Substituent effect on anionic cycloaromatization of 2-(2-substituted ethynyl)benzonitriles and related molecules

Article abstract of DOI:10.1016/S0040-4020(02)00753-6

Methanolysis of 2-(2-substituted ethynyl)benzonitriles based on the nature of substituents gave 5-exo product, isoindolones and 6-endo product, isoquinolones, respectively. When a bulky substituent, such as tert-butyl group, was employed in this cyclization reaction, a 5-exo adduct was obtained. Phenyl and thienyl groups which can stabilize the α-anion affect the cyclization reaction to produce the 5-exo adducts. Pyridinyl and pyrazinyl groups can also stabilize the α-anion, but the formation of a more stable intermediate by coordination of sodium with nitrogen atom leads to the 6-endo products.

Full text of DOI:10.1016/S0040-4020(02)00753-6

Tetrahedron 58 (2002) 7315–7319
Substituent effect on anionic cycloaromatization of
2-(2-substituted ethynyl)benzonitriles and related molecules
Wen-Der Lu,a Chi-Fong Lin,a Chyi-Jia Wang,b Shih-Jen Wangc and Ming-Jung Wua
,
*
aSchool of Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
bSchool of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
cSchool of Chemistry, National Tsing Hua University, Shin-Chu, Taiwan, ROC
Received 22 March 2002; revised 6 June 2002; accepted 27 June 2002
Abstract—Methanolysis of 2-(2-substituted ethynyl)benzonitriles based on the nature of substituents gave 5-exo product, isoindolones and
6-endo product, isoquinolones, respectively. When a bulky substituent, such as tert-butyl group, was employed in this cyclization reaction, a
5-exo adduct was obtained. Phenyl and thienyl groups which can stabilize the a-anion affect the cyclization reaction to produce the 5-exo
adducts. Pyridinyl and pyrazinyl groups can also stabilize the a-anion, but the formation of a more stable intermediate by coordination of
sodium with nitrogen atom leads to the 6-endo products. q 2002 Elsevier Science Ltd. All rights reserved.
Recently, we reported the anionic cyclization reaction of
2-(2-substituted ethynyl)benzonitriles.1 When the sub-
stituent is an alkyl group, an isoquinolone product was
obtained. This cyclization favoring 6-endo pathway rather
than 5-exo is due to the formation of an aromatic ring which
lowers the transition state energy. However, when the
substituent is changed to an aryl group, an isoindolone was
produced. In this case, 5-exo transition state has the lower
energy due to the ability of the aryl group to stabilize the
a-anion (Scheme 1). In order to have more understanding
about the substituent effect on this cyclization pathway,
more analogs of 2-(2-substituted ethynyl)benzonitriles were
prepared by considering both the steric and a-anion
stabilization effects and the results are reported.
nitrile (2) with alkynes 3a–g in 47–88% yields, respec-
tively. The results are summarized in Scheme 2. Compound
4 was obtained by copper-catalyzed homo-coupling3 of
2-ethynylbenzonitrile 5 in 41% yield (Eq. (1)).
ð1Þ
Compounds 1a–g were treated with sodium methoxide
in refluxing methanol for 16 h to give isoindolones 6
and isoquinolones 7 in different ratios. The results
are summarized in Table 1. As we reported earlier,
2-(2-Substituted ethynyl)benzonitriles 1a–g were prepared
by palladium catalyzed coupling reaction2 of 2-iodobenzo-
Scheme 1.
Keywords: cyclization; diynes.
*
Corresponding author. Tel.: þ886-7-3121101x2220; fax: þ886-7-3125339; e-mail: mijuwu@cc.kmu.edu.tw
0040–4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(02)00753-6

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W.-D. Lu et al. / Tetrahedron 58 (2002) 7315–7319
state and gives the isoindolone 6c in 48% yield and the
6-endo product 7c in only 8% yield. Triisopropylsilyl group
and tert-butyl have less a-anion stabilization compared to
phenyl group. Therefore, cyclization of 1d also gave
isoquinolone 7d in 42% yield. Compared to phenyl
substituent, cyclohexenyl group has similar a-anion stabili-
zation ability but less steric hinderence. Cyclization of 1e
gave the 6-endo product 7e as the major product. When the
substituent was switched to 2-pyridinyl, we observed an
interesting result. Methanolysis of 1f gave mainly the
6-endo product 7f in 88% yield. A similar result was
obtained on the methanolysis of 1g to give 7g in 70% yield.
