Chiral bifunctional thiourea-phosphane organocatalysts in asymmetric allylic amination of Morita-Baylis-Hillman acetates

Article abstract of DOI:10.1002/ejoc.201001660

A series of new chiral bifunctional thiourea-phosphane catalysts was synthesized and successfully applied in the catalytic, asymmetric allylic amination of Morita-Baylis-Hillman (MBH) acetates derived from the methyl vinyl ketone (MVK) or ethyl vinyl keto

Full text of DOI:10.1002/ejoc.201001660

FULL PAPER
DOI: 10.1002/ejoc.201001660
Chiral Bifunctional Thiourea–Phosphane Organocatalysts in Asymmetric
Allylic Amination of Morita–Baylis–Hillman Acetates
Hong-Ping Deng,[a] Yin Wei,[a] and Min Shi*[a]
Keywords: Organocatalysis / Asymmetric catalysis / Amination / MBH acetates / Phthalimides
A series of new chiral bifunctional thiourea–phosphane cata-
lysts was synthesized and successfully applied in the cata-
lytic, asymmetric allylic amination of Morita–Baylis–Hillman
(MBH) acetates derived from the methyl vinyl ketone (MVK)
or ethyl vinyl ketone (EVK) system, with phthalimide, afford-
ing the amination products in up to over 99% yield and 90%
ee for a wide range of substrates derived from different aro-
matic aldehydes.
recently, Wang and co-workers also reported the construc-
tion of chiral allylic phosphane oxides by using cinchona
alkaloids as catalysts through substitution of MBH carbon-
ates in excellent yields along with high enantioselectivities.[6]
In these successful examples, acetates or carbonates of
MBH alcohols derived from acrylate are commonly used
starting materials; however, highly enantioselective substi-
tutions of acetates or carbonates of MBH alcohols derived
from methyl vinyl ketone (MVK) or ethyl vinyl ketone
(EVK) have seldom been reported,[2b,3a,4,7] except by our
group using chiral bifunctional phosphanes as catalysts to
enantioselectively construct γ-butenolides in high yields and
ee values.[8] At the present stage, finding new catalysts to
achieve the highly enantioselective substitution of MBH
acetates or carbonates derived from MVK or EVK is still
a highly desirable goal.
Chiral bifunctional phosphane organocatalysts, which
contain Lewis basic and Brønsted acidic sites within one
molecule, have received considerable attention due to their
high efficiency and excellent enantioselectivities in the
asymmetric MBH/aza-MBH reaction, cycloaddition of all-
enic esters, and other related reactions.[9] Thus far, the
groups of Miller[10] and Zhao[11] reported that chiral bifunc-
tional phosphane catalysts derived from amino acids could
catalyze [3+2] cycloaddition between allenic esters and elec-
tron-deficient olefins, affording the cyclopentene derivatives
in excellent diastereo- and enantioselectivities, respectively.
