Highly regioselective asymmetric copper-catalyzed allylic alkylation with dialkylzincs using monodentate chiral spiro phosphoramidite and phosphite ligands

Article abstract of DOI:10.1016/j.tetasy.2003.09.028

The copper complexes of chiral spiro phosphoramidite and phosphite ligands were found to be effective catalysts in the asymmetric allylic alkylations of cinnamyl halides with dialkylzincs. The allylic alkylation products were obtained in high regioselecti

Full text of DOI:10.1016/j.tetasy.2003.09.028

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 3867–3872
Highly regioselective asymmetric copper-catalyzed allylic
alkylation with dialkylzincs using monodentate chiral spiro
phosphoramidite and phosphite ligands
Wen-Jian Shi, Li-Xin Wang, Yu Fu, Shou-Fei Zhu and Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China
Received 19 August 2003; accepted 9 September 2003
Abstract—The copper complexes of chiral spiro phosphoramidite and phosphite ligands were found to be effective catalysts in the
asymmetric allylic alkylations of cinnamyl halides with dialkylzincs. The allylic alkylation products were obtained in high
regioselectivities (SN2%/SN2 up to 98:2) and enantiomeric excesses of up to 74% for SN2% products.
© 2003 Elsevier Ltd. All rights reserved.
1. Introduction
In the previous paper, we have demonstrated that the
chiral spiro phosphoramidite ligands 1–3 were highly
effective in the rhodium-catalyzed hydrogenations of
The alkylation of allylic substrates is an important
reaction for carbon–carbon bond formation in organic
synthesis. Highly enantioselective palladium-catalyzed
allylic alkylations with stabilized carbon anions such as
malonates or related species as carbon nucleophiles
have been described.1 However, enantioselective cop-
per-catalyzed allylic alkylation with organometallic
reagents is quite limited.2 In 1995, Ba¨ckvall and van
Koten reported the first asymmetric copper-catalyzed
allylic alkylation with Grignard reagent in moderate
enantioselectivity.3 Asymmetric copper-catalyzed allylic
alkylation with dialkylzinc reagents was described by
Knochel et al. Employing the copper complexes of
chiral ferrocenylamine ligands Knochel achieved 87%
e.e. in the reaction of cinnamyl chloride with sterically
hindered zinc reagent dineopentylzinc.4 The enantio-
selectivity of copper-catalyzed allylic alkylation with
dialkylzinc was further improved by Hoveyda et al.
Using peptidic Schiff base ligands they obtained up to
97% e.e. in the alkylation of a,b-unsaturated esters
bearing a primary g-phosphate with dialkylzincs.5
Feringa et al. reported that monodentate phospho-
ramidites derived from BINOL could also be efficient
ligands in the copper-catalyzed allylic alkylation of
cinnamyl bromide with dialkylzincs, affording SN2%/SN2
ratio of 85:15 and enantiomeric excesses up to 77% for
the SN2% products.6
7
functionalized olefins and copper-catalyzed 1,4-addi-
tion of dialkylzincs to enones.8 Here we describe an
asymmetric copper-catalyzed allylic alkylations of cin-
namyl halides with dialkylzincs using spiro phospho-
ramidite and phosphite ligands 1–9 (Fig. 1), resulting in
SN2%/SN2 ratio up to 98:2 and enantiomeric excesses up
to 74% for the SN2% products.
2. Results and discussion
The chiral spiro phosphoramidites and phosphites 1–9
were readily prepared from enantiomerically pure 1,1%-
spirobiindane-7,7%-diol.9 Heating the mixture of 1,1%-
spirobiindane-7,7%-diol and P(NMe2)3 in toluene
afforded ligand 1 in 92% yield. Condensation of 1,1%-
spirobiindane-7,7%-diol with PCl3, followed by treat-
ment with the corresponding lithium dialkylamides or
alkoxides provided ligands 2–9 in 40–69% yield.
