A Br?nsted acid and Lewis base organocatalyst for the aza-Morita-Baylis-Hillman reaction

Article abstract of DOI:10.1055/s-2006-933112

(S)-3-[2-(Diphenylphosphino)phenyl]BINOL has been established as an efficient asymmetric bifunctional organocatalyst for the aza-Morita-Baylis- Hillman (aza-MBH) reaction. The Br?nsted acid and Lewis base functionalities cooperate in substrate activation

Full text of DOI:10.1055/s-2006-933112

LETTER
761
A Brønsted Acid and Lewis Base Organocatalyst for the Aza-Morita–Baylis–
Hillman Reaction
O
rganocatalyst for
a
the
A
za-
M
t
orita–B
s
aylis–Hil
u
lmanReactio
y
n
a Matsui, Shinobu Takizawa, Hiroaki Sasai*
The Institute of Scientific and Industrial Research (ISIR), Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Fax +81(6)68798469; E-mail: sasai@sanken.osaka-u.ac.jp
Received 26 December 2005
harmoniously to promote the reaction with high enantio-
control.
Abstract: (S)-3-[2-(Diphenylphosphino)phenyl]BINOL has been
established as an efficient asymmetric bifunctional organocatalyst
for the aza-Morita–Baylis–Hillman (aza-MBH) reaction. The
Brønsted acid and Lewis base functionalities cooperate in substrate
activation to promote the reaction with high enantiocontrol.
We envisioned locating both acid and base units on one
chiral skeleton thereby facilitating a synergistic coopera-
tion. To that end, a Lewis base unit, which would act as a
reaction-promoting functionality in the aza-MBH reac-
tion, could be introduced onto the 3-position of BINOL as
a chiral Brønsted acid, using an aromatic ring as a spacer
(Scheme 1).5 Shi et al. also reported chiral phosphine–
Lewis base organocatalyst for the aza-MBH reaction.4e,f
As the first step towards development of our organocata-
lyst, phosphine units were attached through an aromatic
ring to the 3-position of (S)-BINOL (Figure 1). As expect-
ed, organocatalyst 1a,6 with a 2-(diphenylphosphino)phe-
nyl group attached to the 3-position of BINOL, promoted
the reaction of methyl vinyl ketone (2a) and p-chlorophe-
nyl N-tosylimine (3a) to give the adduct (S)-4a with 70%
ee (entry 5, Table 1). In contrast, organocatalysts 1b,c, in
which the possibility of synergistic cooperation between
the Brønsted acid and the Lewis base in an intramolecular
manner has been eliminated, resulted in low asymmetric
induction in 4a (entries 6 and 7). The reaction mediated by
a mixed reagent, (S)-BINOL (10 mol%) and triphenyl-
Key words: enantioselective aza-Morita–Baylis–Hillman reaction,
bifunctional catalyst, Brønsted acid, Lewis base, organocatalysis
In enzyme-promoted asymmetric reactions, acid–base
functionalities in the catalytic site activate substrates by a
synergistic cooperation affording products in both high
yield and enantioselectivity. The development of asym-
metric catalysts using a small chiral molecule with en-
zyme-like activation for substrates has been a challenge to
organic chemists.1–3 Asymmetric bifunctional catalysts
possessing two or more acid–base functionalities are re-
presentative examples of this type of artificial enzyme.2,3
In this paper, we report (S)-3-[2-(diphenylphosphino)phe-
nyl]BINOL (1a) as a novel asymmetric bifunctional
organocatalyst for the aza-Morita–Baylis–Hillman (aza-
MBH) reaction.4 The Brønsted acid and Lewis base func-
tionalities, for the activation of the substrate, performed
O
O
NHR3
R2
NR3
R1
R1
aza-MBH reaction
+
H
R2
imine
α,β-unsaturated
carbonyl compound
allyl amine
bifunctional organocatalyst
retro-Michael reaction
(β-elimination)
LB: Lewis base
Michael
reaction
BA: Brønsted acid
NR3
R2
LB
LB
O
NR3
R2
Mannich reaction
BA
BA
BA
BA
O
H
R1
R1
Scheme 1 The aza-MBH reaction promoted by asymmetric bifunctional catalysts
SYNLETT 2006, No. 5, pp 0761–0765
1
7.