We believe that the unusual selectivity for 2-pyridinyl and
pyrazinyl is because of the coordination of metal with
nitrogen atom to form a stable intermediate I. This
coordination effect could overcome both the steric effect
and the a-anion stabilization ability which favored the
formation of the 5-exo adduct. Methanolysis of 4 gave a
symmetrical bis-isoindole 8 in 40% yield (Eq. (2)). The
structure of compound was unambiguously determined by
X-ray crystallography.4 (Fig. 1) This result indicates that
cyclization favors 5-exo-pathway due to the good stabili-
zation ability of a-anion by sp carbon on the acetylene.
Scheme 2.
methanolysis of 1a gave isoindolone 6a in 48% yield as the
major product.1 When the phenyl substituent was replaced
by thienyl, cyclization of 1b gave 6b in 82% yield, again it
favors the 5-exo-pathway. For a bulky substituent, such as
tert-butyl group, cyclization of 1c favors the 5-exo transition
Table 1. Methanolysis of 1a–g
ð2Þ
R
Products (yields, %)
1a R¼Ph
6a1 (48)
6b (82)
6c (48)
1b R¼thienyl
1c R¼t-butyl
7c6 (8)
1d R¼triisopropylsilyl
1e R¼cyclohexenyl
1f R¼pyridinyl
1g R¼pyrazinyl
6d7 (14), R¼H
7d8 (42), R¼H
6e (11)
7e (35)
7f9 (88)
7g (70)
Figure 1. X-Ray structure of 8.

W.-D. Lu et al. / Tetrahedron 58 (2002) 7315–7319
7317
Scheme 3.
Further interesting results were observed on the cyclization
of 2-(substituted ethynyl)benzyl alcohols 9a–c. These
compounds were prepared by palladium catalyzed coupling
reaction of 2-iodobenzyl alcohol 10 with alkynes 3a and
3f–g. Methanolysis of 9a–c under the same reaction
conditions gave the 5-exo products 11a–c in all cases
regardless of whether there is a coordination effect or not
(Scheme 3).
methanol was removed in vacuo. To the residue, sat.
NaCl(aq) was added and extracted with EtOAc. The
combined organic layer was dried over anhydrous
MgSO4(s). After filtration and removal of solvent, the
residue was purified by column chromatography to give the
separated products.
1.2.1. 2-(2-Phenylethynyl)benzonitrile (1a).1 Obtained in
54% yield as an oil according to method A. 1H NMR
(CDCl3, 200 MHz) d 7.69–7.55 (m, 5H), 7.43–7.36 (m,
4H); 13C NMR (CDCl3, 50 MHz) d 132.6, 132.3, 131.9,
129.2, 128.4, 128.4, 128.1, 127.2, 122.0, 117.5, 115.3, 96.0,
85.5.
In conclusion, intramolecular nucleophilic addition to triple
bond usually proceeds via a 5-exo-dig transition state.5 In
this study, we found that methanolysis of 2-(2-substituted
ethynyl)benzonitriles gave 6-endo product isoquinolones
and 5-exo product isoindolones based on the nature of the
substituents. The driving force to form the 6-endo product is
the formation of an aromatic ring. However, steric,
electronic and coordination effects also have strong impact
on this cyclization reaction. When a bulky substituent, such
as tert-butyl group, was employed in this cyclization
reaction, a 5-exo adduct was obtained. Phenyl and thienyl
groups which can stabilize the a-anion will affect the
cyclization reaction to produce the 5-exo adducts. Pyridinyl
and pyrazinyl groups can also stabilize the a-anion, but the
formation of a more stable intermediate by coordination of
sodium with nitrogen atom leads to the 6-endo products.
