Chiral N-thiophosphoryl imine-induced diastereoselective aza-Morita-Baylis-Hillman reaction

Article abstract of DOI:10.1016/j.tetasy.2008.08.010

In the presence of an effective air-stable nucleophilic trialkylphosphine organocatalyst, 1,3,5-triaza-7-phosphaadamantane, a chiral N-thiophosphoryl imine bearing a (S)-binaphthalene skeleton induced a diastereoselective aza-MBH reaction with fair chemical yields and moderate to excellent diastereoselectivities (up to >99% de).

Full text of DOI:10.1016/j.tetasy.2008.08.010

Tetrahedron: Asymmetry 19 (2008) 1886–1890
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Chiral N-thiophosphoryl imine-induced diastereoselective
aza-Morita–Baylis–Hillman reaction
*
Aidang Lu, Xinyuan Xu, Peng Gao, Zhenghong Zhou , Haibin Song, Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Tianjin 300071, People’s Republic of China
a r t i c l e i n f o
a b s t r a c t
Article history:
In the presence of an effective air-stable nucleophilic trialkylphosphine organocatalyst, 1,3,5-triaza-7-
phosphaadamantane, a chiral N-thiophosphoryl imine bearing a (S)-binaphthalene skeleton induced a
diastereoselective aza-MBH reaction with fair chemical yields and moderate to excellent diastereoselec-
tivities (up to >99% de).
Received 30 May 2008
Accepted 5 August 2008
Available online 29 August 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
phile, Shi5b and Aggarwal5c developed another variation of the dia-
stereoselective aza-MBH reactions, with diastereoselectivities up
The Morita–Baylis–Hillman (MBH) reaction is an effective and
potentially useful carbon–carbon bond forming reaction, giving
densely multifunctional adducts under mild conditions.1 Due to
its enormous potential in organic synthesis, it has received much
research interest.2 Recent efforts on this reaction have been direc-
ted toward the following two aspects: asymmetric MBH reaction
catalyzed by chiral catalysts,3 and aza-MBH reaction.4,5 For the lat-
ter, major efforts have been focused on the scope of the reaction
and a search for practical catalysts4 including chiral catalysts for
an asymmetric version of the aza-MBH reaction.5 In 1984, Perlmutter
reported the first example of an aza-MBH reaction of N-tosyl
imines and ethyl acrylate catalyzed by DABCO.4a However, this
report did not attract much attention in the following decade,
and only ver recently did new reports emerge.4d–p For example,
Yamamoto first explored the aza-MBH reaction of N-methoxycar-
bonyl-protected imines;4b Bertendshaw established a three-com-
ponent version of an aza-MBH reaction from an activated olefin,
aldehyde, and N-protected amine;4c Adolfsson applied Lewis base
or Lewis acid as a cocatalyst to aza-MBH reaction;4g,h Shi made sig-
nificant contributions to this reaction by expanding the scope of
the substrate activated olefin,4f,l,n,p and employing tertiary phos-
phines4i,j,m as catalysts and N-diphenylphosphinoylimines4i as an
alternative imine substrate. Over the past decades, a catalytic
asymmetric version of the aza-MBH reaction has undergone
remarkable progress.5d–w However, only a few reports have dealt
with a chiral auxiliary-induced diastereoselective aza-MBH reac-
tion.5a–c Kündig reported a DABCO-catalyzed coupling reaction of
methyl acrylate and acrylonitrile with planar chiral arylaldimine
tricarbonylchromium complexes, in which the de values varied in
a range of 68–95%.5a Using chiral N-sulfinylimines as the electro-
to 86% and 64% de being observed, respectively.
Recently, we have developed a convenient method for the prep-
aration of N-thiophosphoryl imines,6 which have been successfully
employed as novel electrophiles in some organic transformations.7
Compared to N-diphenylphosphinoyl imines, the former exhibit
great advantages with their stability and ease of preparation. In
the preliminary report, it was found that in the presence of an
air-stable trialkylphosphine, 1,3,5-triaza-7-phosphaadamantane
(PTA), N-thiophosphoryl imines demonstrate fair reactivity in the
coupling of methyl vinyl ketone (MVK) and methyl acrylate (MA)
(Scheme 1).8 The unique characteristics of N-thiophosphoryl imi-
nes, a tetradentate structure around the phosphorus(V) atom,
would provide a full opportunity to realize the diastereoselective
version of this reaction. Herein, we report the diastereoselective
version of this N-thiophosphoryl imine-based aza-MBH reaction.
2. Results and discussion
2.1. Synthesis of chiral N-thiophosphoryl imines
According to the reported procedure, chiral N-thiophosphoryl
imine 1 containing an adjacent stereogenic phosphorus atom and
chiral N-thiophosphoryl imines 2 bearing a (S)-binaphthalene scaf-
fold were synthesized in good to excellent yield through thermal
condensation of acetals and the corresponding thiophosphora-
mides (Scheme 2).6
2.2. PTA-catalyzed diastereoselective aza-MBH reaction
between chiral N-thiophosphoryl imines 1 and 2 and MVK
With these imines in hand, their chiral induction ability in
the coupling with MVK was investigated. Firstly, diastereoselective
aza-MBH reaction between chiral imine 1 with an adjacent
* Corresponding author. Tel.: +86 22 23504232; fax: +86 22 23508939.