In 2008, Jacobsen developed a series of thiourea–phos-
phane catalysts derived from chiral trans-2-amino-1-(di-
phenylphosphanyl)cyclohexane, which succeeded in catalyz-
ing imine-allene [3+2] cycloaddition with high enantio-
selectivities.[12] More recently, Wu and co-workers reported
thiourea–phosphane catalysts with the trans-2-amino-1-(di-
phenylphosphanyl)cyclohexane skeleton, which could cata-
lyze the asymmetric MBH reaction of aldehydes with MVK
in excellent enantioselectivities,[13a] and thiourea–phos-
phane catalysts derived from amino acids succeeded in cata-
Introduction
β-Hydroxy-α-methylene-carbonyl-containing compounds
or their derivatives are valuable building blocks in organic
synthesis, due to their densely multifunctional characteris-
tics.[1] Recently, efforts to synthesize these chiral com-
pounds have been directed toward the following two as-
pects: the asymmetric Morita–Baylis–Hillman (MBH) reac-
tion and the asymmetric substitution of MBH acetates or
carbonates. Compared with the asymmetric MBH reaction,
the asymmetric substitution of MBH acetates or carbonates
received wider interest from scientists, because it is appli-
cable to a broader range of substrates.[2] In 2004, Krische[2b]
first reported the asymmetric substitution of MBH acetates
with phthalimide and its derivatives, catalyzed by chiral
phosphanes, to give the corresponding substitution prod-
ucts in good yields along with moderate ee values. Later on,
Lu[3a] and Hiemstra[3b] reported the asymmetric substitu-
tion of MBH carbonates with various nucleophiles, cata-
lyzed by 4-(3-ethyl-4-oxa-1-azatricyclo[4,4,0,03,8]dec-5-yl)-
quinolin-6-ol (β-ICD), affording the corresponding amin-
ation products in excellent yields along with modest ee val-
ues. In 2007, Hou and co-workers used planar chiral [2,2]-
paracyclophane monophosphanes as catalysts to provide
the allylic amination products in high regioselectivities and
modest enantioselectivities (9–71% ees).[4] Moreover, thus
far, Chen and co-workers have used (DHQD)2AQN,
(DHQD)2PHAL, (DHQD)2PYR, and β-ICD in asymmet-
ric substitutions of MBH carbonates to achieve C–C
bond,[5a–5d] C–N bond,[5e–5f] and C–O bond[5g–5h] formation
in good yields along with high enantioselectivities. More
[a] State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Road, Shanghai 200032 China
Fax: +86-21-64166128
E-mail: mshi@mail.sioc.ac.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001660.
1956
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Chiral Bifunctional Thiourea–Phosphane Organocatalysts
lyzing inter- and intramolecular asymmetric MBH reac- and lower yield (Table 1, entry 4). Using TP5 as catalyst,
tions.[13b–13c] Our group has also developed a series of chiral we also utilized MBH benzoate or MBH carbonate as sub-
bifunctional phosphane organocatalysts and demonstrated strate instead of MBH acetate in this reaction and found
their excellent catalytic activities and enantioselectivities for that MBH benzoate gave 3a in a lower yield (Table 1, entry
the asymmetric aza-MBH reaction[14] and their good cata- 12) and MBH carbonate afforded 3a in a lower ee value
lytic activities and modest enantioselectivities for the allylic under the standard conditions (Table 1, entry 13) employed.
amination of MBH acetates derived from MVK.[7] As a
Table 1. Catalyst screening for the reaction of MVK-derived MBH
part of our continuing interest in chiral bifunctional phos-
acetate 1a with phthalimide 2.
phane organocatalysts,[15] we developed a series of chiral
bifunctional thiourea–phosphane organocatalysts (TP) and
examined their performance for the allylic amination of
MBH acetates with phthalimide. Herein, we are delighted
to report our new chiral bifunctional thiourea–phosphane
organocatalysts, which can achieve highly enantioselective
allylic amination of acetates of MBH alcohols derived from
MVK and EVK for the first time.
Entry[a]
Catalyst
R
Time [h] Yield [%][a] ee [%][b]
1
2
3
4
5
6
7
8
TP1
TP2
TP3
TP4
TP5
TP6
TP7
TP8
TP9
TP10
TP11
TP5
TP5
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OAc
OBz
OBoc
48
80
18
107
22
24
24
36
15
24
14
69
24
20
23
94
69
80
77
80
83
88
71
86
57
80
26
56
82
82
85
80
81
74
83
74
79
84
67
Results and Discussion
Initially, we tested the chiral bifunctional thiourea–phos-
phane TP1 (Figure 1), which was an excellent catalyst for
the asymmetric aza-MBH reaction,[14g] in the reaction of
MVK-derived MBH acetate 1a with phthalimide 2 in tolu-
ene at room temperature, only to obtain unsatisfactory re-
sults (Table 1, entry 1). We then tuned the Brønsted acidic
site of the catalyst in terms of electronic effects and struc-
tural flexibility, and synthesized catalysts TP2 and TP3
(Figure 1). Catalyst TP2 with more acidic NH protons did
not increase the yield significantly but improved the ee
value to 56% (Table 1, entry 2). Surprisingly, a slightly
9
10
11
12
13
[a] Isolated yields. [b] Determined by chiral HPLC.
