Iridium-catalyzed enantioselective allylic alkylation using chiral phosphoramidite ligand bearing an amide moiety

Article abstract of DOI:10.1002/adsc.200800333

New chiral phosphoramidites with an amide moiety were used for iridium-catalyzed asymmetric allylic alkylation reactions. The best results were obtained with a ligand bearing an oxazolidinone moiety. The reaction of cinnamyl acetate with diethyl sodiomalonate without the use of lithium chloride gave the branched product with 94% ee.

Full text of DOI:10.1002/adsc.200800333

FULL PAPERS
DOI: 10.1002/adsc.200800333
Iridium-Catalyzed Enantioselective Allylic Alkylation using
Chiral Phosphoramidite Ligand Bearing an Amide Moiety
Gen Onodera,a Keijiro Watabe,a Masaki Matsubara,a Kazuhiro Oda,a
Satoko Kezuka,b and Ryo Takeuchia,*
a
Department of Chemistry and Biological Science, Aoyama Gakuin University, 5-10-1 Fuchinobe, Sagamihara, Kanagawa
229-8558, Japan
Fax : (+81)-42-759-6493; e-mail: takeuchi@chem.aoyama.ac.jp
Present address: Department of Applied Chemistry, Tokai University, Hiratsuka 259-1292, Japan
b
Received: June 1, 2008; Revised: September 20, 2008; Published online: November 19, 2008
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800333.
Abstract: New chiral phosphoramidites with an diethyl sodiomalonate without the use of lithium
amide moiety were used for iridium-catalyzed asym- chloride gave the branched product with 94% ee.
metric allylic alkylation reactions. The best results
were obtained with a ligand bearing an oxazolidi- Keywords: allylic substitution; asymmetric catalysis;
À
none moiety. The reaction of cinnamyl acetate with C C bond formation; iridium; phosphoramidites
Introduction
come: (1) a stoichiometric amount of LiCl is needed
for high regio- and enantioselectivity. The reaction
Asymmetric allylic alkylation is one of the most pow- without LiCl gave considerably lower regio- and
erful tools for constructing a new chiral center via a enantioselectivity. For example, the reaction of cin-
carbon-carbon bond-forming reaction from an achiral namyl carbonate with dimethyl sodiomalonate with-
substrate or a racemic substrate.[1] A challenging topic out LiCl gave products in 31% yield with 65%
in this area is the regio- and enantioselective allylic branched product-selectivity.[5d] The enantioselectivity
alkylation of unsymmetrical substrates. In 1997, we was 44% ee. The development of a reaction without
first reported that [IrACHTNUTGRNEUNG
(cod)Cl]2 and triphenylphosphite LiCl is desired.[8] (2) The reaction of acetates is quite
comprised an efficient catalyst system for the allylic slow. For example, it took 18 h to complete the reac-
alkylation reaction of terminally monosubstituted al- tion of cinnamyl acetate with dimethyl sodiomalonate
lylic acetates to give a branched product with high se- even in the presence of LiCl.[4d] The development of
lectivity.[2] We also reported on the highly branched an efficient reaction of acetates is desired. The enan-
product-selective allylic amination in 2001.[3] Based tioselective allylic amination and etherification using
on our results, iridium-catalyzed asymmetric allylic al- a similar phosphoramidite ligand were reported by
kylation has been explored.[4,5,6] Helmchen and co- Hartwig and co-workers.[9] The binaphthol-based
workers reported the first example of iridium-cata- phosphoramidite ligand bearing a chiral bis(1-aryle-
lyzed asymmetric allylic alkylation using a chiral oxa- thyl)amine moiety has been successfully used for
zolinyl-phosphine ligand.[4a]
enantioselective allylic substitution. It has three chiral
Chiral phosphoramidite ligands have become im- elements that are derived from binaphthol and bis(1-
portant in transition metal-catalyzed asymmetric syn- arylethyl)amine.[4d–f,h–l,5,6,9] New ligands are still needed
thesis.[7] Helmchen first used binaphthol-based phos- to expand the scope and enhance the selectivity of al-
phoramidites for iridium-catalyzed enantioselective lylic substitution. We designed a novel phosphorami-
allylic alkylation.[4b] Alexakis and co-workers im- dite P(OR)
2ACTHNUTRGNE(NUG amide) ligand. The planarity of the
proved the enantioselectivity (up to 98% ee) of allylic amide group strongly contributes to a more rigid
alkylation by using a relatively bulky phosphorami- chiral conformation. Furthermore, such a phosphora-
dite ligand bearing a chiral bis[1-(o-methoxyphenyl)- midite ligand is expected to act as a chiral bidentate
ethyl]amine moiety.[5] Although the enantioselectivity ligand through coordination of the carbonyl oxygen
is high, the following limitations still need to be over- and phosphorus atom to the central metal (Figure 1).
