Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and aldehydes

Article abstract of DOI:10.1039/c0ob00915f

Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent enantioselectivities with up to 98% ee and 94% ee, respectively.

Full text of DOI:10.1039/c0ob00915f

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PAPER
Efficient palladium-catalyzed asymmetric allylic alkylation of ketones and
aldehydes†
a
b
a
b
a,b
Xiaohu Zhao, Delong Liu, Fang Xie, Yangang Liu and Wanbin Zhang*
Received 21st October 2010, Accepted 13th December 2010
DOI: 10.1039/c0ob00915f
Palladium-catalyzed asymmetric allylic alkylation of ketones, via enamines generated in situ as
nucleophiles, were carried out smoothly with chiral metallocene-based P,N-ligands. Under the same
conditions, however, reactions of aldehydes could hardly be observed. Subsequently, this obstacle was
resolved by using chiral metallocene-based P,P-ligands. Both ketones and aldehydes afforded excellent
enantioselectivities with up to 98% ee and 94% ee, respectively.
Introduction
activities and excellent enantioselectivities (Fig. 1). These ligands
were also selected here for the palladium-catalyzed asymmetric
allylic alkylation of ketones and aldehydes.
Palladium-catalyzed asymmetric allylic alkylation has become one
of the extremely attractive and powerful tools in asymmetric
1
synthesis. However, the use of simple ketones acting as hard
nucleophiles has remained a challenge in the palladium-catalyzed
2
asymmetric allylic alkylation. Generally, simple ketones cannot
be used directly in palladium-catalyzed asymmetric allylic alkyla-
tion because of their weak nucleophilicity. In order to improve their
reaction activities, simple ketones were always converted to their
2
reactive intermediates, ketone enolates, sometimes by treating
2b
2d
with powerful bases such as LDA and ClMgN(i-Pr) . Consider-
2
Fig. 1 Chiral ligands.
ing that enamines have been widely used as nucleophiles in organic
3
synthesis, we have recently reported the first palladium-catalyzed
asymmetric allylic alkylation with enamines as nucleophiles,
4
At first, the palladium-catalyzed asymmetric allylic alkylation
of 1,3-diphenyl-2-propenyl acetate with cyclohexanone in the
presence of pyrrolidine was examined. Details are summarized
in Table 1.
Initially, the influence of solvents on the alkylation was inves-
tigated using 1a as ligand. As shown in Table 1, the reaction
avoiding using unstable ketone enolates. This procedure contains
several advantages, such as inexpensive reagents, simple operation
and mild reaction conditions. However, some limitations also exist
in enamines: synthesis of the enamines is time-consuming and the
stability of enamines is not good enough in the air atmosphere.
These obstacles prompted us to pursue a new method to make use
of enamines in the reaction system. Herein, we want to report the
first palladium-catalyzed asymmetric allylic alkylation of ketones
and aldehydes via enamines generated in situ as nucleophiles with
excellent enantioselectivities and yields.
hardly occurred using THF, CH
2
Cl
2
, toluene, Et O and 1,4-
2
dioxane as solvents (Table 1, entries 1–5). With the increase
of polarity of the solvents, the reactions could be carried out
successfully. When DMF and DMSO were used as solvents,
excellent enantioselectivities were obtained and a much higher
yield was obtained in DMSO (entries 6–7). Encouraged by the
experimental results, we envisioned that protonic solvents could
Results and discussion
also give the same result. As expected, the reactions with CH OH,
3
EtOH, n-PrOH, i-PrOH as solvents also proceeded smoothly in
excellent enantioselectivities and high yields (entries 8–11). It was
shown that the solvent had a pivotal effect on this reaction and
DMSO was found to be more efficient than the others based on
the asymmetric catalytic behavior.