E-mail address: z.h.zhou@nankai.edu.cn (Z. Zhou).
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.08.010

A. Lu et al. / Tetrahedron: Asymmetry 19 (2008) 1886–1890
1887
R
R
S
NH
O
R
R
S
N
N
P
P
H
PTA (10 or 30 mol-%)
MeCN, rt, 2—108 h
O
+
R1
N
P
Ph
R1
N
Ph
PTA
R = EtO, Ph ; R1 = Me, OMe
57—97%
Scheme 1. PTA-catalyzed aza-MBH reaction of N-thiophosphoryl imines.
S
S
P
P
EtO
Ph
N
120—160 ºC
Ph
+
PhCH(OEt)2
ArCH(OEt)2
NH2
O
P
O
EtO
5 h
H
Ph
91%
1
O
O
120—160 ºC
2—6 h
82—91%
S
N
S
NH2
+
P
H
Ar
2a—f
Scheme 2. Synthesis of chiral N-thiophosphoryl imines.
stereogenic phosphorus atom and MVK was performed in the pres-
ence of 10 mol % of PTA. The reaction ran smoothly to afford the
corresponding aza-MBH adducts with satisfactory yields, albeit in
quite low diastereoselectivities (Scheme 3).
As shown in Table 1, in all cases, the coupling of chiral imines 2
with MVK ran smoothly in the presence of 10 mol % of PTA to give
the corresponding aza-MBH adducts 4 in satisfactory yields. The
diastereoselectivity of this reaction was influenced by the nature
of the substrate imine. For example, only moderate diastereoselec-
tivities were observed for imines 3b, 3c, and 3e (Table 1, entries 2,
3, and 5; 50%, 42%, and 48% de, respectively), while almost perfect
diastereoselectivity was obtained for imine 3f bearing a trifluoro-
methyl group at the para-position on the benzene ring (Table 1, en-
try 6, >99% de). The diastereoselectivity of this type of reaction was
obviously higher than that of the coupling of a chiral imine 1 and
MVK (Scheme 2, 14% de). This means that the chiral induction of
chiral imine containing an adjacent stereogenic phosphorus atom
is far less effective than that of the chiral imine with a bulky (S)-
binaphthalene scaffold.
S
S
O
P
Ph
P
NH
*
O
Ph
10 mol% PTA
CH3CN, rt
N
Et O
+
Et O
Ph
H
Ph
1
3
81 % yield, 14 % de
Scheme 3. PTA-catalyzed diastereoselective aza-MBH reaction of imine 1 with
MVK.
Theoretically, the reaction of 2 with MVK will provide a pair of
diastereomers of adduct 4. With the exception of 4f, the 31P NMR
analysis of 4 clearly showed two singlets (near 80 ppm) corre-
sponding to these two diastereomers. In all cases, the separation
is sufficient to determine the de value by integration. In addition,
it is possible to analyze these adducts by 1H NMR, where many sig-
nals (particularly the acetyl group) could be differentiated between
the two diastereomers. With the exception of 4f, in all cases, the
We then turned our attention to the chiral N-thiophos-
phoryl imine 2 bearing a bulky (S)-binaphthalene scaffold. It is
noteworthy that under otherwise identical conditions, a dramatic
improvement in diastereoselectivity was obtained for the diaste-
reoselective aza-MBH reaction of chiral thiophosphorylimine 2
derived from (S)-1,10-binaphthyl-2,20-diol and MVK. The results
are summarized in Table 1.
Table 1
PTA-catalyzed diastereoselective aza-MBH reaction between 2 and MVK
O
O
O
O
P
O
S
N
S
10 mol % PTA
CH3CN
P
H
+
NH
O
Ar
Ar
2a—f
4a—f
Entry
2 or 4
Ar
Ph
Time (day)
Yielda (%)
deb (%)
Configuration
1
2
3
4
5
6
a
b
c
d
e
f
4
5
5
2
4
3
64
65
70
75
72
66
90
50
42
82
48
(S,S)
(S,S)
(S,S)
(S,R)
(S,S)
(S,S)
4-MeC6H4
4-MeOC6H4
2-ClC6H4
4-BrC6H4
4-F3CC6H4
>99
a
Isolated yield.
b
Determined by 31P NMR and 1H NMR.

1888
A. Lu et al. / Tetrahedron: Asymmetry 19 (2008) 1886–1890
acetyl protons (2.2–2.4 ppm) are clearly distinguished by 1H NMR
analysis. Integration of the two signals also allows the determina-
tion of its de value.
2H, OCH2), 7.44–7.55 (m, 6Harom), 7.98 (d, 2Harom, J = 7.2 Hz),
8.07–8.03 (m, 2Harom), 9.23 (d, 1H, J = 38.8 Hz, CH). Anal. Calcd
for C15H16NOPS: C, 62.27; H, 5.57; N, 4.84. Found: C, 62.43; H,
5.45; N, 4.72.