Adv. Synth. Catal. 2008, 350, 2725 – 2732
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Gen Onodera et al.
FULL PAPERS
Figure 1. Chiral phosphoramidate ligand as
a bidentate
ligand.
To the best of our knowledge, there has been only
one previous example of a chiral phosphoramidite
with an amide moiety: the rhodium-catalyzed enan-
tioselective hydrogenation of enones using the phos-
phoramidite ligand prepared from 1,1’-bi-2-naphthol Figure 3. ORTEP drawing of L1. Hydrogen atoms are omit-
and e-caprolactam.[10] We describe here the iridium-
catalyzed enantioselective allylic alkylation using a
newly prepared chiral phosphoramidite bearing an
amide moiety. Enantioselectivities of up to 94% ee
were achieved by the reaction of acetates without the
use of LiCl.
ted for clarity. Thermal ellipsoids are drawn at 50% proba-
bility. Selected bond lengths (ꢁ), angles (deg), and torsion
À
À
À
angles (deg): P1 O1, 1.654(3); P1 O2, 1.617(5); P1 N1,
1.715(4); O1 P1 O2, 99.76(17); O1 P1 N1, 92.57(19); O2
À
À
À
À
À
À
À
À
À
À
P1 N1, 102.7(2); P1 N1 C21, 120.2(3); P1 N1 C23,
À
À
À
À
128.9(3); C21 N1 C23, 110.6(4); N1 C21 O3, 110.2(5);
À
À
À
À
À
À
À
N1 C21 O4, 126.2(5); O3 C21 O4, 123.5(5); P1 N1 C21
O4, 9.9(13).
Results and Discussion
L3, which shows that these four atoms lie in nearly
The chiral phosphoramidite ligands L1–L9 were pre- the same plane in both cases.
pared from 1,1’-bi-2-naphthol and amides in two
The efficiency of ligands L1–L9 was examined for
steps. A chiral phosphorochloridite was formed from the reaction of cinnamyl acetate (1a) with diethyl so-
phosphorus trichloride and 1,1’-bi-2-naphthol, and diomalonate in the presence of 2 mol% of [Ir-
then coupled with an amide to give the corresponding
ACHTUNGTRNEUN(NG cod)Cl]2 and 4 mol% of ligand. The best ligand for
chiral phosphoramidite (Figure 2). X-ray analyses of the reaction was L1, which had an oxazolidinone
ligands L1 and L3 clearly show the planar framework moiety. The alkylated product was obtained in 94%
of the amide group. ORTEP drawings of L1 and L3 yield with 93% ee (S) without LiCl (Table 1,
are shown in Figure 3 and Figure 4, respectively. The entry 1).[11] The reaction was complete in 1.5 h at
À À
torsion angle of P N C=O is 9.98 in L1 and 10.58 in room temperature. The use of LiCl in the reaction
Figure 2. Newly prepared chiral phosphoramidite ligands.
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Iridium-Catalyzed Enantioselective Allylic Alkylation using Chiral Phosphoramidite Ligand
FULL PAPERS
with L1 did not increase the regio- or enantioselectivi-
ty, and did not accelerate the reaction (entry 3). The
use of NaHMDS or LiHMDS as a base instead of
NaH decreased the yields and enantioselectivities (en-
tries 4 and 5). Replacement of the oxygen atom in the
oxazolidinone moiety with a carbon or nitrogen atom
led to almost the same level of regio- and enantiose-
lectivities given by L1 (entries 6–9). With L2 and L3,
LiCl slightly improved the enantioselectivity. The
enantioselectivity given with L2 derived from pyrroli-
dinone was 90% ee (entry 6). The use of LiCl in-
creased the enantioselectivity to 93% ee (entry 7).
