Palladium catalyzed regioselective β-acetonation-α-allylation of activated olefins in one shot

Article abstract of DOI:10.1021/jo981719g

The reaction of certain activated olefins 4 with allyl acetoacetate 5 in the presence of catalytic amounts of Pd(PPh₃)₄ (5 mol %) in THF at room temperature gave the corresponding β-acetonated α-allylated double addition products 6 regioselectively in good to excellent yields. The nature of the electron-withdrawing group in activated olefins affected significantly the reactivity of substrates; at least one of two electron-withdrawing groups of 4 should be a CN group. A proposed mechanism for this unprecedented three- component coupling reaction involves oxa-π-allyl-π-allylpalladium intermediate 3a (or its synthetic equivalents 3b-d). The in situ generation of activated olefins 4, from the aldehyde 11 and malononitrile 12, followed by the palladium-catalyzed reaction with allyl acetoacetate 5 also worked well, producing the corresponding three-component coupling products in good yields. Furthermore, allyltributylstannane 13 and α-chloro acetone 14 could be used as the α-allylation and β-acetonation components, respectively, instead of allyl acetoacetate 5. The scope and limitations of palladium- catalyzed regioselective β-acetonation-α-allylation reaction of activated olefins are described.

Full text of DOI:10.1021/jo981719g

8470
J . Org. Chem. 1998, 63, 8470-8474
P a lla d iu m Ca ta lyzed Regioselective â-Aceton a tion -r-Allyla tion of
Activa ted Olefin s in On e Sh ot
J ae-Goo Shim, Hiroyuki Nakamura, and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, J apan
Received August 24, 1998
The reaction of certain activated olefins 4 with allyl acetoacetate 5 in the presence of catalytic
amounts of Pd(PPh3)4 (5 mol %) in THF at room temperature gave the corresponding â-acetonated
R-allylated double addition products 6 regioselectively in good to excellent yields. The nature of
the electron-withdrawing group in activated olefins affected significantly the reactivity of substrates;
at least one of two electron-withdrawing groups of 4 should be a CN group. A proposed mechanism
for this unprecedented three-component coupling reaction involves oxa-π-allyl-π-allylpalladium
intermediate 3a (or its synthetic equivalents 3b-d ). The in situ generation of activated olefins 4,
from the aldehyde 11 and malononitrile 12, followed by the palladium-catalyzed reaction with allyl
acetoacetate 5 also worked well, producing the corresponding three-component coupling products
in good yields. Furthermore, allyltributylstannane 13 and R-chloro acetone 14 could be used as
the R-allylation and â-acetonation components, respectively, instead of allyl acetoacetate 5. The
scope and limitations of palladium-catalyzed regioselective â-acetonation-R-allylation reaction of
activated olefins are described.
In tr od u ction
carbon-carbon or carbon-heteroatom bonds under neu-
tral or basic conditions. In addition, the carbon nucleo-
philes of organometallic compounds such as Zn,7 B,8 Al,9
Sn,10 and Si11 can react with π-allylpalladium complexes
1 via transmetalation.
Meanwhile, we recently reported the catalytic double
allylation of activated olefins via an amphiphilic bis-π-
allylpalladium intermediate 2.12 In this instance, one of
the two allyl moieties acted as a nucleophile and the
another as an electrophile toward certain Michael ac-
ceptors, giving the â- and R-double-allylated derivatives
of the activated olefins (Scheme 1).
The carbon-carbon bond-forming reaction is one of the
most powerful tools for making new compounds and for
developing creative synthetic methodologies. Such a
reaction is in general most useful and efficient when
performed catalytically. The use of organometallic com-
pounds for catalytic carbon-carbon bond-forming reac-
tions is quite attractive because the metal may activate
the ligated organic moiety intrinsically and facilitate the
desired reaction.1 Among the complexes of a variety of
transition metals for carbon-carbon bond formation
employed previously, palladium complexes have been
most often used because they display wide reactivity and
higher selectivity than other transition-metal com-
plexes.2,3 Particularly, reactive π-allylpalladium com-
plexes 1 are useful reaction intermediates for the above-
mentioned purposes. In general,π-allylpalladium complexes
1 are electrophilic and react with various nucleophiles
such as malonates,4 â-keto esters,5 and amines6 to form
This result prompted us to search for oxa-π-allyl-π-
allylpalladium intermediate 3a (or its synthetic equiva-
lents 3b-d , vide post) as an unsymmetric and function-
alized version of the amphiphilic bis-π-allylpalladium 2.
(6) (a) Atkins, K. E.; Walker, W. E.; Manyik, R. M. Tetrahedron Lett.