In order to determine the absolute configuration of the newly
generated stereogenic center, single crystals suitable for X-ray
crystallographic analysis were obtained from compound 4f bearing
a trifluoromethyl group. The absolute configuration of 4f was as-
signed to be (S) for the nitrogen-connecting carbon (Fig. 1).9 At
the same time, NMR analysis showed that the signal corresponding
For 2a: White solid, 82% yield, mp 208–211 °C, ½a D20
¼ þ288:5 (c
ꢀ
1.0, CHCl3), 31P NMR (161.7 MHz, CDCl3): d 90.74; 1H NMR (400
MHz, CDCl3): d 7.33 (t, 2Harom, J = 7.6 Hz), 7.43–7.52 (m, 7Harom),
7.63 (d, 2Harom, J = 8.4 Hz), 7.93 (d, 2Harom, J = 7.6 Hz), 7.98 (dd,
2Harom, J = 8.4, 3.6 Hz) 8.02 (d, 1Harom, J = 8.8 Hz), 8.08 (d, 1Har-
om, J = 8.8 Hz), 9.39 (d, J = 40.4 Hz, CH). Anal. Calcd for
to the major diastereomer always appeared at downfield in the 31
P
NMR spectra, and the signal of the acetyl protons corresponding to
the major isomer always appeared upfield in the 1H NMR spectra.
Therefore, the other adducts 4 should have the same (S)-configura-
tion as compound 4f, except for 4d in which the priority of the four
groups is changed when chloro is introduced at the ortho-position
on the benzene ring.
C27H18NO2PS: C, 71.83; H, 4.02; N, 3.10. Found: C, 71.65; H, 3.86;
N, 2.91.
For 2b: White solid, 91% yield, mp 210–211 °C, ½a D20
¼ þ153:9 (c
ꢀ
1.0, CHCl3), 31P NMR (121.3 MHz, CDCl3): d 91.41; 1H NMR
(300 MHz, CDCl3): d 2.44 (s, 3H, CH3), 7.28–7.35 (m, 4Harom),
7.42–7.52 (m, 5Harom), 7.63 (dd, 1Harom, J = 8.7 and 1.2 Hz),
7.82 (d, 2Harom, J = 8.4 Hz), 7.96–8.09 (m, 4Harom), 9.34 (d, 1H,
J = 40.5 Hz, CH). Anal. Calcd for C28H20NO2PS: C, 72.24; H, 4.33;
N, 3.01. Found: C, 72.01; H, 4.12; N, 2.86.
For 2c: White solid, 88% yield, mp 182–184 °C, ½a D20
¼ þ103:5 (c
ꢀ
1.0, CHCl3), 31P NMR (121.3 MHz, CDCl3): d 91.84; 1H NMR
(300 MHz, CDCl3): d 3.89 (s, 3H, CH3), 6.96 (d, 2Harom, J =
8.7 Hz), 7.29–7.34 (m, 2Harom), 7.42–7.52 (m, 5Harom), 7.63
(dd, 1Harom, J = 8.7 and 1.2 Hz), 7.88 (d, 2Harom, J = 8.7 Hz),
7.96–8.08 (m, 4Harom), 9.29 (d, 1H, J = 40.5 Hz, CH). Anal. Calcd
for C28H20NO3PS: C, 69.84; H, 4.19; N, 2.91. Found: C, 69.65; H,
4.04; N, 2.67.
For 2d: White solid, 90% yield, mp 118–122 °C, ½a D20
¼ þ228:5 (c
ꢀ
1.0, CHCl3), 31P NMR (121.3 MHz, CDCl3): d 89.65; 1H NMR
(300 MHz, CDCl3): d 7.43–7.52 (m, 9Harom), 7.92–8.10 (m, 7Har-
om), 9.88 (d, 1H, J = 39.6 Hz, CH). Anal. Calcd for C27H17ClNO2PS:
C, 66.74; H, 3.53; N, 2.88. Found: C, 66.37; H, 3.16; N, 2.49.
For 2e: White solid, 90% yield, mp 208–211 °C (recrystallization
from methanol), ½a D20
ꢀ
¼ þ99:5 (c 1.0, CHCl3), 31P NMR (121.3 MHz,
CDCl3): d 90.14; 1H NMR (300 MHz, CDCl3): d 7.30–7.35 (m, 2Har-
om), 7.40–7.53 (m, 5Harom), 7.60–7.65 (m, 3Harom), 7.78 (d,
2Harom, J = 8.4 Hz) 7.96–8.09 (m, 4Harom), 9.33 (d, J = 39.9 Hz,
CH). Anal. Calcd for C27H17BrNO2PS: C, 61.14; H, 3.23; N, 2.64.
Found: C, 60.97; H, 3.04; N, 2.51.
Figure 1. X-ray structure of enantiomerically pure 4f. Thermal ellipsoids are shown
at 30% probability. Solvent (CH2Cl2) has been omitted for clarity.