Ligand L3 derived from N-methylimidazolidinone
was slightly less effective than L1. The reaction gave
a product in 89% ee (entry 8). The use of LiCl in-
creased the enantioselectivity to 94% ee (entry 9). A
six-membered ring amide moiety was far less effective
Figure 4. ORTEP drawing of L3. Hydrogen atoms are omit-
ted for clarity. Thermal ellipsoids are drawn at 50% proba-
bility. Selected bond lengths (ꢁ), angles (deg), and torsion
À
À
À
angles (deg): P1 O1, 1.6537(11); P1 O2, 1.6394(12); P1
À
À
À À
N1, 1.6768(13); O1 P1 O2, 99.00(6); O1 P1 N1, 94.27(7);
O2 P1 N1, 105.47(7); P1 N1 C21, 119.82(11); P1 N1
À
À
À
À
À
À
À
À
À
À
C22, 130.21(11); C21 N1 C22, 109.68(12); N1 C21 N2,
À
À
À
À
108.10(14);
N1 C21 O3,
125.03(15);
N2 C21 O3,
À
À
À
126.86(16); P1 N1 C21 O3, 10.5(2).
Table 1. Reactions of allylic acetate (1a) with diethyl sodiomalonate (2a) in the presence of [Ir
ACHTUNGTERN(NUNG cod)Cl]2 and phosphorami-
dite ligand (L1–L9).[a]
Entry
Ligand
Additive
Time [h]
Yield [%][b]
3aa/3’aa[c]
ee [%][d]
1
L1
L1
L1
L1
L1
L2
L2
L3
L3
L4
L4
L5
L5
L6
L6
L7
L7
L8
L8
L9
L9
none
none
LiCl
none
none
none
LiCl
none
LiCl
none
LiCl
none
LiCl
none
LiCl
none
LiCl
none
LiCl
none
LiCl
1.5
5
1.5
4
24
2
2
94
88
91
86
23
96
97
98
97
37
88
89
56
83
48
97
97
98
94
96
94
>99/1
>99/1
>99/1
>99/1
96/4
>99/1
>99/1
>99/1
>99/1
94/6
93 (S)
94 (S)
93 (S)
80 (S)
6 (R)
2[e]
3
4[f]
5[g]
6
7
8
90 (S)
93 (S)
89 (S)
94 (S)
28 (S)
23 (S)
39 (S)
33 (S)
37 (S)
50 (S)
91 (S)
93 (S)
91 (S)
91 (S)
16 (S)
55 (S)
1
9
0.5
48
16
7
24
24
24
2.5
2
3
2
4
4
10
11
12
13
14
15
16
17
18
19
20
21
97/3
91/9
75/25
81/19
75/25
>99/1
>99/1
99/1
99/1
93/7
78/22
[a]
All reactions of 1a (1 mmol) with diethyl sodiomalonate (2a) (2 mmol), which was prepared from diethyl malonate and
NaH, were carried out in the presence of [Ir
ACHTUNGTRNE(NUGN cod)Cl]2 (0.02 mmol), and ligand (L1–L9, P/Ir=1) in THF (5 mL) at room
temperature.
Isolated yields.
Determined by H NMR.
Determined by HPLC analysis using Chiralcel OJ-H.
0.08 mmol of L1 was used.
NaHMDS was used instead of NaH.
LiHMDS was used instead of NaH.
[b]
[c]
[d]
[e]
[f]
1
[g]
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Gen Onodera et al.
ACHTUNGTRENNUNG
(cod)Cl]2 and L1.[a]
FULL PAPERS
Table 2. Reactions of cinnamyl acetate (1a) with various sodiomalonates (2) in the presence of [Ir
Entry
NaNu
Additive
Time [h]
Yield [%][b]
3/3’[c]
ee [%][d]
1
2
3
4
5
6
7
8
NaCH
NaCH
NaCH
NaCH
NaCMe
NaCMe
U
none
LiCl
none
LiCl
none
LiCl
none
LiCl
1.5
1.5
2
94
91
94
94
77
59
39
28
>99/1
>99/1
>99/1
>99/1
94/6
91/9
93/7
93/7
93 (S)
93 (S)
89 (S)[e]
93 (S)[e]
75
62
45
69
1
G
E
24
24
48
48
NaC
NaC
U
R
E
[a]
All reactions of 1a (1 mmol) with sodiomalonate (2) (2 mmol), which was prepared from malonate and NaH, were car-
ried out in the presence of [Ir(cod)Cl]2 (0.02 mmol), and ligand (L1, P/Ir=1) in THF (5 mL) at room temperature.
