Bifunctional chiral phosphine-containing Lewis base catalyzed asymmetric Morita-Baylis-Hillman reaction of aldehydes with activated alkenes

Article abstract of DOI:10.1016/j.tetasy.2008.08.019

A series of novel bifunctional chiral phosphine-containing Lewis bases were synthesized and successfully applied to the asymmetric Morita-Baylis-Hillman reaction of aldehydes with methyl vinyl ketone (MVK) and ethyl vinyl ketone (EVK) to give the correspo

Full text of DOI:10.1016/j.tetasy.2008.08.019

Tetrahedron: Asymmetry 19 (2008) 2058–2062
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Bifunctional chiral phosphine-containing Lewis base catalyzed asymmetric
Morita–Baylis–Hillman reaction of aldehydes with activated alkenes
a
Zhi-Yu Lei a, Xu-Guang Liu a, Min Shi a,b, , Meixin Zhao
*
a School of Chemistry and Molecular Engineering, East China University of Science and Technology, Laboratory for Advanced Materials and Institute of Fine Chemicals,
130 Mei Long Road, Shanghai 200237, China
b State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 July 2008
Accepted 6 August 2008
A series of novel bifunctional chiral phosphine-containing Lewis bases were synthesized and successfully
applied to the asymmetric Morita–Baylis–Hillman reaction of aldehydes with methyl vinyl ketone (MVK)
and ethyl vinyl ketone (EVK) to give the corresponding adducts in moderate yields and enantioselectiv-
ities under mild reaction conditions.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
adducts in moderate yields and enantioselectivities under mild
reaction conditions.
The asymmetric Morita–Baylis–Hillman (MBH) reaction is one
of the most useful and attractive C–C bond-forming reactions to
give enantiomerically enriched b-hydroxy carbonyl compounds
2. Results and discussion
bearing an a-alkylidene group, which are valuable building blocks
These newly synthesized chiral phosphine-containing Lewis
bases L1–L10 are shown in Figure 1. They can be prepared easily
by reduction of the corresponding phosphane oxides5 in the pres-
ence of Et3N and HSiCl3.4,6 The chirality at phosphorus atom is lost
during reduction of the phosphane oxide. A pair of inseparable dia-
stereoisomers (diastereoisomeric ratio is about 1:1) were acquired
and used for the asymmetric MBH reaction.
in the synthesis of medicinally relevant compounds.1 Due to the
great potential of the products and the mild reaction conditions,
the catalytic asymmetric version of this reaction has attracted con-
siderable interest and undergone remarkable progress in recent
years.2 However, the asymmetric MBH reaction is often hampered
by a low reaction rate and limited substrate generality because the
reaction outcome is highly sensitive to the substitutions at both
the aldehydes (electrophiles) and Michael acceptors. For example,
the MBH reaction of aldehydes with methyl vinyl ketone (MVK) is
still in its infancy, and satisfactory reaction outcomes are rare.3
Therefore, the design and synthesis of efficient organocatalysts
for the MBH reaction of aldehydes with MVK still remain a great
challenge for organic chemists.
R
OH
OH
OH
PR2
PPhR
PPhBu
Recently, we have reported that optically active 20-(alkylphe-
nylphosphinyl)-[1,10]binaphthalenyl-2-ols are highly effective chi-
ral organocatalysts in the catalytic asymmetric aza-MBH reaction
of N-sulfonated imines with MVK to give the corresponding prod-
ucts in excellent yields and with moderate to good ees within
1–5 h.4 In order to further optimize the catalytic asymmetric
MBH reaction catalyzed by chiral phosphine-containing Lewis
bases, we now wish to report that these chiral organocatalysts
are also fairly effective in the MBH reaction of aldehydes with
MVK and ethyl vinyl ketone (EVK), affording the corresponding
L1: R = Ph
L2: R = Bu
L3: R = Et
L4: R = Pr
L8: R = H
L9: R = Ph
L10: R = Br
i
L5: R = Bu
L6: R = Cy
L7: R = iBu
Figure 1. Chiral phosphine-containing Lewis base catalysts L1–L10.
Initial examinations using 3-phenylpropanal 1a and MVK 2a as
the substrates for the asymmetric MBH reaction in tetrahydrofuran
(THF) in the presence of chiral phosphine-containing Lewis bases
L1–L10 were aimed at determining the most efficient catalyst in
this reaction, and the results of these experiments are summarized
in Table 1. Chiral phosphine-containing Lewis base L1 did not show
any catalytic activity in this reaction (Table 1, entry 1). Using L2 as
* Corresponding author.