1970, 3821. (b) Trost, B. M., Genet, J . P. J . Am. Chem. Soc. 1976, 98,
8516. (c) Gundersen, L.; Bennehe, T.; Undheim, K. Tetrahedron Lett.
1992, 33, 1085.
(1) Davies, S. G. Organotransition Metal Chemistry, Application to
Organic Synthesis; Pergamon Press: New York, 1982; p 116. (b)
Mcquillin, F. J .; Parker, D. G.; Richard Stepenson, G. Transition metal
organometallics for organic synthesis; Cambridge University Press:
New York, 1991; p 95.
(2) For general reviews: (a) Trost, B. M.; Verhoeven, T. R. Com-
prehensive Organometallic Chemistry; Wilkinson, G., Stone, F. G. A.,
Abel, E. W., Eds.; Pergamon Press: New York, 1982; Vol. 8, p 799. (b)
Heck, R. F. Palladium Reagents in Organic Synthesis, Academic
Press: London, 1987; p 117. (c) Tsuji, J . Palladium Reagents and
Catalysts, J ohn Wiley & Sons: Chichester, 1995; p 290. (d) Trost, B.
M. Angew. Chem. 1995, 107, 285; Angew. Chem., Int. Ed. Engl. 1995,
34, 259.
(3) (a) Trost, B. M.; Molander, G. A. J . Am. Chem. Soc. 1981, 103,
5969. (b) Tsuji, J .; Shimiju, I.; Minami, I.; Ohashi, Y.; Sugiura, T.;
Takahashi, K. J . Org. Chem. 1985, 50, 1523. (c) Tsuda, T.; Okada, M.;
Nishi, S.; Saegusa, T. J . Org. Chem. 1986, 51, 412. (d) Masuyama, Y.;
Takahara, J . Kurusa, Y. J . Am. Chem. Soc. 1988, 110, 4473.
(4) (a) Reference 2c. (b) Bosnich, B.; Mackenzie, P. B. Pure Appl.
Chem. 1982, 54, 189. (c) Nilson, Y. I. M.; Anderson, P. G.; Backwall,
J . E. J . Am. Chem. Soc. 1993, 115, 6609.
(7) (a) Kitazume, T.; Ishikawa, N. Chem. Lett. 1982, 137. (b) Erdik,
E. Tetrahedron 1992, 48, 9577. (c) Negishi, E.; Matsushita, H. J . Am.
Chem. Soc. 1981, 103, 2882. (d) Chatterjee, S.; Negishi, E. J . Org.
Chem. 1985, 50, 3406.
(8) (a) Miyaura, N.; Suginome, H.; Suzuki, A. Tetrahedron Lett.
1984, 25, 1543. (b) Legros, J . Y.; Fiaud, J . C. Tetrahedron Lett. 1990,
31, 7453. (c) Godschalx, J .; Stille, J . K. Tetrahedron Lett. 1980, 21,
2599. 1983, 24, 1905.
(9) Reference 7c,d.
(10) (a) Sheffy, F. K.; Stille, J . K. J . Am. Chem. Soc. 1983, 105, 7173.
(b) Sheffy, F. K.; Godschalx, J .; Stille, J . K. J . Am. Chem. Soc. 1984,
106, 4833. (c) Farina, V.; Baker, S. R.; Benigni, D, A.; Sapino, C., J r.
Tetrahedron Lett. 1988, 29, 5739. (d) Kosugi, M.; Ohashi, K.; Akazawa,
K.; Sano, H.; Migita, T. Chem. Lett. 1987, 1237. (e) Trost, B. M.; Keinan,
E. Tetrahedron Lett. 1980, 21, 2591, 2595.
(11) (a) Tsuji, Y.; Yamada, N.; Tanaka, S. J . Org. Chem. 1993, 58,
16. (b) Yoshida, J .; Tamao, K.; Takahashi, M.; Kumada, M. Tetrahedron
Lett. 1978, 19, 2161. (c) Tamao, K.; Kakui, T.; Kumada, M. Tetrahedron
Lett. 1978, 19, 619. (d) Tsuji, J .; Takahashi, K.; Minami, I.; Shimizu,
I. Tetrahedron Lett. 1984, 25, 4783.
(12) Nakamura, H.; Shim, J .-G.; Yamamoto, Y. J . Am. Chem. Soc.
1997, 119, 8113. See also: Nakamura, H.; Iwama, H.; Yamamoto, Y.
J . Am. Chem. Soc. 1996, 118, 6641.
(5) (a) Tsuji, J .; Takahashi, H.; Morikawa, M. Tetrahedron Lett.
