Construction of chiral quaternary carbon centers via palladium-catalyzed asymmetric deconjugative allylation

Article abstract of DOI:10.3987/COM-08-S(N)112

A Pd(0)-catalyzed asymmetric deconjugative allylation of various Knoevenagel products and allylic compounds was investigated. It was found that various compounds, having a quaternary carbon center directly attached to sp²-carbon centers including a 1,3-diene moiety, could be synthesized through this methodology, although the yield and enantiomeric excess varied from low to modest depending on the structure of substrates and the reaction conditions.

Full text of DOI:10.3987/COM-08-S(N)112

HETEROCYCLES, Vol. 76, No. 2, 2008
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HETEROCYCLES, Vol. 76, No. 2, 2008, pp. 1485 - 1495. © The Japan Institute of Heterocyclic Chemistry
Received, 8th May, 2008, Accepted, 27th June, 2008, Published online, 30th June, 2008. COM-08-S(N)112
CONSTRUCTION OF CHIRAL QUATERNARY CARBON CENTERS VIA
PALLADIUM-CATALYZED ASYMMETRIC DECONJUGATIVE
ALLYLATION
Hiroki Yamamoto, Yoshihiro Oonishi, and Yoshihiro Sato*
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812,
Japan. E-mail: biyo@pharm.hokudai.ac.jp
Abstract – A Pd(0)-catalyzed asymmetric deconjugative allylation of various
Knoevenagel products and allylic compounds was investigated. It was found
that various compounds, having a quaternary carbon center directly attached to
sp2-carbon centers including a 1,3-diene moiety, could be synthesized through
this methodology, although the yield and enantiomeric excess varied from low to
modest depending on the structure of substrates and the reaction conditions.
INTRODUCTION
Deconjugative alkylation of alkylidenemalonate1 or alkenylidenemalonate2 is a useful method for the
synthesis of a compound having a quaternary carbon center that is attached to sp2-carbon centers. We
have recently reported a novel Pd(0)-catalyzed deconjugative allylation of alkenylidenemalonates 1
(Scheme 1).3 That is, reactions of dimethyl 2-((E)-but-2-enylidene)malonate derivatives 1 with various
allylic acetates 2 in the presence of a Pd(0) complex and a base proceeded to give the corresponding
α-allylation products 3 in good yields in a stereoselective manner.
R2
OAc
2
Scheme 1
Pd(0)
R2
R1
#
"
R1
%
R1
Pd
#
E
E
E
E
base
"
# E
E
2'
R2
"
$
!-selective
deconjugative
allylation
!
1:!E=CO2R
3
I
This paper is dedicated to Prof. Dr. Ryoji Noyori on the occasion of his 70th birthday.

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HETEROCYCLES, Vol. 76, No. 2, 2008
In this context, we envisaged that this reaction could be used in the synthesis of 5, which has a chiral
quaternary carbon center, if the reaction can proceed in the case of the substrate 4 (S1≠S2) using a Pd(0)
complex in the presence of a chiral ligand (Scheme 2).
Scheme 2. Plan for Asymmetric Deconjugative Allylation
R1
R1
S1
S2
S1
S1
base
Pd(0)/ L*
R2
*
R2
OAc
4:!S1!S2
2
5
A number of biologically active substances occurring from nature contain various types of chiral
quaternary carbon centers in their frameworks, and construction of those chiral centers has been important
and challenging for synthetic organic chemists.4,5 Herein we report a construction of chiral quaternary
carbon centers via Pd(0)-catalyzed asymmetric deconjugative allylation of 4 with allylic acetates.
RESULTS AND DISCUSSION
Initially, we investigated asymmetric deconjugative allylation of (2E,4E)-4a, which was stereoselectively
synthesized via Knoevenagel condensation of methyl cyanoacetate 6 and aldehyde 7 using NaH and
(iPrO)3TiCl according to the literature6 (Scheme 3).
Scheme 3. Synthesis of Substrate (2E,4E)-4a
NaH (1.0 equiv.)