AHCTUNGTRENNUNG
[b]
[c]
[d]
[e]
Isolated yields.
Determined by H NMR.
1
Determined by HPLC analysis using chiral column.
The absolute configuration was determined by comparison of the value of the optical rotation with that reported in the
literature.[5d]
than a five-membered ring amide moiety. With L4 led to better enantioselectivity than L3, except for the
prepared from d-valerolactam, the yield and enantio- reaction of 3-(1-naphthyl)-2-propenyl acetate (1b).
selectivity were considerably decreased (entries 10 All of the reactions without LiCl were highly
and 11). Although ligands L5–L8 had two chiral cen- branched product-selective and were complete within
ters, L1 was better than L5–L8. Ligands L5 and L6 2 h at room temperature. The use of LiCl did not im-
were not effective in the reaction, while reactions prove the rate or regioselectivity in any case. LiCl
using L7 and L8 gave 91% ee (entries 12–19). The ste- had only a slight effect on enantioselectivity. With L1,
reochemistry of the product 3aa was the same when the maximum increase in enantioselectivity with the
L5–L8 were used (entries 12–19). The stereochemistry use of LiCl was only 11% (entries 17 and 18). With
of the binaphthol moiety in the ligand determined the L3, the maximum increase was 15% (entries 29, 30.
stereochemistry of the product. The use of LiCl in the 37, and 38). The reaction of 3-(2-naphthyl)-2-propenyl
reaction with L7 improved the enantioselectivity by acetate (1c) was more enantioselective than that of 3-
only 2% (entry 17). With L8, LiCl did not improve (1-naphthyl)-2-propenyl acetate (1b) (entries 5–12).
the enantioselectivity (entries 18 and 19). The ligand The substituent on the aromatic ring affected the
L9 bearing an acyclic amide moiety was less effective enantioselectivity. The reaction of 3-(4-trifluorome-
than L1 (entries 20 and 21).
thyphenyl)-2-propenyl acetate (1g) gave a lower
Asymmetric allylic alkylations of cinnamyl acetate enantioselectivity than that of a substrate substituted
(1a) with various sodiomalonates (2) in the presence by an electron-rich aromatic ring, such as 1d–1f (en-
of catalytic amounts of [IrACTHNUTRGNEG(NU cod)Cl]2 and L1 are sum- tries 25–28). 2,4-Dienyl acetates (1h–1j) reacted with
marized in Table 2. The reaction with diethyl sodio- diethyl sodiomalonate to give the branched products
malonate (2a) without LiCl was slightly more enantio- (3ha–3ja) in good yields with good enantioselectivities
selective than that with dimethyl sodiomalonate (2b) (entries 29–40).[4e,f,h]
without LiCl (entries 1 and 3). The use of LiCl in the
Construction of a chiral all-carbon-substituted qua-
reaction with dimethyl sodiomalonate (2b) improved ternary carbon center on an allylic site is a challeng-
the enantioselectivity by only 4% (entry 4). The reac- ing problem in enantioselective allylic alkylation.[12]
tion using a-substituted sodiomalonates (2c–d) de- We examined the allylic alkylation of (E)-3-phenyl-2-
creased the yields and the regio- and enantioselectivi- butenyl acetate. Branched-product selective allylic al-
ties (entries 5–8).