This reaction was also carried out with a catalytic amount of
pyrrolidine from 10~50% molar ratio. Unfortunately, the reaction
process was so slow that not more than 50% conversion was
obtained even after a week. This result was not improved by
adding tertiary amines such as TEA and DIPEA for avoiding
It was reported that C
ligands 1, 2 and P,P-ligands 3, 4 had been applied in palladium-
catalyzed asymmetric allylic substitutions with high reaction
2
-symmetric chiral metallocene-based P,N-
3
a,5
6
a
School of Chemistry and Chemical Engineering, Shanghai Jiao Tong
University, 800 Dongchuan Road, Shanghai 200240, P. R. China
b
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road,
Shanghai 200240, P. R. China
†
1
Electronic supplementary information (ESI) available. See DOI:
0.1039/c0ob00915f
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Table 1 Allylica alkylation of cyclohexanone with 1,3-diphenyl-2-
propenyl acetate
b
c,d
e
Entry Solvent
Ligand Time/h Yield/% anti/syn
Ee/%
Scheme 2 Allylic alkylation of acetone with 1,3-diphenyl-2-propenyl
acetate using 1b as ligand .
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
THF
CH Cl
Toluene
Et
1,4-dioxane 1a
DMF
1a
1a
1a
1a
48
48
48
48
48
20
20
15
15
18
20
16
14
14
20
trace
trace
trace
trace
trace
20
95
70
90
90
90
95
82
85
—
—
—
—
—
—
—
—
—
92/92
94/94
89/92
90/92
91/91
90/91
90/90
77/78
81/81
98/97
a
2
2
with the reactions using enamines directly as nucleophiles which
2
O
4b
—
afforded a diastereomer ratio of about 60 : 40. This result could
be explained with the possible reaction mechanism shown in Fig. 2.
If enamine was directly used as nucleophile, the isomerization
of 8 to 9 will occur in sufficient time until the reaction was
quenched by water. However, when using enamines generated
in situ as nucleophiles, two competitive reactions coexisted: the
isomerization of 8 to 9 and hydrolysis of 8 to give the product 5 by
water generated during the formation of enamine. The hydrolysis
might be faster than the isomerization, resulting in a higher
diastereomeric ratio than for the case with enamines directly as
nucleophiles. The existence of enamine generated in situ in the
1a
1a
1a
1a
1a
1a
80/20
83/17
80/20
79/21
70/30
78/22
79/21
77/23
77/23
80/20
DMSO
CH
3
OH
EtOH
0
1
2
3
4
5
n-PrOH
i-PrOH
DMSO
DMSO
DMSO
DMSO
2af
3a
f
4a
1b
95
a
3
Molecular
ratio:
3 5 2
[Pd(h -C H )Cl] /ligand/substrate/pyrrolidine/
ketone = 5.0/6.0/200/200/600; reactions were conducted under N
2
3
atmosphere; the catalysts were prepared by treating [Pd(h -C
3
H
5
)Cl]
2
with
7
above reaction was testified by NMR.
the ligand in suitable solvents at room temperature for 1 h before use.
b
c
1
d
Isolated yield. Determined by H NMR. The absolute configuration
e
of syn/anti-products was determined according to ref. 2d. Determined
by HPLC using chiral AD-H column. 6 mol% ligand was used.
f
the consumption of pyrrolidine. So, a stoichiometric amount of
pyrrolidine was used in the following reaction process.
Then, ligands 2a, 3a and 4a were used with DMSO as solvent
in the presence of a stoichiometric amount of pyrrolidine. All
ligands gave good to excellent enantioselectivities and yields, albeit
a little inferior to 1a (Table 1, entries 12–14). A bulky group on the
oxazolinyl ring had a dramatic effect here, and 1b having a tert-
butyl group afforded the best result with up to 98% ee and 95%
yield in this asymmetric catalysis (Table 1, entry 15). In addition,
a higher diastereomeric ratio (70/30–80/20) was obtained with
enamines generated in situ as nucleophiles, compared with the
Fig. 2 A plausible reaction mechanism.
4b
corresponding results using enamines directly.
Some comparison experiments were performed to further verify
that the higher diastereomeric ratio was caused by the presence
In addition, cyclopentanone and acetone were also used for this
reaction under the above reaction conditions using 1b as ligand.