For 2f: White solid, 83% yield, mp 205–207 °C, ½a D20
¼ þ254:4 (c
ꢀ
1.0, CHCl3), 31P NMR (121.3 MHz, CDCl3): d 89.19; 1H NMR
(300 MHz, CDCl3): d 7.31–7.36 (m, 2Harom), 7.41–7.54 (m, 5Har-
om), 7.63 (dd, 1Harom, J = 9.0 and 1.2 Hz), 7.75 (d, 2Harom,
J = 8.1 Hz), 7.98–8.11 (m, 6Harom), 9.43 (d, 1H, J = 39.6 Hz, CH).
Anal. Calcd for C28H17F3NO2PS: C, 64.74; H, 3.30; N, 2.70. Found:
C, 64.59; H, 3.05; N, 2.52.
3. Conclusion
In conclusion, we have developed a novel chiral N-thiophospho-
ryl imine-induced diastereoselective aza-MBH reaction. The corre-
sponding aza-MBH adducts were obtained in fair to excellent
yields with moderate to excellent diastereoselectivities (>99% de)
in the presence of an efficient air-stable nucleophilic trialkylphos-
phine organocatalyst—PTA.
4.2. General procedure for the PTA-catalyzed diastereoselective
aza-MBH reaction
4. Experimental
A mixture of chiral imine (1.0 mmol), MVK (3.0 mmol), and PTA
(0.10 mmol) in 3.0 mL of acetonitrile was stirred at room temper-
ature until almost total consumption of imine (monitored by
TLC). After removal of solvent, the residue was purified by column
chromatography on silica gel (200–300 meshes, gradient eluted
with petroleum ether/ethyl acetate) to afford the product.
4.1. Synthesis of chiral N-thiophosphoryl imines 1 and 2
A mixture of acetal and the corresponding phosphoramide
(with a molar ratio of 1.3:1) was placed in a round-bottomed flask
equipped with a distilling apparatus. The resulting mixture was
gently heated (the bath temperature was gradually raised to ca.
160 °C) with stirring. The reaction was completed until no more
released ethanol was distilled off from the reaction mixture
(2–6 h). After removal of the excess acetal, the crude product
was purified via recrystallization or column chromatography on
silica gel (200–300 mesh, gradient eluted with petroleum ether
and ethyl acetate).
For 3: Pale yellow oil, 68% yield, 14% de, 31P NMR (161.7 MHz,
CDCl3): d 74.73 (major), 75.93 (minor); 1H NMR (400 MHz, CDCl3):
d 1.23 (t, 1.71 H, J = 7.2 Hz, CH3), 1.32 (t, 1.29 H, J = 7.2 Hz, CH3),
2.17 (s, 1.56H, CH3), 2.21 (s, 1.15H, CH3), 3.80–3.86 (m, 0.56H,
CH), 3.95–4.01 (m, 0.45H, CH), 4.10–4.24 (m, 2H, OCH2), 5.20 (t,
0.56H, J = 11.6 Hz, NH), 5.20 (t, 0.43 H, J = 11.6 Hz, NH), 5.91 (s,
0.52 H, @CH2), 6.01 (s, 0.52 H, @CH2), 6.14 (s, 0.39H, @CH2), 6.16
(s, 0.38H, @CH2), 7.11–7.25 (m, 5Harom), 7.36–7.48 (m, 3Harom),
7.75–7.85 (m, 2Harom). Anal. Calcd for C19H22NO2PS: C, 63.49; H,
6.17; N, 3.90. Found: C, 63.16; H, 5.83; N, 3.62.
For 1: Pale yellow liquid, 91% yield, n1D6 1:6100, ½a D20
¼ ꢁ102:2 (c
ꢀ
1.0, CHCl3), 31P NMR (161.7 MHz, CDCl3):
d
87.3; 1H NMR
(400 MHz, CDCl3): d 1.32 (t, 3H, J = 7.2 Hz, CH3), 4.07–4.15 (m,

A. Lu et al. / Tetrahedron: Asymmetry 19 (2008) 1886–1890
1889
For 4a: White solid, 64% yield, mp 242–245 °C, ½a D20
ꢀ
¼ þ339:3 (c
(s, 0.22H, @CH), 7.20–7.22 (m, 2Harom), 7.33–7.36 (m, 3Harom),
7.44–7.55 (m, 6Harom), 7.91–8.06 (m, 5Harom); 13C NMR
(75 MHz, CDCl3): 26.59, 58.99, 59.05, 120.96, 121.00, 121.46,
125.66, 125.81, 126.54, 126.78, 127.02, 127.18, 127.82, 127.97,
128.32, 128.43, 128.49, 130.62, 130.90, 131.47, 131.59, 131.64,
131.93, 132.36, 132.45, 140.05, 140.12, 147.34, 199.16. Anal. Calcd
for C31H23BrNO3PS: C, 62.01; H, 3.86; N, 2.33. Found: C, 61.84; H,
3.67; N, 2.08.