0
3.
2
0
0
6
Advanced online publication: 09.03.2006
DOI: 10.1055/s-2006-933112; Art ID: U32005ST
© Georg Thieme Verlag Stuttgart · New York

762
K. Matsui et al.
LETTER
Ethereal solvents were relatively efficient when compared
with other solvents (entries 5, and 8–10).7 Although the
organocatalysts 1d–i bearing the ditolylphosphinophenyl
or dianisylphosphinophenyl group on the 3-position of
BINOL were employed, no improvement in catalytic ac-
tivity was observed.8 The best result (90% yield, 92% ee)
was obtained when 1a was used in t-BuOMe at –20 °C un-
der a low concentration of the substrate 3a (0.05 M, entry
11). As shown in Table 2, irrespective of whether the aro-
matic substituent R2 of 3 is electron-withdrawing or elec-
tron-donating, organocatalyst 1a promoted the reaction
with high enantioselectivity. In addition, 1a advances the
substrate scope of the reported organocatalyst (S)-55a
(Figure 2 and Table 2, entries 6, and 12–14). Interesting-
ly, the absolute configurations of the major adduct 4 ob-
tained with catalyst (S)-1a were opposite to those obtained
with (S)-5 which contains a 3-pyridinylamino unit.
3
Lewis base
PPh2
PPh2
OH
OH
OH
Brønsted acid
PPh2
OH
1a
1b
1d
1e
1f
1g
1h
1i
(Ar = 2-tolyl)
(Ar = 3-tolyl)
(Ar = 4-tolyl)
(Ar = 2-anisyl)
(Ar = 3-anisyl)
(Ar = 4-anisyl)
PAr2
OH
OH
OH
OH
1c
Figure 1 Asymmetric bifunctional organocatalysts for the aza-
MBH reaction
phosphine (PPh3, 10 mol%), also produced 4a with low
enantioselectivity (entry 4). These results indicate that the
introduction of the acid and base units at the appropriate
positions on one chiral skeleton dramatically improves the
efficiency of the bifunctional asymmetric organocata-
lysts.
N
2
PPh2
N
OR1
OH
OH
6a: R1 = R2 = Me
OR2
6b: R1 = Me, R2 = H
2'
6c: R1 = H, R2 = Me
(S)-5
Figure 2
Table 1 Enantioselective Aza-MBH Reaction of 2a with 3a Catalyzed by Organocatalysts
NTs
O
NHTs
O
catalyst (10 mol%)
solvent, 0 °C
+
H
Cl
Cl
2a
3a
4a
Entry
1
Organocatalyst
Solventa
Time (h)
24
Yield (%)b
ee (%)c
None
THF
NR
NR
70
75
62
93
88
44
36
72
90
–
2
(S)-BINOL
THF
24
–
3d
4d,e
5
PPh3
THF
3
–
(S)-BINOL + PPh3
THF
4
1
1a
1b
1c
1a
1a
1a
1a
THF
20
70
5
6
THF
18
7d
8
THF
12
1
Et2O
20
79
67
82
92
9
DME
t-BuOMe
t-BuOMe
20
10
11f
20
144
a 0.5 M (substrate concentration of 3a) and 3 equiv of 2a.
b Isolated yield.
c Determined by HPLC (Daicel Chiralpak AD-H).
d Decomposition of 3a was observed.
e 10 mol% of (S)-BINOL and 10 mol% of PPh3 were used.
f Performed at –20 °C in 0.05 M (concentration of 3a).