As shown in Scheme 1 and Scheme 2, excellent enantioselectivities
were also obtained for both ketones although only 20% yield was
obtained for acetone.
˚
of water. On the one hand, if 4 A molecular sieves were added
to the reaction mixture, and as a result, the diastereomeric ratio
decreased from 80/20 to 63/37. This means that a lower amount
of water results in a lower diastereomeric ratio. On the other
hand, if 1 equiv. H O was added to the reaction directly with
2
enamine rather than enamine generated in situ as nucleophile, the
diastereomeric ratio was raised from 55/45 to 75/25. These results
obviously shown that the water generated in situ was related to the
higher diastereomeric ratio.
In addition, to explore the scope of the substrates, we have
made several attempts on palladium-catalyzed asymmetric allylic
alkylation of n-hexaldehyde. No reaction occurred for several
aldehydes using P,N-ligands 1 and 2 (Table 2, entries 1–4).
Then, attentions were focused on the exploration of more effi-
cient chiral ligands again. To our delight, high catalytic activities
and good enantioselectivities were eventually obtained by using
P,P-ligands 3 and 4 (Table 2, entries 5–8). The ester group of 3 and
4 with larger steric hindrance gave better enantioselectivity and 4b
Scheme 1 Allylic alkylation of cyclopentanone with 1,3-diphenyl-
a
2
-propenyl acetate using 1b as ligand .
It can be seen from Table 1 that the palladium-catalyzed asym-
metric allylic alkylation of ketones, via enamines generated in situ
as nucleophiles, gave a higher diastereomeric ratio, compared
1
872 | Org. Biomol. Chem., 2011, 9, 1871–1875
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Table 2 Allylic alkylation of n-hexaldehyde with 1,3-diphenyl-2-propenyl
too (entries 4–5). These results showed that both aliphatic and
aromatic aldehydes could serve as efficient nucleophiles with good
to excellent yields and enantioselectivities here. It was noticed that
the diastereomer ratio is not satisfactory mainly due to the faster
rate of isomerization of the intermediate than hydrolysis.
a
acetate using 1–4 and (R)-Binap as ligands
Finally, palladium-catalyzed asymmetric allylic alkylation of
other allylic acetates, such as cyclohex-2-enyl acetate and
b
c
d
Entry
Ligand
Time/h
Yield/%
anti/syn
Ee/%
(
E)-4-phenylbut-3-en-2-yl acetate, with cyclohexanone and n-
1
2
3
4
5
6
7
8
9
1a
48
48
48
48
16
16
11
11
20
ND
ND
ND
ND
70
72
90
—
—
—
—
53/47
53/47
54/46
56/44
52/48
—
—
—
—
91/91
94/94
90/90
91/91
86/86
hexaldehyde were also examined. Using 1b and 4b as chiral
ligands respectively, high yields (>80%) were obtained for both
cyclohexanone and n-hexaldehyde as nucleophiles. However, very
low enantioselectivities (<20% ee) were obtained.
1b
2a
2b
3a
3b
4a
4b
90
74
Conclusions
(R)-Binap
In summary, we have developed an efficient palladium-catalyzed
asymmetric allylic alkylation of ketones and aldehydes, via
enamines generated in situ as nucleophiles. Firstly, palladium-
catalyzed asymmetric allylic alkylations of ketones were carried
out smoothly with excellent enantioselectivities by using chiral
ferrocene P,N-ligand. Under the same conditions, however, reac-
tions of aldehydes could hardly occur. Subsequently, this obstacle
was resolved by using the metallocene-based P,P-ligands with only
planar chirality. The reaction could be expanded to a series of
both aromatic and aliphatic aldehydes with excellent enantiose-
lectivities. It was obvious that both ketones and aldehydes could
achieve excellent results in the palladium-catalyzed asymmetric
allylic alkylation.
a
3
Molecular
ratio:
[Pd(h -C
3
H
5
)Cl]
2
/ligand/substrate/pyrrolidine/
aldehyde = 5.0/12.0/200/200/600; reactions were conducted under N
2
3
atmosphere; the catalysts were prepared by treating [Pd(h -C H )Cl]
3 5
2
b
with ligand in DMSO at room temperature for 1 h before use. Isolated
c
1
d
yield. Determined by H NMR. Determined by the HPLC using chiral
AD-H column.