E-mail address: Mshi@mail.sioc.ac.cn (M. Shi).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.08.019

Z.-Y. Lei et al. / Tetrahedron: Asymmetry 19 (2008) 2058–2062
2059
Table 1
Optimization of the reaction conditions of the catalytic asymmetric MBH reaction of 3-phenylpropanal 1a with methyl vinyl ketone 2a
OH
O
O
CHO
L (10 mol%)
+
THF, 25 oC, 24 h
3a
2a
1a
Entry
L
Time (h)
Yielda (%)
eeb (%)
Absolute configuration
1
2
3
4
5
6
7
8
9
L1
L2
L3
L4
L5
L6
L7
L8
48
36
24
24
24
24
24
18
36
24
48
18
—
58
85
46
86
51
80
93
50
87
17
78
9
53
38
55
34
46
51
17
40
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
L9
10
11
12c
L10
PPh2Me
PPh2Me
a
Isolated yields.
Determined by chiral HPLC.
10 mol % of 3-nitrophenol was added.
b
c
the catalyst, the corresponding adduct 3a was obtained in 58%
yield and 9% ee in THF at 25 °C (Table 1, entry 2). Under similar
conditions, chiral phosphine-containing Lewis base L3 bearing an
ethyl and a phenyl group on the phosphorus atom resulted in the
corresponding adduct 3a in 85% yield and 53% ee as an (R)-config-
uration on the basis of the sign of specific rotations when com-
pared with the literature value3b,d,f,7a,e (Table 1, entry 3). Hereby,
organocatalysts L4–L7, which are structurally very similar to L3
were examined under identical conditions. The more sterically
encumbered L4, L6 and L7 did not show any improvement on
the enantioselectivity, providing 3a in 38% ee, 34% ee and 46% ee
as an (R)-configuration, respectively (Table 1, entries 4, 6 and 7).
It was found that chiral phosphine-containing Lewis base L5
resulted in the corresponding MBH adduct 3a in 86% yield and
55% ee after 24 h at room temperature (Table 1, entry 5). Moreover,
the chiral H8-BINOL derived phosphine-containing Lewis bases L8
produced the adduct 3a in 93% yield and 51% ee within 18 h under
the standard conditions (Table 1, entry 8). However, the catalytic
activity decreased when using L9 as the catalyst in which a phenyl
was introduced into the ortho-position of the phenolic hydroxy
group (Table 1, entry 9). Using L10 as the catalyst, the yield and
enantioselectivity of 3a dropped slightly (Table 1, entry 10). These
results suggest that the steric bulkiness of these catalysts plays a
crucial role for this asymmetric catalytic process. It should be
noted that using diphenylmethylphosphine (PPh2Me) as the cata-
lyst afforded the corresponding adduct 3a in only 17% yield after
48 h without any additive, whereas in the presence of 10 mol %
of 3-nitrophenol, compound 3a was provided in 78% yield within
18 h, suggesting that a phenol group is essential for this reaction
(Table 1, entries 11 and 12).
Using L5 as a catalyst, we next carefully examined the solvent
effect on this reaction. The results are outlined in Table 2, and
THF was found to be the best solvent in terms of both yield and
ee of 3a (Table 1, entry 5 and Table 2, entries 1–5). Using N,N-
dimethylformamide (DMF) as the solvent, 3a was obtained in
54% ee, but, the reaction time was prolonged for 36 h, affording
3a in lower yield (30% yield) (Table 2, entry 5). In dichloromethane,
3a was not formed (Table 2, entry 1) and in acetonitrile, toluene or
ether, 3a was obtained in 56–88% yields and 4–38% ees as an (R)-
configuration under identical conditions (Table 2, entries 2–4).
Table 2
Optimization of the reaction conditions for the catalytic asymmetric MBH reaction of 3-phenylpropanal 1a with MVK 2a
OH
O
O
CHO
L5 (10 mol%)
+
solvent
3a
2a
1a
Entry
Temperature (°C)
Solvent
Time (h)
Yielda (%)
eeb (%)
Absolute configuration
1
2
3
4
5
6
25
25
25
25
25
0
50
25
25
CH2Cl2
MeCN
PhMe
Et2O
DMF
THF
THF
THF
THF
48
24
36
36
36
36
18
18
36
—
76
56
88
30
85
82
98
74
25
4
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
38
54
49
53
45
56
7
8c
9d
a
Isolated yields.
Determined by chiral HPLC.