1, CHCl3), 90% de, 31P NMR (121.3 MHz, CDCl3): d 82.09 (minor),
82.21 (major); 1H NMR (400 MHz, CDCl3): d 2.27 (s, 2.85H, CH3),
2.35 (s, 0.15H, CH3), 4.60 (dd, 1H, J = 8.0 and 10.8 Hz, CH), 5.63
(dd, 1H, J = 10.8 and 13.2 Hz, NH), 6.12 (s, 1H, @CH2), 6.21 (s, 1H,
@CH2), 6.97–7.00 (m, 1Harom), 7.27–7.58 (m, 12Harom), 7.85–
8.03 (m, 4Harom); 13C NMR (100.6 MHz, CDCl3): 26.67, 59.14,
59.18, 121.12, 121.51, 122.10, 122.27, 122.30, 125.60, 125.72,
126.49, 126.64, 126.68, 126.99, 127.13, 127.47, 127.53, 128.37,
128.48, 128.54, 130.55, 130.83, 131.56, 131.86, 132.32, 132.35,
140.97, 141.02, 146.34, 146.43, 147.37, 147.51, 147.67, 147.72,
199.21. Anal. Calcd for C31H24NO3PS: C, 71.39; H, 4.64; N, 2.69.
Found: C, 71.15; H, 4.64; N, 2.74.
For 4f: White solid, 66% yield, mp 123–127 °C, ½a D20
¼ þ216:6 (c
ꢀ
0.5, CHCl3), >99% de, 31P NMR (121.3 MHz, CDCl3): d 80.95; 1H NMR
(300 MHz, CDCl3): d 2.27 (s, 3H, CH3, CH3), 4.77 (dd, 1H, J = 8.4 and
10.8 Hz, CH), 5.64 (dd, 1 H, J = 10.8 and 13.2 Hz, NH), 6.16 (s, 1H,
@CH2), 6.25 (s, 1H, @CH2), 7.10 (d, 1Harom, J = 8.7 Hz), 7.31–7.36
(m, 3Harom), 7.43–7.49 (m, 4Harom), 7.52–7.64 (m, 4Harom),
7.92–7.99 (m, 3Harom), 8.03 (d, 1Harom, J = 8.7 Hz); 13C NMR
(75.0 MHz, CDCl3): 26.52, 59.25, 59.30, 120.86, 121.43, 122.07,
122.10, 122.34, 126.63, 126.87, 126.96, 127.02, 127.19, 128.48,
128.56, 130.70, 130.97, 131.68, 131.95, 132.36, 132.48, 145.02,
145.09, 146.34, 146.46, 147.05, 147.11, 147.34, 147.53, 199.22.
Anal. Calcd for C32H23F3NO3PS: C, 65.19; H, 3.93; N, 2.38. Found:
C, 65.02; H, 3.67; N, 2.11.
For 4b: White solid, 65% yield, mp 105–110 °C, ½a D20
¼ þ282:5 (c
ꢀ
0.5, CHCl3), 50% de, 31P NMR (121.3 MHz, CDCl3): d 81.03 (minor),
81.19 (major); 1H NMR (300 MHz, CDCl3): d 2.26 (s, 2.25 H, CH3),
2.30 (s, 0.75H, CH3), 2.34 (s, 0.74H, CH3), 2.37 (s, 2.38H, CH3),
4.64 (dd, 0.74H, J = 8.1 and 10.8 Hz, CH), 4.75 (dd, 0.25H, J = 8.1
and 10.8 Hz, CH), 5.48 (dd, 0.26H, J = 10.8 and 13.2 Hz, NH), 5.59
(dd, 0.73 H, JH–H = 10.8 and 13.2 Hz, NH), 6.09 (s, 0.75H, @CH2),
6.16 (s, 0.25H, @CH2), 6.19 (s, 0.72H, @CH2), 6.27 (s, 0.23H,
@CH2), 7.02–7.20 (m, 7Harom), 7.33–7.59 (m, 6Harom), 7.86–
8.03 (m, 3Harom); 13C NMR (75 MHz, CDCl3): 21.06, 26.68, 58.99,
59.04, 121.21, 121.55, 121.58, 122.13, 122.33, 125.58, 125.70,
125.99, 126.47, 126.58, 126.65, 127.04, 127.11, 127.19, 128.36,
128.48, 129.20, 130.50, 130.80, 131.60, 131.90, 132.38, 137.19,
138.02, 138.09, 146.43, 146.54, 147.45, 147.63, 147.99, 148.05,
199.22. Anal. Calcd for C32H26NO3PS: C, 71.76; H, 4.89; N, 2.62.
Found: C, 71.55; H, 4.68; N, 2.43.
4.3. General procedure for acidic methanolysis of the aza-MBH
adducts
A mixture of aza-Morita–Baylis–Hillman adduct 4a (0.52 g,
1 mmol) in 20 mL of 3.75 M HCl/MeOH was stirred at room tem-
perature for 3 h. After removal of solvent, the pale yellow viscous
residue was washed with ether (3 ꢂ 20 mL), and then recrystal-
lized from ether/chloroform to provide the desired product.