(iPrO)3TiCl (1.0 equiv.)
CN
CN
CHO
+
CO2Me
CO2Me
THF, rt, 3 h
7
(2.0 eq)
(2E,4E)-4a: 61%
6
The reaction of lithium enolate of 4a, which was prepared by treatment of 4a with LHMDS at room
temperature for 15 minutes, and allyl acetate 2a using Pd2dba3·CHCl3 (2.5 mol%) and BINAPO7a (5
mol%) in THF at 0 °C gave the product 5aa in 49% yield. The enantiomeric excess of 5aa was
determined by HPLC analysis (DAICEL CHIRALCEL OJ-H, hexane-2-propanol, 95:5) to be 7% (Table
i
1, run 1). An asymmetric deconjugative allylation of 4a utilizing DTBM-SEGPHOS7b, Pr-phox7c, or
BPPFA7d as a chiral ligand was investigated under similar conditions, but only low enantiomeric excesses
were obtained (runs 2-4). On the other hand, the reaction of 4a and 2a using 87e as a chiral ligand
produced 5aa in 57% yield and 29% ee (run 5). The reaction using 97e or 107f as a chiral ligand was very
slow, and the desired product 5aa was obtained in 46% yield and 30% ee or in 27% yield and 9% ee after
48 or 121 hours, respectively (runs 6 and 7).

HETEROCYCLES, Vol. 76, No. 2, 2008
1487
Table 1. Asymmetric Deconjugative Allylation of (2E,4E)-4a with Allyl Acetate Using Various Chiral Ligands
Pd2dba3·CHCl3 (2.5 mol%)
chiral ligand
LHMDS
(1.3 equiv.)
CN
CN
*
OAc
(1.2 eq)
2a
THF, rt, 15 min
CO2Me
CO2Me
(2E,4E)-4a
5aa
THF, 0 °C
run
ligand
time (h)
yield (%)
ee (%)
1
2
3
4
5
6
7
BINAPOa
4
3
49
48
48
36
57
46c
27
7
7
DTBM-SEGPHOSb
iPr-phoxa
BPPFAa
8b
85
2
1
3
3
29
30
9
9a
10a
48
121
a 5 mol% of ligand was used.
b 7.5 mol% of ligand was used.
c 4a was recovered in 6%.
O
O
PPh2
NMe2
O
OPPh2
OPPh2
PAr2
PAr2
tBu
H Me
PPh2
Fe
O
O
N
PPh2
Ar =
OMe
tBu
DTBM-SEGPHOS
iPr-phox
O
BPPFA
O
BINAPO
O
Ph
Ph
O
O
O
NH HN
PPh2
Ph2P
NH HN
PPh2
Ph2P
NH HN
PPh2
Ph2P
8
9
10
Table 2. Asymmetric Deconjugative Allylation of 4a Using Various Bases
Pd2dba3·CHCl3 (2.5 mol%)
8 (7.5 mol%)
OAc
CN
CN
(1.2 equiv.)
2a
*
CO2Me
CO2Me
base (1.3 equiv.), THF, 0 °C
5aa
4a
run
base
time (h)
yield (%) ee (%)
1a NaHMDS
3
5
25
12
38
60
59
57
35
36
25
28
28
27
2a
KHMDS
3
1.5
20
15
120
DBU
4
5a
K2CO3
Cs2CO3
none
6
a 5 mol% of 8 was used.

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HETEROCYCLES, Vol. 76, No. 2, 2008
Thus, effects of bases were investigated in the reaction of 4a and 2a using 8 as a ligand, and the results
are summarized in Table 2. The reaction using NaHMDS or KHMDS as a base slightly improved the
enantiomeric excess of 5aa, compared to that using LHMDS (Table 1, run 5), but the yield of 5aa was
decreased (Table 2, runs 1 and 2). The use of an organic base such as DBU was not so effective (run 3),
while both the yield and enantiomeric excess of 5aa in the reaction using inorganic bases such as K2CO3
and Cs2CO3 were comparable to those in the reaction using LHMDS (runs 4 and 5), although the reaction
rate was relatively slow. It is interesting that the reaction of 4a and 2a without bases also occurred
under similar conditions to give 5aa in 57% yield and 27% ee, although the reaction rate was very slow
(run 6).