1.0 equiv of H2O was added.
4 Å MS were added.
b
c
d

2060
Z.-Y. Lei et al. / Tetrahedron: Asymmetry 19 (2008) 2058–2062
Table 3
Adding 1.0 equiv of H2O into the reaction system afforded 3a in
nearly quantitative yield and 45% ee within 18 h at 25 °C, suggest-
ing that water may take part in intermolecular hydrogen bonding
to accelerate the reaction rate (Table 2, entry 8). When 4 Å MS
(200 mg) were added into the reaction system to remove the ambi-
ent moisture, the yield of 3a decreased to 74% along with 56% ee
after a prolonged reaction time (Table 2, entry 9). Based on the
above results, we established the optimal reaction conditions:
using 10 mol % of L5 as the catalyst and THF as the solvent to per-
form the reaction at 25 °C.
Asymmetric MBH reaction of various aldehydes 1 with activated olefins 2 catalyzed
by L5
O
OH
O
L5 (10 mol%)
R1CHO
+
R2
R1
R2
THF, 25 oC
1
2
3
Entry R1
R2 Product
Time Yielda (%) eeb (%)
(h)
3
3
To investigate the scope and limitations of this catalytic asym-
metric MBH reaction of aldehydes with MVK and ethyl vinyl
ketone (EVK), we examined a variety of aldehydes under the
optimized conditions. The results are summarized in Table 3. All
reactions proceeded smoothly to give the corresponding products
3 in moderate yields and 28–51% ees as an (R)-configuration under
the optimal conditions. Using isobutyraldehyde and cyclohexane-
carbaldehyde as the substrates afforded the corresponding prod-
ucts 3b and 3c in 77% yield and 51% ee as well as 78% yield and
50% ee, respectively (Table 3, entries 1 and 2). Lower enantioselec-
tivities were obtained for linear aliphatic aldehydes, particularly
for propanal, affording the corresponding adduct 3d in 77% yield
and 28% ee (Table 3, entry 3). When increasing the length of linear
aliphatic aldehydes, an improvement of enantioselectivities could
be realized under identical conditions (Table 3, entries 4–6). Using
aromatic aldehyde 1h as the substrate produced the corresponding
product 3h in 75% yield and 29% ee (Table 3, entry 7). As for the
reaction of phenylpropanal with EVK, the corresponding adduct
3i was formed in 76% yield and 44% ee after 30 h (Table 3, entry 8).
A possible transition state of this asymmetric MBH reaction can
be explained as a Michael addition and an aldol reaction on the
basis of generally accepted reaction mechanism as illustrated in
Scheme 1.2b Intermediate A is first formed from the Michael addi-
tion of L5 with MVK combined with an intramolecular hydrogen
bonding, which undergoes aldol reaction with aldehyde from si
face to give the product in an (R)-configuration.
OH O
1
2
Me
Me
24
77
51
3b
OH O
24
78
50
3c
OH O
3
4
C2H5–
Me
Me
24
24
77
70
28
38
3d
C2H5
OH O
n-C3H7–
3e
n-C3H7
OH O
OH O
5
6
n-C4H9–
Me
Me
24
24
65
68
40
42
3f
n-C4H9
n-C7H15
–
3g
n-C7H15
OH O
7
8
Me
Et
24
30
75
76
29
44
3h
Cl
Cl
OH O
3. Conclusion
3i
In conclusion, we have designed and synthesized a series of
novel chiral bifunctional phosphine-containing Lewis base catalysts
for the asymmetric MBH reaction of aldehydes with MVK and EVK.
We have found that these catalysts performed well under mild
conditions and resulted in the formation of corresponding adducts
in moderate yields as well as moderate enantioselectivities. These
results could lead the way for a highly diastereoselective and/or
highly enantioselective reaction of a catalytic asymmetric MBH
a
Isolated yields.
Determined by chiral HPLC.
b
The examination of temperature revealed that no significant
improvement upon yield and enantioselectivity of 3a could be real-
ized at either 50 °C or 0 °C, respectively (Table 2, entries 6 and 7).
OH
O
O
MBH reaction
Ph
L5
L5
Michael addition
H
H
O
O
O
O
O
aldol reaction
H
Ph
Ph
P
PhBu
P
PhBu
O
A
B
Scheme 1. Proposed mechanism for the asymmetric MBH reaction of aldehyde with MVK.

Z.-Y. Lei et al. / Tetrahedron: Asymmetry 19 (2008) 2058–2062
2061
reaction with chiral phosphine-containing Lewis bases. Efforts are
in progress to elucidate the mechanistic details of this reaction and
to study its scope and limitations.
