An unusual reaction of a pyridinium ylide with 1,1-dicyanoethylene derivatives

Article abstract of DOI:10.1246/cl.2008.628

A reaction of pyridinium perfluorophenacylide generated from pyridinium salt 1 with 1,1-dicyanoethylene derivatives 2 produced unusual products 3, which have an ylide structure with a cyano group at the C2 and a cis-acrylonitrile moiety at the o-position of the perfluorophenyl group. A plausible mechanism involving intramolecular aromatic nucleophilic substitution and 1,3-migration of the cyano group is proposed for this reaction. Copyright

Full text of DOI:10.1246/cl.2008.628

628
Chemistry Letters Vol.37, No.6 (2008)
An Unusual Reaction of a Pyridinium Ylide with 1,1-Dicyanoethylene Derivatives
Shinji Yamadaꢀ and Emiko Ohta
Department of Chemistry, Faculty of Science, Ochanomizu University, Bunkyo-ku, Tokyo 112-8610
(Received March 24, 2008; CL-080312; E-mail: yamada.shinji@ocha.ac.jp)
A reaction of pyridinium perfluorophenacylide generated
Table 1. Reaction of alkene 2 with a pyridinium ylide generat-
ed from 1
from pyridinium salt 1 with 1,1-dicyanoethylene derivatives 2
produced unusual products 3, which have an ylide structure with
a cyano group at the C2 and a cis-acrylonitrile moiety at the o-
position of the perfluorophenyl group. A plausible mechanism
involving intramolecular aromatic nucleophilic substitution
and 1,3-migration of the cyano group is proposed for this
reaction.
It has been reported that the reaction of a pyridinium ylide1
with an electron-deficient olefin produces indolidine2 or cyclo-
propane3 derivatives depending on the properties of the olefin
and the pyridinium nucleus. When benzylidenemalononitrile
is employed as an electrophile, cyclopropane is predominantly
produced,3 whereas, the reaction with acrylonitrile gives
indolidine derivatives (Scheme 1).2
We recently reported the first example of the enantioselec-
tive cyclopropanation of electron-deficient olefins with chiral
pyridinium ylide derivatives.4 In addition, we found that when
the phenacyl group was replaced with the perfluorophenacyl
group, the ylide became significantly stable and could be
isolated.5
Entry Alkene (equiv) Temp/ꢂC Time/h Yield of 3/%a
1
2
3
4
5
6
7
8
9
2a(1)
2a(1)
2a(1)
2a(2)
2a(2)
2a(3)
2b(2)
2c(2)
2d(2)
rt
rt
ꢁ40
rt
rt
rt
rt
rt
rt
24
3.5
53
15
n.r.
70
79
67
68
7b
24
16
24
18
24
24
24
25b
aIsolated yield. bThe rest is a complex mixture.
In this letter, we describe that the reaction of the stable
pyridinium perfluorophenacylide 4 generated from 1 with 1,1-di-
cyanoethylene derivatives 2 provided no expected cyclopro-
panes, but gave unexpected products 3.
The reaction of benzylidenemalononitrile (2a) and pyridini-
um salt 1 in the presence of Et3N afforded an unusual product
3a6 (Table 1). The structure of 3a was determined by X-ray
crystallographic analysis (Figure 1).7 It is remarkable that this
product has a cyano group at the C2 and an acrylonitrile moiety
at the o-position of the aromatic ring with Z configuration. Both
substituents could originate from the benzylidenemalononitrile
(2a). The planar geometry of C1 and C2, and the much shorter
˚
˚
1.391 A C1–C2 bond length and the much longer 1.239 A
C=O bond length than the corresponding general case8 strongly
suggest the ylide structure of 3.
The reaction required about 24 h at rt for completion; a
Figure 1. X-ray structure of 3a.