Next, we further examined the solvent and temperature
structurally more flexible catalyst, TP3, afforded product effects with TP3 or TP5 as catalyst in this reaction. The
3a in high yield (94%) along with good enantioselectivity results are summarized in Table 2. It was found that toluene
(82% ee) (Table 1, entry 3). On the basis of these results, is the best solvent to afford 3a in higher yield as well as
we continued to modify the catalysts and synthesized a good enantioselectivity (Table 2, entries 1–6 and 8), with
series of chiral bifunctional thiourea–phosphane catalysts, TP3 as catalyst. Decreasing the temperature, diluting the
TP4–TP11, whose structures are also summarized in Fig- concentration of substrates, and changing the ratio of sub-
ure 1 (for synthetic details, see the Supporting Information). strates did not afford 3a in higher yield and ee (Table 2,
Under identical reaction conditions, catalysts TP4–TP11 entries 6–11). Using TP5 as catalyst, we found that toluene,
were all effective for this reaction, giving the desired prod- benzene, and 1,2-dichlorobenzene (DCE) were better sol-
uct 3a in modest to good yields and ee values (Table 1, en- vents than others, affording 3a in higher ee values (Table 2,
tries 4–11). Among these catalysts, TP5 showed the best entries 12–17). Choosing 1,2-dichlorobenzene as solvent
enantioselectivity in this reaction, producing 3a in 80% due to its better solubility for phthalimide, we found that,
yield along with an value of 85% ee (Table 1, entry 5), and when the reaction was carried out at 10 °C, 3a was obtained
TP4 was less effective because of its slower reaction rate in higher yield and ee. Furthermore, when we increased the
Figure 1. Chiral bifunctional thiourea–phosphane organocatalysts TP1–TP11.
Eur. J. Org. Chem. 2011, 1956–1960
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1957

H.-P. Deng, Y. Wei, M. Shi
Table 2. Optimization of the reaction conditions for the reaction of MVK-derived MBH acetate 1a with phthalimide 2.
FULL PAPER
Entry
Catalyst
Solvent [mL]
T [°C]
t [h]
Yield [%][a] ee [%][b]
1
2
3
4
5
6
7
8
TP3
TP3
TP3
TP3
TP3
TP3
TP3
TP3
TP3
TP3
TP3
TP5
TP5
TP5
TP5
TP5
TP5
TP5
CH3CN (0.5)
DCM (0.5)
CCl4 (0.5)
DCE (0.5)
para-xylene (0.5)
THF (0.5)
room temp.
room temp.
room temp.
room temp.
room temp.
room temp.
0
room temp.
10
0
room temp.
room temp.
room temp.
room temp.
room temp.
room temp.
room temp.
10
40
40
60
24
36
24
34
60
43
69
51
80
71
74
81
70
85
75
73
77
THF (0.5)
42
toluene (0.5)
toluene (0.5)
toluene (0.5)
toluene (2.0)
DCE (1.0)
18, 24[c]
94, 88[c]
40
82, 82[c]
83
9
48
42
10
11
12
13
14
15
16
17
18
49
63
82
82
30
56, 80[c]
69, 77[c]
91
82, 83[c]
80
CHCl3 (1.0)
21
57
24
12
para-xylene (1.0)
toluene (0.5)
benzene (0.5)
1,2-dichlorobenzene (0.5)
1,2-dichlorobenzene (0.5)
68
80
91
86
80
85
85
83
22
72[d], 61[d,e]
94[d], 91[d,e] 89[d], 90[d,e]
[a] Isolated yields. [b] Determined by chiral HPLC. [c] The reaction was performed by using 1a (0.2 mmol), 2 (0.1 mmol). [d] 4 Å molecular
sieves (MS) was added. [e] 25 mol-% catalyst was used.
amount of catalyst employed to 25 mol-% and added 4 Å Table 3. Asymmetric allylic amination of various MBH acetates 1
with phthalimide 2 catalyzed by TP 5.
molecular sieves (MS), we obtained 3a in 91% yield and
90% ee (Table 2, entries 17 and 18).