(br, 1H, OH), 4.84 (br, 1H, OH), 6.28 (d, J = 9.0 Hz, 1H, ArH), 6.72–
6.78 (m, 1H, ArH), 6.93–7.07 (m, 6H, ArH), 7.12–7.51 (m, 16H,
ArH), 7.78 (d, J = 8.1 Hz, 1H, ArH), 7.88–7.96 (m, 7H, ArH), 8.03 (t,
J = 8.7 Hz, 2H, ArH); 31P NMR (CDCl3, 121 MHz, 85% H3PO4) d
ꢁ10.03, ꢁ12.40; MS (EI) m/e 420.2 (M+, 58.95), 403.2 (M+ꢁ17,
100), 377.1 (M+ꢁ43, 80.13), 252.1 (M+ꢁ168, 25.60); HRMS (EI)
calcd for C29H25OP requires 420.1643, found: 420.1643.
4. Experimental
4.1. General remarks
4.5. (R)-1-(2-((Butyl(phenyl)phosphanyl)naphthalen-1-
yl)naphthalen-2-ol L5
1H NMR, 31P NMR and 13C NMR spectra were recorded on a Var-
ian Mercury vx-300 spectrometer for solution in DMSO or CDCl3
with tetramethylsilane (TMS) as an internal standard. Chiral HPLC
was performed on a SHIMADZU SPD-10A series with chiral col-
umns. Elementary analysis (CHN) was taken on a Carlo-Erba 1106
analyzer. Mass spectra were recorded by EI, and HRMS was mea-
sured on a HP-5989 instrument. Flash column chromatography
was performed using Silica Gel (300–400 mesh). Melting points
were uncorrected. All solvents were purified by distillation. Unless
otherwise noted, all commercially obtained reagents were used
without further purification. All reactions were carried out under
an argon atmosphere. Phosphane oxides were synthesized accord-
ing to literature procedures.5 Chiral phosphine-containing Lewis
bases catalysts L1–L6 were prepared by the methods previously
described.4,6 Products 3a–3i are known compounds.7 The absolute
configuration of MBH adducts 3 was determined by the sign of
specific rotations compared with the literature value.3b,d,f,7a,e
White solid; yield: 584 mg (67%); mp 68–70 °C; ½a D25
¼ ꢁ14:3 (c
ꢀ
0.83, CH2Cl2); IR (CH2Cl2)
m 3057, 2969, 1719, 1588, 1509, 1419,
1140, 940 cmꢁ1
; d 0.68 (t,
1H NMR (CDCl3, 300 MHz, TMS)
J = 6.9 Hz, 3H, CH3), 0.84 (t, J = 6.9 Hz, 3H, CH3), 1.11–1.15 (m, 4H,
CH2), 1.34–1.43 (m, 4H, CH2), 1.88 (t, J = 7.5 Hz, 2H, CH2), 2.04 (t,
J = 7.5 Hz, 2H, CH2), 4.54 (br, 1H, OH), 4.83 (br, 1H, OH), 6.54 (d,
J = 8.7 Hz, 1H, ArH), 6.87–7.06 (m, 7H, ArH), 7.15–7.38 (m, 14H,
ArH), 7.47–7.52 (m, 2H, ArH), 7.60–7.64 (m, 1H, ArH), 7.71–7.79
(m, 2H, ArH), 7.87–8.02 (m, 7H, ArH); 31P NMR (CDCl3, 121 MHz,
85% H3PO4) d ꢁ24.68; MS (EI) m/e 434.2 (M+, 53.07), 417.2
(M+ꢁ17, 100), 377.1 (M+ꢁ57, 25.42), 268.1 (M+ꢁ166, 53.69);
HRMS (EI) calcd for C30H27OP requires 434.1800, found: 434.1780.