3-[Amino(phenyl)methyl]but-3-en-2-one hydrochloride: White
solid, 0.13 g, 60% yield, mp 153–156 °C, 1H NMR (400 MHz, D2O): d
2.19 (s, 3H, CH3), 5.23 (s, 1H, CH), 6.05 (s, 1H, @CH2), 6.51 (s, 1H,
@CH2), 7.21–7.38 (m, 5Harom).
For 4c: White solid, 70% yield, mp 108–112 °C, ½a D20
¼ þ133:5 (c
ꢀ
0.5, CHCl3), 42% de, 31P NMR (121.3 MHz, CDCl3): d 80.90 (minor),
81.10 (major); 1H NMR (300 MHz, CDCl3): d 2.26 (s, 2.12H, CH3),
2.34 (s, 0.87H, CH3), 3.77 (s, 0.81H, OCH3), 3.84 (s, 2.03H, OCH3),
4.61 (dd, 0.65H, JH–H = 8.1 and 10.5 Hz, CH), 4.75 (dd, 0.27H,
JH–H = 8.1 and 10.5 Hz, CH), 5.47 (dd, 1H, JH–H = 10.5 and 12.6 Hz,
NH), 5.59 (dd, 1H, JH–H = 10.5 and 12.6 Hz, NH), 6.08 (s, 0.66H,
@CH2), 6.15 (s, 0.27H, @CH2), 6.18 (s, 0.65H, @CH2), 6.26 (s,
0.26H, @CH2), 6.80–6.91 (m, 2Harom), 6.99–7.10 (m, 2Harom),
7.30–8.59 (m, 8Harom) 7.86–8.04 (m, 4Harom); 13C NMR
(100.6 MHz, CDCl3): 27.00, 27.07, 55.49, 55.54, 55.58, 55.65,
58.74, 58.88, 114.00, 114.12, 120.97, 121.41, 121.78, 122.36,
122.56, 125.89, 126.00, 126.77, 126.97, 127.26, 127.40, 127.53,
128.18,128.66, 128.76, 130.80, 131.11, 131.82, 132.11, 132.59,
133.42, 133.46, 146.61, 146.70, 147.63, 147.77, 148.11, 148.16,
158.99, 159.20, 199.53, 199.61. Anal. Calcd for C32H26NO4PS: C,
69.68; H, 4.75; N, 2.54. Found: C, 69.41; H, 4.48; N, 2.26.
Acknowledgment
We are grateful to the National Natural Science Foundation of
China (Nos. 20472033, 20772058) for generous financial support
for our programs.
References
1. (a) Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn. 1968, 41, 2815; (b) Baylis,
A. B.; Hillman, M. E. D. Ger. Offen. 2155113; Chem. Abstr. 1972, 77, 34174g.
2. For reviews of MBH reaction, see: (a) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001; (b) Ciganek, E. Org. React. 1997, 51, 201; (c) Langer,
P. Angew. Chem., Int. Ed. 2000, 39, 3049; (d) Cai, J. X.; Zhou, Z. H.; Tang, C. C. Chem.
Res. (in Chinese) 2001, 12, 54; (e) Basavaiah, D.; Rao, A. J.; Satyanarayana, T.
Chem. Rev. 2003, 103, 811; (f) Masson, G.; Housseman, C.; Zhu, J. Angew. Chem.,
Int. Ed. 2007, 46, 4614; Basavaiah, D.; Rao, K. V.; Reddy, R. J. Chem. Soc. Rev. 2007,
36, 1581.
3. (a) Barrett, A. G. M.; Dozzo, P.; White, A. J. P.; Williams, D. J. Tetrahedron 2002, 58,
7303; (b) Hayashi, Y.; Tamura, T.; Shoji, M. Adv. Synth. Catal. 2004, 346, 1106; (c)
Iwabuchi, Y.; Hatakeyama, S. J. Synth. Org. Chem. Jpn. 2002, 60, 1; (d) Shi, M.;
Jiang, J. K. Tetrahedron: Asymmetry 2002, 13, 1941; (e) Krishina, P. R.; Kannan, V.;
Reddy, P. V. N. Adv. Synth. Catal. 2004, 346, 603; (f) Shi, M.; Jiang, J. K.; Li, C. Q.
Tetrahedron Lett. 2002, 43, 127; (g) Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J.
Org. Lett. 2003, 5, 3741; (h) Yang, K. S.; Lee, W. D.; Pan, J. F.; Chen, K. M. J. Org.
Chem. 2003, 68, 915; (i) Aroyan, C. E.; Vashinder, M. M.; Miller, S. J. Org. Lett.
2005, 7, 3849; (j) Walsh, L. M.; Winn, C. L.; Goodman, J. M. Tetrahedron Lett.
2002, 43, 8219; (k) McDougal, N. T.; Trevellini, W. L.; Rodgen, S. A.; Kliman, L. T.;
Schaus, S. E. Adv. Synth. Catal. 2004, 346, 1231; (l) Sohtome, Y.; Tanatani, A.;
Hashimoto, Y.; Nagasawa, K. Tetrahedron Lett. 2004, 45, 5589; (m) McDougal, N.