The fact that inorganic bases instead of LHMDS could be used in this reaction enabled us to carry out the
reaction in various solvents. Thus, solvent effects were investigated in the reaction of 4a and 2a using 8
in the presence of K2CO3 as a base, and the results are summarized in Table 3.
Table 3. Solvent Effects in Asymmetric Deconjugative Allyaltion of 4a
Pd2dba3·CHCl3 (2.5 mol%)
8 (7.5 mol%)
OAc
CN
CN
(1.2 equiv.)
2a
*
K2CO3 (1.3 equiv.), 0 °C
CO2Me
CO2Me
5aa
4a
run solvent time (h)
yield (%) ee (%)
MeCN
70
20
52
72
24
2
1
1
2
3
4
5
CH2Cl2
52
60
46
68
23
39
43
48
CPME
Et2O
toluene
CPME=cyclopentyl methy ether
Polar solvents such as MeCN retarded the reaction, giving a trace amount of 5aa as an almost racemic
form (run 1). The use of CH2Cl2 was tolerated in the reaction to give 5aa in 52% yield and 23% ee (run
2). Ethers such as CPME and Et2O were more effective than THF, and the enantiomeric excesses of 5aa
were increased to 39% and 43%, respectively (runs 3 and 4). Finally, we found that the use of toluene
gave the best result, producing 5aa in 68% yield and 48% ee (run 5).
Next, the reaction of 4a and 2a was carried out at a lower temperature with the intention of improving the
enantiomeric excess of the product. As expected, the reaction of 4a and 2a using K2CO3 as a base at
-20 °C gave 5aa in 46% and 56% ee (Table 4, run 1). When the reaction was carried out at -50 °C, the
enantiomeric excess of 5aa was slightly improved to 60%, but the yield was greatly decreased,

HETEROCYCLES, Vol. 76, No. 2, 2008
1489
presumably due to the insolubility of K2CO3 at a lower temperature (run 2). Thus, the addition of
18-crown-6 to the reaction mixture at -50 °C, which might help K2CO3 dissolve in toluene at a lower
temperature, improved the enantiomeric excess up to 68%, although the yield was still low (run 3). On
the other hand, since the reaction of 4a and 2a using LHMDS as a base in toluene gave no products (run
4), THF was used as a solvent in these reaction conditions. When the reaction was carried out at -20 °C,
the yield and enantiomeric excess of 5aa were improved to 71% and 36% (run 5), compared to those in
the above-mentioned reaction at 0 °C (cf. Table 1, run 5). Further lowering of the temperature did not
affect the yield and enantiomeric excess, and the reaction at -50 °C gave 5aa in almost the same yield and
enantiomeric excess as those when the reaction was carried out at -20 °C (run 6).
Table 4. Asymmetric Deconjugative Allylation of 4a at Lower Temperature
Pd2dba3·CHCl3 (2.5 mol%)
8 (7.5 mol%)
OAc
CN
(1.2 equiv.)
CN
2a
*
base (1.3 equiv.)
CO2Me
CO2Me
4a
5aa
run
base
solvent temp. (°C) time (h) yield (%) ee (%)
1
2
3
4
5
6
K2CO3
K2CO3
K2CO3b toluene
toluene
toluene
-20
-50
-50
0
120
75
48
17
3
46
3a
16
—
71
71
56
60
68
—
LHMDS toluene
LHMDS
LHMDS
THF
THF
-20
-50
36
37
3
a 4a was recovered in 22%.
b 18-Crown-6 (1.3 equiv.) was added.
