrict the addition of A at the 4-posi-
tion, since the reduction of 6-methyl substituted 1a (1d) with ben-
zophenone gave McMurry-type adduct 7 as a sole product (Scheme
7).
In addition, it was found that the two-to-one adducts 2a and 3a
were readily, quantitatively, and stereospecifically transformed to
cyclic ether 8 and diol 9,9 respectively, by treatment with 1 M
HCl at 25 °C for 1 h (Scheme 8). The stereostructure of 8 was
undoubtedly determined by X-ray crystallographic analysis
(Fig. 1).10 The cis stereoconfiguration of 9 was estimated by the
DFT calculations at the B3LYP/6-311+G(2d,p) level, that is, the cis
isomer 9 is much more stable (4.25 kcal/mol in gas phase) than
its trans isomer (trans-9). The formation of 8 and 9 seems to
Ph
Ph
O
Ph
Ph
Zn-TiCl4
NMe
O
4
NMe
O
+
O
THF
reflux, 2 h
N
N
Me
Me
(2 equiv)
6 57%
5
Scheme 5. Reductive coupling of 5 with benzophenone by Zn–TiCl4.
THF, the intermediate E is further reduced to F by low-valent tita-
nium. The work-up of F with water produces 3a. On the other
hand, 4 is slowly subjected to further addition of A at the 6-posi-
tion to give G, and then 3a is furnished by the work-up of G.
Next, the reductive coupling of 5-fluoro substituted 1a(1b) with
benzophenone (5 equiv) by Zn–TiCl4 at 25 °C gave two-to-one ad-
duct 2b (Scheme 6).8 The 74% yield of 2b was higher than the 53%
yield of 2a (Table 1, run 4). This result shows that the substitution
of a fluoro group at 5-position of 1a enhances the reactivity as an
accepter for A. In contrast to the formation of 3a (Table 1, runs
4–6), further reduced product of 2b could not be detected at all.
Even when the reduction by Zn–TiCl4 was carried out under reflux
conditions, 2b was obtained in 48% yield as a sole product. This fact
implies that the reduction of E to F in Scheme 4 proceeds through
the coordination of low-valent titanium to the C4–C5 double bond
in E, and the substitution of a fluoro group at the 5-position of E
strongly prevents the coordination of low-valent titanium to the
C4–C5 double bond, because of the great electron negativity of
fluorine atom. Unexpectedly, the reaction of 5-methyl substituted
1a (1c) with benzophenone by Zn–TiCl4 afforded no cross coupled
product even under reflux conditions and almost all 1c was recov-
ered (>90%). This result means that the substitution of a methyl
Ph
Ph
O
N
Ph
Ph
Zn-TiCl4
NMe
O
NMe
O
+
O
THF
reflux, 2 h
Me
N
Me
Me
Me
(5 equiv)
7 50%
1d
Scheme 7. Reductive coupling of 1d with benzophenone by Zn–TiCl4.
Ph
Ph
HO
HO
Ph
1 M HCl
dioxane
O
Ph
NMe
NMe
Ph
Ph
HO
Ph
25 °C, 1 h
N
O
N
O
Me
Me
Ph
2a
8 quant.
Ph
HO
Ph
NMe
O
O
N
Ph
F
F
Ph
Ph
Zn-TiCl4
THF
Ph
Ph
Ph
NMe
O
+
Ph
HO
HO
Ph
1 M HCl
dioxane
O
N
NMe
NMe
O
HO
Ph
(5 equiv)
Me
Me
HO
Ph
Ph
25 °C, 1 h
N
O
N
1b
2b
Me
Me
Ph
9 quant.
25 °C, 6 h
reflux, 2 h
74%
48%
3a
Scheme 6. Reductive coupling of 1b with benzophenone by Zn–TiCl4.
Scheme 8. Treatment of 2a and 3a with 1 M HCl.
Figure 1. X-ray crystal structures of 8 and 10.