4.6. (R)-1-(2-(Cyclohexyl(phenyl)phosphanyl)naphthalen-1-
yl)naphthalen-2-ol L6
White solid; yield: 560 mg (61%); mp 74–76 °C; ½a D25
¼ ꢁ18:8 (c
ꢀ
4.2. General procedure for the reduction of the phosphane
oxides
0.54, CH2Cl2); IR (CH2Cl2)
m 3055, 2926, 1708, 1619, 1596, 1513,
1433, 1144, 814 cmꢁ1 1H NMR (CDCl3, 300 MHz, TMS) d 0.92–
;
At 0 °C, HSiCl3 (8.0 mmol, 0.8 mL) was carefully added to a mix-
ture of phosphane oxide (2.0 mmol) and triethylamine (16 mmol,
2.1 mL) in toluene (50 mL) in a three-necked round-bottomed flask
under argon atmosphere. The reaction mixture was heated at
reflux for 16–24 h. After being cooled to room temperature, the
mixture was diluted with Et2O and quenched with small amount
of saturated NaHCO3. The resulting suspension was filtered
through Celite, and the solid was washed with Et2O. The combined
organic layers were dried over anhydrous MgSO4 and concentrated
under reduced pressure. The crude product was purified by flash
column chromatography (SiO2, EtOAc/petroleum ether, 1/10) to
give the product as a colourless solid (a pair of diastereoisomers).
1.43 (m, 8H, CH2), 1.51–1.78 (m, 12H, CH2), 2.25–2.44 (m, 2H,
CH), 4.24 (br, 1H, OH), 4.81 (br, 1H, OH), 6.31 (d, J = 8.7 Hz, 1H,
ArH), 6.74–6.79 (m, 1H, ArH), 6.95–6.97 (m, 5H, ArH), 7.03–7.53
(m, 17H, ArH), 7.76–8.05 (m, 10H, ArH); 31P NMR (CDCl3,
121 MHz, 85% H3PO4) d ꢁ15.35, ꢁ17.26; MS (EI) m/e 460.2 (M+,
85.00), 443.2 (M+ꢁ17, 100), 377.1 (M+ꢁ83, 89.54), 268.1
(M+ꢁ192, 55.87); HRMS (EI) calcd for C32H29OP requires
460.1956, found: 460.1956.
4.7. (R)-1-(2-(Isobutyl(phenyl)phosphanyl)naphthalen-1-
yl)naphthalen-2-ol L7
White solid; yield: 62%; mp 80.4–81.8 °C; ½a D25
¼ ꢁ14:8 (c 0.87,
ꢀ
4.3. (R)-1-(2-(Ethyl(phenyl)phosphano)naphthalen-1-
yl)naphthalen-2-ol L3
CH2Cl2); IR (CH2Cl2)
m 3054, 2952, 1727, 1616, 1590, 1461, 1434,
1335, 973 cmꢁ1 1H NMR (CDCl3, 300 MHz, TMS) d 0.55–0.60 (m,
;
6H), 0.92 (d, J = 6.6 Hz, 6H), 1.48–1.62 (m, 2H), 1.67–1.74 (m,
1H), 1.86–2.04 (m, 3H), 4.64 (br, 1H), 4.79 (br, 1H), 6.61 (d,
J = 8.7 Hz, 1H), 6.91–6.97 (m, 2H), 7.01–7.09 (m, 5H), 7.17–7.39
(m, 14H), 7.46–7.54 (m, 3H), 7.65–7.69 (m, 1H), 7.79 (d,
J = 8.4 Hz, 1H), 7.87–7.98 (m, 7H); 31P NMR (CDCl3, 121 MHz, 85%
H3PO4) d ꢁ27.87, ꢁ28.45; MS (EI) m/e 434.2 (M+, 59.58), 417.2
(M+ꢁ17, 72.80), 377.1 (M+ꢁ57, 48.28), 299.1 (M+ꢁ135, 18.99),
268.1 (M+ꢁ166, 100); HRMS (EI) calcd for C30H27OP requires
434.1800, found: 434.1802.
White solid; yield: 520 mg (64%); mp 168–170 °C; ½a D25
¼ ꢁ16:4
ꢀ
(c 0.93, CH2Cl2); IR (CH2Cl2)
m 3054, 2927, 1708, 1621, 1595, 1514,
1434, 1144, 815 cmꢁ1; 1H NMR (CDCl3, 300 MHz, TMS) d 0.79–0.89
(m, 3H, CH3), 1.01 (dt, J = 7.2 Hz, 17.4 Hz, 3H, CH3), 1.92 (q,
J = 7.5 Hz, 2H, CH2), 2.06 (q, J = 7.2 Hz, 2H, CH2), 4.50 (br, 1H,
OH), 4.84 (br, 1H, OH), 6.54 (d, J = 8.4 Hz, 1H, ArH), 6.86–7.05 (m,
7H, ArH), 7.14–7.38 (m, 14H, ArH), 7.46–7.51 (m, 2H, ArH), 7.64–
7.78 (m, 3H, ArH), 7.86–8.01 (m, 7H, ArH); 31P NMR (CDCl3,
121 MHz, 85% H3PO4) d ꢁ20.41, ꢁ20.83; MS (EI) m/e 406.1 (M+,
40.59), 405.1 (M+ꢁ1, 26.48), 390.2 (M+ꢁ16, 25.11), 389.1
(M+ꢁ17, 100), 252.1 (M+ꢁ154, 13.55); HRMS (EI) calcd for
4.8. (R)-1-(2-(Butyl(phenyl)phosphanyl)-5,6,7,8-tetra-
hydronaphthalen-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol L8
C
28H23OP requires 406.1487, found: 406.1487.