Thus, the scope and limitations for substrates 4 and allylic compounds 2 were investigated in the reaction
in toluene using K2CO3 as a base at 0 °C, and the results are summarized in Table 5. The reaction of 4a
and 2b, having a phenyl group at the C-3 position, gave the corresponding product 5ab in 19% yield and
24% ee (run 1), while the reaction of 4a and 2c, having a phenyl group at the C-2 position, gave the
corresponding product 5ac in 45% yield and 7% ee (run 2), indicating that the structure of the allylic
compound affected the yield and enantiomeric excess of the product. Allyl carbonate 2d was applicable
in the reaction, and 5aa was obtained in 25% yield and 43% ee in the reaction with 4a (run 3). In this
reaction, bases are not necessary because MeO- would be formed via oxidative addition of 2d to Pd(0)
complex and operate as a base. Thus, it is noteworthy that 5aa was obtained in almost the same
enantiomeric excess with that in the reaction of 4a and 2a in the presence of K2CO3 (cf. Table 3, run 5),
although the yield was lower. The reaction of (2E,4E)-4b and 2a gave the corresponding product 5ba in
67% yield and 39% ee (run 4).

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HETEROCYCLES, Vol. 76, No. 2, 2008
Table 5. Scope and Limitations of Asymmetric Deconjugative Allylation
Pd2dba3·CHCl3 (2.5 mol%)
8 (7.5 mol%)
+
5
4
2 (1.2 equiv.)
K2CO3 (1.3 equiv.)
toluene, 0 °C
allylic compound 2
substrate 4
product
yield (%) ee (%)
run
1
time (h)
CN
*
CN
Ph
OAc
CO2Me
19
45
25
67
19
40
24a
66
63
164
24
6
Ph
CO2Me
4a
4a
2b
Ph
5ab
CN
Ph
7a
*
OAc
2
CO2Me
2c
5ac
OCO2Me
2d
3b
43
4a
5aa
CN
CN
OAc
*
39c
i
4
CO2 Pr
i
CO2 Pr
2a
2a
4b
4c
5ba
CN
CN
2a
*
5
COPh
COPh
5ca
O
5a
O
CN
6
9
2a
*
CN
4d
5da
a The ees of the products 5ab, 5ac, 5ca, and 5da were determined by HPLC analysis (5ab: DAICEL
CHIRALPAK AD-H, hexane-2-propanol, 95:5; 5ac: DAICEL CHIRALCEL OJ-H, hexane-2-propanol, 9:1;
5ca: DAICEL CHIRALCEL OJ-H, hezane-2-propanol, 95:5; 5da: DAICEL CHIRALPAK AS-H, hexane-2-
propanol, 95:5).
b The reaction was carried out without K2CO3.
! The ee of 5ba was determined after conversion to 5aa.
The substrate (2E,4E)-4c, having a ketone moiety, was not suitable for the reaction, giving 5ca in a low
yield as an almost racemic form. Cyclic substrate 4d8 was tolerated in the reaction, and the reaction with
2a gave the corresponding product 5da in 40% yield, although the enantiomeric excess was relatively
low.
In summary, a Pd(0)-catalyzed asymmetric deconjugative allylation of various Knoevenagel products and
allylic compounds was investigated. It was found that various compounds, having a quaternary carbon
center directly attached to sp2-carbon centers including a 1,3-diene moeity, could be synthesized through

HETEROCYCLES, Vol. 76, No. 2, 2008
1491
this methodology, although the yield and enantiomeric excess varied from low to modest depending on
the structure of substrates and the reaction conditions.
EXPERIMENTAL
All manipulations were performed under an argon atmosphere. THF and toluene were purified using
Glass Contour Solvent Purification System. Solvents were distilled from sodium-benzophenone (Et2O
and CPME) CaH2 (DMF and CH2Cl2), or P2O5-CaH2 (MeCN), respectively. All other solvents and
reagents were purified when necessary by standard procedures. Column chromatography was performed
on silica gel 60 (Merck, 70-230 mesh), and flash chromatography on silica gel (Meck, 230-400 mesh)
with the indicated solvent as eluent. IR spectra were obtained on a Jasco FT/IR-460 plus, and 1H NMR
13
and C NMR spectroscopy were carried out on Jeol EX270, Jeol AL400 NMR spectromerter, or Jeol
ECA500 NMR. Mass spectra were obtained on Shimadzu GCMS-QP5050A, Jeol JMS-FAB mate, or
JMS-HX110. Optical rotation was measured on a JASCO P-1030.