The allylic alkylation reaction was initially carried out
with cinnamyl bromide and diethylzinc (1.2 eq. to
cinnamyl bromide) in the presence of copper catalyst (1
mol%) prepared in situ from (CuOTf)2.C6H6 and ligand
(R,S,S)-3 in ether (Scheme 1). After 3 days at −30°C,
50% of substrate was converted and the alkylation
products were produced in 36% yield. The ratio of two
regioisomers (SN2%/SN2) was 64:36, and the enan-
* Corresponding author. E-mail: qlzhou@public.tpt.tj.cn
0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2003.09.028

3868
W.-J. Shi et al. / Tetrahedron: Asymmetry 14 (2003) 3867–3872
Figure 1. Spiro phosphoramidite and phosphite ligands.
Scheme 1.
tiomeric excess of SN2% product was 56%. Screening of
the solvents led to the finding that both regioselectivity
and enantioselectivity are improved in chelating sol-
vent, with dimethoxyethane (DME) and diglyme being
the solvents of choice (Table 1). In diglyme, the alkyla-
tion products were obtained in 62% yield with 88:12 of
SN2%/SN2 ratio and 71% e.e. for the SN2% product (entry
4). Both regioselectivity and enantioselectivity
decreased when the reaction was performed at 0°C or
15°C although the rates of reactions were faster and the
yields of alkylation products were higher at these tem-
peratures (entries 5 and 6).
lyst in copper-catalyzed allylic alkylation with
organometallic reagents.2c,6 We examined different cop-
per(I) and copper(II) salts with ligands (R,S,S)-3 and
(R)-8 in the reaction of cinnamyl bromide and diethyl-
zinc. As shown in Table 2, all the copper salts tested
can be used as copper source of the catalyst. In the
reactions using phosphoramidite ligand (R,S,S)-3,
(CuOTf)2.C6H6 gave highest enantioselectivity. But, in
the reactions using phosphite ligand (R)-8, Cu(OTf)2
was superior to other copper salts in both regioselectiv-
ity and enantioselectivity. The optimal copper/ligand
ratio was found to be 1:2. Lowering or increasing the
Cu/L ratio resulted in a decrease in either yield of
reaction or enantiomeric excess of SN2% product (entries
3 and 4 versus entry 2).
The source of copper has been reported to have a
strong influence on the activity and selectivity of cata-
Table 1. Enantioselective copper-catalyzed allylic alkylation of cinnamyl bromide with diethylzinc using ligand (R,S,S)-3.
Solvent effecta
c
Entry
Solvent
Temp. (°C)
Time (h)
Yield (%)b SN2%+SN2
SN2%/SN2
E.e. (%)d SN2%
1
2
3
4
5
6
7
8
9
Et2O
THF
DME
Diglyme
Diglyme
Diglyme
EA
CH2Cl2
toluene
−30
−30
−30
−30
0
72
72
72
72
5
36
81
50
62
72
77
45
53
64
64:36
89:11
86:14
88:12
81:19
76:24
83:17
73:27
78:22
56
58
71
71
54
28
63
9
15
5
−30
−30
−30
72
72
72
5
a 0.5 mol% (CuOTf)2·C6H6, Cu/L=1:2.
b Determined by GC.
c Determined by GC.
d Determined by chiral GC using a Suplco b-DEX 120 column.

W.-J. Shi et al. / Tetrahedron: Asymmetry 14 (2003) 3867–3872
3869
Table 2. Asymmetric allylic alkylation of cinnamyl bromide with diethylzinc. Copper salt effecta
Entry
Ligand
Cu salt
Yield (%) SN2%+SN2
SN2%/SN2
E.e. (%) SN2%
1
2
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R,S,S)-3
(R)-8
CuBr·Me2S
77
62
78
35
70
77
84
77
74
45
72
86
83
83
97
90
83:17
88:12
82:18
89:11
85:15
86:14
79:21
91:9
88:12
85:15
88:12
93:7
46
71
41
74
60
55
46
62
56
64
21
42
46
27
53
59
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·Tol
Cu(MeCN)4PF6
CuBr2
3b
4c
5
6
7
8
9
10
11
12
13
14
15
16
Cu(OTf)2
Cu(OAc)2·H2O
CuSO4·5H2O
CuBr.Me2S
(CuOTf)2·C6H6
(CuOTf)2·Tol
Cu(MeCN)4PF6
CuBr2
(R)-8
(R)-8
(R)-8
(R)-8
94:6
91:9
94:6
98:2
(R)-8
Cu(OTf)2
a 1 mol% Cu, Cu/L=1:2 unless stated otherwise, diglyme as solvent, −30°C.
b Cu/L=1:1.
c Cu/L=1:3.