1965, 4387. (b) Tsuji, J . Acc. Chem. Res. 1969, 2, 144.
10.1021/jo981719g CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/27/1998

â-Acetonation-R-Allylation of Activated Olefins
J . Org. Chem., Vol. 63, No. 23, 1998 8471
Ta ble 2. P d Ca ta lyzed â-Aceton a tion -r-Allyla tion of 4
Sch em e 1
w ith 5a
Ta ble 1. P d -Ca ta lyzed â-Aceton a tion -r-Allyla tion of
Ben zylid en em a lon on itr ile 4a w ith Allyl Acetoa ceta te 5a
entry
catalyst
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
solvent
yield of 6a ,b %
1
2d
3e
4
5
6
7
8
9
10
THF
THF
THF
CH3CN
EtOH
CH2Cl2
toluene
THF
97 (89)c
71
94
74
54
47
<5
no reaction
54
69
Pd2(dba)3‚CHCl3
Pd2(dba)3‚CHCl3-2DPPE
Pd2(dba)3‚CHCl3-2DPPB
THF
THF
a
All reactions were conducted at room temperature for 2 h in
the presence of 5 mol % of catalyst, except where otherwise
indicated. b 1H NMR yield. p-Xylene was used as an internal
d
standard. c Isolated yield, based on 4a . The reaction was carried
out at 40 oC for 1 d. e The reaction was carried out at 70 oC for 2
h.
After a number of trials, we found that the reaction of
certain activated olefins 4 with allyl acetoacetate 5 in
the presence of Pd(PPh3)4 catalyst gave the â-acetona-
tion-R-allylation products 6 in one shot in high chemical
yields (eq 1).13-15
a
Reactions were conducted in THF at room temperature.
Isolated yield, based on 4. c Diastereomeric ratios were indicated
b
in parentheses and the stereochemistries of those isomers were
not determined since the selectivities were low.
5 mol % of Pd(PPh3)4 gave 6a in 94% 1H NMR yield, while
1
the reaction at 40 °C for 1 day afforded 6a in 71% H
NMR yield (entries 2 and 3). The use of CH3CN, EtOH,
1
and CH2Cl2 as a solvent gave 6a in 47-74% H NMR
yields (entries 4-6), while the use of toluene afforded 6a
in less than 5% yield (entry 7). The reaction did not
proceed in the presence of Pd2(dba)3‚CHCl3 catalyst (entry
8). A palladium-bidentate phosphine ligand system,
such as Pd2(dba)3‚CHCl3-2DPPE or Pd2(dba)3‚CHCl3-
2DPPB, was also tested (entries 9-10), but the yields of
6a were lower than those in the case of Pd(PPh3)4. Other
transition metal catalysts, such as Ni(PPh3)2(CO)2, RuCl2-
(PPh3)3, and RhCl(PPh3)3, were totally ineffective. As a
result of extensive examination of various reaction condi-
tions, we found that the reaction of benzylidenemalono-
nitrile 4a with allyl acetoacetate 5 proceeded very
smoothly at room temperature in the presence of Pd-
(PPh3)4 catalyst in THF to give the corresponding â-ac-
etonated and R-allylated product 6a in good yields.16
Resu lts a n d Discu ssion
The reaction of benzylidenemalononitrile 4a (0.5 mmol)
with allyl acetoacetate 5 (1.2 equiv) in THF in the
presence of Pd(PPh3)4 (5 mol %) at room temperature was
monitored by analytical TLC, and the starting material
4a was consumed completely after 2 h. GLPC analysis
of the reaction mixture revealed that 5,5-dicyano-4-
phenyl-7-octen-2-one 6a was produced in essentially
quantitative yield. Purification with silica gel column
chromatography using n-hexane-ethyl acetate (10:1) as
eluent gave 6a in 89% isolated yield (Table 1, entry 1).
The reaction at 70 °C for 2 h in THF in the presence of
(13) The palladium(II) enolate complex may be formally expressed
in three different structures: (1) palladiun(II) enolate, (2) oxa-π-
allylpalladium(II), and (3) 2-oxoalkylpalladium(II) complex. See also:
(a) Tsuda, T.; Chujo, Y.; Nishi, S.-I.; Tawara, K.; Saegusa, T. J . Am.
Chem. Soc. 1980, 102, 6381. (b) Reference 10c.
(14) It was reported that palladium catalysts induced decarboxyla-
tion of allylic â-keto carboxylates to produce R-allylic ketones via a
π-allylpalladium enolate; ref 13a.