6630
N. Kise et al. / Tetrahedron Letters 52 (2011) 6627–6631
Ph
Ph
Ph
O
O
Zn-TiCl4
THF
Ph
NMe
HO
KHSO4
xylene
NMe
O
Ph
Ph
+
NMe
O
HO
Ph
N
N
Me
reflux, 3 h
N
O
Me
Me
16 (5 equiv)
1a
Ph
+H
10 65%
9
2H2O
Ph
H
HO
OH
NMe
O
Ph
Ph
Ph
N
NMe
Me
NMe
O
Ph
Ph
NMe
O
N
O
Ph
Me
N
N
Me
Me
Ph
17
53%
30%
18
38%
56%
H
I
25 °C, 6 h
reflux, 2 h
Scheme 9. Dehydration of 9 to 10.
Scheme 11. Reductive coupling of 1a with 16 by Zn–TiCl4.
O
Ar
Ar
Zn-TiCl4
THF
NMe
+
O
N
O
Me
11 (5 equiv)
1a
Ar =
p-FC6H4
Ar
N
Ar
Ar
Ar
Ar
Ar
O
N
HO
Ar
Ar
NMe
O
NMe
O
NMe
O
NMe
O
HO
Ar
HO
Ar
HO
Ar
N
N
Me
Me
Me
Me
Ar
12
8%
-
13
33%
17%
14
36%
-
15
-
49%
25 °C, 6 h
reflux, 2 h
Scheme 10. Reductive coupling of 1a with 11 by Zn–TiCl4.
proceed through the protonation at the 5-position of 2a and 3a. On
the other hand, it is noted that the two-to-one adduct 2b was en-
tirely unchanged under the same conditions. This result suggests
that the 5-fluoro group in 2b perfectly inhibits the protonation at
the 5-position. The diol 9 completely resisted dehydration under
reflux in toluene in the presence of KHSO4. However, 9 was dehy-
drated by refluxing in xylene to give not 3a but cyclopropane 10
(Scheme 9), which was confirmed by X-ray crystallography
(Fig. 1).9,10 It is likely that the unexpected product 10 was formed
through cationic intermediates H and I.
further reduced product 3a. The reaction of 5-fluoro analog of 1a
(1b) under the same conditions produced similar two-to-one ad-
duct 2b. On the other hand, 5-methyl analog of 1a (1c) was com-
pletely inert under the same conditions. The two-to-one adducts
2a and 3b were quantitatively converted to cyclic ether 8 and diol
9, respectively, by treatment with 1 M HCl. However, 2b was inac-
tive against both Zn–TiCl4 and 1 M HCl. We are continuing to ex-
plore the scope and limitation of the reductive coupling for the
synthesis of new classes of multi-functionalized pyrimidin-2(1H)-
ones from uracils and carbonyl compounds.
To explore the scope of this reductive coupling, we are attempt-
ing other aromatic ketones than benzophenone. Preliminary re-
sults using 4,40-difluorobenzophenone (11) and dibenzosuberone
(16) as an aromatic ketone are shown in Schemes 10 and 11. The
reaction of 1a with 11 gave two-to-one adducts 14 and 15 along
with one-to-one 1,4- and 1,2-adducts 12 and 13. In contrast, the
reaction of 1a with 16 afforded two-to-one adduct 18 with one-
to-one 1,2-adduct 17, and further reduced product of 18 corre-
sponding to 3a and 15 did not detected. In any event, more optimi-
zation of reaction conditions is required on each substrate for the
selective synthesis of the two-to-one adducts.
References and notes
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.
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,
In summary, the reduction of 1a and benzophenone with Zn–
TiCl4 in THF gave unusual two-to-one coupled product 2a and its

N. Kise et al. / Tetrahedron Letters 52 (2011) 6627–6631
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.
6631
1H, J = 16.9 Hz), 7.03–7.08 (m, 2H), 7.21–7.36 (m, 14H), 7.51–7.57 (m, 4H); 13
C
NMR (CDCl3) d 34.4 (q), 37.5 (q), 66.2 (d, JCCF = 26.9 Hz), 78.7 (s), 80.2 (s), 126.5
(d), 126.6 (d), 126.7 (d), 126.8 (d), 127.49 (d), 127.51 (d), 127.7 (d), 127.8 (d),
128.0 (d), 128.09 (d), 128.11 (d), 128.3 (d), 129.3 (s, JCCF = 18.2 Hz), 140.1 (s),
142.2 (s), 142.3 (s), 143.0 (s), 146.4 (s), 157.4 (s).