Ligands 1–9 were compared in the copper-catalyzed
allylic alkylation of cinnamyl bromide with diethylzinc,
and the results are summarized in Table 3. Among the
phosphoramidite ligands tested, ligands 1 and 4, having
smallest alkyl groups at nitrogen atom afforded highest
regioselectivity (entries 1 and 4). However, ligand
(R,S,S)-3, bearing a (S,S)-di(1-phenylethyl)amine moi-
ety, gave best enantioselectivity (entry 3). In contrast
with phosphoramidite ligands, phosphite ligands 7–9
are more active. The reactions with these ligands com-
pleted within one day and the yields of allylic alkylation
products were higher. It was more exciting to see that
the reactions using phosphite ligands have excellent
regioselectivities (SN2%/SN2 up to 98:2).
The allylic alkylations of different cinnamyl halides
were performed with diethylzinc using ligand (R,S,S)-3
and (CuOTf)2·C6H6 (Table 4). Comparing to cinnamyl
Table 3. Enantioselective copper-catalyzed allylic alkylation of cinnamyl bromide using spiro phosphoramidite and phosphite
ligandsa
Entry
Ligand
Cu salt
Time (h)
Yield (%) SN2%+SN2
SN2%/SN2
E.e. (%) SN2%
1
2
3
4
5
6
7
8
1
2
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
(CuOTf)2·C6H6
Cu(OTf)2
72
72
72
72
72
72
72
72
72
24
24
24
86
80
62
39
80
70
58
82
81
82
90
95
93:7
17
47
71
61
16
27
−11
8
28
34
59
56
87:13
88:12
80:20
93:7
90:10
82:18
88:12
87:13
96:4
(R,S,S)-3
(R,R,R)-3
4
(R,R)-5
(R,S)-5
(R,R)-6
(R,S)-6
7
8
9
9
10
11
12
Cu(OTf)2
Cu(OTf)2
98:2
98:2
a 1 mol% of Cu, Cu/L=1:2, diglyme as solvent, −30°C.
Table 4. Enantioselective copper-catalyzed allylic alkylation of cinnamyl halidesa
Entry
Subs.
R2Zn
Yield (%) SN2%+SN2
SN2%/SN2
E.e. (%) SN2%
1
2
3
4
5
6
7
Ar=Ph, X=Cl
Ar=Ph, X=Br
Ar=Ph, X=Br
Ar=Ph, X=I
Ar=4-MePh, X=Br
Ar=2-ClPh, X=Br
Ar=4-ClPh, X=Br
R=Et
R=Et
R=i-Pr
R=Et
R=Et
R=Et
R=Et
11
62
82
53
80
42
57
86:14
88:12
91:9
42:58
88:12
80:20
82:18
47
71
67
71
74
60
59
a 0.5 mol% (CuOTf)2·C6H6, 2 mol% (R,S,S)-3, diglyme as solvent, −30°C.

3870
W.-J. Shi et al. / Tetrahedron: Asymmetry 14 (2003) 3867–3872
bromide, cinnamyl chloride was less reactive (entry 1)
and cinnamyl iodide provided the allylic alkylation
products in low regioselectivity (entry 4). 4-Methylcin-
namyl bromide showed the activity (80% yield) and
enantioselectivity (74% e.e.) which are slightly better
than those with cinnamyl bromide (entry 5). The reac-
tions of 2-chloro- and 4-chlorocinnamyl bromides pro-
duced allylic alkylation products in lower yields and
lower enantioselectivities (entries 6 and 7). The cin-
namyl acetate and carbonate were not active under the
same reaction conditions. In addition to diethylzinc,
diisopropylzinc, a bulkier zinc reagent, was also tested
in the allylic alkylation of cinnamyl bromide using
ligand (R,S,S)-3 and (CuOTf)2·C6H6 with 91:9 of
regioselectivity and 67% of e.e. (entry 3), which are
close to those obtained from diethylzinc.
vided higher regioselectivity and faster rate of reaction.