(2E,4E)-Methyl 2-cyanohexa-2,4-dienoate (4a) and (2E,4E)-Isopropyl 2-cyanohexa-2,4-dienoate
(4b).
To a suspension of NaH (60% dispersion in mineral oil, 720 mg, 18 mmol) in THF (50 mL) was added
methyl cyanoacetate (6) (1.6 mL, 18 mmol) at 0 °C, and the mixture was stirred at the same temperature
for 30 min. To the mixture was added (iPrO)3TiCl (1.0 M hexane solution, 18.0 mL, 18 mmol) at -78 °C,
and the mixture was stirred at the same temperature for 1 h. To the mixture was added aldehyde 7 (3.0
mL, 36 mmol) at -78 °C, and the mixture was warmed to rt and stirred for 3 h. To the mixture was
added 10% HCl aq. at 0 °C, and the mixture was extracted with Et2O. The combined organic layer was
washed with brine, and dried over MgSO4. After removal of the solvent, the residue was purified by
column chromatography on silica gel (hexane/CPME, 10:1, 5:1) to afford 4a (1.65 g, 61%) as a colorless
solid along with 4b (585 mg, 15%) as a colorless oil.
4a: mp 56-57 °C (recrystallized from hexane, white needles); Ir (Nujol) 2226, 1739, 1635, 1590, 1250
cm-1; 1H NMR (270 MHz, C6D6) δ 1.18 (dd, J = 6.9, 1.3 Hz, 3 H), 3.27 (s, 3 H), 5.57 (dq, J = 14.9, 6.9 Hz,
1 H), 6.39 (ddq, J = 14.9, 11.9, 1.3 Hz, 1 H), 7.50 (d, J = 11.9 Hz, 1 H);13C NMR (67.8 MHz, CDCl3)
δ 19.4, 52.9, 102.9, 114.1, 127.8, 150.1, 155.9, 162.7; LRMS (EI) m/z 151 (M+), 136, 119, 92, 65, 39;
HRMS (EI) calcd for C8H9NO2 151.0633, found 151.0636. Anal. Calcd for C8H9NO2: C, 63.56; H, 6.00;
N, 9.27. Found: C, 63.55; H, 5.83; N, 9.22.
1
4b: Ir (neat) 2225, 1719, 1634, 1587, 1251 cm-1: H NMR (500 MHz, C6D6) δ 0.99 (d, J = 6.3 Hz, 6 H),
1.16 (dd, J = 6.9, 1.7 Hz, 3 H), 4.98 (qq, J = 6.3, 6.3 Hz, 1 H), 5.54 (dq, J = 14.9, 6.9 Hz, 1 H), 6.41 (ddq,
J = 14.9, 11.5, 1.7 Hz, 1 H), 7.57 (d, J = 11.5 Hz, 1 H): 13C NMR (67.8 MHz, CDCl3) δ 19.5, 21.7, 70.2,

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HETEROCYCLES, Vol. 76, No. 2, 2008
104.0, 114.3, 127.9, 149.5, 155.5, 161.8; LRMS (EI) m/z 179 (M+), 137, 120, 93, 66, 43, 39; HRMS (EI)
calcd for C10H13NO2 179.0946, found 179.0948.
(2E,4E)-2-Benzoylhexa-2,4-dienenitrile (4c).