Synlett 2006, No. 5, 761–765 © Thieme Stuttgart · New York

LETTER
Organocatalyst for the Aza-Morita–Baylis–Hillman Reaction
763
Table 2 Enantioselective Aza-MBH Reaction of 2 with 3 Catalyzed by (S)-1a9
O
O
NHTs
R2
NTs
R2
(S)-1a (10 mol%)
t-BuOMe, –20 °C
+
R1
R1
H
2
3
(S)-4
Entry
1
R1
R2
Time (d)
Yield (%)a
ee (%)b,c
92 (95)
87 (87)
93 (93)
92 (94)
95 (94)
92 (62)
82
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Me (2a)
Et (2b)
p-Cl-C6H4 (3a)
Ph (3b)
6
9
90
2
97
3
p-Et-C6H4 (3c)
p-Br-C6H4 (3d)
p-MeO-C6H4 (3e)
o-Cl-C6H4 (3f)
p-NO2-C6H4 (3g)
p-NO2-C6H4 (3g)
p-NO2-C6H4 (3g)
p-NO2-C6H4 (3g)
p-NO2-C6H4 (3g)
p-NO2-C6H4 (3g)
2-Furyl (3h)
8
Quant.
87
4
4
5
9
90
6
6
96
7
2
95
8d
9
4
93
88 (91)
85
2.5
6
87
10d
11
12d
13
14
15
Et (2b)
87
89 (88)
82
Ph (2c)
Ph (2c)
Me (2a)
Me (2a)
Me (2a)
3
89
8
85
84 (58)
94 (88)
90 (70)
89 (91)
3
93
1-Naphthyl (3i)
2-Naphthyl (3j)
12
8
85
91
a Isolated yield.
b Determined by HPLC (Daicel Chiralpak AD-H or OD-H).
c The ee in parentheses were obtained by using (S)-5 under optimal conditions (a mixed solvent system consisting of toluene and cyclopentyl
methyl ether in a 1:9 ratio, –15 °C).
d Performed at –40 °C.
Since the diprotected catalyst 6a and the monoprotected
catalysts 6b,c resulted in no activity or low selectivity,
both the phenolic hydroxyl groups in 1a seem to be
required to promote the aza-MBH reaction.10
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan. We thank the technical staff of the Materials
Analysis Center of ISIR, Osaka University.
In conclusion, efficient asymmetric bifunctional organo-
catalysis for the aza-MBH reaction has been established
with (S)-3-[2-(diphenylphosphino)phenyl]BINOL (1a)
bearing the phenyl-binaphthyl skeleton for the positioning
of functionalities. The acid and base functionalities suit-
ably positioned on the skeleton work synergistically to
furnish the product with high enantioselectivity. Efforts
are currently underway to provide the mechanistic infor-
mation.
References and Notes
(1) (a) Asymmetric Organocatalyst – From Biomimetic Concept
to Application in Asymmetric Synthesis; Berkessel, A.;
Gröger, H., Eds.; Wiley-VCH: Weinheim, 2005. (b) Dalko,
P. I.; Moisan, L. Angew. Chem. Int. Ed. 2004, 43, 5138.
(c) Seayad, J.; List, B. Org. Biomol. Chem. 2005, 3, 719.
(2) For reviews see: (a) Shibasaki, M.; Sasai, H.; Arai, T.
Angew. Chem., Int. Ed. Engl. 1997, 36, 1236. (b) Gröger,
H. Chem. Eur. J. 2001, 7, 5246. (c) Kanai, M.; Kato, N.;
Ichikawa, E.; Shibasaki, M. Synlett 2005, 1491.
(d) Shibasaki, M.; Kanai, M.; Funabashi, K. Chem.
Commun. 2002, 1989.
Synlett 2006, No. 5, 761–765 © Thieme Stuttgart · New York

764
K. Matsui et al.
LETTER
separated. The aqueous phase was extracted twice with
(3) (a) Somei, H.; Asano, Y.; Yoshida, T.; Takizawa, S.;
Yamataka, H.; Sasai, H. Tetrahedron Lett. 2004, 45, 1841.
(b) Imbriglio, J. E.; Vasbinder, M. M.; Miller, S. J. Org. Lett.