Table 3 Allylic alkylation of several aldehydes with 1,3-diphenyl-2-
propenyl acetate using 4b as ligand
a
Experimental
General
1
2
b
c
d
Entry
R
R
Time/h
Yield/%
anti/syn
Ee/%
All reactions were performed under a nitrogen atmosphere, and
the workup was carried out in air. The reaction solvents were
distilled prior to use (tetrahydrofuran was distilled from sodium-
benzophenone ketyl; dichloromethane, N,N-dimethylformamide
1
2
3
4
5
Et
Et
Cy
Ph
Bn
H
Me
H
H
H
11
11
11
15
15
86
88
62
60
71
55/45
54/46
—
56/44
53/47
92/93
89/89
79
87/87
90/90
and toluene were distilled from CaH ). The commercially available
2
a
3
reagents were used without further purification. The substrate of
asymmetric allylic alkylation was prepared according to literature
procedure. TLC was run on 2 cm ¥ 5 cm silica plate. Column
Molecular ratio: [Pd(h -C
3
H
5
)Cl]
2
/ligand/substrate/pyrrolidine/alde-
at-
with
ligands in DMSO at room temperature for 1 h before use. Isolated yield.
hyde = 5.0/12.0/200/200/600; reactions were conducted under N
mosphere; the catalysts were prepared by treating [Pd(h -C H )Cl]
3 5 2
2
3
b
1
c
1
d
chromatography was run on silica gel (100–200 mesh). H NMR
Determined by H NMR. Determined by the HPLC using chiral AD-H,
1
3
OD-H and OJ-H column.
(400 MHz) and C NMR (100 MHz) spectra were recorded on
a Varian MERCURY plus-400 spectrometer. The ee values were
determined by HPLC using Daicel Chiralcel AD-H, OD-H, OJ-H
column.
afforded a much higher yield but a little lower enantioselectivity
than 3b (entries 5–8). Furthermore, (R)-Binap was also used in
the above reaction but lower enantioselectivities and catalytic
activities were obtained compared with 3 and 4 (entry 9).
Thus, ligand 4b was applied in the palladium-catalyzed asym-
metric allylic alkylation reactions for several other aldehydes
General procedure for palladium-catalyzed asymmetric allylic
alkylation
A mixture of ligand (for 1 and 2 7.5 mmol; for 3 and 4 15 mmol)
3
(
Table 3).
and [Pd(h -C
3
H
5
)Cl]
2
(2.3 mg, 6.3 mmol) in dry DMSO (1 mL) was
atmosphere for 1 h and 1,3-
As shown in Table 3, the reactions with the linear aldehydes
stirred at room temperature under N
2
proceeded smoothly in high yields and excellent enantioselectivi-
ties (Table 3, entries 1–2). When the linear aldehyde was changed
to a cyclic aldehyde, good yield and enantioselectivity was also
obtained (entry 3). Then, to further investigate the influences
of aldehydes on the reaction, we changed aliphatic aldehyde to
aldehyde with aromatic groups in the side chain. As expected, the
reactions afforded good yields and excellent enantioselectivities
diphenyl-2-propenyl acetate (126 mg, 0.500 mmol) was added for
another 10 min followed by the addition of pyrrolidine (0.50 mmol)
and ketone or aldehyde (1.50 mmol). The reaction was monitored
by TLC for the disappearance of 1,3-diphenyl-2-propenyl acetate.
The reaction mixture was quenched by iced saturated NH Cl
4
solution (10 mL) for 2 h and the aqueous layer was extracted
with ethyl ether (5 mL ¥ 3). The combined organic extract was
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washed with water, brine, dried over Na
2
SO
4
and concentrated
27.6, 27.7, 29.3, 29.5, 50.2, 50.4, 56.6, 56.8, 126.5, 126.6, 127.1,
127.2, 127.7, 128.1, 128.2, 128.7, 128.8, 129.0, 129.1, 130.4, 130.8,
under reduced pressure after filtration. The ratio of anti- and
7
1
+
syn-configuration was determined by H NMR of the mixture
and the residue was purified on silica gel column chromatography
with petrol ether-ethyl acetate (10 : 1) to afford pure product of
anti-configuration and syn-configuration, respectively. For the
determination of ee value by HPLC, a mixture of the products
of anti- and syn-configuration was used.