1.2.2. 2-(2-Thienylethynyl)benzonitrile (1b). Obtained in
62% yield as an oil according to method A. 1H NMR
(CDCl3, 200 MHz) d 7.68–7.51 (m, 3H), 7.45–7.36 (m,
3H), 7.04 (dd, 1H, J¼5.2, 3.6 Hz); 13C NMR (CDCl3,
50 MHz) d 133.4, 132.6, 132.2, 131.9, 131.9, 128.7, 128.2,
127.3, 126.9, 121.8, 117.4, 114.8, 111.9, 89.2. MS (EI): 209
(Mþ, 100), 219 (13), 194 (12), 97 (17). HRMS (EI) calcd for
C13H7NS 209.0300, found 209.0304.
1.2.3. 2-(2-tert-Butylethynyl)benzonitrile (1c). Obtained
1
in 52% yield as an oil according to method A. H NMR
(CDCl3, 200 MHz) d 7.60 (dd, 1H, J¼7.6, 0.8 Hz), 7.57–
7.46 (m, 2H), 7.30 (td, 1H, J¼7.6, 0.8 Hz), 1.35 (s, 9H); 13C
NMR (CDCl3, 50 MHz) d 132.4, 132.4, 132.1, 131.9, 128.0,
127.4, 117.6, 115.5, 105.8, 30.6, 28.2. MS (EI): 183 (Mþ,
44), 167 (100), 140 (13), 107 (12). HRMS (EI) calcd for
C13H13N 183.1048, found 183.1048.
1. Experimental
1.1. General procedure of the coupling reaction of
2-substituted ethyne with 2-iodobenzonitrile (method A)
1.2.4. 2-(2-Triisopropylsilylethynyl)benzonitrile (1d).
Obtained in 57% yield as an oil according to method A.
1H NMR (CDCl3, 200 MHz) d 7.62 (dd, 1H, J¼7.6, 1.2 Hz),
7.57–7.30 (m, 3H), 1.51–1.37 (m, 3H), 1.25 (d, 18H, J¼
7.0 Hz); 13C NMR (CDCl3, 50 MHz) d 132.7, 132.5, 132.1,
128.3, 127.2, 117.3, 115.7, 102.3, 98.9, 18.7, 18.6. MS (EI):
283 (Mþ, 15), 240 (100), 184 (50), 170 (53), 154 (22).
HRMS (EI) calcd for C18H25SiN 283.1757, found 283.1742.
A degassed solution of 2-iodobenzonitrile (12 mmol) in dry
ether (30 mL) containing Pd(PPh3)4 (0.8 mmol) and CuI
(3.2 mmol) was added to a solution of acetylene (24 mmol)
containing n-butylamine (34 mmol). The resulting solution
was stirred for 6 h at 258C, quenched with saturated aqueous
NH4Cl and Na2CO3 solutions and extracted with EtOAc.
The organic layer was separated and dried over MgSO4.
After filtration, the solvent was evaporated in vacuo. The
residue was purified by flash chromatography to give the
products.
1.2.5.
2-(2-Cyclohexenylethynyl)benzonitrile
(1e).
Obtained in 47% yield as an oil according to method A.
1H NMR (CDCl3, 200 MHz) d 7.65 (td, 1H, J¼7.4, 1.2 Hz),
7.51–7.29 (m, 3H), 6.41–6.30 (m, 1H), 2.27–2.12 (m, 4H),
1.70–1.57 (m, 4H); 13C NMR (CDCl3, 50 MHz) d 138.2,
133.0, 132.8, 132.7, 129.2, 128.1, 120.6, 118.1, 115.5, 98.6,
83.7, 30.8, 29.4, 23.4, 22.6. MS (EI): 207 (Mþ, 82), 206
(100), 179 (25), 165 (54), 140 (51), 77 (22). HRMS (EI)
calcd for C15H13N 207.1017, found 207.1049.