White solid; yield: 69%; mp 104.5–106.0 °C; ½a D25
¼ þ5:0 (c
ꢀ
4.4. (R)-1-(2-(Isopropyl(phenyl)phosphanyl)naphthalen-1-
yl)naphthalen-2-ol L4
0.62, CH2Cl2); IR (CH2Cl2)
m 3047, 2929, 2857, 1730, 1591, 1475,
1434, 1276 cmꢁ1 1H NMR (CDCl3, 300 MHz, TMS) d 0.79–0.86
;
(m, 6H), 1.55–1.82 (m, 19H), 1.87–1.96 (m, 6H), 2.01–2.39 (m,
8H), 2.54–2.70 (m, 3H), 2.75–2.88 (m, 8H), 3.65 (br, 1H), 4.38 (br,
1H), 6.56 (d, J = 8.1 Hz, 1H), 6.82 (d, J = 8.1 Hz, 1H), 6.98–7.03 (m,
2H), 7.14–7.26 (m, 12H), 7.32–7.36 (m, 2H); 31P NMR (CDCl3,
121 MHz, 85% H3PO4) d ꢁ26.03, ꢁ26.87; MS (EI) m/e 442.2 (M+,
White solid; yield: 486 mg (58%); mp 149–150 °C; ½a D25
¼ ꢁ13:0
ꢀ
(c 0.58, CH2Cl2); IR (CH2Cl2)
m 3055, 2944, 1714, 1621, 1595, 1515,
1434, 1144, 815 cmꢁ1; 1H NMR (CDCl3, 300 MHz, TMS) d 0.83–0.99
(m, 8H, CH3), 1.12–1.19 (m, 4H, CH3), 2.58–2.66 (m, 2H, CH), 4.25

2062
Z.-Y. Lei et al. / Tetrahedron: Asymmetry 19 (2008) 2058–2062
52.45), 425.2 (M+ꢁ17, 100), 383.2 (M+ꢁ59, 23.75), 276.2 (M+ꢁ166,
14.24), 268.1 (M+ꢁ174, 23.87); HRMS (EI) calcd for C30H35OP re-
quires 442.2426, found: 442.2428.
Acknowledgements
We thank the Shanghai Municipal Committee of Science and
Technology (04JC14083, 06XD14005), and the National Natural
Science Foundation of China for financial support (20472096,
203900502, 20672127, 20772030 and 20732008).
4.9. (R)-1-(2-(Butyl(phenyl)phosphanyl)-5,6,7,8-tetra-
hydronaphthalen-1-yl)-5,6,7,8-tetrahydro-3-phenyl-
naphthalen-2-ol L9
References
White solid; yield: 58%; mp 45.6–47.1 °C; ½a D25
¼ ꢁ43:2 (c 0.84,
ꢀ
1. For reviews of MBH or aza-MBH reaction, see: (a) Basavaiah, D.; Rao, P. D.;
Hyma, R. S. Tetrahedron 1996, 52, 8001–8062; (b) Drewes, S. E.; Roos, G. H. P.
Tetrahedron 1988, 44, 4653–4670; (c) Ciganek, E. Org. React. 1997, 51, 201–350;
(d) Langer, P. Angew. Chem., Int. Ed. 2000, 39, 3049–3051; (e) Cai, J.-X.; Zhou, Z.-
H.; Tang, C.-C. Huaxue Yanjiu 2001, 12, 54–64; (f) Iwabuchi, Y.; Hatakeyama, S. J.
Synth. Org. Chem. Jpn. 2002, 60, 2–14; (g) Basavaiah, D.; Rao, A. J.; Satyanarayana,
T. Chem. Rev. 2003, 103, 811–892; (h) Masson, G.; Housseman, C.; Zhu, J. Angew.
Chem., Int. Ed. 2007, 46, 4614–4628; (i) Basavaiah, D.; Rao, K. V.; Reddy, R. J.