4. (a) Kise, N.; Mano, T.; Sakurai, T. Org. Lett. 2008, 10, 4617; (b) Kise, N.; Isemoto,
S.; Sakurai, T. Org. Lett. 2009, 11, 4902; (c) Kise, N.; Sakurai, T. Tetrahedron Lett.
2010, 51, 70; (d) Kise, N.; Fukazawa, K.; Sakurai, T. Tetrahedron Lett. 2010, 51,
5767.
5. The photochemical [2+2] cycloaddition of 1,3-dimethyluracil with
benzophenone has been reported: Song, Q. H.; Hei, X.; Xu, Z.; Zhang, X.; Guo,
Q. Eur. J. Org. Chem. 2006, 1790.
9. Compound 8: White solid; Rf 0.35 (hexanes–EtOAc, 1:1); mp 272–273 °C; 1H
NMR (CDCl3) d 2.20 (br s, 1H), 2.31 (s, 3H), 2.50 (d, 1H, J = 10.5 Hz), 2.91 (s, 3H),
4.27 (d, 1H, J = 3.7 Hz), 6.96–7.55 (m, 20H); 13C NMR (CDCl3) d 33.1 (q), 36.1 (q),
39.3 (t), 63.7 (d), 80.5 (s), 95.9 (s), 100.6 (s), 125.8 (d), 126.2 (d), 126.8 (d), 127.0
(d), 127.2 (d), 127.3 (d), 127.4 (d), 127.5 (d), 127.7 (d), 128.1 (d), 128.2 (d),
142.8 (s), 143.1 (s), 157.4 (s). Compound 9: Colorless paste; Rf 0.45 (hexanes–
EtOAc, 1:1); 1H NMR (CDCl3) d 2.22 (dd, 1H, J = 4.1, 11.0 Hz), 2.40 (s, 3H), 2.70
(d, 1H, J = 11.0 Hz), 2.96 (s, 3H), 4.26 (d, 1H, J = 4.1 Hz), 4.87 (s, 1H), 6.95–7.33
(m, 20H); 13C NMR (CDCl3) d 29.6 (q), 36.2 (q), 36.6 (t), 55.4 (d), 64.4 (d), 93.8
(s), 97.5 (s), 125.5 (d), 126.1 (d), 126.2 (d), 126.4 (d), 126.7 (d), 127.0 (d), 127.5
(d), 127.6 (d), 127.9 (d), 128.3 (d), 128.9 (d), 130.8 (d), 139.88 (s), 139.94 (s),
143.0 (s), 143.1 (s), 157.2 (s). Compound 10: White solid; Rf 0.65 (hexanes–
EtOAc, 1:1); mp 250–251 °C; 1H NMR (CDCl3) d 1.83 (s, 3H), 2.93 (d, 1H,
J = 9.6 Hz), 3.21 (d, 1H, J = 9.6 Hz), 3.31 (s, 3H), 7.10–7.45 (m, 20H); 13C NMR
(CDCl3) d 34.4 (d), 36.5 (q), 37.9 (q), 41.4 (s), 47.9 (d), 124.6 (d), 126.4 (d), 126.5
(d), 126.8 (d), 127.0 (d), 127.3 (d), 128.1 (d), 128.2 (d), 128.6 (d), 128.9 (d),
129.5 (d), 130.3 (d), 130.6 (d), 134.5 (s), 136.5 (s), 141.5 (s), 142.9 (s), 143.5 (s),
154.0 (s).
6. Typical procedure for reductive coupling of 1a with benzophenone by Zn–TiCl4
(Table 1, run 4) is as follows. To
a solution of 1a (140 mg, 1 mmol),
benzophenone (910 mg, 5 mmol), and zinc powder (650 mg, 10 mmol) in
THF (10 mL) was added TiCl4 (0.55 mL, 5 mmol) dropwise at 0 °C and the dark
blue suspension was stirred at 25 °C for 6 h. To the mixture was slowly added
satd NaHCO3 water (30 mL) at 0 °C and the mixture was stirred at 25 °C for
30 min. After the mixture (white suspension) was filtered, the filtrate 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 crude
mixture was purified by column chromatography on silica gel to give 1a (<3%),
2a (58%), 3a (<3%), and 4 (18%).