1.2. General procedure for methanolysis of 2-(2-substi-
tuted ethynyl)benzonitrile (method B)
To a solution of 2-(2-substituted ethynyl)benzonitrile
(1 mmol) in 10 mL of methanol was added freshly cut
sodium metal (5 mmol), the solution was heated to reflux
and stirred for 16 h. After cooling to room temperature, the

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W.-D. Lu et al. / Tetrahedron 58 (2002) 7315–7319
1.2.6. 2-(2-Pyridinylethynyl)benzonitrile (1f). Obtained in
88% yield as an oil according to method A. 1H NMR
(CDCl3, 200 MHz) d 8.64 (dd, 1H J¼7.6, 0.8 Hz), 7.73–
7.57 (m, 5H), 7.45 (td, 1H, J¼7.6, 1.2 Hz), 7.31–7.27 (m,
1H); MS (EI): 204 (Mþ, 100), 177 (13), 151 (8). HRMS (EI)
calcd for C14H8N2 204.0688, found 204.0692.
a yellow solid according to method B and they were not
1
separated by liquid chromatography. From the H NMR
spectrum, a mixture of 6d (14%) and 7d (42%) were
1
assumed. The following spectrum belongs to 7d. H NMR
(CDCl3, 400 MHz) d 10.80 (bs, 1H), 8.41 (dd, 1H, J¼7.6,
0.8 Hz), 7.69 (td, 1H, J¼7.6, 0.8 Hz), 7.58 (d, 1H,
J¼8.0 Hz), 7.52 (td, 1H, J¼7.6, 0.8 Hz), 7.18 (d, 1H,
J¼7.2 Hz), 6.60 (d, 1H, J¼7.2 Hz); the following peaks of
1.2.7. 2-(2-Pyrazinylethynyl)benzonitrile (1g). Obtained
1
in 51% yield as an oil according to method A. H NMR
1
the spectrum belong to 6d. H NMR (CDCl3, 400 MHz) d
(CDCl3, 400 MHz) d 8.88 (d, 1H, J¼1.6 Hz), 8.62 (td, 2H,
J¼8.0, 1.0 Hz), 7.77–7.51 (m, 4H); 13C NMR (CDCl3,
100 MHz) d 148.2, 144.5, 143.6, 139.3, 132.8, 132.8, 132.5,
129.6, 125.3, 117.0, 115.8, 91.4, 88.5. MS (EI): 205 (Mþ,
100), 152 (48), 53 (7). HRMS (EI) calcd for C13H7N3
205.0641, found 205.0646.
8.25 (bs, 0.33H), 5.21 (d, 0.33H, J¼2.0 Hz), 4.98 (d, 0.33H,
J¼2.0 Hz), the other peaks of aromatic could not be
separated from 7d.
1.2.13. 3-(2-Cyclohexenylmethylene)isoindol-1-one (6e)
and 3-(cyclohexenyl)isoquinolin-1-one (7e). Compound
6e was obtained in 11% yield and 7e in 35% yield as
a yellow oil according to method B. 6e: 1H NMR
(CDCl3, 200 MHz) d 7.97 (bs, 1H), 7.87–7.82 (m, 1H),
7.68–7.63 (m, 1H), 7.59–7.54 (m, 1H), 7.48–7.43 (m,
1H), 6.05–6.01 (m, 1H), 5.50 (d, 1H, J¼8.0 Hz), 2.39–2.32
(m, 2H), 2.23–2.03 (m, 2H), 1.86–1.62 (m, 4H). MS (EI):
225 (Mþ, 10), 212 (100), 184 (56), 147 (68), 141 (90), 130
(47). HRMS (EI) calcd for C15H15ON 225.1154, found
225.1158.
1.2.8. Bis-(2-ethynylbenzonitrile) (4). To a solution of
2-ethynylbenzonitrile (1 mmol) in 5 ml of DMF was added
CuI (1 mmol), the solution was stirred for 2 h. To the
solution, sat. NaCl(aq) was added and extracted with
EtOAc. The combined organic layer was dried over
anhydrous MgSO4(s). After filtration and removal of
solvent, the residue was purified by column chromatography
to give the product 4 (41%). 1H NMR (CDCl3, 200 MHz) d
7.71–7.45 (m, 4H). MS (EI): 252 (Mþ, 100), 225 (10), 126
(6). HRMS (EI) calcd for C18H8N2 252.0688, found
252.0691.