A solution of benzoylacetonitrile (500 mg, 3.4 mmol), aldehdye 7 (0.28 mL, 3.4 mmol),, and piperidine
(6.8 mL, 0.068 mmol) in benzene (3.4 mL) was stirred at rt for 4 h. The mixture was diluted with Et2O,
and the solution was washed with 10% HCl aq. and brine, dried over Na2SO4. After removal of the
solvent, the residue was purified by column chromatography on silica gel (hexane/AcOEt, 9:1) to afford
4c as a colorless solid, which was recrystallized from CH2Cl2/hexanane to give 4c (71 mg, 11%) as a
yellowish needles: mp 86-87 °C; Ir (Nujol) 2212, 1664, 1617, 1595, 1551, 715 cm-1; 1H NMR (270 MHz,
C6D6) δ 1.20 (dd, J = 6.9, 1.6 Hz, 3 H), 5.54 (dq, J = 14.5, 6.9 Hz, 1 H), 6.52 (ddq, J = 14.5, 11.2, 1.6 Hz,
13
1 H), 6.95-7.09 (m, 3 H), 7.35 (d, J = 11.2 Hz, 1 H), 7.73-7.77 (m, 2 H); C NMR (100 MHz, CDCl3) δ
19.7, 110.3, 115.6, 128.3, 128.5, 128.9, 133.1, 136.0, 150.7, 156.6, 188.2.; LRMS (EI) m/z 197 (M+), 182,
105, 77, 51; HRMS (EI) calcd for C13H11NO 197.0841, found 197.0840.
General procedure for asymmetric deconjugative allylation in toluene by Pd2dba3·CHCl3 in the
presence of chiral ligand 8 using K2CO3 as a base.
A suspension of Pd2dba3·CHCl3 (2.5 mol% to the substrate 4), ligand 8 (7.5 mol% to 4), and K2CO3 (1.3
equiv. to 4) in degassed toluene (0.016 M to Pd complex) was stirred at rt for 15 min. To the mixture
was added a solution of 4 and 2 (1.2 equiv. to 4) in toluene (0.12 M to 4) at 0 °C, and the mixture was
stirred at the same temperature. After the reaction was completed, sat. aqueous NH4Cl was added to the
reaction mixture, and the mixture was extracted with AcOEt. The combined organic layer was washed
with brine, dried over Na2SO4. After removal of the solvent, the residue was purified by column
chromatography on silica gel to give the product.
Typical procedure for asymmetric deconjugative allylation of 4a and 2a in THF using LHMDS as a
base at lower temperature (Table 4, run 6).
A suspension of Pd2dba3·CHCl3 (8.6 mg, 0.0083 mmol) and ligand 8 (18.3 mg, 0.025 mmol) in degassed
THF (0.5 mL) was stirred at rt for 15 min. To a solution of 4a (50 mg, 0.33 mmol) in THF (1.5 mL)
was added LHMDS (1.9 M in THF, 0.43 mL) at 0 °C, and the mixture was stirred at rt for 15 min. To
the solution of lithium salt of 4a were added the above-mentioned catalyst mixture and 2a (0.043 mL, 0.4
mmol) at -50 °C, and the mixture was stirred at the same temperature for 3 h. To the mixture was added
sat. aqueous NH4Cl, and the mixture was extracted with AcOEt. The combined organic layer was
washed with brine, dried over Na2SO4. After removal of the solvent, the residue was purified by flash

HETEROCYCLES, Vol. 76, No. 2, 2008
1493
column chromatography on silica gel (hexane/Et2O, 10:1) to give 5aa (45 mg, 71%, 37% ee) as a
yellowish oil.
Spectral data of deconjugative allylation products.
1
(E)-Methyl 2-allyl-2-cyanohexa-3,5-dienoate (5aa): Ir (neat) 2248, 1743, 1643, 1602, 1228 cm-1; H
NMR (270 MHz, CDCl3) δ 2.61 (dd, J = 13.9, 6.6 Hz, 1 H), 2.80 (dd, J = 13.9, 7.9 Hz, 1 H), 3.82 (s, 3 H),
5.23-5.29 (m, 3 H), 5.38 (d, J = 16.5 Hz, 1 H), 5.66 (d, J = 15.2 Hz, 1 H), 5.70-5.85 (m, 1 H), 6.34 (ddd, J
= 16.5, 9.9, 9.9 Hz, 1 H), 6.57 (dd, J = 15.2, 9.9 Hz, 1 H); 13C NMR (126 MHz, CDCl3) δ 42.0, 51.8, 53.7,
116.9, 120.8, 121.2, 126.2, 130.1, 134.4, 134.5, 167.5; LRMS (EI) m/z 191 (M+), 132, 65, 59, 41, 39;
HRMS (EI) calcd for C11H13NO2 191.0946, found 191.0949. Anal. Calcd for C11H13NO2: C, 69.09; H,
6.85; N, 7.32. Found: C, 69.18; H, 7.00; N, 7.24. [α]D27 -49.9 (c 0.99, CHCl3) (48% ee).