Studies of other transition metal-catalyzed reactions
using novel spiro phosphoramidite and phosphite lig-
ands are in progress in our laboratory.
,
Table 5. Selected bond lengths [A] and bond angles [°] in
the complex [CuBr((R)-1)2]2
,
Bond lengths [A]
Bond angles [°]
P(1)-Cu-P(2)
Cu(1)-P(1)
2.260(2)
2.254(2)
2.542(1)
2.523(1)
1.629(5)
1.649(4)
1.635(4)
113.57(6)
115.56(5)
111.98(5)
106.72(5)
111.73(5)
95.94(3)
Cu(1)-P(2)
Cu(1)-Br(1)
Cu(1)-Br(2)
P(1)-N(1)
P(1)-O(1)
P(1)-Cu-Br(1)
P(1)-Cu-Br(2)
P(2)-Cu-Br(1)
P(2)-Cu-Br(2)
Br(1)-Cu-Br(2)
Cu(1)-Br(1)-Cu(2)
P(1)-O(2)
83.39(3)
To investigate the structure of catalyst, we grew a single
crystal of copper complex from CuBr·Me2S and phos-
phoramidite ligand 1 suitable for X-ray crystallogra-
phy. The structure of [CuBr((R)-1)2]2 is shown in
Figure 2.10 Selected bond lengths and bond angles are
listed in Table 5. The complex in the crystal is C2-sym-
metric dimer with two bromine atoms as bridges. Each
copper atom was coordinated with two phosphoramid-
ite ligands. This structure is different from the copper
complex of Feringa’s MonoPhos ligand, which is a
monomer with three ligands coordinated to copper.11
4. Experimental
4.1. General
All reactions and manipulations were performed in a
nitrogen atmosphere using standard Schlenk tech-
niques. Toluene, ether, diglyme and THF were distilled
from sodium-benzophenone ketyl under nitrogen.
Methylene chloride and ethyl acetate were distilled
from CaH2. Starting (R)-1,1%-spirobiindane-7,7%-diol
and the ligands 1, 2 and 3 were prepared by the
previously reported methods.8,9
3. Conclusion
We have found that the spiro phosphoramidites and
phosphites are effective ligands in the copper-catalyzed
allylic alkylation of cinnamyl halides with dialkylzinc
reagents. The alkylation products were obtained in
good yields with high regioselectivities up to 98:2 of
SN2%/SN2 ratio and enantiomeric excesses up to 74% for
SN2% products. Phosphoramidite ligands possessed
higher enantioselectivity, while phosphite ligands pro-
4.2. Syntheses of spiro phosphoramidite ligands 4–6
4.2.1. O,O%-[(R)-1,1%-Spirobiindane-7,7%-diyl]-P-(1-pyrro-
lidinyl)phosphonite (R)-4. General procedure. A solution
of (R)-1,1%-spirobiindane-7,7%-diol (505 mg, 2.0 mmol)
in 8 mL THF was added over a period of 5 min to a
cooled solution of PCl3 (175 mL, 2.0 mmol), Et3N (556
Figure 2. Crystal structure of complex [CuBr((R)-1)2]2.

W.-J. Shi et al. / Tetrahedron: Asymmetry 14 (2003) 3867–3872
3871
mL, 4.0 mmol), and THF (50 mL) at −78°C. The
reaction mixture was stirred for another 0.5 h, warmed
to room temperature over a period of 2 h, and filtered.