1
7e: H NMR (CDCl3, 200 MHz) d 9.48 (bs, 1H), 8.34 (d,
1H, J¼8.0 Hz), 7.64 (td, 1H, J¼7.6, 1.2 Hz), 7.52 (d, 1H,
J¼7.6 Hz), 7.44 (td, 1H, J¼7.6, 1.2 Hz), 7.39–7.35 (m,
1H), 6.51 (s, 1H), 2.42–2.38 (m, 2H), 2.31–2.27 (m, 2H),
1.82–1.77 (m, 2H), 1.72–1.66 (m, 2H); 13C NMR (CDCl3,
50 MHz) d 163.2, 139.3, 138.4, 132.9, 130.3, 127.6, 127.3,
126.4, 126.3, 112.0, 102.9, 29.6, 25.7, 22.3, 21.7. MS (EI):
225 (Mþ, 100), 196 (39), 161 (37), 149 (32), 85 (37), 43
(44). HRMS (EI) calcd for C15H15ON 225.1154, found
225.1160.
1.2.9. 3-(Phenylmethylene)isoindol-1-one (6a).1 Obtained
in 48% yield as a solid according to method B. Mp¼187–
1888C; 1H NMR (CDCl3, 400 MHz) d 8.25 (bs, 1H), 7.88 (d,
1H, J¼7.6 Hz), 7.79 (d, 1H, J¼7.6 Hz), 7.64 (td, 1H, J¼7.6,
1.2 Hz), 7.52 (t, 1H, J¼7.6 Hz), 7.47–7.41 (m, 4H), 7.33–
7.29 (m, 1H), 6.56 (s, 1H); 13C NMR (CDCl3, 50 MHz) d
169.0, 138.2, 134.9, 133.1, 132.2, 132.2, 129.2, 128.7,
128.5, 127.7, 123.5, 119.8, 105.9.
1.2.14. 3-Pyridinylisoquinolin-1-one (7f).9 Obtained in
88% yield as a solid according to method B. Mp¼143–
1448C; 1H NMR (CDCl3, 200 MHz) d 10.65 (bs, 1H), 8.61–
8.57 (m, 2H), 8.38 (d, 1H, J¼7.6 Hz), 7.89 (dt, 1H, J¼7.6,
1.0 Hz), 7.67–7.58 (m, 3H), 6.39 (s, 1H); 13C NMR (CDCl3,
50 MHz) d 169.2, 156.2, 149.6, 138.6, 138.3, 137.1, 132.5,
130.2, 103.0, 124.8, 124.2, 121.5, 120.5, 102.4.
1.2.10.
Obtained in 82% yield as a solid according to method
3-(Thienylmethylene)isoindol-1-one
(6b).
1
B. Mp¼144–1458C; H NMR (CDCl3, 200 MHz) d 8.06
(bs, 1H), 7.86 (dd, 1H, J¼7.4, 1.4 Hz), 7.74 (dd, 1H, J¼7.6,
3.0 Hz), 7.66–7.37 (m, 3H), 7.17–7.08 (m, 2H), 6.71 (s,
1H).; 13C NMR (CDCl3, 50 MHz) d 168.3, 138.0, 132.3,
131.2, 129.0, 128.5, 128.0, 128.0, 127.8, 126.1, 123.8, 119.6,
99.3. MS (EI): 227 (Mþ, 100), 198 (14), 183 (12), 97 (17).
HRMS (EI) calcd for C13H9ONS 227.0405, found 227.0410.
1.2.15. 3-Pyrazinylisoquinolin-1-one (7g). Obtained in
70% yield as a solid according to method B. Mp¼186–
1878C; 1H NMR (CDCl3, 200 MHz) d 10.56 (bs, 1H), 8.43
(td, 2H, J¼7.8, 1.2 Hz), 8.24 (d, 1H, J¼8.0 Hz), 7.74–7.63
(m, 2H), 7.56–7.38 (m, 2H), 6.29 (s, 1H); 13C NMR
(CDCl3, 50 MHz) d 168.1, 151.2, 144.9, 143.0, 140.9,
139.9, 137.0, 132.1, 129.9, 128.7, 123.3, 120.0, 111.7. MS
(EI): 223 (Mþ, 94), 222 (100), 195 (12), 130 (9). HRMS (EI)
calcd for C13H9ON3 223.0747, found 223.0740.