Chem. Soc. Rev. 2007, 36, 1581–1588; (j) Shi, Y. L.; Shi, M. Eur. J. Org. Chem. 2007,
18, 2905–2916.
CH2Cl2); IR (CH2Cl2)
m 2927, 2858, 1731, 1455, 1434, 1275,
975 cmꢁ1 1H NMR (CDCl3, 300 MHz, TMS) d 0.87–0.94 (m, 6H),
;
1.62–1.99 (m, 26H), 2.10–2.47 (m, 8H), 2.68–2.72 (m, 3H), 2.79–
2.83 (m, 7H), 3.91 (br, 1H), 4.66 (br, 1H), 7.06–7.35 (m, 18H),
7.40–7.46 (m, 5H), 7.62-7.65 (m, 3H); 31P NMR (CDCl3, 121 MHz,
85% H3PO4) d ꢁ24.94, ꢁ26.36; MS (EI) m/e 518.3 (M+, 51.04),
501.3 (M+ꢁ17, 100), 459.2 (M+ꢁ59, 16.89), 279.2 (M+ꢁ239, 8.88);
HRMS (EI) calcd for C36H39OP requires 518.2739, found: 518.2740.
2. For selected asymmetric MBH reactions, see: (a) Miller, S. J. Acc. Chem. Res. 2004,
37, 601–610; (b) Wang, J.; Li, H.; Yu, X. H.; Zu, L. S.; Wang, W. Org. Lett. 2005, 7,
4293–4296; (c) Berkessel, A.; Roland, K.; Neudörfl, J. M. Org. Lett. 2006, 8, 4195–
4198; (d) Lattanzi, A. Synlett 2007, 2106–2110; (e) Shi, M.; Liu, X. G. Org. Lett.
2008, 10, 1043–1046; (f) Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.;
Hatakeyama, S. J. Am. Chem. Soc. 1999, 121, 10219–10220; (g) Yang, K.-S.; Lee,
W.-D.; Pan, J.-F.; Chen, K.-M. J. Org. Chem. 2003, 68, 915–919; (h) McDougal, N.
T.; Schaus, S. E. J. Am. Chem. Soc. 2003, 125, 12094–12095; (i) McDougl, N. T.;
Trevellini, W. L.; Rodgen, S. A.; Kliman, L. T.; Schaus, S. E. Adv. Synth. Catal. 2004,
346, 1231–1240; (j) Maher, D. J.; Connon, S. J. Tetrahedron Lett. 2004, 45, 1301–
1305; (k) Sohtome, Y.; Tanatani, A.; Hashimoto, Y.; Nagasawa, K. Tetrahedron
Lett. 2004, 45, 5589–5592; (l) Roussel, C.; Roman, M.; Andreoli, F.; Delrio, A.;
Faure, R.; Vanthuyne, N. Chirality 2006, 18, 762–771; (m) Matsui, K.; Takizawa,
S.; Sasai, H. Tetrahedron Lett. 2005, 46, 1943–1946; For recent mechanistic
investigations of the MBH reaction, see: (n) Price, K. E.; Broadwater, S. J.; Jung, H.
M.; McQuade, D. T. Org. Lett. 2005, 7, 147–150; (o) Aggarwal, V. K.; Fulford, S. Y.;
Lloyd-Jones, G. C. Angew. Chem., Int. Ed. 2005, 44, 1706–1708; (p) Price, K. E.;
Broadwater, S. J.; Walker, B. J.; McQuade, D. T. J. Org. Chem. 2005, 70, 3980–
3987.
4.10. (R)-3-Bromo-1-(2-(butyl(phenyl)phosphanyl)-5,6,7,8-
tetrahydronaphthalen-1-yl)-5,6,7,8-tetrahydronaphthalen-2-ol
L10
White solid; yield: 66%; mp 119.3–120.9 °C; ½a D25
¼ ꢁ47:2 (c
ꢀ
0.68, CH2Cl2); IR (CH2Cl2)
m 3529, 2930, 2858, 1726, 1452, 1433,
1266, 1136, 1070 cmꢁ1 1H NMR (CDCl3, 300 MHz, TMS) d 0.80–
;
0.87 (m, 6H), 1.13–1.45 (m, 4H), 1.50–1.79 (m, 20H), 1.84–2.42
(m, 11H), 2.61–2.65 (m, 3H), 2.73–2.83 (m, 6H), 4.10 (br, 1H),
5.03 (br, 1H), 7.12–7.28 (m, 15H), 7.34–7.38 (m, 1H); 31P NMR
(CDCl3, 121 MHz, 85% H3PO4) d ꢁ25.61, ꢁ25.70; MS (EI) m/e
522.2 (M++2, 100), 520.2 (M+, 99.15), 503.2 (M+ꢁ17, 94.85),
461.1 (M+ꢁ59, 41.44), 275.1 (M+ꢁ247, 21.36); HRMS (EI) calcd
for C30H34BrOP requires 520.1531, found: 520.1536.