kylation gives a product bearing a chiral all-carbon-
The results of the reactions of various allylic ace- substituted quaternary carbon center. The reaction of
tates (1) with diethyl sodiomalonate (2a) using L1 or (E)-3-phenyl-2-butenyl acetate in refluxing THF for
L3 are shown in Table 3. These reactions were per- 48 h gave no alkylated product with a quantitative re-
formed in the absence or presence of LiCl. Ligand L1 covery of the starting material. The carbonate was
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Iridium-Catalyzed Enantioselective Allylic Alkylation using Chiral Phosphoramidite Ligand
FULL PAPERS
Table 3. Reactions of various allylic acetates (1) with diethyl sodiomalonate (2a) in the presence of [Ir
(L1 or L3).[a]
ACHTUNGTRNE(NNUG cod)Cl]2 and ligand
Entry
R
Ligand
Additive
Time [h]
Yield [%][b]
3/3’[c]
ee [%][d]
1
2
3
4
L1
L1
L3
L3
none
LiCl
none
LiCl
1.5
1.5
1
94
91
98
97
>99/1
>99/1
>99/1
>99/1
93 (S)
93 (S)
89 (S)
94 (S)
0.5
5
6
7
8
L1
L1
L3
L3
none
LiCl
none
LiCl
1
0.5
1
88
94
93
94
>99/1
>99/1
>99/1
>99/1
72
80
81
81
0.5
9
L1
L1
L3
L3
none
LiCl
none
LiCl
1.5
1.5
1
84
88
94
92
>99/1
>99/1
>99/1
>99/1
89
89
80
93
10
11
12
1
13
14
15
16
L1
L1
L3
L3
none
LiCl
none
LiCl
1
1
1
0.5
95
95
91
94
>99/1
>99/1
>99/1
>99/1
87
89
87
94
17
18
19
20
L1
L1
L3
L3
none
LiCl
none
LiCl
1
1
1
0.5
85
92
84
83
>99/1
>99/1
>99/1
>99/1
84
91
77
92
21
22
23
24
L1
L1
L3
L3
none
LiCl
none
LiCl
1
0.5
1
91
90
89
95
>99/1
>99/1
>99/1
>99/1
90
89
88
93
0.5
25
26
27
28
L1
L1
L3
L3
none
LiCl
none
LiCl
1
1
1
1
90
87
92
95
>99/1
>99/1
>99/1
>99/1
79
77
78
87
29
30
31
32
L1
L1
L3
L3
none
LiCl
none
LiCl
2
1
1.5
1.5
85
83
90
90
>99/1
>99/1
>99/1
>99/1
72
83
71
80
33
34
35
36
L1
L1
L3
L3
none
LiCl
none
LiCl
1.5
1.5
1.5
1.5
74
74
80
76
>99/1
>99/1
>99/1
>99/1
72
79
64
78
37
38
39
40
L1
L1
L3
L3
none
LiCl
none
LiCl
1.5
1
1.5
1
82
84
82
87
>99/1
>99/1
>99/1
>99/1
72
83
70
81
[a]
All reactions of 1 (1 mmol) with diethyl sodiomalonate (2a) (2 mmol), which was prepared from diethyl malonate and
NaH, were carried out in the presence of [Ir
ACHTUNGTRNE(NUGN cod)Cl]2 (0.02 mmol), and ligand (L1 or L3, P/Ir=1) in THF (5 mL) at
room temperature.
[b]
[c]
[d]
Isolated yields.
Determined by H NMR.
1
Determined by HPLC analysis using chiral column.
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Gen Onodera et al.
FULL PAPERS
Scheme 1.
more reactive than the acetate. The reaction of (E)-3- hydrogen of the terminal allylic carbon suggests that
phenyl-2-butenyl ethyl carbonate (1k) gave the transition state B is less favored.
branched product 3ka in low yield (Scheme 1).
To obtain insight into the mechanism, we examined
the 31P NMR spectrum of a 1:2 mixture of [Ir
and L1 in THF-d8. The chemical shift of L1 was
G
140.3 ppm, while the spectrum of a 1:2 mixture of [Ir- In summary, we have prepared new chiral phosphor-
A
ACHTUNGTRENaNUNG midites with an amide framework, and found that
111.2 ppm. This result indicated that a single iridium these phosphoramidites were useful ligands for iridi-
species coordinated by one molecule of L1 was um-catalyzed asymmetric allylic alkylation. Further
formed.
synthetic applications and investigations of mechanis-
Two plausible transition states of the nucleophilic tic details are currently in progress.
attack to p-allyliridium intermediates are shown in
Figure 5. Ligand L1 acts as a bidentate ligand. The
phosphorus atom and carbonyl oxygen atom in L1 co-
ordinate to iridium to form five-membered ring chela-
tion, which leads to a stable chiral structure. The effi-
ciency of L1 is due to the planarity of the amide
group and bidentate coordination. The phosphorus
atom coordinates with the iridium trans to the substi-
tuted allylic terminus to deliver sodiomalonate at the
substituted allylic terminus. Considering that the ab-
solute configuration of alkylated product was (S)
when L1 was used as a ligand, transition state A
seems to be more favorable than transition state B.