131.6, 131.9, 137.0, 137.1, 141.5, 141.6, 204.6, 204.9. HRMS (EI )
+
m/z calculated for C21
H
24O [M + 1] : 293.1905; found 293.1911.
-
1
IR(n/cm ): 3086, 3063, 3030, 2957, 2929, 2871, 2860, 1724, 1693,
1638, 1603, 1566, 1493, 1455, 1416, 1379, 966, 749, 699.
9
(E)-2-Ethyl-3,5-diphenylpent-4-enal (11a and 11b)
1
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 0.82–0.87 (t, J = 7.2 Hz,
4b
(
S)-2-((S,E)-1,3-Diphenylallyl)cyclohexanone (5a)
3
H), 0.91–0.96 (t, J = 7.2 Hz, 3H), 1.39–1.79 (m, 4H), 2.69–2.77
1
Colorless oil. H NMR (CDCl
1
2
3
, 400 Hz): d 1.33–1.41 (m, 1H),
(m, 2H), 3.71–3.77 (m, 2H), 6.27–6.51 (m, 2H), 7.18–7.40 (m,
.56–1.63 (m, 1H), 1.70–1.81 (m, 3H), 1.90–1.95 (m, 1H), 2.31–
.46 (m, 2H), 2.83–2.89 (m, 1H), 3.87 (t, J = 8.4 Hz, 1H), 6.32 (d,
20H), 9.49–9.51 (d, J = 4.4 Hz, 1H), 9.65–9.68 (d, J = 4.4 Hz, 1H).
1
3
C NMR (CDCl , 100 Hz): d 11.7, 11.7, 21.1, 21.2, 49.9, 50.2,
3
J = 16 Hz, 1H), 6.44 (dd, J = 8.0, 16 Hz, 1H), 7.12–7.32 (m, 10H).
126.5, 126.6, 127.1, 127.2, 127.7, 128.1, 128.3, 128.6, 128.7, 128.8,
129.0, 129.1, 129.2, 130.5, 130.8, 131.6, 131.9.
1
3
C NMR (CDCl , 100 Hz): d 24.2, 28.8, 32.4, 42.5, 48.6, 56.1,
3
126.5, 126.8, 127.4, 128.6, 128.7, 128.9, 130.7, 132.2, 137.6, 140.1,
212.7.
(S)-2-((S,E)-1,3-Diphenylallyl)cyclohexanone (12a)
1
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 0.96–1.02 (t, J = 7.2 Hz,
4b
(
R)-2-((S,E)-1,3-Diphenylallyl)cyclohexanone (5b)
6
1
1
1
H), 1.75–1.79 (m, 1H), 2.67–2.73 (m, 1H), 3.96–4.01 (t, J = 7.2 Hz,
1
H), 2.31–2.46 (m, 2H), 2.83–2.89 (m, 1H), 3.87 (t, J = 9.6 Hz,
H), 6.25–6.31 (dd, J = 8.4, 8.8 Hz, 1H), 6.42–6.47 (d, J = 16.0 Hz,
Colorless oil. H NMR (CDCl
.86–2.10 (m, 2H), 2.15–2.37 (m, 3H), 2.85–2.91 (m, 1H), 3.97 (t,
J = 8.4 Hz, 1H), 6.25 (dd, J = 9.6, 15.6 Hz, 1H), 6.45 (d, J =
3
, 400 Hz): d 1.57–1.77 (m, 3H),
1
1
3
H), 7.19–7.37 (m, 10H), 9.79–9.81 (d, J = 5.2 Hz, 1H). C NMR
, 100 Hz): d 17.6, 21.8, 28.2, 48.0, 61.7, 126.5, 127.1, 127.7,
1
3
(CDCl
3
1
2
1
5.6 Hz, 1H), 7.14–7.33 (m, 10H). C NMR (CDCl , 100 Hz): d
4.8, 28.6, 32.1, 42.6, 48.7, 55.9, 126.5, 126.6, 127.5, 128.1, 128.7,
28.8, 131.3, 131.6, 137.5, 143.5, 211.8.