In a Schlenk tube, to the solution of pyrrolidine (167
mL, 2.0 mmol) and 5.0 mL THF, butyllithium (1.5 M
solution in hexane, 1.4 mL, 2.1 mmol) was added at
−30°C, then stirred for another 10 min. After warmed
to room temperature, the solution was transferred to
the above filtrate by syringe, the resulted mixture was
stirred at −78°C for another 1 h, and warmed to room
temperature. Concentration and chromatography
purification using petroleum ether/EtOAc (10:1) on a
silica gel column afforded (R)-4 as a white powder (460
mg, 65% yield). Mp 140–142°C, [h]2D5 +366 (c 1.0,
4.2.5. O,O%-[(R)-1,1%-Spirobiindane-7,7%-diyl]-P-[1-((S)-
3,5 - dihydro - 4H - binaphth - [2,1 - c:1%,2% - e] - azepinyl)]-
phosphonite (R,S)-6. Ligand (R,S)-6 was synthesized in
47% yield from (R)-1,1%-spirobiindane-7,7%-diol and (S)-
3,5-dihydro-4H-binaphth-[2,1-c:1%,2%-e]-azepine by using
the same procedure as that for (R)-4. White solid, mp
1
257–258°C. [h]2D5 −263 (c 0.1, CHCl3). H NMR: 7.95–
7.93 (d, 3H, J=8.4 Hz), 7.48–6.68 (m, 15H), 3.87 (s,
2H), 3.57 (m, 2H), 3.20–2.80 (m, 4H), 2.30–1.90 (m,
4H). 13C NMR: 146.1, 145.9, 135.1, 133.8, 133.3, 131.6,
128.9, 128.4, 128.0, 127.6, 126.0, 125.7, 122.4, 121.4,
120.7, 61.1, 59.7, 59.1, 50.5, 48.5, 44.1, 38.5, 38.4, 31.5,
31.1, 30.8, 29.9, 24.1, 18.4. 31P NMR: 127.8. HR-MS
(FAB) calcd for C39H30NO2P+H: 576.2087. Found
576.2089.
1
CH2Cl2). H NMR: 7.20–6.65 (m, 6H), 3.00 (s, 4H),
2.85–2.77 (m, 2H), 2.51 (s, 2H), 2.17–2.18 (m, 2H),
2.04–1.91 (m, 2H), 1.67–1.56 (m, 4H). 13C NMR: 149.0,
146.6, 146.0, 145.7, 142.6, 141.3, 128.7, 128.0, 122.2,
121.3, 120.6, 59.0, 45.6, 45.4, 44.8, 38.5, 38.3, 31.4, 31.2,
30.8, 26.1. 31P NMR: 128.0. MS (m/z, %): 351 (M+,
100). Anal. calcd for C21H22NO2P: C, 71.76; H, 6.32; N,
3.99. Found: C, 71.90; H, 6.39; N, 3.73.
4.3. Syntheses of spiro phosphite ligands 7-9
4.3.1. Phenyl-[(R)-1,1%-spirobiindane-7,7%-diyl]-phosphite
(R)-7. General procedure. To the chilled solution of
PCl3 (110 mL, 1.3 mmol), Et3N (380 mL, 2.7 mmol), and
THF (25 mL), a solution of (R)-1,1%-spirobiindane-7,7%-
diol (308 mg, 1.2 mmol) in 5 mL THF was added at
−78°C. The reaction mixture was stirred for 2 h, then
warmed to room temperature and filtered. The filtrate
was cooled to −78°C and treated with lithium phenolate
prepared from phenol (128 mg, 1.36 mmol) and butyl-
lithium (1.6 M solution in hexane, 0.85 mL, 1.36 mmol)
in 5 mL THF at −30°C. The resulted solution was
warmed to room temperature, and stirred overnight.