The steric repulsion between a naphthyl moiety and a
Experimental Section
General
1H, 13C, and 31P NMR spectra were measured on a JEOL
JNM-ECP 500 A spectrometer using Me4Si and phosphoric
acid as an internal standard. Samples were dissolved in
CDCl3. GC analyses were performed on a Shimadzu GC-
14B using 3.2 mmꢂ2 m glass columns packed with 5% OV-
17 on 60/80 mesh Chromosorb WAW-DMCS. The products
were purified by column chromatography on 63–210 mesh
silica gel (Kanto Kagaku; Silica Gel 60N). Optical rotations
were measured on a Jasco P-1020 Polarimeter. High-resolu-
tion mass spectra were obtained with a JEOL Mstation
JMS-700.
Figure 5. Two plausible transition states of the nucleophilic attack to p-allyliridium intermediates.
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Iridium-Catalyzed Enantioselective Allylic Alkylation using Chiral Phosphoramidite Ligand
FULL PAPERS
area detector with graphite monochromated Mo-Ka radia-
tion. Details of crystal and data collection parameters are
summarized in the Supporting Information. The structure
was solved by direct methods SHELXS-97 and refined by
full-matrix least-squares against F2 using SHELXL-97 soft-
ware.[17] Crystallographic data for L1: C23H16NO4P, fw =
401.34, hexagonal, P65, a=15.251(3) ꢁ, c=15.465(4) ꢁ, V=
3115.2(11) ꢁ3, Z=6, 17135 reflections measured, 4785
unique (Rint =0.0780), R1 =0.0923, wR2 =0.2325, GOF=
1.362. CCDC 687334 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Materials
All reagents and solvents were dried and purified before use
by the usual procedures. (S)-1,1’-Bi-2-naphthol, phosphoryl
chloride, 2-oxazolidinone, 2-pyrrolidinone, 2-piperidinone,
(R)-(À)-4-phenyl-2-oxazolidinone, (S)-(+)-4-phenyl-2-oxa-
zolidinone, and maleimide were purchased. N-Methyl-2-imi-
dazolidinone,[13] (R)-5-phenyl-2-oxazolidinone,[14] and (S)-5-
phenyl-2-oxazolidinone[14] were prepared as described in the
literature. 3-Substituted-2-propen-1-ols were prepared as de-
scribed in the literature.[3a] [Ir
ACTHNUTRGEN(NUG cod)Cl]2 was prepared as de-
scribed in the literature.[15] (E)-3-Phenyl-2-butenyl ethyl car-
bonate (1k) was prepared from acetophenone in three
steps.[16]
X-Ray Crystallographic Studies of L3
Synthesis of Chiral Phosphoramidite Ligands
Colorless crystals of L3 suitable for X-ray analysis were ob-
tained by recrystallization from CH2Cl2/n-hexane. A single
crystal was mounted using liquid paraffin to a 0.4–0.5 mm
cryoloop (Hampton Research) and used for data collection.
All measurements were made on a Bruker APEX II CCD
area detector with graphite monochromated Mo-Ka radia-
tion. Details of crystal and data collection parameters are
summarized in supporting information. The structure was
solved by direct methods SHELXS-97 and refined by full-
matrix least-squares against F2 using SHELXL-97 soft-
ware.[17] Crystallographic data for L3: C24H19N2O3P, fw =
414.38, orthorhombic, P212121, a=7.9277(16) ꢁ, b=
14.406(3) ꢁ, c=17.957(4) ꢁ, V=2050.8(7) ꢁ3, Z=4, 10611
reflections measured, 4436 unique (Rint =0.0556), R1 =
0.0398, wR2 =0.0661, GOF=1.493. CCDC 687335 contains
the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cam-
bridge Crystallographic Data Centre via www.ccdc.cam.
ac.uk/data_request/cif.
