Synthetic application of intramolecular cyanoboration on the basis of removal and conversion of a tethering group by palladium-catalyzed retro-allylation

Article abstract of DOI:10.1055/s-2008-1032075

A new synthetic strategy, involving utilization of a tethered intramolecular reaction with a removable tether, was demonstrated by the intramolecular cyanoboration-retro-allylation sequence. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1032075

LETTER
423
Synthetic Application of Intramolecular Cyanoboration on the Basis of
Removal and Conversion of a Tethering Group by Palladium-Catalyzed
Retro-Allylation
Cyanoboration
o
s
-
Catalyz
h
ed Retro-Ally
i
lationmichi Ohmura,a Tomotsugu Awano,a Michinori Suginome,*a Hideki Yorimitsu,*b Koichiro Oshima*b
a
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
Fax +81(75)3832722; E-mail: suginome@sbchem.kyoto-u.ac.jp
b
Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Fax +81(75)3832438; E-mail: yori@orgrxn.mbox.media.kyoto-u.ac.jp; E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Received 24 October 2007
N(i-Pr)2
CN
N(i-Pr)2
Abstract: A new synthetic strategy, involving utilization of a teth-
ered intramolecular reaction with a removable tether, was demon-
strated by the intramolecular cyanoboration–retro-allylation
sequence.
B
O
B
O
R3
CN
R3
R1
intramolecular
cyanoboration
R1
R2
R2
I
II
Key words: alkenes, arylation, nitriles, palladium, retro-allylation
Suzuki–Miyaura
coupling
Silicon- and boron-tethered intramolecular reactions are
attractive methods for the synthesis of organic molecules
that are not easily accessible via the corresponding inter-
molecular reactions.1–3 Attractive features of the intramo-
lecular reaction involve high reaction efficiency,
regioselectivity, and stereoselectivity. On the other hand,
a major drawback of the intramolecular reactions is the
need for the tethering groups, which significantly limit the
variation of the substrate scope. It seems to be highly de-
sirable to remove and convert the tethering group into oth-
er functional groups after the intramolecular cyclization
step.
R4
OH R4
retro-allylation
O
R5
R3
CN
CN
R3
R1
R2
IV
III
R1
R2
Scheme 1 A synthetic application of intramolecular cyanoboration
based on removal of tethering unit
R4Br
N(i-Pr)2
Pd(dba)2 (4.0 mol%)
O
B
OH R4
Me
P(t-Bu)3 (4.4 mol%)
CN
CN
n-Pr
n-Pr
KF, dioxane–H2O
80 °C, 4–5 h
We expected that the removal and conversion of the teth-
ering group would be possible by palladium-catalyzed ret-
ro-allylation, in which allylic C–C bonds in homoallylic
alcohols are cleaved and converted into other C–C bonds.4
Because many silicon- and boron-tethered reactions are
designed for homopropargylic alcohol derived sub-
strates,3g,5 the retro-allylation would work well. Herein,
we demonstrate the strategy involving palladium-cata-
lyzed intramolecular cyanoboration, which allows for the
addition of boryl and cyano groups to alkynes.6,7 The Su-
zuki–Miyaura coupling of the cyanoboration products II
followed by retro-allylative coupling allows the synthesis
of highly substituted a,b-unsaturated nitriles IV, in which
no tethering group is left (Scheme 1).
Me
1
2a (R4 = 4-MeOC6H4) 91%
2b (R4 = Ph) 93%
2c (R4 = 4-EtO2CC6H4) 95%
Equation 1
We then examined palladium-catalyzed retro-allylative
coupling of 2 with aryl bromides 3. Reaction of cyano-
substituted homoallylic alcohol 2a with 4-bromotoluene
(3a) was carried out in the presence of Pd(OAc)2 (5
mol%), PCy3 (10 mol%), and Cs2CO3 (1.2 equiv) (entry 1
in Table 1).4 Retro-allylative coupling took place smooth-
ly by heating the reaction mixture at 110 °C, giving alkene
4a in 90% yield after three hours. It should be noted that
the reaction proceeded efficiently even for the homoallyl-
ic alcohol bearing the trisubstituted C–C double bond, in
spite of the fact that the retro-allylation has been found
difficult with internal alkenes.4 It is also noted that the ge-
ometry of the double bond isomerized from Z to E (E/Z =
85:15) in the course of the reaction, indicating that the re-
action proceeded via a p-allyl palladium intermediate (see
below). A small amount of protonated product 5a (9%)
was formed along with 4a.