Concentration and flash chromatography purification
on a silica gel column using petroleum ether/EtOAc
(30:1) afforded (R)-7 as a white solid (310 mg, 69%
yield). Mp 104–105°C. [h]2D5 +72 (c 0.5, CHCl3). 1H
NMR: 7.35–6.77 (m, 11H), 3.12–3.03 (m, 2H), 2.87–
4.2.2. O,O%-[(R)-1,1%-Spirobiindane-7,7%-diyl]-P-[1-((R)-
2-methoxymethylpyrro-lidinyl)]phosphonite (R,R)-5. Lig-
and (R,R)-5 was synthesized in 40% yield from
(R)-1,1%-spirobiindane-7,7%-diol and (R)-2-methoxy-
methylpyrrolidine by using the same procedure as that
for (R)-4. White solid, mp 46–47°C. [h]2D5 +216 (c 0.5,
1
CHCl3). H NMR: 7.27–6.75 (m, 6H), 3.73 (m, 1H),
3.42 (s, 3H), 3.38–1.82 (m, 16H). 13C NMR: 149.1,
146.7, 146.6, 145.4, 142.5, 141.5, 128.7, 128.0, 122.1,
121.3, 120.6, 114.5, 59.0, 58.3, 58.0, 44.5, 38.5, 31.2,
30.8, 28.6, 28.6, 25.1. 31P NMR: 120.7. HR-MS (FAB)
calcd for C23H26NO3P+H: 396.1723. Found 396.1723.
2.80 (m, 2H), 2.28–2.22 (m, 2H), 2.07–2.00 (m, 2H). 13
C
4.2.3. O,O%-[(R)-1,1%-Spirobiindane-7,7%-diyl]-P-[1-((S)-2-
methoxymethylpyrro-lidinyl)]phosphonite (R,S)-5. Lig-
and (R,S)-5 was synthesized in 50% yield from
(R)-1,1%-spirobiindane-7,7%-diol and (S)-2-methoxy-
methylpyrrolidine by using the same procedure as that
for (R)-4. White solid, mp 37–39°C. [h]2D5 +188 (c 0.5,
NMR: 151.2, 145.1, 144.7, 143.8, 142.3, 141.9, 138.7,
128.7, 127.6, 126.9, 123.2, 122.8, 121.1, 120.9, 120.6,
119.7, 118.5, 58.2, 37.5, 36.9, 29.9, 29.4, 28.6. 31P
NMR: 120.5. HR-MS (FAB) calcd for C23H19O3P+H:
375.1140. Found 375.1144.
1
CHCl3). H NMR: 7.26–6.67 (m, 6H), 3.80 (m, 1H),
3.42–1.50 (m, 19H). 13C NMR: 148.7, 146.3, 145.7,
145.5, 142.1, 140.8, 128.5, 127.8, 122.0, 121.0, 120.4,
59.0, 58.8, 56.7, 56.4, 45.0, 38.2, 38.1, 30.9, 30.5, 29.4,
24.0. 31P NMR: 128.7. HR-MS (FAB) calcd for
C23H26NO3P+H: 396.1723. Found 396.1723.
4.3.2. tert-Butyl-[(R)-1,1%-spirobiindane-7,7%-diyl]-phos-
phite (R)-8. Ligand (R)-8 was synthesized in 65% yield
with sodium tert-butoxide by using the same procedure
as that for (R)-7. White solid, mp 57–58°C. [h]2D5 +80 (c
1
0.5, CHCl3). H NMR: 7.20–6.76 (m, 6H), 3.08–3.02
(m, 2H), 2.85–2.81 (m, 2H), 2.24–2.18 (m, 2H), 2.04–
2.00 (m, 2H), 1.48 (s, 9H). 13C NMR: 145.1, 144.8,
144.4, 142.9, 142.0, 139.1, 127.3, 126.2, 121.8, 120.8,
120.5, 119.9, 58.0, 37.4, 36.9, 29.9, 29.5. 31P NMR:
128.1. HR–MS (FAB) calcd for C21H23O3P+H:
355.1457. Found 355.1463
4.2.4. O,O%-[(R)-1,1%-Spirobiindane-7,7%-diyl]-P-[1-((R)-
3,5 - dihydro - 4H - binaphth - [2,1 - c:1%,2% - e] - azepinyl)]-
phosphonite (R,R)-6. Ligand (R,R)-6 was synthesized in
43% yield from (R)-1,1%-spirobiindane-7,7%-diol and
(R)-3,5-dihydro-4H-binaphth-[2,1-c:1%,2%-e]-azepine by
using the same procedure as that for (R)-4. White solid,
1
mp 249–250°C. [h]D25 −405 (c 0.1, CHCl3). H NMR:
4.3.3. Diphenylmethyl-[(R)-1,1%-spirobiindane-7,7%-diyl]-
phosphite (R)-9. Ligand (R)-9 was synthesized in 43%
yield with diphenylmethanol by using the same proce-
dure as that for (R)-7. White solid, mp 77–79°C. [h]D25
8.00–7.95 (t, 4H), 7.60–6.14 (m, 14H), 4.15–4.09 (m,
2H), 3.20–2.71 (m, 6H), 2.35–1.84 (m, 4H). 13C NMR:
148.8, 146.2, 145.0, 142.3, 141.0, 135.6, 133.8, 133.2,
131.6, 129.1, 128.7, 128.5, 127.5, 126.0, 120.0, 121.5,
120.6, 66.0, 58.9, 46.6, 38.5, 31.1, 30.7, 15.4. 31P NMR:
122.1. HR-MS (FAB) calcd for C39H30NO2P+H:
576.2087. Found 576.2080.
1
+218 (c 0.53, CHCl3). H NMR: 7.31–6.30 (m, 16H),
6.153 (d, 1H), 3.13–1.91 (m, 8H). 13C NMR: 146.4,
145.9, 145.5, 144.0, 143.8, 142.8, 141.8, 141.7, 139.9,
128.3, 128.2, 127.9, 127.6, 127.5, 127.4, 126.6, 123.3,

3872
W.-J. Shi et al. / Tetrahedron: Asymmetry 14 (2003) 3867–3872
122.6, 121.7, 121.1, 79.2, 19.0, 59.1, 38.5, 37.9, 31.0, 30.5.
31P NMR: 126.4. HR-MS (EI) calcd for C30H25O3P:
464.1541. Found 464.1546.
References
1. (a) Trost, B. M.; van Vranken, D. L. Chem. Rev. 1996,
96, 395; (b) Comprehensive Asymmetric Catalysis, Vol.
I–III; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H. Eds;
Springer: Berlin, 1999; (c) Helmchen, G.; Pfaltz, A.
Acc. Chem. Res. 2000, 33, 336.
4.4. General procedure for enantioselective copper-cata-
lyzed allylic alkylation
Under a nitrogen atmosphere the phosphite ligand (R)-9
(9.3 mg, 0.02 mmol) and Cu(OTf)2 (3.5 mg, 0.01 mmol)
were dissolved in diglyme (10 mL) and stirred at room
temperature for 30 min. After cooling to −30°C, the
solution was added Et2Zn (1 M in hexane, 1.2 mL, 1.2
mmol) and stirred for 5 min. Then cinnamyl bromide (198
mg, 1.0 mmol) was added and the resulting mixture was
stirred at −30°C for 24 h. The reaction was quenched with
10% aqueous H2SO4, and 68.0 mg n-tridecane was added
as a standard. The aqueous layer was extracted 2 times
with diethyl ether. The combined organic layers were
treated with brine, dried over anhydrous Na2SO4. After
purification on a short silica gel pad, the yield and
SN2%/SN2 ratio of allylic alkylation products were deter-
mined to be 95% and 98:2 respectively by GC [HP-5
column, started at 35°C, programmed at 5°C/min to
160°C, tR (SN2%)=10.50 min, tR (SN2)=14.06 min, and
tR(n-C13H28)=16.15 min]. The enantiomeric excess of
SN2% product was determined to be 56% by chiral GC
(Supelco b-DEX-120 column, 30 m, 0.25 mm, 65°C
constant, tR=65.15 and 66.62 min). The GC conditions
for the determinations of e.e. values of other allylic
alkylation products are as follows.
2. (a) Karlstro¨m, A. S. E.; Huerta, F. F.; Meuzelaar, G.