T.; Schaus, S. E. J. Am. Chem. Soc. 2003, 125, 12094; (n) Nakano, A.; Ushiyama, M.;
Iwabuchi, Y.; Hatakeyama, S. Adv. Synth. Catal. 2005, 347, 1790; (o) Wang, J.; Li,
H.; Yu, X.; Zu, L.; Wang, W. Org. Lett. 2005, 7, 4293; (p) Pereira, S. I.; Adrio, J.;
Silva, A. M. S.; Carretero, J. C. J. Org. Chem. 2005, 70, 10175; (q) Tang, H. Y.; Zhao,
G. F.; Zhou, Z. H.; Zhou, Q. L.; Tang, C. C. Tetrahedron Lett. 2006, 47, 5717; (r)
Tang, H. Y.; Gao, P.; Zhao, G. F.; Zhou, Z. H.; He, L. N.; Tang, C. C. Catal. Commun.
2007, 1811; (s) Tang, H. Y.; Zhao, G. F.; Zhou, Z. H.; Gao, P.; He, L. N.; Tang, C. C.
Eur. J. Org. Chem. 2008, 126.
For 4d: White solid, 75% yield, mp 115–119 °C, ½a D20
¼ þ216:6 (c
ꢀ
1, CHCl3), 82% de, 31P NMR (121.3 MHz, CDCl3): d 80.14 (minor),
80.69 (major); 1H NMR (300 MHz, CDCl3): d 2.25 (s, 2.67H, CH3),
2.27 (s, 0.26H, CH3), 4.81 (dd, 1H, J = 9.0 and 10.8 Hz, CH), 6.01
(dd, 1H, J = 10.8 and 13.5 Hz, NH), 6.25 (s, 1H, @CH2), 6.26 (s, 1H,
@CH2), 7.30–7.43 (m, 4Harom), 7.46–7.59 (m, 8Harom), 7.86 (d,
1Harom, J = 8.7 Hz), 7.93 (d, 2Harom, J = 8.7 Hz), 8.01 (d, 1Harom,
J = 8.7 Hz); 13C NMR (100.6 MHz, CDCl3): d 26.74, 56.08, 56.13,
120.38, 121.05, 121.43, 121.52, 121.55, 122.05, 122.08, 122.33,
122.36, 125.61, 125.74, 126.51, 126.61, 126.71, 126.80, 126.99,
127.15, 128.35, 128.42, 128.48, 128.67, 128.75, 128.95, 129.30,
129.49, 129.61, 129.87, 130.70, 130.53, 130.85, 131.60, 131.87,
132.33,132.42,132.75, 132.92, 138.01, 138.06, 199.39. Anal. Calcd
for C31H23ClNO3PS: C, 66.96; H, 4.17; N, 2.52. Found: C, 66.78; H,
4.05; N, 2.34.
For 4e: White solid, 72% yield, mp 108–112 °C, ½a D20
¼ þ168:7 (c
ꢀ
1, CHCl3), 31P NMR (121.3 MHz, CDCl3): d 80.90 (minor), 80.96 (ma-
jor); 1H NMR (300 MHz, CDCl3): d 2.26 (s, 2.22H, CH3), 2.36 (s,
0.78H, CH3), 4.66–4.84 (m, 1H, CH), 5.43–5.59 (m, 1H, NH), 6.11
(s, 0.62H, @CH2), 6.19 (s, 0.22H, @CH), 6.21 (s, 0.65H, @CH2), 6.30

1890
A. Lu et al. / Tetrahedron: Asymmetry 19 (2008) 1886–1890
4. (a) Perlmutter, P.; Teo, C. C. Tetrahedron Lett. 1984, 25, 5951; (b) Yamamoto, K.;
Takagi, M.; Tsuji, J. Bull. Chem. Soc. Jpn. 1988, 61, 319; (c) Bertenshaw, S.; Kahn,
M. Tetrahedron Lett. 1989, 30, 2731; (d) Kamimura, A.; Gunjigake, Y.; Mitsudera,
H.; Yokeyama, S. Tetrahedron Lett. 1998, 39, 7323; (e) Richter, H.; Jung, G.
Tetrahedron Lett. 1998, 39, 2729; (f) Shi, M.; Xu, Y. M. Chem. Commun. 2001,
1876; (g) Balan, D.; Adolfsson, H. J. Org. Chem. 2001, 66, 6498; (h) Balan, D.;
Adolfsson, H. J. Org. Chem. 2002, 67, 2329; (i) Shi, M.; Zhao, G. L. Tetrahedron Lett.
2002, 43, 4499; (j) Shi, M.; Xu, Y. M. Eur. J. Org. Chem. 2002, 696; (k) Azizi, N.;
Saidi, M. R. Tetrahedron Lett. 2002, 43, 4305; (l) Shi, M.; Xu, Y. M.; Zhao, G. L.; Wu,
X. F. Eur. J. Org. Chem. 2002, 3666; (m) Huang, J. W.; Shi, M. Adv. Synth. Catal.
2003, 345, 953; (n) Shi, M.; Xu, Y. M. J. Org. Chem. 2003, 68, 4784; (o) Back, T. G.;
Rankic, D. A.; Sorbetti, J. M.; Wulff, J. E. Org. Lett. 2005, 7, 2377; (p) Zhao, G. L.;
Shi, M. J. Org. Chem. 2005, 70, 9975; (q) Shi, Y. L.; Shi, M. Eur. J. Org. Chem. 2007,
2905.