2003, 5, 3741. (c) Ooi, T.; Ohara, D.; Tamura, M.; Maruoka,
K. J. Am. Chem. Soc. 2004, 126, 6844. (d) Ishii, T.;
Fujioka, S.; Sekiguchi, Y.; Kotsuki, H. J. Am. Chem. Soc.
2004, 126, 9558. (e) Okino, T.; Hoashi, Y.; Takemoto, Y. J.
Am. Chem. Soc. 2003, 125, 12672. (f) Li, H.; Wang, Y.;
Tang, L.; Deng, L. J. Am. Chem. Soc. 2004, 126, 9906.
(g) Mermerian, A. H.; Fu, G. C. J. Am. Chem. Soc. 2003,
125, 4050. (h) Uraguchi, D.; Sorimachi, K.; Terada, M. J.
Am. Chem. Soc. 2004, 126, 11804. (i) Akiyama, T.; Itoh, J.;
Yokota, K.; Fuchibe, K. Angew. Chem. Int. Ed. 2004, 43,
1566. (j) Sammis, G. M.; Danjo, H.; Jacobsen, E. N. J. Am.
Chem. Soc. 2004, 126, 9928. (k) Matsui, K.; Takizawa, S.;
Sasai, H. Tetrahedron Lett. 2005, 46, 1943. (l) Wang, J.; Li,
H.; Yu, X.; Zu, L.; Wang, W. Org. Lett. 2005, 7, 4293.
(m) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Adv. Synth.
Catal. 2005, 347, 1643.
CH2Cl2 (2 × 10 mL). The combined organic extracts were
dried (Na2SO4) and concentrated. The residue was purified
by flash chromatography (SiO2, EtOAc–hexane = 1:4) to
give the compound (S)-II (121.9 mg, 0.3 mmol, 100%).
Compound (S)-II: orange solid; mp 58–59 °C (EtOAc–
hexane). IR (neat): n = 3354, 3039, 2915, 2830 cm–1. 1H
NMR (270 MHz, CDCl3): d = 8.02 (1 H, d, J = 9.2 Hz), 8.00
(1 H, s), 7.93 (1 H, d, J = 8.6 Hz), 7.89 (1 H, d, J = 8.6 Hz),
7.59 (1 H, d, J = 7.8 Hz), 7.46 (1 H, dt, J = 8.6, 1.3 Hz),
7.41–7.17 (8 H, m), 7.08 (1 H, d, J = 8.9 Hz), 3.82 (3 H, s),
3.24 (3 H, s). 13C NMR (67.7 MHz, CDCl3): d = 154.6,
153.8, 152.2, 133.8, 133.2, 131.8, 131.5, 131.3, 131.1,
129.8, 129.4, 128.8, 128.1, 127.9, 126.8, 126.6, 126.3,
125.8, 125.5, 125.3, 124.8, 123.5, 121.1, 118.2, 113.2, 61.4,
56.3. HRMS (ESI): m/z calcd for C28H22NaO3: 429.1467 [M
+ Na]+; found: 429.1466. [a]D20 –63.9 (c 0.6, CHCl3).
To a solution of (S)-II (121.9 mg, 0.3 mmol) with pyridine
(72 mL, 0.9 mmol) in CH2Cl2 (3 mL) was added trifluoro-
methanesulfonic anhydride (100 mL, 0.6 mmol) at 0 °C. The
mixture was then warmed to r.t. and was kept overnight. The
mixture was quenched with H2O and extracted with CH2Cl2
(2 × 10 mL). The combined organic extracts were dried
(Na2SO4). The filtrate was evaporated in vacuo, and the
residue was purified by flash chromatography (SiO2,
EtOAc–hexane = 1:4) to give (S)-III (159.9 mg, 0.297
mmol, 99%).