J.; Ba¨ckvall, J.-E. Synlett 2001, 923; (b) Alexakis, A.;
Malan, C.; Lea, L.; Benhaim, C.; Fournioux, X. Synlett
2001, 927; (c) Alexakis, A.; Croset, K. Org. Lett. 2002,
4, 4147; (d) Ongeri, S.; Piarulli, U.; Roux, M.; Monti,
C.; Gennari, C. Helv. Chim. Acta 2002, 85, 3388.
3. (a) Van Klaveren, M.; Persson, E. S. M.; del Villar, A.;
Grove, D. M.; Ba¨ckvall, J.-E.; van Koten, G. Tetra-
hedron Lett. 1995, 36, 3059; (b) Meuzelaar, G. J.; Karl-
stro¨m, A. S. E.; van Klaveren, M.; Persson, E. S. M.;
del Villar, A.; van Koten, G.; Ba¨ckvall, J.-E. Tetra-
hedron 2000, 56, 2895.
4. (a) Du¨bner, F.; Knochel, P. Angew. Chem. Int. Ed.
1999, 38, 379; (b) Du¨bner, F.; Knochel, P. Tetrahedron
Lett. 2000, 41, 9233.
5. (a) Luchaco-Cullis, C. A.; Mizutani, H.; Murphy, K.
E.; Hoveyda, A. H. Angew. Chem., Int. Ed. 2001, 40,
1456; (b) Murphy, K. E.; Hoveyda, A. H. J. Am.
Chem. Soc. 2003, 125, 4690.
6. Malda, H.; van Zijl, A. W.; Arnold, L. A.; Feringa, B.
L. Org. Lett. 2001, 3, 1169.
7. (a) Fu, Y.; Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang,
L.-X.; Zhou, Q.-L. Chem. Commun. 2002, 480; (b) Hu,
A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X.;
Zhou, Q.-L. Angew. Chem., Int. Ed. 2002, 41, 2348.
8. Zhou, H.; Wang, W.-H.; Fu, Y.; Xie, J.-H.; Shi, W.-J.;
Wang, L.-X.; Zhou, Q.-L. J. Org. Chem. 2003, 68,
1582.
9. (a) Birman, V. B.; Rheingold, A. L.; Lam, K.-C. Tetra-
hedron: Asymmetry 1999, 10, 125; (b) Zhang, J.-H.;
Liao, J.; Cui, X.; Yu, K.-B.; Deng, J.-G.; Zhu, S.-F.;
Wang, L.-X.; Zhou, Q.-L.; Chung, L.-W.; Ye, T. Tetra-
hedron: Asymmtry 2002, 13, 1363.
3-(4-Methylphenyl)-1-pentene:
Supelco
b-DEX-120
column (30 m, 0.25 mm ID) at 75°C constant, tR=74.61
and 76.37 min.
3-(2-Chlorophenyl)-1-pentene: Chiraldex G-TA column
(50 m, 0.25 mm ID) at 100°C constant, tR=28.48 and
31.68 min.
3-(4-Chlorophenyl)-1-pentene:
Supelco
b-DEX-120
column (30 m, 0.25 mm ID) at 100°C constant, tR=45.24
and 46.47 min.
10. Crystal data: Monoclinic, space group P2(1); a=
,
11.2872(2), b=27.1587(16), c=12.0384(7) [A]; V=
4-Methyl-3-phenyl-1-pentene:
Supelco
b-DEX-120
3
,
3642.5(4) [A ], Z=4, Crystal dimensions=0.22 x 0.20 x
column (30 m, 0.25 mm ID) at 75°C constant, tR=51.27
0.12 mm, T=293(2) K, radiation=MoKa, l=0.71073
[A], unique data=13500, R=0.0343. Crystallographic
and 53.78 min.
,
data (excluding structure factors) for the structure
reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication no. CCDC 210546. Copies of the data
can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ: [fax:
+44(0) 1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
11. De Vries, A. H. M.; Meetsma, A.; Feringa, B. L.
Angew Chem., Int. Ed. 1996, 35, 2374.
Acknowledgements
Financial supports from the National Natural Science
Foundation of China, the Major Basic Research Devel-
opment Program (Grant No. G2000077506), and the
Ministry of Education of China are gratefully
acknowledged.