3. (a) Walsh, L. M.; Winn, C. L.; Goodman, J. M. Tetrahedron Lett. 2002, 43, 8219–
8222; (b) Oishi, T.; Oguri, H.; Hirama, M. Tetrahedron: Asymmetry 1995, 6, 1241–
1244; (c) Barrett, A. G. M.; Cook, A. S.; Kamimura, A. Chem. Commun. 1998,
2533–2534; (d) Shi, M.; Jiang, J.-K. Tetrahedron: Asymmetry 2002, 13, 1941–
1947; (e) List, B. Tetrahedron 2002, 58, 5573–5590; (f) Imbriglio, J. E.; Vasbinder,
M. M.; Miller, S. J. Org. Lett. 2003, 5, 3741–3743; (g) Shi, M.; Liu, Y. H.; Chen, L. H.
Chirality 2007, 19, 124–128.
4.11. Typical procedure for L5-catalyzed Morita–Baylis–Hillman
reaction of aldehyde 1a with MVK
To a solution of 3-phenylpropanal 1a (26.8 mg, 0.2 mmol), L5
4. Lei, Z. Y.; Ma, G. N.; Shi, M. Eur. J. Org. Chem. 2008, 3817–3820.
(8.7 mg, 0.02 mmol) in THF (1.0 mL) was added methyl vinyl
5. (a) Busacca, C. A.; Lorenz, J. C.; Grinberg, N.; Haddad, N.; Hrapchak, M.; Latli, B.;
Lee, H.; Sabila, P.; Saha, A.; Sarvestani, M.; Shen, S.; Varsolona, R.; Wei, X.;
Senanayake, C. H. Org. Lett. 2005, 7, 4277–4280; (b) Olszewski, T. K.; Boduszek,
B.; Sobek, S.; Kozłowski, H. Tetrahedron 2006, 62, 2183–2189; (c) Bigeault, J.;
Giordano, L.; Buono, G. Angew. Chem., Int. Ed. 2005, 44, 4753–4757.
6. (a) Uozumi, Y.; Tanahashi, A.; Lee, S.-Y.; Hayashi, T. J. Org. Chem. 1993, 58, 1945–
1948; (b) Ito, K.; Eno, S.; Saito, B.; Katsuki, T. Tetrahedron Lett. 2005, 46, 3981–
3985.
7. (a) Barrett, A. G. M.; Kamimura, A. J. Chem. Soc., Chem. Commun. 1995, 1755–
1756; (b) Bailey, M.; Marko, I. E.; Ollis, W. D.; Rasmussen, P. R. Tetrahedron Lett.
1990, 31, 4509–4512; (c) Iwamura, T.; Fujita, M.; Kawakita, T.; Kinoshita, S.;
Watanabe, S.; Kataoka, T. Tetrahedron 2001, 57, 8455–8462; (d) Basavaiah, D.;
Hyma, R. S.; Kumaragurubaran, N. Tetrahedron 2000, 56, 5905–5908; (e) Koenig,
C. M.; Harms, K.; Koert, U. Org. Lett. 2007, 9, 4777–4779.
ketone (34
lL, 0.4 mmol). Then reaction mixture was stirred at
25 °C. When the reaction was completed as monitored by TLC
plate, the solvent was removed and the residue was purified by a
flash column chromatography (SiO2, eluent: EA/PE = 1/4) to afford
4-hydroxy-3-methylene-6-phenylhexan-2-one 3a as a colourless
oil; yield: 35.2 mg (86%). 1H NMR (CDCl3, TMS, 300 MHz): d
1.89–1.97 (m, 2H), 2.35 (s, 3H), 2.63–2.85 (m, 3H), 4.41–4.47 (m,
1H), 6.01 (s, 1H), 6.11 (s, 1H), 7.16–7.31 (m, 5H); ½a D25
¼ þ18:6 (c
ꢀ
1.34, CH2Cl2) for 56% ee; Chiralcel AS, hexane/i-PrOH = 90/10,
0.7 mL/min, 230 nm, tmajor = 10.45 min, tminor = 13.25 min.