Under these optimal conditions, we next examined the
generality of this reaction with various MBH acetates 1,
and the results are summarized in Table 3. All of the reac-
tions proceeded smoothly under the optimal conditions,
producing the desired products 3 in good to excellent yields
(71–99%) along with good to excellent enantioselectivities
(81–90% ees), regardless of whether they had electron-with-
drawing or electron-donating substituents on their aromatic
rings (Table 3, entries 1–12). The substrates derived from
ethyl vinyl ketone (EVK) also exhibited good results under
identical conditions (Table 3, entry 13). Multiple substitu-
ents on the aromatic ring (Table 3, entry 14) also gave the
corresponding product 3n in excellent yield along with a
good ee value. The absolute configuration of products 3 was
unequivocally assigned as (R) by X-ray diffraction analysis
of 3e bearing a bromine atom on the benzene ring (see the
Supporting Information). This asymmetric catalytic system
is not applicable to MBH acetates derived from acrylates,
because these chiral bifunctional thiourea–phosphane cata-
lysts showed lower catalytic activities toward MBH acetates
derived from acrylates.
Entry[a] R1
R2
Time [h] Yield [%][b] ee [%][c]
1
2
3
4
5
6
7
8
1a, 4-NO2
Me 61
Me 65
Me 85
Me 87
Me 86
Me 96
Me 87
Me 86
Me 86
Me 118
Me 111
Me 111
3a, 91
3b, 80
3c, 78
3d, Ͼ99
3e, 86
3f, 73
3g, 77
3h, 82
3i, 71
3j, 83
3k, 75
3l, 72
3m, 85
3n, 99
90
85
87
85
88
84
86
84
85
85
83
81
90
80
1b, 3-NO2
1c, 4-CF3
1d, 4-CN
1e, 4-Br
1f, 2-Br
1g, 4-Cl
1h, 3-Cl
1i, 2-Cl
9
10
11
12
13
14
1j, 4-Me
1k, 3-Me
1l, H
1m, 4-NO2
Et
70
62
1n, 3,5-(CF3)2 Et
[a] Reaction was carried out with 1 (0.1 mmol), 2 (0.2 mmol), and
4 Å molecular sieves (MS) (20 mg) in 0.5 mL of 1,2-dichloro-
benzene. [b] Isolated yields. [c] Determined by chiral HPLC.
We have further explored the transformation of the ob-
tained products 3 in order to illustrate their synthetic versa-
tility. For example, product 3j could be smoothly trans-
formed into a synthetically more useful compound through stereomeric product 4j in 84% isolated yield with ee value
[3+2] cycloaddition with chlorobenzaldoxime in dichloro- retained (the total diastereomeric selectivity was 6:1)
methane (DCM) at 0 °C, affording the major dia- (Scheme 1).[5e]
1958
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Eur. J. Org. Chem. 2011, 1956–1960

Chiral Bifunctional Thiourea–Phosphane Organocatalysts
system reported here afforded the amination products 3 in
up to Ͼ99% yield along with 90% ee. Current efforts are
in progress to use these chiral bifunctional thiourea–phos-
phane catalysts for other asymmetric substitutions of MBH
acetates.
Scheme 1. [3+2] Cycloaddition of product 3j with chlorobenzaldox-
ime.
Experimental Section
General Remarks: Melting points were determined with a digital
melting point apparatus. Optical rotations were determined at
589 nm (sodium D line) by using a Perkin–Elmer-341 MC digital
On the basis of the experimental results and Krische’s
proposed tandem SN2Ј–SN2Ј mechanism,[2c,2d] a plausible
1
polarimeter. Values of [α]D are given in units of 10 °–1 cm2 g–1. H
mechanism and an activation model are outlined in NMR spectra were recorded with a Bruker AM-300 and an AM-
400 spectrometer for solution in CDCl3 with tetramethylsilane
(TMS) as an internal standard; coupling constants, J, are given in
Hz. 13C NMR spectra were recorded with Bruker AM-300 or AM-
400 spectrophotometers (75 or 100 MHz, respectively) with com-
plete proton decoupling spectrophotometers (CDCl3: 77.0 ppm).