(3E)-Methyl 2-cinnamyl-2-cyanohexa-3,5-dienoate (5ab): Ir (neat) 2247, 1742, 1652, 1601, 1577, 1257
cm-1; 1H NMR (400 MHz, CDCl3) δ 2.78 (dd, J = 13.6, 6.8 Hz, 1 H), 2.95 (dd, J = 13.6, 7.7 Hz, 1 H), 3.82
(s, 3 H), 5.27 (d, J = 10.4 Hz, 1 H), 5.39 (d, J = 16.8 Hz, 1 H), 5.72 (d, J = 15.4 Hz, 1 H), 6.13 (ddd, J =
15.9, 7.7, 6.8 Hz, 1 H), 6.35 (ddd, J = 16.8, 10.4, 10.4 Hz, 1 H), 6.57 (d, J = 15.9 Hz, 1 H), 6.59 (dd, J =
13
15.4, 10.4 Hz, 1 H), 7.22-7.38 (m, 5 H); C NMR (100 MHz, CDCl3) δ 41.6, 52.1, 53.8, 117.0, 121.0,
121.1, 126.2, 126.5, 127.9, 128.6, 134.50, 134.52, 136.0, 136.3, 167.6; LRMS (FAB) m/z 268 (M++H),
236, 117; HRMS (FAB) calcd for C17H18NO2 (M++H) 268.1338, found 268.1337. [α]D -13.7 (c 0.54,
19
CHCl3) (24% ee).
(E)-Methyl 2-cyano-2-(2-phenylallyl)hexa-3,5-dienoate (5ac): Ir (neat) 2248, 1742, 1628, 1601, 1575,
1225 cm-1; 1H NMR (400 MHz, CDCl3) δ 3.01 (dd, J = 14.0, 0.9 Hz, 1 H), 3.32 (dd, J = 14.0, 0.9 Hz, 1 H),
3.43 (s, 3 H), 5.21 (d, J = 10.0 Hz, 1 H), 5.33 (d, J = 16.8 Hz, 1 H), 5.34 (d, J = 0.9 Hz, 1 H), 5.43 (d, J =
0.9 Hz, 1 H), 5.65 (d, J = 15.0 Hz, 1 H), 6.23 (ddd, J = 16.8, 10.4, 10.0 Hz, 1 H), 6.52 (dd, J = 15.0, 10.4
Hz, 1 H), 7.25-7.33 (m, 5 H); 13C NMR (100 MHz, CDCl3) δ 43.8, 52.2, 53.4, 116.7, 119.4, 120.6, 126.8,
126.9, 127.9, 128.2, 133.7, 134.5, 140.0, 142.4, 167.4; LRMS (FAB) m/z 268 (M++H), 226, 208; HRMS
(FAB) calcd for C17H18NO2 (M++H) 268.1338, found 268.1342. [α]D20 +6.2 (c 0.98, CHCl3) (7% ee).