We first carried out Suzuki–Miyaura coupling of boryl-
alkene 1, which was prepared via palladium-catalyzed in-
tramolecular cyanoboration of cyanoboryl homopropargyl
ether. The coupling reactions with aryl bromides took
place under the Fu’s conditions,8 giving cyano-substituted
homoallylic alcohols 2a–c in high yields (Equation 1).
SYNLETT 2008, No. 3, pp 0423–0427
x
x.
x
x.
2
0
0
8
Advanced online publication: 23.01.2008
DOI: 10.1055/s-2008-1032075; Art ID: U10107ST
© Georg Thieme Verlag Stuttgart · New York

424
T. Ohmura et al.
LETTER
Table 1 Screening of Ligand in Palladium-Catalyzed Retro-Allylative Coupling of 2a with 3aa
OMe
OMe
OMe
Me
Br
3a
Me
Pd(OAc)2 (5 mol%)
ligand (10 mol%)
+
OH
Me
Me
CN
Cs2CO3, toluene
110 °C
n-Pr
CN
CN
5a
2a
4a
Entry
Ligand
Time (h)
Yield (%),b (E/Z)c
4a
5a
1
2
3
4
5
6
7
8
9f
PCy3
3
18
18
18
6
90 (77)d (85:15)
31 (84:16)
74 (84:16)
57 (n.a.)
87 (75:25)
78 (85:15)
31 (76:24)
0
9 (n.a.)e
PCy2Ph
37 (88:12)
23 (87:13)
7 (n.a.)
PCyPh2
PPh3
P(4-MeOC6H4)3
P(4-CF3C6H4)3
P(Oi-Pr)3
P(OPh)3
8 (n.a.)
18
6
15 (90:10)
52 (91:9)
85 (88:12)
(89)d (88:12)
2
P(OPh)3
2
–
a Reaction conditions: Pd(OAc)2 (0.010 mmol), ligand (0.020 mmol), Cs2CO3 (0.24 mmol), 2a (0.20 mmol), and 3a (0.24 mmol) were stirred
at 110 °C unless otherwise noted.
b GC yield.
c Determined by 1H NMR of crude mixture.
d Isolated yield.
e n.a.: not analyzed.
f Carried out in the absence of 3a.
As reported recently,4b PCy3 was found to be the most ef- Retro-allylative coupling of 2a–c with various aryl bro-
fective ligand for the reaction of 2a with 3a (entry 1). mides 3 was then examined (Table 3). The coupling with
Slower reaction rate or formation of a significant amount bromobenzene (3c) and para-substituted bromobenzenes
of 5a was observed with PCy2Ph, PCyPh2, and PPh3 (en- 3a and 3d–f was carried out in the presence of Pd–PCy3
tries 2–4). The reaction was also catalyzed well by elec- catalyst (entries 1–4, 7, and 9).9 These reactions were
tron-donating P(4-MeOC6H4)3, whereas the reaction rate completed within 4–10 hours, and the corresponding 4
was reduced by the use of electron-deficient P(4- was isolated in 61–77% yields. The results indicate that
CF3C6H4)3 (entries 5 and 6). It is interesting to note that the electronic property of the aryl groups (R4 and R5) did
phosphite ligands tended to promote protonative retro-al- not affect the reaction. On the other hand, coupling reac-
lylation (entries 7 and 8). Alkene 5a was selectively ob- tions with bulky aryl bromide 3b, 3g, and 3h also gave the
tained by a palladium catalyst bearing P(OPh)3 (entry 8). coupling product in high yields after 7–15 hours in the
The protonative retro-allylation took place with a Pd– presence of the Pd–PPh3 catalyst (entries 5, 6, 8, and 10).
P(OPh)3 catalyst even in the absence of aryl halides, giv-
ing 5a in 89% yield (entry 9).
Homoallylic alcohols 6 bearing a tetrasubstituted double
bond were subjected to retro-allylative coupling with 3a
When a bulky aryl bromide was used in the coupling reac- in the presence of Pd–PCy3 catalyst (Equation 2). The re-
tion, we observed different tendency of the ligands–selec- action of 6a (R3 = Ph) completed in six hours and gave the
tivity relationship. Thus, retro-allylative coupling of 2a desired product 7a in 30% yield along with a significant
with sterically hindered 2-bromo-1,3-dimethylbenzene amount of the protonated product 8a. On the other hand,
(3b) afforded 4b in only 19% yield along with major for- 6b (R3 = Me) gave 7b selectively (72%), despite the much
mation of 5a under the conditions using PCy3 (entry 1 in slower reaction rate.