A typical experimental procedure for the synthesis of chiral
phosphoramidite ligands (L1–L9) is described below. Into a
two-necked flask with a stirring bar was placed (S)-(À)-1,1’-
bi-2-naphthol (1.43 g, 5.0 mmol). The flask was evacuated
and filled with argon. PCl3 (8.0 mL) was added to the flask.
The reaction mixture was heated under reflux temperature
(708C) overnight to form the phosphorochloridite. Excess
PCl3 was removed by azeotropic distillation with toluene at
1408C. To a stirred solution of 2-oxazolidinone (434 mg,
5.0 mmol) in anhydrous THF (30 mL) was added triethyl-
amine (2.0 mL) at 08C, and to this was added the solution
of phosphorochloridite in anhydrous THF (3 mL). After
being stirred at room temperature for 40 h, the reaction
mixture was filtered on Florisil. Recrystallization from
CH2Cl2/n-hexane gave phosphoramidite L1; yield: 957 mg
(2.4 mmol, 48%); [a]D28: +491.9 (c 1.00, CHCl3). 1H NMR
(500 MHz, CDCl3): d=2.64 (ddd, J=10.1, 8.7 and 6.9 Hz,
1H), 3.55 (ddd, J=10.1, 8.7 and 6.9 Hz, 1H), 4.14 (ddd, J=
8.7, 8.7 and 6.9 Hz, 1H), 4.19 (ddd, J=8.7, 8.7 and 6.9 Hz,
1H), 7.25–7.53 (m, 8H), 7.94–8.03 (m, 4H); 13C NMR
(125 MHz, CDCl3): d=42.4, 42.5, 64.57, 64.58, 120.7, 121.03,
121.04, 123.00, 123.02, 123.7, 123.8, 125.38, 125.40, 126.57,
126.63, 126.7, 126.8, 128.41, 128.45, 130.5, 131.0, 131.1, 131.7,
132.42, 132.43, 132.61, 132.62, 148.0, 148.30, 148.34, 159.0,
159.2; 31P NMR (202 MHz, CDCl3): d=138.2: HR-MS: m/
z=401.0804, calcd for C23H16NO4P (M+): 401.0817.
Asymmetric Allylic Alkylation
A typical procedure of asymmetric allylic alkylation is de-
scribed below.
A flask was charged with [IrACHTUNTGNERUG(N cod)Cl]2
(14.2 mg, 0.02 mmol) and L1 (16.5 mg, 0.04 mmol). The flask
was evacuated and filled with argon. To the flask were
added THF (2.5 mL) and cinnamyl acetate (187.8 mg,
1.07 mmol). Diethyl sodiomalonate was prepared in another
flask. To the flask which contained a THF (2.5 mL) solution
of sodium hydride (60% in oil, 83.4 mg, 2.1 mmol) was
added diethyl malonate (360.7 mg, 2.3 mmol) at 08C. A
THF solution of sodium malonate was added to the reaction
mixture. The mixture was stirred at room temperature for
2 h. The progress of the reaction was monitored by GLC.
After the reaction was complete, to the mixture was added
saturated aqueous NH4Cl, and the aqueous layer was ex-
tracted with ether. The combined organic layers were dried
with Mg2SO4. The solvent was evaporated under vacuum.
Column chromatography of the residue gave 3aa as a color-
L3; yield: 40%; [a]D23: +351.9 (c 0.21 CHCl3). 1H NMR
(500 MHz, CDCl3): d=2.50 (ddd, J=9.6, 9.2 and 6.9 Hz,
1H), 2.83 (s, 3H), 3.12 (ddd, J=9.2, 8.7 and 6.4 Hz, 1H),
3.16 (ddd, J=9.2, 8.7 and 6.4 Hz, 1H), 3.34 (ddd, J=9.6, 9.2
and 6.4 Hz, 1H), 7.21–7.30 (m, 3H), 7.37–7.51 (m, 5H),
7.90–7.98 (m, 4H); 13C NMR (125 MHz, CDCl3): d=30.3,
38.96, 39.01, 46.3, 121.2, 121.3, 121.4, 122.96, 122.98, 123.79,
123.83, 125.0, 125.1, 126.30, 126.33, 126.7, 126.8, 128.3, 128.4,
130.2, 130.7, 130.9, 131.5, 132.4, 132.5, 132.63, 132.64, 148.7,
149.0, 149.1, 160.3, 160.5; 31P NMR (202 MHz, CDCl3): d=
140.6; HR-MS: m/z=414.1129, calcd. for C24H19N2O3P
(M+): 414.1133.