The results for a variety of substrates are shown in
Table 2. The activated olefins 4a -d bearing two CN
groups reacted effectively with allyl acetoacetate 5 to
afford the desired products 6a -d in good to excellent
yields (entries 1-4). The application of this methodology
(15) (a) Shimizu, I.; Yamada, T.; Tsuji, J . Tetrahedron Lett. 1980,
21, 3199. (b) Tsuji, J .; Minami, I.; Shimizu, I. Tetrahedron Lett. 1983,
24, 1793.
(16) In the case of compound 4a , the use of Pd(OAc)2, PdCl2(PPh3)2,
and PdCl2(PhCN)2 did not induce the desired reaction.

8472 J . Org. Chem., Vol. 63, No. 23, 1998
Shim et al.
Sch em e 2
onic complex 10). The reductive elimination of Pd(0)
would give the desired double-addition products 6.19
In general, activated olefins 4 were synthesized from
the reaction of aldehydes and acidic methylene com-
pounds. The Michael acceptors containing active protons
at the γ-position of activated olefins could not be prepared
in allowable yields. Therefore, the substrates that have
no γ-protons were utilized in Table 2. The reason for this
instability of such substrates is not clear, but the pres-
ence of TBAF during the isolation step may cause the
decomposition of the product. Accordingly, we attempted
the in situ generation of the olefins followed by the
palladium catalyzed double addition (all in one pot) (eq
2).
to activated olefins 4e,f having CN and CO2Et as
electron-withdrawing groups afforded the desired double-
addition products 6e-f as the major product along with
minor amounts of the monoaddition products 7a -b
(entries 5-6). In the case of 4a ,b, even the use of 1 mol
% of the catalyst was enough to complete the reaction;
6a and 6b were obtained in 81% and 81% yield, respec-
tively.
Cyclohexyl carboxaldehyde 11b was treated with ma-
lononitrile 12 in THF in the presence of tetrabutylam-
monium fluoride (TBAF) (10 mol %) at room temperature
for 1 h. The reaction progress was monitored by TLC.
After the malononitrile 12 was consumed completely, 5
mol % of Pd(PPh3)4 and allyl acetoacetate 5 (1.2 equiv)
were added successively. The resulting mixture was
stirred at room temperature for an additional 1 h. The
mixture was then extracted with Et2O. The organic layer
was dried over MgSO4, concentrated in vacuo, and
subjected to column chromatography on silical gel using
n-hexane-ethyl acetate (10:1) as eluent. The desired
compound 6g was obtained as a light yellow oil (74%).
Very similarly, isobutyraldehyde 11c underwent the
condensation and subsequent acetonation-allylation
smoothly to give the desired product 6h in 63% yield. By
a similar procedure, benzaldehyde 11a afforded 6a in
66% yield. However, the reaction using n-hexanal 11d
afforded 6i in 48% yield. It seems that n-pentyleth-
ylidenemalononitrile was decomposed slowly under the
reaction conditions even prepared in situ from the
n-hexanal 11d and malononitrile 12.
When other activated olefins, such as RCHdCHCO2-
Et and RCHdC(CO2Et)2, or simple olefins were used, no
double addition products were obtained, and the starting
activated or nonactivated olefins were recovered. How-
ever, as shown above, the present double-addition reac-
tion smoothly proceeded when we used cyano-substituted
activated olefins, such as RCHdC(CN)2 and RCHd
C(CN)(CO2Et). This difference on the reactivity of acti-
vated olefins may be explained by the concept of steric
inhibition of resonance proposed by Boeckman;17 com-
plete coplanarity of two esters is difficult due to the steric
interaction, but the small cyano produces much less
disruption than the ester overlap and the coplanarity can
be maintained. Accordingly, the carbanion intermediate
10 (vide infra) is more stabilized in the case of the CN
substituted olefins, promoting the double-addition reac-
tion.
A mechanistic rationale for the present three-compo-
nent coupling reaction is shown in Scheme 2. The
oxidative addition of Pd(0) to allyl acetoacetate 5 would
afford π-allylpalladium â-keto carboxylate 8,18 which
would undergo decarboxylation to produce oxa-π-allyl-π-
allylpalladium intermediate 3a (or its synthetic equiva-
lents 3b-d ). It is not possible at the present time to
make clear which is the real intermediate. Activated
olefins 4 would react with this intermediate to give the
corresponding â-acetonated derivative 9 (or its zwitteri-
Furthermore, it occurred to us that the three-compo-
nent coupling reaction may take place by using R-halo
ketone and allyltributylstannane as an acetonate and an
allyl source, respectively. After screening the various
reaction conditions, we found that the reaction of acti-
vated olefins 4 (0.5 mmol), allyltributylstannane 13 (1.2
equiv), and R-chloro acetone 14 (1.2 equiv) took place in
the presence of Pd(PPh3)4 (10 mol %) at 70 °C to give the
corresponding regioselective â-acetonation-R-allylation
products 6 in moderate to good yields (eq 3).