Table 2). Improvement of the reaction yield was achieved
by the use of Pd–PCyPh2 or PPh3 catalysts, with which 4b
was obtained in good yields (entries 3 and 4).
Homoallylic alcohols 2 and 6 were also subjected to the
Pd–P(OPh)3 catalyst system that promotes the protonative
Synlett 2008, No. 3, 423–427 © Thieme Stuttgart · New York

LETTER
Cyanoboration via Palladium-Catalyzed Retro-Allylation
425
(entries 1–3). Although a slow reaction rate was observed
for the reaction of 6b, 8b was finally isolated in 97% yield
after 42 hours (entry 4). It should be noted that the palla-
dium-catalyzed retro-allylative coupling described above
and the protonative retro-allylation worked effectively for
the homoallylic alcohols bearing a tetrasubstituted double
bond (Equation 2 and entries 3 and 4 in Table 4), while the
previous study demonstrated the failure of the retro-ally-
lation of homoallylic alcohols bearing E-alkene moiety.4
Table 2 Screening of Ligand in Palladium-Catalyzed Retro-Allyla-
tive Coupling of 2a with Sterically Hindered 3ba
Me
Br
OMe
OMe
OMe
Me 3b
Pd(OAc)2 (5 mol%)
ligand (10 mol%)
Me
Me
OH
Me
+
CN
Me
CN
Cs2CO3, toluene
110 °C
n-Pr
CN
The present retro-allylative coupling reaction is remark-
able in that a substituted C=C bond including tetrasubsti-
tuted alkene is involved. To understand the high reactivity
of the present retro-allylation, we examined the reaction
of 9 (Equation 3). Homoallylic alcohol 9, which does not
have the aryl groups on the double bond, was subjected to
the retro-allylative coupling with 3b in the presence of the
Pd–PPh3 catalyst (Equation 3). The reaction proceeded
smoothly to afford alkene 10 in 69% yield, in contrast to
the poor reactivity of internal disubstituted alkenes such
as the (E)-pent-3-en-1-ol derivatives observed previous-
ly.4 This result clearly indicates that the cyano group en-
hances the reactivity of homoallylic alcohol in palladium-
catalyzed retro-allylation.
2a
4b
5a
Entry
Ligand
Time (h) Yield (%),b (E/Z)c
4b
5a
1
2
3
4
PCy3
3
19 (90:10)
44 (92:8)
29 (94:6)
4 (n.a.)d
3 (n.a.)
PCy2Ph
PCyPh2
PPh3
3
40 (89:11)
1
70 (89:11)
2.5
88 (84)e (87:13)
a Reaction conditions: Pd(OAc)2 (0.010 mmol), ligand (0.020 mmol),
Cs2CO3 (0.24 mmol), 2a (0.20 mmol), and 3b (0.24 mmol) were
stirred at 110 °C.
b GC yield.
The possible reaction mechanism for the retro-allylative
coupling is shown in Scheme 2. Oxidative addition of
Ar1Br to Pd(0) followed by the substitution of the halogen
atom on Pd with the alkoxide gives intermediate T. Retro-
allylation of T provides s-allylpalladium complex U,
which isomerizes to p-allylpalladium complex V. The fol-
lowing reductive elimination affords product W with re-
generation of Pd(0). The cyano group may decrease the
c Determined by 1H NMR of crude mixture.
d n.a.: not analyzed.
e Isolated yield.