1.2.11. 3-(tert-Butylmethylene)isoindol-1-one (6c) and
3-(tert-butyl)isoquinolin-1-one (7c).6 Compounds 6c and
7c obtained in 56% as a yellow solid according to method B
and they were not separated by liquid chromatography, from
1H NMR spectrum, it shows as a mixture of 6c (48%) and 7c
(8%). The following spectrum belongs to 6c. 1H NMR
(CDCl3, 200 MHz) d 7.98 (bs, 1H), 7.82 (dd, 1H, J¼7.6,
0.8 Hz), 7.63 (dd, 1H, J¼7.6, 0.8 Hz), 7.56 (td, 1H, J¼7.6,
0.8 Hz), 7.45 (td, 1H, J¼7.6, 1.0 Hz), 5.58 (s, 1H), 1.30 (s,
9H). The following peaks of the spectrum belong to 7c. 1H
NMR (CDCl3, 200 MHz) d 10.30 (bs, 0.16H), 6.52 (s,
0.16H), 1.40 (s, 1.44H), the other peaks of aromatic could
not be separated from 6c.
1.2.16. Bis-(3-methyleneisoindol-1-methyl ether) (8).
Obtained in 40% yield as a solid according to method
1
B. Mp¼250–2518C; H NMR (CDCl3, 200 MHz) d 7.88
(dt, 2H, J¼8.0, 1.0 Hz), 7.59 (s, 2H), 7.55 (dd, 2H, J¼7.8,
1.2 Hz), 7.47–7.37 (m, 4H), 4.31 (s, 6H); 13C NMR (CDCl3,
50 MHz) d 131.1, 129.3, 128.1, 127.8, 124.2, 123.5, 120.5,
120.0, 117.3, 56.1. MS (EI): 316 (Mþ, 36), 301 (52), 286
(38), 186 (24), 32 (25), 28 (100). HRMS (EI) calcd for
C20H16N2O2 316.1213, found 316.1202.
1.2.12. 3-Methyleneisoindol-1-one (6d)7 and isoquinolin-
1-one (7d).8 Compounds 6d and 7d were obtained in 56% as

W.-D. Lu et al. / Tetrahedron 58 (2002) 7315–7319
7319
1.2.17. 2-(2-Phenylethynyl)benzyl alcohol (9a).10
Acknowledgements
Obtained in 82% yield as an oil according to method A.
1H NMR (CDCl3, 200 MHz) d 7.62–7.46 (m, 4H), 7.43–
7.21 (m, 5H), 4.91 (s, 2H), 3.00 (bs, 1H); 13C NMR (CDCl3,
50 MHz) d 142.0, 131.5, 131.0, 128.2, 127.9, 126.7, 126.7,
126.4, 122.4, 120.5, 93.7, 86.3, 63.0.
We thank the National Science Council of the Republic of
China for financial support of this program.
1.2.18. 2-(2-Pyrazinylethynyl)benzyl alcohol (9b).
Obtained in 84% yield as an oil according to method A.
1H NMR (CDCl3, 400 MHz) d 8.59 (d, 1H, J¼4.4 Hz), 7.32
(td, 1H, J¼7.8, 1.2 Hz), 7.60–7.50 (m, 3H), 7.35 (td, 1H,
J¼7.6, 1.2 Hz), 7.30–7.26 (m, 2H), 4.95 (s, 2H), 2.70 (bs,
1H). MS (EI): 208 (Mþ, 53), 179 (100), 152 (11). HRMS
(EI) calcd for C14H11ON 209.0841, found 209.0847.
References
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1.2.19. 2-(2-Pyrazinylethynyl)benzyl alcohol (9c).
Obtained in 80% yield as an oil according to method A.