3
+
128.1, 128.7, 129.1, 131.0, 131.6, 137.0, 141.7, 205.9. HRMS (EI )
+
m/z calculated for C20H22O [M + 1] : 278.1671; found 278.1668.
IR (v/cm ): 3088, 3060, 3027, 2960, 2926, 2871, 2855, 1721, 1659,
1599, 1578, 1494, 1464, 1452, 1389, 1371, 965, 799, 745, 697.
-
1
4b
(
S)-2-((R,E)-1,3-Diphenylallyl)cyclopentanone (6a)
1
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 1.70–1.78 (m, 1H),
.93–2.03 (m, 3H), 2.16–2.23 (m, 1H), 2.27–2.34 (m, 1H), 2.55–
.61 (m, 1H), 4.09–4.12 (m, 1H), 6.40 (d, J = 4.4 Hz, 1H), 6.41 (s,
(
E)-1-(1,3-Diphenylallyl)cyclohexanecarbaldehyde (13)
1
2
1
3
1
1
Colorless oil. H NMR (CDCl
1.99–2.03 (d, J = 12.4 Hz, 1H), 2.16–2.19 (d, J = 12.4 Hz, 1H),
3
3
, 400 Hz): d 0.09–1.58 (m, 8H),
1
3
H), 7.17–7.35 (m, 10H). C NMR (CDCl , 100 Hz): d 20.9, 26.1,
9.1, 48.0, 55.1, 126.5, 126.7, 127.6, 128.1, 128.7, 128.8, 129.3,
32.6, 137.4, 143.0, 219.3.
3
.46–3.48 (d, J = 9.6 Hz, 1H), 6.44–6.68 (d, J = 15.6 Hz, 1H), 6.56–
.62 (dd, J = 9.6, 15.6 Hz, 1H), 7.19–7.40 (m, 10H), 9.61 (s, 1H).
6
1
3
C NMR (CDCl , 100 Hz): d 23.1, 23.2, 25.7, 30.5, 30.6, 53.2,
3
4b
57.9, 126.6, 127.1, 127.7, 128.1, 128.6, 128.8, 129.3, 133.1, 137.3,
(
R)-2-((R,E)-1,3-Diphenylallyl)cyclopentanone (6b)
+
+
1
3
2
39.9, 208.5. HRMS (EI ) m/z calculated for C22
H
24O [M + 1] :
1
-
1
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 1.70–1.86 (m, 1H),
.94–2.11 (m, 3H), 2.18–2.28 (m, 1H), 2.29–2.38 (m, 1H), 2.58–
.64 (m, 1H), 4.05–4.10 (m, 1H), 6.44 (d, J = 3.2 Hz, 1H), 6.45 (s,
04.1827; found 304.1833. IR (n/cm ): 3086, 3060, 3028, 2931,
1
2
1
3
1
855, 1703, 1600, 1582, 1495, 1451, 1415, 965, 770, 745, 701.
1
3
H), 7.20–7.41 (m, 10H). C NMR (CDCl
9.1, 48.0, 55.1, 126.4, 126.6, 128.7, 129.2, 129.3, 132.5, 132.6,
32.7, 137.4, 143.1, 219.3.