retro-allylation (Table 4).10 The reactions of 2b, 2c, and
6a took place at 110 °C within two hours to give crotono-
nitrile derivatives 5b, 5c, and 8a in good to high yields
Table 3 Palladium-Catalyzed Retro-Allylative Coupling of 2a
Pd(OAc)2 (5 mol%)
R4
OH R4
ligand (10 mol%)
R5
R5Br
+
CN
Cs2CO3, toluene
110 °C
n-Pr
Me
CN
2
3
4
Entry
2
R5Br
Ligand
PCy3
PCy3
PCy3
PCy3
PPh3
PPh3
PCy3
PPh3
PCy3
PPh3
Time (h)
Product
4c
Yield (%),b (E/Z)c
68 (86:14)
63 (85:15)
67 (82:18)
77 (83:17)
61 (90:10)
60 (92:8)
1
2
2a
2a
2a
2a
2a
2a
2b
2b
2c
2c
PhBr (3c)
9
4
4-MeOC6H4Br (3d)
4d
4e
3
4-EtO2CC6H4Br (3e)
4
4
4-CF3C6H4Br (3f)
6
4f
5
2-MeC6H4Br (3g)
15
11
10
7
4g
6
1-bromonaphtalene (3h)
4h
4i
7
3a
3b
3a
3b
68 (84:16)
89 (90:10)
61 (82:18)
73 (90:10)
8
4j
9
8
4k
4l
10
7
a Reaction conditions: Pd(OAc)2 (0.010 mmol), ligand (0.020 mmol), Cs2CO3 (0.24 mmol), 2 (0.20 mmol), and 3 (0.24 mmol) were stirred at
110 °C.
b Isolated yield.
c Determined by 1H NMR of crude mixture.
Synlett 2008, No. 3, 423–427 © Thieme Stuttgart · New York

426
T. Ohmura et al.
LETTER
OMe
OMe
OMe
Me
Br
3a
Pd(OAc)2 (5 mol%)
PCy3 (10 mol%) Me
OH
Me
+
R3
Cs2CO3
toluene, 110 °C
CN
R3
CN
n-Pr
Me
R3
CN
6a (R3 = Ph)
7a 30%
8a 43%
(6 h, E/Z = 74:26)
7b 72%
(E/Z = 64:36)
8b < 10%
6b (R3 = Me)
(42 h, E/Z = 56:44)
Equation 2
NC
Table 4 Palladium-Catalyzed Protonative Retro-Allylation of 2
and 6a
Ar1
Ar1 Br
Ar2
Pd(0)
OH R4
R4
Pd(OAc)2 (5 mol%)
W
P(OPh)3 (10 mol%)
CN
R3
n-Pr
Me
Ar1
Pd
S
NC
Pd
Cs2CO3, toluene
110 °C
Me
R3
CN
5, 8
2, 6
Ar1
Br
Ar2
CN
OH
V
Entry Substrate R3 R4
Time Product Yield (%),b
(h)
(E/Z)c
Ar2
Ar1
Ar1
Pd
1
2
3
4
2b
2c
6a
6b
H
H
Ph
2
5b
5c
8a
8b
67 (89:11)
63 (89:11)
92 (62:38)
97 (33:67)
Ar1
CN
Ar2
CN
Ar2
Pd
CN
Ar2
O
4-EtO2CC6H4
2
Ph 4-MeOC6H4
Me 4-MeOC6H4
6
O
X
U
T
42
Scheme 2 Possible mechanism for retro-allylative coupling
a Reaction conditions: Pd(OAc)2 (0.010 mmol), P(OPh)3 (0.020
mmol), Cs2CO3 (0.24 mmol), and 2 or 6 (0.20 mmol) were stirred at
110 °C.
b Isolated yield.
Acknowledgment
c Determined by 1H NMR of crude mixture.
This work was supported by Grants-in-Aid for Scientific Research
on Priority Areas, ‘Advanced Molecular Transformations of Car-
bon Resources,’ Nos. 17065012 and 18037030, from the Ministry
of Education, Culture, Sports, Science and Technology, Japan.
Me
Br
Me
3b
OH
Me
Me (1.2 equiv)
References and Notes
CN
n-Pr
Pd(OAc)2 (5 mol%)
PPh3 (10 mol%)
Cs2CO3, toluene
110 °C, 10 h
(1) For reviews of temporary-tethering strategy, see: (a) Bols,
M.; Skrydstrup, T. Chem. Rev. 1995, 95, 1253.
Me
CN
9
10
(b) Fensterbank, L.; Malacria, M.; Sieburth, S. M. Synthesis
1997, 813. (c) Gauthier, D. R. Jr.; Zandi, K. S.; Shea, K. J.
Tetrahedron 1998, 54, 2289.
69% (E/Z = 41:59)
Equation 3
(2) For selected recent examples of silicon-tethered
intramolecular reaction, see: (a) Evans, P. A.; Baum, E. W.
J. Am. Chem. Soc. 2004, 126, 11150. (b) Chouraqui, G.;
Petit, M.; Aubert, C.; Malacria, M. Org. Lett. 2004, 6, 1519.