Compound (S)-III: orange solid; mp 42–43 °C (EtOAc–
hexane). IR (neat): n = 3056, 2917, 2833, 1389, 1182 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.99 (1 H, d, J = 9.2 Hz),
7.93 (1 H, s), 7.90 (1 H, d, J = 8.6 Hz), 7.85 (1 H, d, J = 7.3
Hz), 7.69–7.65 (1 H, m), 7.48–7.16 (9 H, m), 3.80 (3 H, s),
3.06 (3 H, s). 13C NMR (67.7 MHz, CDCl3): d = 154.7,
153.6, 147.6, 134.2, 133.9, 132.7, 132.5, 131.0, 130.2,
129.7, 129.2, 129.1, 128.9, 128.0, 127.7, 126.6, 125.4,
125.2, 125.1, 124.9, 123.6, 121,2. 118.8, 113.2, 60.4, 56.3.
HRMS (ESI): m/z calcd for C29H21F3NaO5S: 561.0960 [M +
Na]+; found: 561.0955. [a]D20 –78.4 (c 0.5, CHCl3).
To a solution of (S)-III (161.6 mg, 0.3 mmol) in DMSO (6
mL) were added Ph2(O)PH (121.3 mg, 0.6 mmol) and DPPB
(12.8 mg, 0.03 mmol) at r.t. followed by Pd(OAc)2 (3.4 mg,
0.015 mmol) and i-Pr2NEt (209 mL, 1.2 mmol). After the
mixture was stirred for 12 h at 100 °C, it was cooled to r.t.,
and EtOAc (10 mL) was added. The organic phase was
washed twice with H2O, dried over Na2SO4 and evaporated
(4) Aza-MBH reactions are accelerated in the presence of acidic
and basic catalysts. See: (a) Matsui, K.; Takizawa, S.; Sasai,
H. J. Am. Chem. Soc. 2005, 127, 3680. (b) Shi, M.; Xu, Y.-
M. Angew. Chem. Int. Ed. 2002, 41, 4507. (c) Balan, D.;
Adolfsson, H. Tetrahedron Lett. 2003, 44, 2521.
(d) Kawahara, S.; Nakano, A.; Esumi, T.; Iwabuchi, Y.;
Hatakeyama, S. Org. Lett. 2003, 5, 3103. (e) Shi, M.; Chen,
L.-H. Chem. Commun. 2003, 1310. (f) Shi, M.; Chen, L.-H.;
Li, C.-Q. J. Am. Chem. Soc. 2005, 127, 3790. (g) Shi, M.;
Li, C.-Q. Tetrahedron: Asymmetry 2005, 16, 1385. (h) Shi,
M.; Xu, Y.-M.; Shi, Y.-L. Chem. Eur. J. 2005, 11, 1794.
(i) Raheem, I. T.; Jacobsen, E. N. Adv. Synth. Catal. 2005,
347, 1701.
(5) Asymmetric catalysts bearing metal coordination units on
the axial linkage have been reported. See: (a) Aikawa, K.;
Mikami, K. Angew. Chem. Int. Ed. 2003, 42, 5458.
(b) Maruoka, K.; Murase, N.; Yamamoto, H. J. Org. Chem.
1993, 58, 2938. (c) Simonson, D. L.; Kingsbury, K.; Xu, M.-
H.; Hu, Q.-S.; Sabat, M.; Pu, L. Tetrahedron 2002, 58, 8189.
(6) General Procedure for the Synthesis of (S)-1a (Scheme 2)
To a solution of (S)-I11 (132.0 mg, 0.3 mmol) and
2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol
(79.2 mg, 0.36 mmol) in THF (6 mL) were added 1 M
K2CO3 aq (3 mL) and Pd(PPh3)4 (17.3 mg, 0.015 mmol). The
mixture was refluxed for 12 h, and then cooled to r.t. Then,
CH2Cl2 (5 mL) was added and the organic phase was
O
B
O
OH
3
3
3
I
Ph2(O)PH, Pd(OAc)2
DPPB, i-Pr2NEt
OTf
OMe
OH
OMe
Pd(PPh3)4, 1 M K2CO3 aq
THF, reflux
Tf2O, pyridine
OMe
OMe
OMe
OMe
CH2Cl2, 0 °C to r.t.
