Enantioselective synthesis of the optically active α-methylene- β-hydroxy esters, equivalent compounds to Morita-Baylis-Hillman adducts, using successive asymmetric aldol reaction and oxidative deselenization

Article abstract of DOI:10.1021/jo051276y

The asymmetric aldol reaction of a tetra-substituted ketene silyl acetal including an alkylseleno group with aldehydes has been developed by the promotion of Sn(OTf)₂ coordinated with a chiral diamine to afford the corresponding aldols having c

Full text of DOI:10.1021/jo051276y

Enantioselective Synthesis of the Optically Active
r-Methylene-â-hydroxy Esters, Equivalent Compounds to
Morita-Baylis-Hillman Adducts, Using Successive Asymmetric
Aldol Reaction and Oxidative Deselenization
Isamu Shiina,* Yu-suke Yamai, and Takahisa Shimazaki
Department of Applied Chemistry, Faculty of Science,
Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
shiina@ch.kagu.tus.ac.jp
Received June 22, 2005
The asymmetric aldol reaction of a tetra-substituted ketene silyl acetal including an alkylseleno
group with aldehydes has been developed by the promotion of Sn(OTf)2 coordinated with a chiral
diamine to afford the corresponding aldols having chiral quaternary centers at the R-positions.
The facile oxidative deselenization of these aldol compounds produces optically active R-methylene-
â-hydroxy esters which correspond to adducts prepared by the asymmetric Morita-Baylis-Hillman
reaction.
Introduction
nucleophilic addition of alkenylmetallic species to alde-
hydes2 or an aldol reaction of a sulfur-substituted enolate
with aldehydes followed by successive elimination of the
R-alkylthio group in the intermediates.3 Furthermore, an
alternative method for the synthesis of optically active
Morita-Baylis-Hillman adducts had been investigated
via a sequential approach combining the Michael addition
of chalcogens to R,â-unsaturated esters and consecutive
diastereoselective aldol reactions of the generated eno-
lates with aldehydes.4
Recently, an asymmetric aldol reaction of a tetra-
substituted ketene silyl acetal with achiral aldehydes has
been developed by our group and this method was applied
to the synthesis of various optically active â-hydroxy
Optically active R-methylene-â-hydroxy esters are
frequently employed for the synthesis of natural compli-
cated molecules because these compounds simultaneously
include both useful R,â-unsaturated ester moieties and
asymmetric allylic alcohol systems. One of the most
powerful methods for the synthesis of R-methylene-â-
hydroxy esters is the reaction of R,â-unsaturated esters
with aldehydes promoted by bases, the so-called Morita-
Baylis-Hillman reaction;1 however, there are limitations
for the asymmetric version concerning chemical yields
and generality of the substrates. On the other hand,
several other approaches for the preparation of R-meth-
ylene-â-hydroxy esters have been developed, such as the
(2) (a) Marino, J. P.; Floyd, D. M. Tetrahedron Lett. 1975, 16, 3897-
3900. (b) Tsuda, T.; Yoshida, T.; Saegusa, T. J. Org. Chem. 1988, 53,
1037-1040. (c) Ramachandran, P. V.; Krzeminski, M. P. Tetrahedron
Lett. 1999, 40, 7879-7881.
(3) (a) Bernardi, A.; Cardani, S.; Gennari, C.; Poli, G.; Scolastico,
C. Tetrahedron Lett. 1985, 26, 6509-6512. (b) Bernardi, A.; Cardani,
S.; Colombo, L.; Poli, G.; Schimperna, G.; Scolastico, C. J. Org. Chem.
1987, 52, 888-891.
(4) (a) Kamimura, A.; Mitsudera, H.; Asano, S.; Kidera, S.; Kakehi,
A. J. Org. Chem. 1999, 64, 6353-6360. (b) Kamimura, A. J. Synth.
Org. Chem. Jpn. 2004, 62, 705-715. (c) Kataoka, T.; Kinoshita, H.
Eur. J. Org. Chem. 2005, 45-58.
(1) General review: (a) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001-8062. (b) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811-891. Review for the
asymmetric synthesis: (c) Langer, P. Angew. Chem., Int. Ed. 2000,
39, 3049-3052. (d) Langer, P. In Organic Synthesis Highlights V;
Schmalz, H.-D., Wirth, T., Eds.; Wiley-VCH: Weinheim, 2003; pp 165-
177. (e) Iwabuchi, Y.; Hatakeyama, S. J. Synth. Org. Chem. Jpn. 2002,
60, 2-14. See also: (f) Iwabuchi, Y.; Nakatani, M.; Yokoyama, N.;
Hatakeyama, S. J. Am. Chem. Soc. 1999, 121, 10219-10220. (g)
Kawahara, S.; Nakano, A.; Esumi, T.; Iwabuchi, Y.; Hatakeyama, S.
Org. Lett. 2003, 5, 3103-3105 and references therein.
10.1021/jo051276y CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/08/2005
J. Org. Chem. 2005, 70, 8103-8106
8103