Infrared spectra were recorded with a Perkin–Elmer PE-983 spec-
trometer with absorption in cm–1. Flash column chromatography
was performed by using 300–400 mesh silica gel. For thin-layer
chromatography (TLC), silica gel plates (Huanghai GF254) were
used. Chiral HPLC was performed with a SHIMADZU SPD-10A
Scheme 2. The direct addition of nucleophilic bifunctional
thiourea–phosphane catalyst to the MBH acetate generates
the electrophilic leaving group (OAc–) ion pair. In the
mechanism proposed by Krische, the acetate engages in an
acid–base equilibrium involving deprotonation of the pro-
nucleophile. In our case, the pKa value of pronucleophile
phthalimide (pKa = 8.3)[16] is larger than that of acetic acid
(pKa = 4.8),[17] which should not allow the acetate to depro-
tonate the phthalimide. Thus, we propose that the phthal-
imide directly attacks the βЈ-position of the olefin from Re vp series instrument with chiral columns [Chiralpak AD-H, OD-
H, and IC-H columns 4.6ϫ250 mm, (Daicel Chemical Ind., Ltd.)].
Mass spectra (EI, ESI, MALDI, and HRMS) were measured with
a HP-5989 instrument.
face of the olefin due to a steric repulsion between the aro-
matic group of the catalyst and the phthalimide if it attacks
from the Si face of the olefin. Finally, the acetate takes off
a proton to produce the product. It is worth noting that
catalyst TP1, subtly modified by adding one methylene
group between the thiourea moiety and the phenyl ring, is
very important in increasing the catalytic activity and
enantioselectivity. Presumably, it gives some structural flexi-
bility and prevents the catalyst and the MBH acetate from
approaching too closely to react with the nucleophile.
General Procedure for the Preparation of Catalysts
(R)-1-[2Ј-(Diphenylphosphanyl)-1,1Ј-binaphthyl-2-yl]-3-(2-meth-
oxybenzyl)thiourea (TP5): The compound was prepared according
to General Procedure C (see p. 20 in the Supporting Information).
Under an argon atmosphere, a mixture of (R)-2Ј-(diphenylphos-
phanyl)-1,1Ј-binaphthyl-2-amine (II)[14i,18] (363 mg, 1.0 equiv.) and
isothiocyanate (287 mg, 2.0 equiv.) in THF (1.0 mL) was heated at
reflux for 4 d. Then, the solvent was removed under reduced pres-
sure, and the residue was chromatographed on silica gel (elution
with petroleum ether/EtOAc 20:1–8:1) to give catalyst TP5. Yield:
275 mg, 54%; syrupy oil. IR (CH Cl ): ν = 3375, 2956, 2925, 2855,
˜
2
2
1740, 1671, 1592, 1529, 1461, 1434, 1377, 1315, 1277, 1246, 1163,
1136, 1094, 1027, 950, 817, 744, 697, 660, 623 cm–1 1H NMR
.
(400 MHz, CDCl3, TMS): δ = 3.63 (s, 3 H), 4.20–4.25 (m, 1 H),
4.73–4.76 (m, 1 H), 6.73–6.81 (m, 4 H), 6.95–7.05 (m, 5 H), 7.08–
7.13 (m, 5 H), 7.16–7.22 (m, 3 H), 7.28–7.30 (m, 3 H), 7.34–7.41
(m, 2 H), 7.46–7.50 (m, 2 H), 7.85 (d, J = 8.0 Hz, 1 H), 7.90 (dd,
J = 6.0, 8.0 Hz, 2 H), 7.95 (d, J = 8.8 Hz, 1 H) ppm. 31P NMR
(161.93 MHz, CDCl3, 85% H3PO4): δ = –14.76 ppm. MS (ESI):
m/z (%) = 633.5 (100) [M + 1]+. HRMS (ESI): calcd. for
C41H33N2NaOPS+1 [M + Na]+ 655.1943; found 655.1961. [α]2D0
+197.0 (c = 1.0, CHCl3).