DMSO, 120 °C
(S)-I
(S)-II
(S)-III
3
3
3
P(O)Ph2
OMe
OMe
P(O)Ph2
OH
HSiCl3, Et3N
BBr3
PPh2
OH
CH2Cl2, 0 °C to r.t.
toluene, 50 °C
OH
OH
(S)-IV
(S)-V
(S)-1a
Scheme 2
Synlett 2006, No. 5, 761–765 © Thieme Stuttgart · New York

LETTER
Organocatalyst for the Aza-Morita–Baylis–Hillman Reaction
reduced pressure. The residue was purified by column
765
in vacuo. The residue was purified by flash chromatography
(SiO2, EtOAc–hexane = 4:1) to give the compound (S)-IV
(147.1 mg, 0.249 mmol, 83%).
chromatography on silica gel (EtOAc–hexane = 1:4) to give
the compound (S)-1a (65.6 mg, 0.12 mmol, 60%).
Compound (S)-IV: white solid; mp 77–78 °C (EtOAc–
hexane). IR (neat): n = 3055, 2932, 2844, 1438, 1158 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.96 (1 H, d, J = 9.2 Hz),
7.75 (1 H, s), 7.85–7.04 (22 H, m), 7.54 (1 H, d, J = 7.5 Hz),
Compound (S)-1a: white solid; mp 105–106 °C (EtOAc–
hexane). IR (neat): n = 3370, 3050, 2902, 2824, 1444 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.96 (1 H, d, J = 9.2 Hz),
7.88 (1 H, d, J = 7.3 Hz), 7.80–6.98 (23 H, m), 5.18 (1 H, br
s). 13C NMR (67.7 MHz, CDCl3): d = 152.8, 150.2, 149.7,
143.1, 142.7, 133.8, 133.6, 133.5, 133.3, 132.0, 131.9,
130.9, 129.2, 129.2, 129.2, 128.9, 128.8, 128.6, 128.4,
128.3, 128.2, 128.1, 126.9, 126.9, 125.2, 124.7, 123.8,
123.6, 118.1, 111.8, 111.7. 31P NMR (162 MHz, CDCl3):
d = –10.46, –11.71. HRMS (ESI): m/z calcd for
6.99 (1 H, d, J = 8.1 Hz), 3.78 (3 H, s), 2.99 (3 H, s). 13
C
NMR (67.7 MHz, CDCl3): d = 154.6, 153.6, 144.6, 134.1,
133.9, 133.8, 133.5, 133.3, 133.2, 133.2, 133.1, 132.0,
131.9, 131.6, 131.5, 131.4, 131.4, 131.3, 131.2, 131.0,
130.9, 130.9, 129.4, 129.3, 129.2, 128.8, 128.8, 128.3,
128,1, 128.0, 127.9, 127.7, 127.4, 127.4, 126.4, 126.2,
126.2, 125.9,124.9, 124.2, 123.4, 113.6, 60.1, 56.8. 31
P
C38H27NaO2P: 569.1646 [M + Na]+; found: 569.1631. [a]D
20
NMR (162 MHz, CDCl3): d = 29.37, 28.95. HRMS (ESI):
m/z calcd for C40H31NaO5P: 613.1909 [M + Na]+; found:
613.1898. [a]D20 –64.3 (c 0.4, CHCl3).
–73.2 (c 0.6, CHCl3).
(7) Results of the aza-MBH reaction of 2a with 3a catalyzed by
1a using various solvents (0.5 M; substrate concentration of
3a) at 0 °C for 20 h: CH2Cl2 (36% yield, 45% ee), toluene
(24% yield, 56% ee), MeCN (38% yield, 48% ee), DMF
(34% yield, 21% ee), MeOH (22% yield, 21% ee).
(8) Results of the aza-MBH reaction of 2a with 3a catalyzed by
organocatalysts 1d–i in t-BuOMe (0.05 M; substrate
concentration of 3a) at –20 °C for 144 h: 1d (no reaction), 1e
(71% yield, 88% ee), 1f (80% yield, 86% ee), 1g (no
reaction), 1h (14% yield, 73% ee), 1i (29% yield, 77% ee).