Shiina et al.
TABLE 1. Synthesis of the Optically Active
r-Alkylseleno-â-hydroxy Esters Using Chiral Sn(II) Lewis
Acid
SCHEME 1. Determination of the Relative
Stereochemistry of the Aldol Adducts
entry
R1
R2 additive yielda/% syn/anti ee/% (syn)
1
2
3
4
5
6
Ph
Ph
4
4
4
5
4
5
54
12
86
70
55
39
86/14
62/38
92/8
87/13
77/23
86/14
92
48
93
86
75
94
Ph(CH2)2 Ph
Ph
Ph
Me
Me
Ph(CH2)2 Me
Ph(CH2)2 Me
a Combined yield of the isolated syn- and anti-isomers.
esters having chiral quaternary centers at the R-posi-
tions.5 This successful result prompted us to explore a
new way to produce optically active R-methylene-â-
hydroxy esters which correspond to adducts prepared by
the asymmetric Morita-Baylis-Hillman reaction. Here,
we report a new method for the synthesis of optically
active R-methylene-â-hydroxy esters using the successive
combination of the asymmetric aldol reaction6 of tetra-
substituted ketene silyl acetal including alkylseleno
group with aldehydes and facile oxidative deselenization.
TABLE 2. Synthesis of a Variety of Optically Active
r-Alkylseleno-â-hydroxy Esters Using Chiral Sn(II) Lewis
Acid
entry
R
additive yielda/% syn/anti adduct ee/%
Results and Discussion
1
2
3
4
5
6
7
8
Ph
4
4
4
4
5
5
4
4
86
88
80
94
39
66
66
85
92/8
92/8
96/4
93/7
86/14
89/11
95/5
94/6
6a
6b
6c
6d
6e
6f
93
93
95
95
93
90
94
94
4-MeC6H4
4-MeOC6H4
4-ClC6H4
PhCH2CH2
CH3(CH2)6
(E)-PhCHdCH
(E)-CH3CHdCH
First, a stereoisomeric mixture of ketene silyl acetal 1
(KSA 1) was prepared from methyl 2-phenylselenopro-
panoate by treatment with LDA and chlorotrimethylsi-
lane according to a similar procedure reported by Guin-
don et al.7 The asymmetric aldol reaction of 1 with
benzaldehyde in the presence of di-n-butyltin diacetate
(4) and a Sn(II) complex 3 generated in situ from Sn-
(OTf)2 with chiral diamine gave the corresponding syn-
aldol adduct with high diastereo- and enantioselectivities
(see Table 1, entry 1). However, the reactivity of 1 is not
sufficient and an unsatisfactory yield was attained in the
reactions of 1 with an aliphatic aldehyde (entry 2).
Therefore, the newly designed KSA 2 was prepared from
methyl 2-methylselenopropanoate under conditions simi-
lar to those used for the preparation of 1. Because the
yield of the asymmetric aldol reaction of 2 with benzal-
dehyde increased without loss of the optical purity of the
aldol adduct (entry 3), a further examination was carried
6g
6h
a Combined yield of the isolated syn- and anti-isomers.
out using 2 instead of 1. Use of the additive 4 gave a
fairly good yield and stereoselectivities as shown in entry
3, although it was found that the tri-n-butyltin fluoride
(5) was not a suitable co-reagent for the reaction of the
aromatic aldehyde (entry 4). On the other hand, better
stereoselectivities were observed for the reaction of
3-phenylpropanal, an aliphatic aldehyde, by promotion
of the Sn(II) complex 3 combined with the Sn(IV)
compound 5 (entry 6).
Relative stereochemistry of the aldol adducts was
determined as follows. The ester group of each stereo-
isomer was reduced by DIBAL to give the corresponding
1,3-diol, which was converted to acetonide-A or -B. As
depicted in Scheme 1, the NOE experiment of ac-
etonide-A and -B showed that major aldol product has
syn configuration and the other has anti configuration.
Examples of the optically active syn-aldols prepared
by the present protocol are listed in Table 2. The reaction
of 2 with aromatic aldehydes (entries 1-4) and R,â-
unsaturated aldehydes (entries 7 and 8) smoothly pro-
ceeded at -78 °C in the presence of the chiral Sn(II)
(5) (a) Kobayashi, S.; Shiina, I.; Izumi, J.; Mukaiyama, T. Chem.
Lett. 1992, 373-376. (b) Mukaiyama, T.; Shiina, I.; Izumi, J.; Koba-
yashi, S. Heterocycles 1993, 35, 719-724. (c) Shiina, I.; Ibuka, R.
Tetrahedron Lett. 2001, 42, 6303-6306.
(6) (a) Kobayashi, S.; Uchiro, H.; Fujishita, Y.; Shiina, I.; Mu-
kaiyama, T. J. Am. Chem. Soc. 1991, 113, 4247-4252. (b) Kobayashi,
S.; Uchiro, H.; Shiina, I.; Mukaiyama, T. Tetrahedron 1993, 49, 1761-
1772. (c) Mukaiyama, T.; Shiina, I.; Uchiro, H.; Kobayashi, S. Bull.
Chem. Soc. Jpn. 1994, 67, 1708-1716. (d) Shiina, I. In Modern Aldol
Reactions; Mahrwald, R., Ed.; Wiley-VCH: Weinheim, 2004; Vol. 2,
pp 105-165.
(7) Guindon, Y.; Houde, K.; Pre´vost, M.; Cardinal-David, B.; Landry,
S. R.; Daoust, B.; Bencheqroun, M.; Gue´rin, B. J. Am. Chem. Soc. 2001,
123, 8496-9501.
8104 J. Org. Chem., Vol. 70, No. 20, 2005