1H NMR (CDCl3, 400 MHz) d 8.75 (s, 1H), 8.54 (s, 1H),
8.49 (s, 1H), 7.60 (dd, 1H, J¼7.6, 1.2 Hz), 7.54 (dd, 1H,
J¼7.8, 1.0 Hz), 7.42 (td, 1H, J¼7.6, 1.2 Hz), 7.30 (td, 1H,
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210 (Mþ, 49), 181 (100), 127 (11). HRMS (EI) calcd for
C13H10ON2 210.0794, found 210.0795.
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furan (11a).11 Obtained in 80% yield as an oil according
1
to method B. H NMR (CDCl3, 200 MHz) d 7.90 (d, 1H,
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7. (a) Chikara, K.; Toshihiko, N.; Chiemi, M. Heterocycles 1982,
19, 2275. (b) Norisuke, H. Bull. Chem. Soc. Jpn 1986, 59,
2723. (c) Harjit, S.; Sunil, K. A.; Nageshwar, M. Synthesis
1983, 10, 791.
J¼7.6 Hz), 7.63 (dd, 1H, J¼7.6, 1.0 Hz), 7.53–7.26 (m,
7H), 6.06 (s, 1H), 5.53 (s, 2H); 13C NMR (CDCl3, 50 MHz)
d 156.4, 139.2, 136.4, 134.8, 128.7, 128.4, 128.0, 127.8,
125.3, 121.2, 119.9, 96.2, 74.9.
1.2.21. 1-(Pyridinylmethylidene)-1,3-dihydroisobenzo-
furan (11b). Obtained in 80% yield as an oil according to
method B. H NMR (CDCl3, 400 MHz) d 8.52 (d, 1H,
J¼4.4 Hz), 8.05 (d, 1H, J¼8.0 Hz), 7.63–7.59 (m, 2H),
7.38–7.32 (m, 3H), 6.98 (dd, 1H, J¼8.0, 1.0 Hz), 6.22 (s,
1H), 5.52 (s, 2H). MS (EI): 209 (Mþ, 70), 180 (81), 152
(11). HRMS (EI) calcd for C14H11ON 209.0841, found
209.0848.
8. (a) Yasuhiro, U.; Eiko, M.; Miwako, M.; Masakatsu, S.
J. Organomet. Chem. 1990, 399, 93. (b) Flitsh, W.; Schindler,
S. R. Synthesis 1975, 685. (c) Yasuhiro, U.; Naofumi, K.;
Eiko, M.; Miwako, M.; Masakatsu, S. J. Am. Chem. Soc. 1989,
11, 3725.
1
9. Jacqueline, E. M. K.; Henk, T.; Regina, L.; Henk, G.; Adriaan,
P. I. J. Med. Chem. 1998, 41, 3987.
10. (a) Albert, P.; Keith, E. K.; David, W. M. J. Org. Chem. 1995,
60, 5595. (b) Tovar, J. D.; Swager, T. M. J. Org. Chem. 1999,
64, 6499. (c) Orita, A.; Yoshioka, N.; Struwe, P.; Braier, A.;
Beckmann, A.; Otera, L. J. Chem. Eur. J. 1999, 5, 1355.
11. (a) Albert, P.; Keith, E. K.; David, W. M. J. Org. Chem. 1995,
60, 5595. (b) Sanath, K. M.; Russell, R. Synthesis 1989, 12,
942. (c) Yasuo, H.; Mikako, W.; Tooru, F.; Takeshi, T. J. Am.
Chem. Soc. 1997, 119, 1127.
1.2.22. 1-(Pyrazinylmethylidene)-1,3-dihydroisobenzo-
furan (11c). Obtained in 63% yield as an oil according to
method B. 1H NMR (CDCl3, 200 MHz) d 9.30 (s, 1H), 8.46
(s, 1H), 8.25 (s, 1H), 7.64 (dd, 1H, J¼8.0, 1.0 Hz), 7.49–
7.37 (m, 3H), 6.14 (1H), 5.59 (s, 2H). MS (EI): 210 (Mþ,
100), 180 (32), 127 (10). HRMS (EI) calcd for C13H10ON2
210.0794, found 210.0786.