(9) General Experimental Procedure (Table 2)
To a solution of organocatalyst 1a (2.7 mg, 0.005 mmol, 10
mol%) in t-BuOMe (1.0 mL) were added 2 (0.15 mmol) and
imine 312 (0.05 mmol) at –20 °C. The mixture was stirred
until the reaction had reached completion by monitoring
with TLC analysis. The mixture was directly purified by
flash column chromatography (SiO2, EtOAc–hexane = 1:2)
to give the corresponding adduct 4. All products were
characterized by 1H NMR, 13C NMR, MS, and IR
spectroscopy. Absolute configurations of 5 were determined
by comparing the assign of the optical rotations with those in
the literature.4
(10) The aza-MBH reaction of 2a with 3a was performed in t-
BuOMe (0.05M; substrate concentration of 3a) at 0 °C; 6a:
no reaction; 6b: (S)-4a, 86 h, 5% yield, 63% ee; 6c: (R)-4a,
48 h, 95% yield, 61% ee.
(11) Meng, Y.; Slaven, W. T. IV; Wang, D.; Liu, T.-J.; Chow, H.-
F.; Li, C.-J. Tetrahedron: Asymmetry 1998, 9, 3693.
(12) (a) ten Have, R.; Huisman, M.; Meetsma, A.; van Leusen, A.
M. Tetrahedron 1997, 53, 11355. (b) Lee, K. Y.; Lee, C. G.;
Kim, J. M. Tetrahedron Lett. 2003, 44, 1231.
To a solution of (S)-IV (177.2 mg, 0.3 mmol) in CH2Cl2 (3
mL) was added BBr3 (0.9 mL, 0.9 mmol, 1 M in CH2Cl2) at
0 °C and the resulting solution was stirred for 30 min. The
reaction mixture was quenched with H2O and extracted with
CH2Cl2 (2 × 10 mL). The combined organic extracts were
dried (Na2SO4) and evaporated in vacuo. The residue was
purified by flash chromatography (SiO2, EtOAc–hexane =
1:4) to give the compound (S)-V (153.6 mg, 0.273 mmol,
91%).
(S)-V: white solid; mp 149–150 °C (EtOAc–hexane). IR
(neat): n = 3356, 3053, 2912, 2853, 1448, 1166 cm–1. 1H
NMR (270 MHz, CDCl3): d = 7.89 (1 H, d, J = 8.9 Hz), 7.84
(1 H, d, J = 7.8 Hz), 7.80–6.98 (22 H, m). 13C NMR (67.7
MHz, CDCl3): d = 153.3, 150.9, 143.1, 134.0, 133.3, 133.0,
132.8, 132.7, 132.3, 132.1, 132.0, 131.8, 131.7, 131.5,
131.4, 131.2, 130.8, 130.6, 129.8, 129.8, 128.6, 128.4,
128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 127.7, 127.0,
126.9, 126.8, 126.2, 126.0, 124.9, 124.8, 123.1, 122.8,
119.6, 115.0, 112.9. 31P NMR (162 MHz, CDCl3): d = 31.17.
HRMS (ESI): m/z calcd for C38H27NaO5P: 585.1596 [M +
Na]+; found: 585.1615. [a]D20 +86.4 (c 0.6, CHCl3).
To a solution of (S)-V (112.5 mg, 0.2 mmol) and Et3N (279
mL, 2.0 mmol) in toluene (6.7 mL) was added HSiCl3 (404
mL, 4.0 mmol) at 0 °C. After being stirred at 50 °C for 12 h,
the mixture was cooled to r.t., diluted with EtOAc and then
quenched with a small amount of sat. aq NaHCO3. The
resulting suspension was filtered through Celite® and the
solid was washed with EtOAc (2 × 10 mL). The combined
organic layer was dried over Na2SO4 and concentrated under
Synlett 2006, No. 5, 761–765 © Thieme Stuttgart · New York