Z
shorter reaction time resulted in a significantly lower yield with
recovery of the ylide 4, and no reaction proceeded at ꢁ40 ꢂC
(Entries 2 and 3). The highest yield was obtained when two
equiv of the alkene was used at rt (Entry 5). The nucleophilic ad-
dition to 2b also gave a similar result (Entry 7). For the reactions
using alkyl-substituted olefins, 2c and 2d, similar products were
obtained despite the lower yields (Entries 8 and 9). All products
are obtained as a single stereoisomer about the olefinic moiety.
Scheme 2 outlines a plausible pathway for the formation of
product 3. The nucleophilic addition of the ylide 4 to the alkene
2a produces the intermediary betaine A. While a betaine with a
R
R
COPh
b
a
a
Z
Z
b
N
N
R
Z
COPh
COPh
R
N
COPh
Scheme 1. Two general reaction modes of a pyridinium ylide
with electron-deficient olefins.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.6 (2008)
629
um ylide. The reaction of pyridinium perfluorophenacylide
with 1,1-dicyanoethylene derivatives gave unusual adducts 3
via intramolecular aromatic nucleophilic substitution and 1,3-
migration of a cyano group.
This work was partly supported by a Grant-in-Aid for
Scientific Research (B) (no. 17350046) from the Japan Society
for the Promotion of Science.
References and Notes
1
For reviews, see: a) S. Wanda, Heterocycles 1996, 43, 2005.
b) A. Kakehi, J. Synth. Org. Chem. Jpn. 2005, 63, 222.
a) Y. Tamura, N. Tsujimoto, Y. Sumida, M. Ikeda, Tetra-
hedron 1972, 28, 21. b) T. Sasaki, K. Kanematsu, A. Kakehi,
G. Ito, Tetrahedron 1972, 28, 4947. c) O. Tsuge, S. Kanemasa,
S. Takenaka, Bull. Chem. Soc. Jpn. 1985, 58, 3137. d) S.
Kanemasa, S. Takenaka, H. Watanabe, O. Tsuge, J. Org.
Chem. 1989, 54, 420. e) L. Zhang, F. Liang, L. Sun, Y. Hu,
H. Hu, Synthesis 2000, 1733. f) K. Wu, Q.-Y. Chen, Synthesis
2003, 35. g) Z. Xia, T. Przewloka, K. Koya, M. Ono, S. Chen,
L. Sun, Tetrahedron Lett. 2006, 47, 8817.
2
3
4
a) A. M. Shestopalov, Y. A. Sharanin, V. P. Litvinov, O. M.
Nefedov, Zh. Org. Khim. 1989, 25, 1111. b) N. H. Vo, C. J.
Eyermann, C. N. Hodge, Tetrahedron Lett. 1997, 38, 7951.
c) S. Kojima, K. Fujitomo, Y. Shinohara, M. Shimizu, K.
Ohkata, Tetrahedron Lett. 2000, 41, 9847.
S. Yamada, J. Yamamoto, E. Ohta, Tetrahedron Lett. 2007, 48,
855.
5
6
S. Yamada, E. Ohta, Acta Crystallogr., Sect. C 2008, 64, o230.
3a: yellow crystal; mp 175.8–176.5 ꢂC; IR (KBr) 3094, 2213,
Scheme 2. Plausible reaction pathway for the formation of 3.