Q. Tetrahedron: Asymmetry 2005, 16, 1385; (o) Raheen, I. T.; Jacobsen, E. N. Adv.
Synth. Catal. 2005, 347, 1701; (p) Matsai, K.; Tanaka, K.; Horii, A.; Takizawa, S.;
Sasai, H. Tetrahedron: Asymmetry 2006, 17, 578; (q) Matsui, K.; Takizawa, S.;
Sasai, H. Synlett 2006, 761–765; (r) Liu, Y. H.; Chen, L. H.; Shi, M. Adv. Synth.
Catal. 2006, 348, 973; (s) Ito, K.; Nishida, K.; Gotanda, T. Tetrahedron Lett. 2007,
48, 6147; (t) Shi, Y. L.; Shi, M. Adv. Synth. Catal. 2007, 349, 2129; (u) Qi, M. J.; Ai,
T.; Shi, M.; Li, G. Tetrahedron 2008, 64, 1181; (v) Liu, Y. H.; Shi, M. Adv. Synth.
Catal. 2008, 350, 122; (w) Guang, X. Y.; Jiang, Y. Q.; Shi, M. Eur. J. Org. Chem. 2008,
2150.
6. (a) Xu, X. Y.; Wang, C. G.; Zhou, Z. H.; Zeng, Z. B.; Ma, X. P.; Zhao, G. F.; Tang, C. C.
Lett. Org. Chem. 2006, 3, 640; (b) Xu, X. Y.; Wang, C. G.; Zhou, Z. H.; Zeng, Z. B.;
Ma, X. P.; Zhao, G. F.; Tang, C. C. Heteroatom Chem. 2008, 19, 238.
7. Ma, X. P.; Xu, X. Y.; Wang, C. G.; Zhao, G. F.; Zhou, Z. H.; Tang, C. C. J. Organomet.
Chem. 2007, 692, 3685.
5. (a) Kündig, E. P.; Xu, L.-H.; Schnell, B. Synlett 1994, 413; (b) Shi, M.; Xu, Y. M.
Tetrahedron: Asymmetry 2002, 13, 1195; (c) Aggarwal, V. K.; Castro, A. M. M.;
Mereu, A.; Adams, H. Tetrahedron Lett. 2002, 43, 1577; (d) Genisson, Y.;
Massardier, C.; Gautier-Luneau, I.; Greene, A. E. J. Chem. Soc., Perkin Trans. 1 1996,
2869; (e) Shi, M. l.; Xu, Y. M. l. Angew. Chem., Int. Ed. 2002, 41, 4507; (f) Shi, M.;
Chen, L. H. Chem. Commun. 2003, 1310; (g) Kawahara, S.; Nakano, A.; Esumi, T.;
Iwabuchi, Y.; Hatakeyama, S. Org. Lett. 2003, 5, 3103; (h) Balan, D.; Adolfsson, H.
Tetrahedron Lett. 2003, 44, 2521; (i) Shi, M.; Xu, Y. M.; Shi, Y. L. Chem. Eur. J. 2005,
11, 1794; (j) Matsui, K.; Takizawa, S.; Sasai, H. J. Am. Chem. Soc. 2005, 127, 3680;
(k) Shi, M.; Chen, L. H.; Tang, W. D. Adv. Synth. Catal. 2005, 347, 1781; (l) Shi, M.;
Chen, L. H.; Li, C. Q. J. Am. Chem. Soc. 2005, 127, 3790; (m) Buskens, P.;
Klankermayer, J.; Leitner, W. J. Am. Chem. Soc. 2005, 127, 16762; (n) Shi, M.; Li, C.
8. Xu, X. Y.; Wang, C. G.; Zhou, Z. H.; Tang, X. F.; He, Z. J.; Tang, C. C. Eur. J. Org.
Chem. 2007, 4487.
9. Crystal data for enantiomerically pure 8f
C
32H23F3NO3PSꢃCH2Cl2 (674.47),
orthorhombic,
space
group
P212121,
a = 8.0179(3),
b = 10.2679(4),
c = 37.4726(13) Å, V = 3085.0(2) Å3, Z = 4, specimen, 0.22 ꢂ 0.20 ꢂ 0.18 mm3,
T = 113(2) K, Rigaku Saturn CCD area detector, absorption coefficient
0.384 mmꢁ1
,
reflections collected/unique 27,246/7338 [Rint
refinement by full-matrix least-squares on F2, data/restraints/parameters
7338/100/423, Goodness-of-fit on indices [I > 2 (I)]
2 = 1.045, final
R1 = 0.0420, wR2 = 0.0930, indices (all data) R1 = 0.0459, wR2 = 0.0954,
=
0.0455],
F
R
r
R
absolute structure parameter ꢁ0.05(5), largest difference in peak and hole
0.361 and ꢁ0.385 e Åꢁ3
.