=
General Procedure for the Asymmetric Allylic Amination of Morita–
Baylis–Hillman Acetates: Under an argon atmosphere, a solution
of MBH acetate 1a (0.1 mmol, 26 mg), compound 2 (0.2 mmol,
29 mg), catalyst TP5 (0.025 mmol, 16 mg), and 4 Å molecular si-
eves (MS) (20 mg) in 1,2-dichlorobenzene (0.5 mL) was stirred at
10 °C. After compound 1a was completely consumed, the solvent
was removed under reduced pressure, and the residue was chro-
matographed on silica gel (elution with petroleum ether/EtOAc
10:1–4:1) to provide compound 3a (32 mg, 91% yield).
Scheme 2. Possible mechanism and activation model.
In summary, we have synthesized a series of chiral bi-
functional thiourea–phosphane catalysts and developed a
new highly efficient catalytic, asymmetric allylic amination
of MBH acetates derived from the MVK or EVK system
for the first time, which is applicable to a wide range of
(R)-2-[2-Methylene-1-(4-nitrophenyl)-3-oxobutyl]isoindoline-1,3-di-
one (3a): This is a known compound.[2b] 1H NMR (300 MHz,
substrates from different aromatic aldehydes. The catalytic CDCl3, TMS): δ = 2.43 (s, 3 H, CH3), 5.77 (s, 1 H, CH), 6.44 (s, 1
Eur. J. Org. Chem. 2011, 1956–1960
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1959

H.-P. Deng, Y. Wei, M. Shi
FULL PAPER
Peng, J. Lei, K. Jiang, Y.-C. Chen, Angew. Chem. 2009, 121,
5847–5850; Angew. Chem. Int. Ed. 2009, 48, 5737–5740; g) Z.-
K. Hu, H.-L. Cui, K. Jiang, Y.-C. Chen, Sci. China, Ser.B
Chem. 2009, 52, 1309–1313; h) X. Feng, Y.-Q. Yuan, H.-L. Cui,
K. Jiang, Y.-C. Chen, Org. Biomol. Chem. 2009, 7, 3660–3662.
[6] a) L. Hong, W.-S. Sun, C.-X. Liu, D.-P. Zhao, R. Wang, Chem.
Commun. 2010, 46, 2856–2858; b) W.-S. Sun, L. Hong, C.-X.
Liu, R. Wang, Org. Lett. 2010, 12, 3914–3917.
[7] G.-N. Ma, S.-H. Cao, M. Shi, Tetrahedron: Asymmetry 2009,
20, 1086–1092. In this paper, enantioselective allylic substitu-
tion of Morita–Baylis–Hillman (MBH) acetates with phthal-
imide was realized in the presence of a new l-proline-derived
chiral trifunctional phosphane amide ligand to give the corre-
sponding allylic amination adducts in good yields (70–95%)
and modest to good enantioselectivities (34–78% ee).
[8] Y.-Q. Jiang, Y.-L. Shi, M. Shi, J. Am. Chem. Soc. 2008, 130,
7202–7203.
H, CH), 6.53 (s, 1 H, CH), 7.57 (d, J = 8.7 Hz, 2 H, ArH), 7.73–
7.76 (m, 2 H, ArH), 7.83–7.86 (m, 2 H, ArH), 8.21 (d, J = 8.7 Hz,
2 H, ArH) ppm. The enantiomeric excess was determined by HPLC
with a Chiralcel OD-H column [λ = 214 nm; eluent: Hexane/Iso-
propyl alcohol 70:30; flow rate: 0.7 mL/min; tmajor = 21.19 min,
tminor = 30.55 min; ee% = 90%. [α]2D0 = +66.5 (c = 1.0, CHCl3)].
Supporting Information (see footnote on the first page of this arti-
cle): Spectroscopic data and chiral HPLC traces of the compounds
shown in Tables 1, 2, and 3, X-ray crystallographic data for 3e, and
the detailed descriptions of the experimental procedures.
Acknowledgments
Financial support from the Shanghai Municipal Committee of Sci-
ence and Technology (08dj1400100–2), National Basic Research
Program of China [(973)-2010CB833302], and the National Natu-
ral Science Foundation of China (21072206, 20472096, 20902019,
20872162, 20672127, 20821002, 20732008, and 20702059) is greatly
acknowledged. We thank Professor Jie Sun for performing the X-
ray diffraction analysis.