7. The products 2a, 3a, and 4 were assigned by 1H NMR and 13C NMR analyses.
Compound 2a: White solid; Rf 0.25 (hexanes–EtOAc, 1:1); mp 169–170 °C; 1H
NMR (CDCl3) d 2.48 (s, 3H), 2.72 (s, 3H), 2.90 (br s, 1H), 3.22 (br s, 1H), 4.27 (d,
1H, J = 6.2 Hz), 4.70 (d, 1H, J = 6.2 Hz), 7.05–7.10 (m, 2H), 7.12–7.34 (m, 14H),
7.45–7.53 (m, 4H); 13C NMR (CDCl3) d 32.8 (q), 38.1 (q), 65.7 (d), 80.6 (s), 81.2
(s), 104.2 (d), 126.3 (d), 126.7 (d), 127.0 (d), 127.16 (d), 127.22 (d), 127.7 (d),
128.0 (d), 128.1 (d), 128.2 (d), 143.8 (s), 144.1 (s), 144.7 (s), 145.0 (s), 157.3 (s).
Compound 3a: Colorless paste; Rf 0.55 (hexanes–EtOAc, 1:2); 1H NMR (CDCl3) d
2.54 (br s, 1H), 2.58 (s, 3H), 2.73 (s, 3H), 4.13 (d, 1H, J = 6.0 Hz), 4.74 (d, 1H,
J = 6.0 Hz), 4.86 (s, 1H), 6.86–6.90 (m, 2H), 6.99–7.32 (m, 14H), 7.44–7.48 (m,
4H); 13C NMR (CDCl3) d 29.5 (q), 38.1 (q), 52.5 (d), 65.8 (d), 81.5 (s), 101.5 (d),
126.39 (d), 126.42 (d), 126.6 (d), 126.7 (d), 126.87 (d), 126.90 (d), 127.3 (d),
127.4 (d), 127.8 (d), 128.0 (d), 128.4 (d), 128.6 (d), 128.9 (d), 131.1 (d), 139.6
(s), 140.5 (s), 143.17 (s), 143.21 (s), 143.5 (s), 155.8 (s). Compound 4: Pale
yellow paste; Rf 0.7 (hexanes–EtOAc, 1:1); 1H NMR (CDCl3) d 2.81 (s, 3H), 3.17
(s, 3H), 5.81 (d, 1H, J = 8.1 Hz), 5.99 (d, 1H, J = 8.1 Hz), 7.05–7.09 (m, 1H), 7.12–
7.30 (m, 3H); 13C NMR (CDCl3) d 35.7 (q), 38.9 (q), 104.6 (d), 116.6 (s), 126.1 (d),
126.3 (d), 127.9 (d), 128.3 (d), 129.2 (d), 130.4 (d), 131.0 (d), 137.5 (s), 142.4 (s),
143.0 (s), 154.0 (s).
10. All measurements of X-ray crystallographic analysis were made on a Rigaku
RAXIS imaging plate area detector with graphite monochromated Mo 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 are as follows: CCDC
842228 and 842579 contain the supplementary crystallographic data. These
data can be obtained free of charge from The Cambridge Crystallographic Data
Center via http://www.ccdc.cam.ac.uk/data_request/cif.
8 (CCDC 842228): C32H30N2O3, FW = 490.58, mp 272–273 °C, monoclinic, P21/c
(no 14), colorless block, a = 15.820(3) Å, b = 10.453(3) Å, c = 16.296(4) Å,
b = 106.839(10), V = 2579.3(10) Å3, T = 298 K, Z = 4, Dcalcd = 1.263 g/cm3,
l
= 0.81 cmꢀ1, GOF = 1.017.
10 (CCDC 842579): C32H28N2O, FW = 456.56, mp 250–251 °C, monoclinic, P21/n
(no 14), colorless block, a = 15.036(2) Å, b = 11.0685(17) Å, c = 15.039(3) Å,
b = 87.551(8), V = 2500.6(7) Å3, T = 298 K, Z = 4, Dcalcd = 1.213 g/cm3,
l = 0.73
cmꢀ1, GOF = 0.960.
8. Compound 2b: White solid; Rf 0.4 (hexanes–EtOAc, 1:2); mp 169–170 °C; 1H
NMR (CDCl3) d 2.54 (br s, 1H), 2.56 (s, 3H), 2.57 (s, 3H), 2.87 (br s, 1H), 4.82 (d,