3
, 100 Hz): d 21.0, 26.1,
(E)-2,3,5-Triphenylpent-4-enal (14a and 14b)
1
Colorless oil. H NMR (CDCl
4
3
, 400 Hz): d 4.09–4.13 (m, 2H),
.31–4.37 (m, 2H), 6.12–6.24 (m, 2H), 6.43–6.57 (m, 2H), 7.08–
8
7.45 (m, 30H), 9.66–9.68 (d, J = 2.8 Hz, 1H), 9.83–9.85 (d, J =
(
E)-4,6-Diphenylhex-5-en-2-one (7)
1
3
3
.6 Hz, 1H). C NMR (CDCl , 100 Hz): d 49.8, 50.2, 64.1, 64.5,
3
1
Colorless oil. H NMR (CDCl
(
7
4
1
3
, 400 Hz): d 2.11 (s, 3H), 2.93–2.97
m, 2H), 4.05–4.12 (dd, J = 6.8, 7.2 Hz, 1H), 6.28–6.41 (m, 2H),
.17–7.36 (m, 10H). C NMR (CDCl , 100 Hz): d 21.0, 26.1, 39.1,
8.0, 55.1, 126.4, 126.6, 128.7, 129.2, 129.3, 132.5, 132.6, 132.7,
126.4, 126.6, 126.8, 127.3, 127.5, 127.7, 127.8, 128.1, 128.4, 128.5,
128.6, 128.7, 128.8, 128.9, 129.0, 129.1, 129.2, 129.3, 129.7, 130.0,
130.3, 130.9, 131.9, 132.1, 134.4, 134.5, 137.1, 137.3, 140.7, 141.6,
13
3
+
+
199.4, 199.8. HRMS (EI ) m/z calculated for C H O [M + 1] :
2
3
20
-
1
37.4, 143.1, 219.3.
312.1514; found 312.1512. IR (n/cm ): 3082, 3060, 3027, 2924,
852, 2818, 2716, 1723, 1683, 1664, 1599, 1577, 1493, 1452, 1387,
965, 745, 697.
2
(
E)-2-(1,3-Diphenylallyl)hexanal (10a and 10b)
1
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 0.77–0.81 (t, J = 9.6 Hz,
(
2S,3R,E)-2-Benzyl-3,5-diphenylpent-4-enal (15a)
3
H), 0.83–0.88 (t, J = 9.6 Hz, 3H), 1.11–1.38 (m, 8H), 1.47–1.72
1
(
m, 4H), 2.72–2.82 (m, 2H), 3.67–3.77 (m, 2H), 6.25–6.52 (m, 4H),
Colorless oil. H NMR (CDCl
3
, 400 Hz): d 2.68–2.96 (m, 2H),
7
4
.16–7.38 (m, 20H), 9.47–9.50 (d, J = 4.0 Hz, 1H), 9.62–9.66 (d, J =
3.20–3.28 (m, 1H), 3.76–3.83 (t, J = 8.0 Hz, 1H), 6.34–6.49 (m,
1
3
13
.0 Hz, 1H). C NMR (CDCl
3
, 100 Hz): d 14.0, 14.1, 22.8, 22.9,
2H), 7.05–7.43 (m, 15H), 9.73–9.75 (d, J = 2.8 Hz, 1H).
C
1
874 | Org. Biomol. Chem., 2011, 9, 1871–1875
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NMR (CDCl
3
, 100 Hz): d 34.3, 50.0, 58.3, 126.6, 126.7, 127.3,
and T. Hayashi, J. Am. Chem. Soc., 2006, 128, 5628–5629; (v) B. M. Trost,
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1
3
2
6
27.9, 128.3, 128.7, 128.8, 129.1, 129.2, 129.8, 132.4, 136.9, 138.8,
41.4, 204.4. HRMS (EI ) m/z calculated for C24H22O [M + 1] :
26.1701; found 326.1671. IR (n/cm ): 3083, 3060, 3027, 2924,
851, 2724, 1724, 1681, 1600, 1583, 1494, 1453, 1393, 966, 745,
+
+
7
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This work was partly supported by the National Natural Science
Foundation of China (No. 20872091), Science and Technol-
ogy Commission of Shanghai Municipality (09JC1407800) and
Nippon Chemical Industrial Co, Ltd. We thank Prof. Tsuneo
Imamoto and Dr Masashi Sugiya for helpful discussion and the
Instrumental Analysis Center of Shanghai Jiao Tong University
for HRMS analysis.
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