(c) Someya, H.; Kondoh, A.; Sato, A.; Ohmiya, H.;
Yorimitsu, H.; Oshima, K. Synlett 2006, 3061. (d) Ohmura,
T.; Furukawa, H.; Suginome, M. J. Am. Chem. Soc. 2006,
128, 13366. (e) Chen, C.-L.; Sparks, S. M.; Martin, S. F. J.
Am. Chem. Soc. 2006, 128, 13696. (f) Kim, Y. J.; Lee, D.
Org. Lett. 2006, 8, 5219.
(3) For examples of boron-tethered intramolecular reaction,
see: (a) Shimada, S.; Osoda, K.; Narasaka, K. Bull. Chem.
Soc. Jpn. 1993, 66, 1254. (b) Nicolaou, K. C.; Liu, J.-J.;
Yang, Z.; Ueno, H.; Sorensen, E. J.; Claiborne, C. F.; Guy,
R. K.; Hwang, C.-K.; Nakada, M.; Nantermet, P. G. J. Am.
Chem. Soc. 1995, 117, 634. (c) Batey, R. A.; Thadani, A.
rate of reductive elimination from U, leading to V via s–
p isomerization that is not involved in the retro-allylation
of cyano-free homoallylic alcohols.4
In summary, we have established a synthetic transforma-
tion of intramolecular cyanoboration products via C–C
bond formation by Suzuki–Miyaura coupling followed by
palladium-catalyzed retro-allylation. Efficient removal of
a tethering group used in intramolecular cyanoboration
was achieved through retro-allylation. Our new strategy,
which utilizes ‘intramolecular reaction with removable
tether’, allows collecting advantages of both the intra- and
intermolecular reactions such as high reaction efficiency,
selectivity, and wide reaction scope.
Synlett 2008, No. 3, 423–427 © Thieme Stuttgart · New York

LETTER
N.; Lough, A. J. J. Am. Chem. Soc. 1999, 121, 450.
Cyanoboration via Palladium-Catalyzed Retro-Allylation
427
enenitrile (4a): 1H NMR (400 MHz, CDCl3): d = 7.38 (d, J =
8.8 Hz, 2 H), 7.02–7.12 (m, 4 H), 6.83 (d, J = 8.8 Hz, 2 H),
(d) Batey, R. A.; Smil, D. V. Angew. Chem. Int. Ed. 1999,
38, 1798. (e) Micalizio, G. C.; Schreiber, S. L. Angew.
Chem. Int. Ed. 2002, 41, 3272. (f) Yamamoto, Y.; Ishii, J.;
Nishiyama, H.; Itoh, K. J. Am. Chem. Soc. 2005, 127, 9625.
(g) Yamamoto, A.; Suginome, M. J. Am. Chem. Soc. 2005,
127, 15706.
5.65 (s, 1 H), 4.16 (s, 2 H), 3.80 (s, 3 H), 2.28 (s, 3 H). 13
C
NMR (126 MHz, CDCl3): d = 161.6, 161.2, 136.3, 134.0,
129.5, 129.4 (2 × C), 128.20 (2 × C), 128.18 (2 × C), 118.0,
114.1 (2 × C), 94.8, 55.3, 39.0, 21.0. IR (neat): 2211 (CN),
1605 (C=C) cm–1. LRMS (EI): m/z = 263 (100) [M+], 248
(18), 158 (38), 133 (40), 105 (41). HRMS (EI): m/z [M+]
calcd for C18H17NO: 263.1310; found: 263.1311. The
geometry of the double bond was assigned as E by NOE
experiments.
(4) (a) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J.
Am. Chem. Soc. 2006, 128, 2210. (b) Iwasaki, M.; Hayashi,
S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem. Soc.
2007, 129, 4463. (c) Hayashi, S.; Hirano, K.; Yorimitsu, H.;
Oshima, K. J. Am. Chem. Soc. 2007, 129, 12650.
(5) For examples, see: (a) Tamao, K.; Maeda, K.; Tanaka, T.;
Ito, Y. Tetrahedron Lett. 1988, 29, 6955. (b) Murakami,
M.; Oike, H.; Sugawara, M.; Suginome, M.; Ito, Y.
Tetrahedron 1993, 49, 3933. (c) Suginome, M.; Kinugasa,
H.; Ito, Y. Tetrahedron Lett. 1994, 35, 8635. (d) Ojima, I.;
Vidal, E.; Tzamarioudaki, M.; Matsuda, I. J. Am. Chem. Soc.