[9] Y. Wei, M. Shi, Acc. Chem. Res. 2010, 43, 1005–1018.
[10] B. J. Cowen, S. J. Miller, J. Am. Chem. Soc. 2007, 129, 10988–
10989.
[11] H. Xiao, Z. Chai, C.-W. Zheng, Y.-Q. Yang, W. Liu, J.-K.
Zhang, G. Zhao, Angew. Chem. 2010, 122, 4569–4572; Angew.
Chem. Int. Ed. 2010, 49, 4467–4470.
[12] Y.-Q. Fang, E. N. Jacobsen, J. Am. Chem. Soc. 2008, 130,
5660–5661.
[13] a) K. Yuan, L. Zhang, H.-L. Song, Y. Hu, X.-Y. Wu, Tetrahe-
dron Lett. 2008, 49, 6262–6264; b) J.-J. Gong, K. Yuan, X.-Y.
Wu, Tetrahedron: Asymmetry 2009, 20, 2117–2120; c) K. Yuan,
H.-L. Song, Y. Hu, J.-F. Fang, X.-Y. Wu, Tetrahedron: Asym-
metry 2010, 21, 903–908.
[1] For selected reviews on the Morita–Baylis–Hillman reaction,
see: a) S. E. Drewes, G. H. P. Roos, Tetrahedron 1988, 44, 4653–
4670; b) D. Basavaiah, P. D. Rao, R. S. Hyma, Tetrahedron
1996, 52, 8001–8062; c) E. Ciganek in Organic Reactions (Ed.:
L. A. Paquette), Wiley, New York, 1997, vol. 51, pp. 201–350;
d) P. Langer, Angew. Chem. 2000, 112, 3177–3180; Angew.
Chem. Int. Ed. 2000, 39, 3049–3051; e) D. Basavaiah, A. J. Rao,
T. Satyanarayana, Chem. Rev. 2003, 103, 811–892; f) Y.-L. Shi,
M. Shi, Eur. J. Org. Chem. 2007, 2905–2916; g) G. Masson, C.
Housseman, J.-P. Zhu, Angew. Chem. 2007, 119, 4698–4712;
Angew. Chem. Int. Ed. 2007, 46, 4614–4628; h) D. Basavaiah,
K. V. Rao, R. J. Reddy, Chem. Soc. Rev. 2007, 36, 1581–1588;
i) C. Menozzi, P. I. Dalko, “Organocatalytic Enantioselective
Morita–Baylis–Hillman Reactions in Enantioselective Organ-
ocatalysis” in Reactions and Experimental Procedures (Ed.: P. I.
Dalko), Wiley-VCH, Weinheim, 2007; j) V. Dederck, J. Matti-
nez, F. Lamaty, Chem. Rev. 2009, 109, 1–48; k) G.-N. Ma, J.-J.
Jiang, M. Shi, Y. Wei, Chem. Commun. 2009, 45, 5496–5514; l)
D. Basavaiah, B. S. Reddy, S. S. Badsara, Chem. Rev. 2010, 110,
5447–5674.
[14] a) M. Shi, L.-H. Chen, Chem. Commun. 2003, 39, 1310–1311;
b) M. Shi, L.-H. Chen, C.-Q. Li, J. Am. Chem. Soc. 2005, 127,
3790–3800; c) M. Shi, C.-Q. Li, Tetrahedron: Asymmetry 2005,
16, 1385–1391; d) M. Shi, L.-H. Chen, W.-D. Teng, Adv. Synth.
Catal. 2005, 347, 1781–1789; e) Y.-H. Liu, L.-H. Chen, M. Shi,
Adv. Synth. Catal. 2006, 348, 973–979; f) M. Shi, G.-N. Ma, J.
Gao, J. Org. Chem. 2007, 72, 9779–9781; g) Y.-L. Shi, M. Shi,
Adv. Synth. Catal. 2007, 349, 2129–2135; h) M. Shi, Y.-H. Liu,
L.-H. Chen, Chirality 2007, 19, 124–128; i) M.-J. Qi, T. Ai, M.