(17) Boeckman, R. K., J r.; Ko, S. S. J . Am. Chem. Soc. 1982, 104,
1033. See also: Shim, J .-G.; Yamamoto, Y. J . Org. Chem. 1998, 63,
3067.
(18) (a) Shimizu, I.; Tsuji, J . J . Am. Chem. Soc. 1982, 104, 5844. (b)
Nokami, J .; Watanabe, H.; Mandai, T.; Kawada, M.; Tsuji, J . Tetra-
hedron Lett. 1989, 30, 4829.
(19) Reductive elimination of Pd(0) from π-allylpalladium complexes,
in which a π-allyl group and a stabilized carbanion are coordinated to
palladium, is known. (a) Takahashi, Y.; Sakai, S.; Ishii, Y. Chem.
Commun. 1967, 1092. (b) Hata, G.; Takahashi, K.; Miyake, A. J . Org.
Chem. 1971, 36, 2116. (c) J olly, P. W.; Mynott, R.; Raspel, B.; Schick,
K.-P. Organometallics 1986, 5, 473. (d) Reference 12.

â-Acetonation-R-Allylation of Activated Olefins
J . Org. Chem., Vol. 63, No. 23, 1998 8473
was isolated in 66% yield (0.084 g) by column chromatography
on silica gel using n-hexane-ethyl acetate (10:1) as eluent.
Th r ee-Com p on en t Rea ction of Activa ted Olefin s 4,
Allyltr ibu tylsta n n a n e 13 a n d r-Ch lor o Aceton e 14 Ca ta -
lyzed by P d (0). The synthesis of 6a from 4a is representa-
tive. To a solution of 4a (0.077 g, 0.5 mmol), allyltributyl-
stannane 13 (0.199 g, 0.6 mmol), and Pd (PPh3)4 (0.578 g, 10
mol %) in THF (5 mL) was added R-chloro acetone 14 (0.048
mL, 0.6 mmol) at room temperature under argon atmosphere.
The reaction mixture was moved to a preheated (70 °C) oil
bath and then stirred for 1 day at that temperature. The
reaction mixture was quenched with water and then extracted
with Et2O. The organic layer was dried over MgSO4 and
concentrated in vacuo. The resulting crude oil was treated
with EtOAc and a saturated KF solution. The mixture was
stirred for 5 h and then extracted with Et2O. The organic layer
was washed with a saturated NaCl solution, dried over MgSO4,
and concentrated in vacuo. The product 6a was isolated in
62% yield (0.079 g) by column chromatography on silica gel
using n-hexane-ethyl acetate (10:1) as eluent.
Con clu sion s
5,5-Dicya n o-4-p h en yl-7-octen -2-on e (6a ): white solid;
The results presented here are intrinsically interesting
and useful as a new carbon-carbon bond-forming method.
The two organic components of the oxa-π-allyl-π-allylpal-
ladium complex 3a (or its synthetic equivalents 3b-d )
are completely utilized for the addition reaction, and
thus, the present three-component coupling is an atom
economic reaction. The ordinary Michael addition fol-
lowed by alkylation inevitably needs displacement step
at the alkylation stage, which leads to release of a leaving
group.20
1
mp 64-65 °C; H NMR (CDCl3) δ 7.38 (s, 5H), 5.94-5.80 (m,
1H), 5.36 (m, 2H), 3.75 (dd, 1H, J ) 3.6, 10.0 Hz), 3.39 (dd,
1H, J ) 10.0, 17.4 Hz), 3.17 (dd, 1H, J ) 3.6, 17.4 Hz), 2.47
(dd, 1H, J ) 7.2, 13.9 Hz), 2.35 (dd, 1H, J ) 7.2, 13.9 Hz),
2.11 (s, 3H); 13C NMR (CDCl3) δ 203.401, 135.316, 129.180,
129.098, 128.802, 128.530, 123.307, 115.091, 114.326, 45.961,
45.837, 42.868, 40.253, 30.597; HRMS calcd for C16H16N2O
252.1261, found 252.1260. Anal. Calcd: C, 76.165; H, 6.392;
N, 11.103. Found: C, 76.439; H, 6.560; N, 11.128.