1995, 117, 6797. (e) O’Malley, S. J.; Leighton, J. L. Angew.
Chem. Int. Ed. 2001, 40, 2915. (f) Denmark, S. E.; Pan, W.
Org. Lett. 2002, 4, 4163. (g) Trost, B. M.; Ball, Z. T. J. Am.
Chem. Soc. 2003, 125, 30.
(E)-4-(2,6-Dimethylphenyl)-3-(4-methoxyphenyl)but-2-
enenitrile (4b): 1H NMR (400 MHz, CDCl3): d = 7.06–7.11
(m, 3 H), 6.98–7.03 (m, 2 H), 6.78 (d, J = 8.8 Hz, 2 H), 5.49
(t, J = 1.2 Hz, 1 H), 4.17 (d, J = 1.2 Hz, 2 H), 3.78 (s, 3 H),
2.29 (s, 6 H). 13C NMR (126 MHz, CDCl3): d = 162.7, 160.6,
137.5 (2 × C), 133.5, 131.1, 128.3 (2 × C), 127.8 (2 × C),
127.1, 116.6, 113.7 (2 × C), 96.3, 55.2, 35.7, 20.5 (2 × C). IR
(KBr): 2207 (CN), 1605 (C=C) cm–1. LRMS (EI): m/z = 277
(80) [M+], 237 (100), 119 (40). HRMS (EI): m/z [M+] calcd
for C19H19NO: 277.1467; found: 277.1474. The geometry of
the double bond was assigned as E by NOE experiments.
(10) General Procedure for the Palladium-Catalyzed
Protonative Retro-Allylation of 2 (Entry 9 in Table 1 and
Table 4): Cesium carbonate was dried in vacuo by heating
with a heat gun prior to use. Under a nitrogen atmosphere, a
mixture of Pd(OAc)2 (0.010 mmol), P(OPh)3 (0.020 mmol),
Cs2CO3 (0.24 mmol), and 2 (0.20 mmol) was heated at
110 °C. The reaction was monitored by GC. After
consumption of 2, volatiles were removed and the crude
product was purified by PTLC.
(6) (a) Suginome, M.; Yamamoto, A.; Murakami, M. J. Am.
Chem. Soc. 2003, 125, 6358. (b) Suginome, M.; Yamamoto,
A.; Murakami, M. J. Organomet. Chem. 2005, 690, 5300.
(7) We have also developed intermolecular cyanoboration of
alkynes, see: Suginome, M.; Yamamoto, A.; Murakami, M.
Angew. Chem. Int. Ed. 2005, 44, 2380.
(8) Littke, A. F.; Dai, C.; Fu, G. C. J. Am. Chem. Soc. 2000, 122,
4020.
(9) General Procedure for the Palladium-Catalyzed Retro-
Allylative Coupling of 2 with 3 (Tables 1–3): Cesium
carbonate was dried in vacuo by heating with a heat gun
prior to use. Under a nitrogen atmosphere, a mixture of
Pd(OAc)2 (0.010 mmol), PCy3 or PPh3 (0.020 mmol),
Cs2CO3 (0.24 mmol), 2 (0.20 mmol), and 3 (0.24 mmol) was
heated at 110 °C. The reaction was monitored by GC.
Heating was stopped as soon as 2 was consumed, since
prolonged heating led to a drop in the product yield.
Volatiles were removed and the crude product was purified
by PTLC.
(E)-3-(4-Methoxyphenyl)but-2-enenitrile (5a): 1H NMR
(400 MHz, CDCl3): d = 7.41–7.45 (m, 2 H), 6.89–6.93 (m, 2
H), 5.55 (d, J = 0.8 Hz, 1 H), 3.85 (s, 3 H), 2.45 (d, J = 0.8
Hz, 3 H). 13C NMR (126 MHz, CDCl3): d = 161.3, 158.8,
130.4, 127.3 (2 × C), 118.1, 114.1 (2 × C), 93.2, 55.4, 20.0.
IR (KBr): 2205 (CN), 1603 (C=C) cm–1. LRMS (EI): m/z =
173 (100) [M+], 158 (41), 103 (35). HRMS (EI): m/z [M+]
calcd for C11H11NO: 173.0841; found: 173.0841. The
geometry of the double bond was assigned as E by NOE
experiments.
(E)-3-(4-Methoxyphenyl)-4-(4-methylphenyl)but-2-
Synlett 2008, No. 3, 423–427 © Thieme Stuttgart · New York

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