1
2187, 1572, 1467, 1389 cmꢁ1; H NMR (400 MHz, CDCl3) ꢁ
phenyl group (R = H) preferentially attacks the C2 to produce
cyclopropane 5 as reported in the literature,3 betaine A possess-
ing a perfluorophenyl group (R = F) undergoes an intramolecu-
lar aromatic nucleophilic substitution to give the intermediary
bicyclic product B. The deprotonation of the C2-proton would
produce the second ylide C. The anion-mediated cyano group
migration through a four-membered intermediate affords betaine
D. The Grob-type fragmentation9 of D results in the product
ylide 3a, the Z configuration of which would be a result of the
fragmentation controlled by the overlap between the ꢀꢀ orbital
of the C2–C3 bond and the sp3 orbital of the carbanion. The driv-
ing force of this rearrangement would be the formation of ylide
3a stabilized with a cyano group at C2.10 A similar 1,3-cyano
migration has been reported for the radical-mediated reactions
via the four-membered iminyl radical intermediate.11
9.29 (d, J ¼ 5:86 Hz, 2H), 8.03 (t, J ¼ 7:81 Hz, 1H), 7.87
(m, 2H), 7.79 (t, J ¼ 7:32 Hz, 2H), 7.45 (m, 4H); MS m=z
421 (Mþ, 0.4%), 369 (89), 338 (100), 242 (24), 195 (41), 94
(32), 57 (26). 13C NMR (100 MHz, CDCl3) ꢁ 92.8, 99.4,
116.4, 117.8, 119.2, 124.4, 126.7, 128.7, 129.3, 131.1, 132.6,
139.0, 139.2, 140.0, 142.4, 143.3, 145.8. 150.9, 168.9.
7
Crystallographic data for 3a: C23H11F4N3O, Mr ¼ 421:35,
monoclinic, P21=a, a ¼ 14:3211ð3Þ, b ¼ 7:08750ð10Þ, c ¼
ꢂ
3
˚
18:2058ð4Þ A, ꢂ ¼ 94:6735ð10Þ , V ¼ 1841:76ð6Þ A , T ¼
298 K, Z ¼ 4, Dcalcd ¼ 1:519 g cmꢁ1, A total of 27699 reflec-
tions were collected and 3356 are unique (Rint ¼ 0:057). R1
and wR2 are 0.0630 [I > 2ꢀðIÞ] and 0.2225 (all data), respec-
tively. CCDC 682165.
8
9
F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G.
Orpen, R. Taylor, J. Chem. Soc., Perkin Trans. 2 1987, S1.
For a review, see: C. A. Grob, P. W. Schiess, Angew. Chem.,
Int. Ed. Engl. 1967, 6, 1.
When methyl acrylate was used as an electrophile, the 1,3-
dipolar addition proceeded to give the tetrahydroindolidine
and indolidine derivatives in 11 and 35% yields, respectively
(Scheme 3). The structure of the indolidine 6 was confirmed
by X-ray structural analysis.12 It should be noted that no product
related to 3 was obtained in this reaction.
10 The role of a cyano group on the stabilization of pyridinium
ylides is established: a) Y. Karzazi, G. Surpateanu, C. N.
Lungu, G. Vergoten, J. Mol. Struct. 1997, 406, 45. b) Y.
Karzazi, G. Vergoten, G. Surpateanu, J. Mol. Struct. 1997,
435, 35.
In summary, we found a new type of reaction with pyridini-
11 A. Bury, P. Bougeard, S. J. Corker, M. D. Johnson, M.
Perlmann, J. Chem. Soc., Perkin Trans. 2 1982, 1367.
12 Crystallographic data for 6: C17H8F5NO3, Mr ¼ 369:25,
monoclinic, P21=c, a ¼ 7:0294ð5Þ, b ¼ 23:8012ð17Þ, c ¼
CO2Me
CO2Me
Et3N
1
CO2Me
N
CH2Cl2
18:4727ð13Þ A, ꢂ ¼ 94:405ð3Þꢂ, V ¼ 3081:5ð4Þ A3, T ¼
N
˚
COC6F5
COC6F5
298 K, Z ¼ 8, Dcalcd ¼ 1:592 g cmꢁ1, A total of 45501 reflec-
tions were collected and 5399 are unique (Rint ¼ 0:107). R1
and wR2 are 0.0736 [I > 2ꢀðIÞ] and 0.2311 (all data), respec-
tively. CCDC 682166.
11%
5
35%
6
Scheme 3. Reaction of 1 with methyl acrylate in the presence
of Et3N.
Published on the web (Advance View) May 10, 2008; doi:10.1246/cl.2008.628