1
(E)-Isopropyl 2-allyl-2-cyanohexa-3,5-dienoate (5ba): Ir (neat) 2248, 1740, 1644, 1603, 1234 cm-1; H
NMR (270 MHz, CDCl3) δ 1.29 (d, J = 6.6 Hz, 3 H), 1.30 (d, J = 6.6 Hz, 3 H), 2.60 (dd, J = 13.9, 6.9 Hz,
1 H), 2.78 (dd, J = 13.9, 7.9 Hz, 1 H), 5.07 (qq, J = 6.6, 6.6 Hz, 1 H), 5.22-5.29 (m, 3 H), 5.37 (d, J =
17.2 Hz, 1 H), 5.67 (d, J = 15.2 Hz, 1 H), 5.70-5.85 (m, 1 H), 6.34 (ddd, J = 17.2, 10.2, 10.2 Hz, 1 H),
6.56 (dd, J = 15.2, 10.2 Hz, 1 H); 13C NMR (100 MHz, CDCl3) δ 21.5, 21.6, 42.1, 52.0, 71.3, 117.1, 120.6,

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HETEROCYCLES, Vol. 76, No. 2, 2008
121.2, 126.5, 130.2, 134.2, 134.7, 166.5; LRMS (EI) m/z 219 (M+), 132, 43, 41; HRMS (EI) calcd for
C13H17NO2 219.1259, found 219.1258. [α]D20 -33.9 (c 1.05, CHCl3) (39% ee).
1
(E)-2-Allyl-2-benzoylhexa-3,5-dienenitrile (5ca): Ir (neat) 2239, 1693, 1643, 1597, 1580, 689 cm-1; H
NMR (400 MHz, CDCl3) δ 2.69 (dd, J = 13.8, 7.2 Hz, 1 H), 2.98 (dd, J = 13.8, 7.0 Hz, 1 H), 5.20-5.29 (m,
3 H), 5.41 (dd, J = 17.0, 0.6 Hz, 1 H), 5.69 (d, J = 15.5 Hz, 1 H), 5.74-5.85 (m, 1 H), 6.35 (ddd, J = 17.0,
10.4, 10.4 Hz, 1 H), 6.67 (dd, J = 15.5, 10.4 Hz, 1 H), 7.45-7.49 (m, 2 H), 7.58-7.61 (m, 1 H), 8.02-8.04
13
(m, 2 H); C NMR (100 MHz, CDCl3) δ 41.4, 54.6, 118.9, 120.9, 121.2, 127.6, 128.5, 129.5, 130.7,
133.8, 134.4, 134.6, 134.8, 191.5; LRMS (EI) m/z 236 (M+-H), 105, 77, 51; HRMS (EI) calcd for
C16H15NO 237.1154, found 237.1157. [α]D18 +6.0 (c 0.58, CHCl3) (2% ee).
1
1-Allyl-6-oxocyclohex-2-enecarbonitrile (5da): Ir (neat) 2242, 1724, 1642 cm-1; H NMR (400 MHz,
C6D6) δ 1.51-1.68 (m, 2 H), 1.83 (ddd, J = 14.3, 7.2, 7.2 Hz, 1 H), 2.13 (ddd, J = 14.3, 6.6, 6.6 Hz, 1 H),
2.21 (dd, J = 13.7, 7.9 Hz, 1 H), 2.31 (dd, J = 13.7, 6.8 Hz, 1 H), 4.88 (d, J = 16.9 Hz, 1 H), 4.93 (d, J =
10.2 Hz, 1 H), 5.18 (ddd, J = 9.6, 1.7, 1.5 Hz, 1 H), 5.25 (ddd, J = 9.6, 4.0, 3.8 Hz, 1 H), 5.59 (dddd, J =
13
16.9, 10.2, 7.9, 6.8 Hz, 1 H); C NMR (100 MHz, CDCl3) δ 26.2, 35.8, 41.5, 49.4, 117.9, 121.2, 125.5,
130.2, 130.7, 201.3; LRMS (EI) m/z 161 (M+), 132, 118, 104, 91, 41, 39; HRMS (EI) calcd for C10H11NO
161.0841, found 161.0851. [α]D17 -5.2 (c 0.67, CHCl3) (5% ee).
ACKNOWLEDGEMENTS
This work was partly supported by a Grant-in-Aid for Scientific Research on Priority Areas (No.
20037002, Chemistry of Concerto Catalysis) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan and by a Grant-in-Aid for Scientific Research (B) (No. 19390001) from the Japan
Society for the Promotion of Science (JSPS). We thank Takasago International Corporation for the gift
of DTBM-SEGPHOS and Zeon Corporation, Japan for the gift of CPME.
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