Shi, G. Li, Tetrahedron 2008, 64, 1181–1186; j) Y.-H. Liu, M.
Shi, Adv. Synth. Catal. 2008, 350, 122–128; k) Z.-Y. Lei, G.-N.
Ma, M. Shi, Eur. J. Org. Chem. 2008, 3817–3820; l) Z.-Y. Lei,
X.-G. Liu, M. Shi, M. Zhao, Tetrahedron: Asymmetry 2008,
19, 2058–2062; m) X.-Y. Guan, Y.-Q. Jiang, M. Shi, Eur. J.
Org. Chem. 2008, 2150–2155.
[15] We initially synthesized a series of chiral bifunctional amide–
phosphane organocatalysts (AP) and used them in the catalytic
asymmetric allylic amination of MBH acetates derived from
MVK with phthalimide, but the obtained results are not suc-
cessful (see Table S1 in the Supporting Information).
[2] For selected reports on SN2Ј–SN2Ј substitution of Morita–
Baylis–Hillman acetates or carbonates, see: a) B. M. Trost,
M. R. Machacek, H. C. Tsui, J. Am. Chem. Soc. 2005, 127,
7014–7024; b) C.-W. Cho, J.-R. Kong, M. J. Krische, Org. Lett.
2004, 6, 1337–1339; c) C.-W. Cho, M. J. Krische, Angew. Chem.
2004, 116, 6857–6859; Angew. Chem. Int. Ed. 2004, 43, 6689–
6691; d) H. Park, C.-W. Cho, M. J. Krische, J. Org. Chem. 2006,
71, 7892–7894; e) S. Kobbelgaard, S. Brandes, K. A. Jørgensen,
Chem. Eur. J. 2008, 14, 1464–1471.
[3] a) Y.-S. Du, X.-L. Han, X.-Y. Lu, Tetrahedron Lett. 2004, 45,
4967–4971; b) D. J. V. C. van Steenis, T. Marcelli, M. Lutz,
A. L. Spek, J. H. van Maarseveen, H. Hiemstra, Adv. Synth.
Catal. 2007, 349, 281–286.
[4] T.-Z. Zhang, L.-X. Dai, X.-L. Hou, Tetrahedron: Asymmetry
2007, 18, 1990–1994.
[5] a) K. Jiang, J. Peng, H.-L. Cui, Y.-C. Chen, Chem. Commun.
2009, 45, 3955–3957; b) H.-L. Cui, J. Peng, X. Feng, W. Du,
K. Jiang, Y.-C. Chen, Chem. Eur. J. 2009, 15, 1574–1577; c)
H.-L. Cui, J.-R. Huang, J. Lei, Z.-F. Wang, S. Chen, L. Wu,
Y.-C. Chen, Org. Lett. 2010, 12, 720–723; d) J. Peng, X. Huang,
H.-L. Cui, Y.-C. Chen, Org. Lett. 2010, 12, 4260–4263; e) S.-J.
Zhang, H.-L. Cui, K. Jiang, R. Li, Z.-Y. Ding, Y.-C. Chen,
Eur. J. Org. Chem. 2009, 5804–5809; f) H.-L. Cui, X. Feng, J.
[16] R. P. Bell, W. C. E. Higginson, Proc. R. Soc. 1949, 197, 141–
159.
[17] J. F. J. Dippy, S. R. C. Hughes, A. Rozanski, J. Chem. Soc.
1959, 2492–2498.
[18] a) K. Sumi, T. Ikariya, R. Noyori, Can. J. Chem. 2000, 78,
697–703; b) P. N. M. Botman, O. David, A. Amore, J. Dinke-
laar, M. T. Vlaar, K. Goubitz, J. Fraanje, H. Schenk, H. Hiem-
sta, J. H. van Maarseveen, Angew. Chem. 2004, 116, 3553–
3555; Angew. Chem. Int. Ed. 2004, 43, 3471–3473.
Received: December 11, 2010
Published Online: February 15, 2011
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