less
oil
(n-hexane/AcOEt=95/5);
yield:
278.1 mg
(1.01 mmol, 94%). The ee value was determined by HPLC
analysis with a Chiralcel OJ-H column [eluent: n-hexane/
ethanol=99/1, flow rate: 0.5 mLminÀ1, column temperature:
358C, retention time: 25.75 min (S) and 29.23 min (R)].
[a]2D4: À26.2 (c 1.01, CHCl3) [94% ee (S)]. 1H NMR
(500 MHz, CDCl3): d=0.98 (t, J=7.3 Hz, 3H), 1.27 (t, J=
7.3 Hz, 3H), 3.83 (d, J=11.0 Hz, 1H), 3.89–3.98 (m, 2H),
X-Ray Crystallographic Studies of L1
Colorless crystals of L1 suitable for X-ray analysis were ob-
tained by recrystallization from CH2Cl2/n-hexane. A single
crystal was mounted using liquid paraffin to a 0.4–0.5 mm
cryoloop (Hampton Research) and used for data collection.
All measurements were made on a Bruker APEX II CCD
Adv. Synth. Catal. 2008, 350, 2725 – 2732
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2731

Gen Onodera et al.
FULL PAPERS
4.10 (dd, J=11.0 and 8.2 Hz, 1H), 4.21 (q, J=7.3 Hz, 2H),
5.08 (d, J=10.1 Hz, 1H), 5.12 (d, J=17.0 Hz, 1H), 6.00
(ddd, J=17.0, 10.1 and 8.2 Hz, 1H), 7.21–7.30 (m, 5H);
13C NMR (125 MHz, CDCl3): d=13.7, 14.1, 49.6, 57.4, 61.2,
61.5, 116.4, 127.0, 128.0 (2C), 128.5 (2C), 137.9, 140.0, 167.4,
167.8.
Org. Lett. 2004, 6, 3529; c) D. Polet, A. Alexakis, Org.
Lett. 2005, 7, 1621; d) D. Polet, A. Alexakis, K. Tissot-
Croset, C. Corminboeuf, K. Ditrich, Chem. Eur. J.
2006, 12, 3596; e) A. Alexakis, S. E. Hajjaji, D. Polet,
X. Rathgeb, Org. Lett. 2007, 9, 3393.
[6] a) T. Graening, J. F. Hartwig, J. Am. Chem. Soc. 2005,
127, 17192; b) D. J. Weix, J. F. Hartwig, J. Am. Chem.
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Dai, S.-L. You, Org. Lett. 2007, 9, 4339.
Supporting Information
Experimental procedures, compound characterization data,
crystal structure analysis, and NMR spectra are available in
the Supporting Information.
[7] For reviews, see: a) B. L. Feringa, Acc. Chem. Res.
2000, 33, 346; b) A. J. Minnaard, B. L. Feringa, L.
Lefort, J. G. de Vries, Acc. Chem. Res. 2007, 40, 1267.
[8] It is well known that the Pd-catalyzed reaction of allyl
carbonate with malonate gives a product under neutral
conditions, see: J. Tsuji, I. Minami, Acc. Chem. Res.
1987, 20, 140. Recently, Helmchen et al. used this
chemistry under Ir catalysis. The reaction without LiCl
gave the product in high enantioselectivity. However,
this methodology is limited to allyl carbonate and re-
quires preactivation of the Ir catalyst.[4l].
Acknowledgements
This research was supported financially by a grant from the
Ministry of Education, Culture, Sports, Science and Technol-
ogy of Japan and a grant from Research Institute of Aoyama
Gakuin University.
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2732
asc.wiley-vch.de
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2008, 350, 2725 – 2732