5,5-Dicya n o-4-(2-fu r yl)-7-octen -2-on e (6b): white solid;
1
mp 50-51 °C; H NMR (CDCl3) δ 7.42 (m, 1H), 6.39 (m, 2H),
5.95-5.81 (m, 1H), 5.38 (m, 2H), 3.95 (dd, 1H, J ) 3.3, 10.5
Hz), 3.38 (dd, 1H, J ) 10.5, 17.5 Hz), 3.08 (dd, 1H, J ) 3.3,
17.5 Hz), 2.57-2.42 (m, 2H), 2.17 (s, 3H); 13C NMR (CDCl3) δ
202.956, 148.441, 143.177, 128.241, 123.355, 114.448, 113.765,
110.747, 109.974, 43.846, 41.987, 39.643, 30.151; IR (neat)
2971, 2248, 1720, 1419, 1168, 746 cm-1; HRMS calcd for
Exp er im en ta l Section
Gen er a l In for m a tion . All solvents were purified and
dried before use according to standard procedures. Reactions
were conducted under an argon atmosphere in oven-dried
glassware. The starting activated olefins (4) were prepared
by the Knoevenagel condensation of aldehydes with acidic
methylenes. Allyl acetoacetate (5) was purchased from Merck
Co. Allyltributylstannane (13) and R-chloro acetone (14) were
purchased from Aldrich Chemical Co. Pd(PPh3)4 was prepared
according to the method in the literature.21
Gen er a l P r oced u r e (5,5-Dicya n o-4-p h en yl-7-oct en -2-
on e, 6a ). To a solution of 4a (0.077 g, 0.5 mmol) and Pd(PPh3)4
(0.289 g, 0.025 mmol) in THF (5 mL) was added 5 (0.082 mL,
0.6 mmol) at room temperature under argon atmosphere, and
the mixture was stirred for 2 h. The reaction progress was
monitored by TLC, and reaction mixture was quenched with
water when the starting ethylidene malononitrile 4a was
consumed completely. The mixture was extracted with Et2O
and dried over MgSO4. After the usual workup, the analyti-
cally pure product 6a was isolated in high yield (0.112 g, 89%)
by column chromatography on silica gel using n-hexane-ethyl
acetate (10:1) as eluent.
On e-P ot Rea ction of Ald eh yd e 11, Ma lon on itr ile 12,
a n d Allyl Acetoa ceta te 5 Ca ta lyzed by P d (0). The syn-
thesis of 6a from 11a is representative. A mixture of 11a
(0.051 mL, 0.5 mmol), malononitrile 12 (0.033 g, 0.5 mmol),
and tetrabutylammonium fluoride (TBAF) (0.050 mL, 0.05
mmol) in 1 M THF solution was dissolved in THF (5 mL) at
room temperature under argon atmosphere. The reaction
mixture was stirred for 2 h. The reaction progress was
monitored by TLC. After malononitrile 12 was consumed
completely, Pd(PPh3)4 (0.289 g, 0.025 mmol) and allyl acetoac-
etate 5 (0.082 mL, 0.6 mmol) were added successively. The
resulting mixture was stirred at room temperature for ad-
ditional 2 h. Then the mixture was extracted with Et2O and
dried over MgSO4. After the usual workup, the product 6a
C
14H14N2O2 242.1054, found 242.1049. Anal. Calcd: C,
69.406; H, 5.824; N, 11.563. Found: C, 69.285; H, 6.113; N,
11.415.
5,5-Dicya n o-4-(m -m eth oxyp h en yl)-7-octen -2-on e (6c):
1
white solid; mp 96-97 °C; H NMR (CDCl3) δ 7.30 (m, 2H),
6.90 (m, 2H), 5.94-5.80 (m, 1H), 5.35 (m, 2H), 3.80 (s, 3H),
3.70 (dd, 1H, J ) 3.6, 10.2 Hz), 3.35 (dd, 1H, J ) 10.2, 17.2
Hz), 3.14 (dd, 1H, J ) 3.6, 17.2 Hz), 2.48 (dd, 1H, J ) 7.0,
14.0 Hz), 2.34 (dd, 1H, J ) 7.0, 14.0 Hz), 2.11 (s, 3H); 13C NMR
(CDCl3) δ 203.531, 159.923, 129.845, 128.554, 126.974, 123.150,
115.114, 114.456, 114.366, 55.212, 45.926, 45.219, 42.974,
40.153, 30.587; IR (neat) 2966, 2243, 1716, 1515, 1258, 837
cm-1; HRMS calcd for C17H18N2O 281.1368, found 242.1381.
5,5-Dicya n o-4-(2-n a p h th yl)-7-octen -2-on e (6d ): colorless
1
oil; H NMR (CDCl3) δ 7.84 (m, 4H), 7.52 (m, 3H), 5.95-5.81
(m, 1H), 5.34 (m, 2H), 3.93 (dd, 1H, J ) 3.3, 10.3 Hz), 3.52
(dd, 1H, J ) 10.3, 17.4 Hz), 3.26 (dd, 1H, J ) 3.3, 17.4 Hz),
2.50 (dd, 1H, J ) 7.3, 14.0 Hz), 2.36 (dd, 1H, J ) 7.3, 14.0
Hz), 2.11 (s, 3H); 13C NMR (CDCl3) δ 203.359, 133.299,
133.110, 132.649, 129.088, 128.471, 128.364, 128.109, 127.665,
126.851, 126.744, 125.848, 123.314, 115.122, 114.374, 46.107,
45.992, 42.842, 40.292, 30.571; IR (neat) 3059, 2928, 2247,
1722, 1364, 1167, 756 cm-1; HRMS calcd for C20H18N2O
302.1418, found 302.1430.
Eth yl 2-cya n o-2-a llyl-3-(m -m eth oxyp h en yl)-5-oxoh ex-
a n oa te (6e): yellowish green oil; 1H NMR (CDCl3) δ 7.26 (m,
1H, minor diastereomer), 7.20 (m, 1H, minor diastereomer),
6.95 (m, 3H, major diastereomer), 6.83 (m, 3H, monor diaste-
reomer), 5.74 (m, 1H, minor diastereomer), 5.69 (m, 1H, major
diastereomer), 5.25 (m, 2H, minor diastereomer), 5.12 (m, 2H,
major diastereomer), 4.28 (q, 2H, major diastereomer, J ) 7.1
Hz), 3.92 (q, 2H, minor diastereomer, J ) 7.1 Hz), 3.81 (s, 3H,
major diastereomer), 3.78 (s, 3H, minor diastereomer), 3.74
(m, 2H, major and 1H, minor diastereomer), 3.27 (m, 1H, minor
diastereomer), 3.22 (m, 1H, minor diastereomer), 3.02 (dd, 1H,
minor diastereomer J ) 4.0, 7.4 Hz), 2.80 (m, 1H, minor
diastereomer), 2.74 (m, 1H, major diastereomer), 2.58 (dd, 1H,
(20) The present reaction releases CO2 from 5, and instead, the two
carbon atoms of the activated olefins are introduced into the position
at which CO2 occupied in 5.
(21) Coulson, D. R. Inorg. Synth. 1972, 13, 121.

8474 J . Org. Chem., Vol. 63, No. 23, 1998
Shim et al.
minor diastereomer, J ) 6.8, 13.6 Hz), 2.47 (dd, 1H, major
diastereomer, J ) 8.1, 13.8 Hz), 2.09 (s, 3H, minor diastere-
omer), 2.05 (s, 3H, major diastereomer), 1.33 (t, 3H, major
diastereomer, J ) 7.1 Hz), 0.98 (t, 3H, minor diastereomer, J
) 7.1 Hz); IR (neat) 2984, 2243, 1740, 1722, 1222 cm-1; HRMS
calcd for C19H23NO4 329.1627, found 329.1642. Anal. Calcd:
C, 69.281; H, 7.038; N, 4.252. Found: C, 69.210; H, 7.406; N,
4.230.
HRMS calcd for C16H22N2O 258.1730, found 258.1728. Anal.
Calcd: C, 74.382; H, 8.583; N, 10.843. Found: C, 74.094; H,
8.409; N, 11.053.
5,5-Dicya n o-4-isop r op yl-7-octen -2-on e (6h ): light yellow
1
oil; H NMR (CDCl3) δ 5.99-5.85 (m, 1H), 5.41 (m, 2H), 2.75
(m, 2H), 2.65-2.50 (m, 3H), 2.32 (m, 1H), 2.26 (s, 3H), 1.05
(d, 3H, J ) 6.8 Hz), 0.90 (d, 3H, J ) 6.8 Hz); 13C NMR (CDCl3)
δ 204.477, 128.537, 123.166, 115.213, 114.588, 42.291, 41.765,
40.934, 39.774, 29.929, 29.452, 21.605, 16.366; IR (neat) 2968,
2881, 2247, 1720, 1369, 1169 cm-1; HRMS calcd for C13H18N2O
218.1418, found 218.1417. Anal. Calcd: C, 71.527; H, 8.311;
N, 12.832. Found: C, 71.214; H, 8.383; N, 12.691.
Eth yl 2-cya n o-2-a llyl-3-(2-fu r yl)-5-oxoh exa n oa te (6f):
yellow oil; 1H NMR (CDCl3) δ 7.39 (m, 1H, major diastere-
omer), 7.34 (m, 1H, minor diastereomer), 6.33 (m, 2H, major
diastereomer), 6.29 (m, 1H, minor diastereomer), 6.21 (m, 1H,
minor diastereomer), 5.78 (m, 1H, minor diastereomer), 5.70
(m, 1H, major diastereomer), 5.26 (m, 2H, minor diastereomer),
5.15 (m, 2H, major diastereomer), 4.27 (qd, 2H, major diaste-
reomer, J ) 7.1, 1.5 Hz), 4.12 (q, 2H, minor diastereomer, J )
7.1 Hz), 3.96 (dd, 1H, major diastereomer and 1H, minor
diastereomer, J ) 3.6, 10.4 Hz), 3.26 (dd, 1H, major diaste-
reomer, J ) 10.4, 17.2 Hz), 3.24 (dd, 1H, minor diastereomer,
J ) 9.6, 17.5 Hz), 2.97 (dd, 1H, minor diastereomer, J ) 4.0,
7.4 Hz), 2.69 (dd, 1H, major diastereomer and 1H, minor
diastereomer, J ) 3.6, 17.2 Hz), 2.56 (m, 1H, major diastere-
omer and 1H, minor diastereomer), 2.20 (dd, 1H, major
diastereomer, J ) 6.6, 12.7 Hz), 2.14 (s, 3H, minor diastere-
omer), 2.09 (s, 3H, major diastereomer), 1.32 (t, 3H, major
diastereomer, J ) 7.1 Hz), 1.19 (t, 3H, minor diastereomer, J
) 7.1 Hz); IR (neat) 2986, 2245, 1740, 1723, 1225 cm-1; HRMS
calcd for C16H19NO4 289.1312, found 289.1329. Anal. Calcd:
C, 66.421; H, 6.619; N, 4.841. Found: C, 66.594; H, 6.596; N,
5.331.
5,5-Dicya n o-4-n -p en tyl-7-octen -2-on e (6i): colorless oil;
1H NMR (CDCl3) δ 5.95-5.84 (m, 1H), 5.40 (m, 2H), 2.68 (m,
4H), 2.55 (dd, 1H, J ) 7.3, 14.1 Hz), 2.25 (s, 3H), 1.55 (m, 2H),
1.29 (m, 6H), 0.89 (m, 3H); 13C NMR (CDCl3) δ 204.312,
128.611, 123.010, 114.744, 114.596, 44.807, 42.990, 39.552,
38.326, 31.656, 31.467, 30.052, 26.400, 22.247, 13.800; IR
(neat) 2934, 2862, 2247, 1722, 1364, 1167, 935 cm-1; HRMS
calcd for C15H22N2O 246.1732, found 258.1716. Anal. Calcd:
C, 73.133; H, 9.002; N, 11.371. Found: C, 72.887; H, 9.030;
N, 11.270.
Eth yl 2-cya n o-3- (m -m eth oxyp h en yl)-5-oxoh exa n oa te
(7a ): light yellow oil; IR (neat) 2983, 2250, 1743, 1716, 1259
cm-1; HRMS calcd for C16H19NO4 289.1312, found 289.1311.
Anal. Calcd C, 66.421; H, 6.619; N, 4.841. Found: C, 66.146;
H, 6.428; N, 4.946.
Eth yl 2-cya n o-3-(2-fu r yl)-5-oxoh exa n oa te (7b): orange
oil; IR (neat) 2986, 2253, 1744, 1717, 1252 cm-1; HRMS calcd
for C13H15NO4 249.1001, found 249.1007.
5,5-Dicya n o-4-cycloh exyl-7-octen -2-on e (6g): light yel-
1
low oil; H NMR (CDCl3) δ 5.99-5.85 (m, 1H), 5.38 (m, 2H),
2.84 (dd, 1H, J ) 5.5, 18.7 Hz), 2.70 (m, 1H), 2.56 (m, 3H),
2.26 (s, 3H), 1.96-1.67 (m, 5H), 1.54-0.88 (m, 6H); 13C NMR
(CDCl3) δ 204.586, 128.670, 123.332, 115.453, 114.737, 42.506,
41.585, 41.108, 41.050, 40.154, 31.888, 30.103, 27.126, 26.336,
Ack n ow led gm en t. J .-G.S. thanks the Ministry of
Education, Science and Culture of J apan for a Mon-
busho Scholarship.
25.933; IR (neat) 2930, 2856, 2245, 1722, 1364, 1165 cm-1
;
J O981719G