Enantioselective Synthesis of R-Methylene-â-hydroxy Esters
TABLE 3. Synthesis of a Variety of Optically Active
r-Methylene-â-hydroxy Esters via
r-Alkylseleno-â-hydroxy Esters Using Oxidative
Deselenization (Method A)
SCHEME 2. Synthesis of the Optically Active
r-Methylene-â-hydroxy Esters via
r-Alkylseleno-â-hydroxy Esters Using Oxidative
Deselenization
step I
step II
entry
R
yielda/% ee/% yieldb/% olefin ee/%
1
2
3
4
5c
6
7
Ph
79
81
77
87
59
63
80
93
93
95
95
90
94
94
94
81
69
83
88
86
64
7a
7b
7c
7d
7f
7g
7h
93
94
95
95
95
95
95
4-MeC6H4
4-MeOC6H4
4-ClC6H4
CH3(CH2)6
(E)-PhCHdCH
(E)-CH3CHdCH
Lewis acid to give the desired aldols in good yields with
high stereoselectivities. Although the chemical yields
were moderate when aliphatic aldehydes were used as
shown in entries 5 and 6, the desired syn-aldols were
obtained with satisfactorily high enantioselectivities.
Next, the conversion of the formed aldol adducts to the
corresponding R-methylene-â-hydroxy esters was exam-
ined. When the syn- and anti-aldols derived from ben-
zaldehyde with KSA 2 were treated with H2O2 in THF
at 0 °C,8 the desired deselenization rapidly proceeded to
afford the eliminated compounds regioselectively as
shown in Scheme 2. Since the HPLC analysis revealed
that these R,â-unsaturated esters have an identical
R-configuration at the C3 position, the same enantioface-
selectivity of the benzaldehyde was observed for produc-
ing both diastereomers in this asymmetric aldol reaction.
Based on the HPLC analysis for the other aldol adduct
couples, it was found that all of the other C3 configura-
tions of the syn- and anti-aldols are also identical.
The right column in Table 3 shows the yields and ee’s
of a variety of R-methylene-â-hydroxy esters formed by
deselenization (method A). The yields and ee’s of the
corresponding syn-aldols generated by the asymmetric
aldol reaction are listed in the left column as supple-
mentary data. The optical purity of the aldol adducts
remains in all cases to give the desired Morita-Baylis-
Hillman type compounds. Recently, several asymmetric
Morita-Baylis-Hillman reactions were developed to
produce the optically active coupling products with good
to excellent ees,1f,g however, a long period of reaction time
is required for the synthesis of certain adducts, such as
the ones derived from aromatic or R,â-unsaturated alde-
hydes. On the other hand, it is noted that our new
protocol provides a wide generality to produce the opti-
cally active R-methylene-â-hydroxy esters from all types
of aldehydes including aromatic, aliphatic, and R,â-
unsaturated aldehydes.
a Isolated yield of syn-aldol. b Isolated yield. c Tri-n-butyltin
fluoride (5) was used as an additive.
TABLE 4. Synthesis of a Variety of Optically Active
r-Methylene-â-hydroxy Esters via
r-Alkylseleno-â-hydroxy Esters Using Oxidative
Deselenization without Separation of the Diastereomeric
Aldol Isomers (Method B)
step I
step II
entry
R
yielda/% syn/anti yieldb/% olefin ee/%
1
2
3
4
Ph
85
84
83
89
42
78
70
92/8
92/8
97/3
90/10
80/20
95/5
96/4
87
86
86
76
90
81
69
7a
7b
7c
7d
7e
7g
7h
90
86
94
88
82
86
92
4-MeC6H4
4-MeOC6H4
4-ClC6H4
5c PhCH2CH2
6
7
(E)-PhCHdCH
(E)-CH3CHdCH
a Combined yield of the mixture of syn- and anti-isomers.
b Isolated yield. c Tri-n-butyltin fluoride (5) was used as an addi-
tive.
separation of the intermediates, which have similar
polarity after step I. This facile protocol could dispense
chromatographic separation of the stereoisomers and the
ee’s of the final products, Morita-Baylis-Hillman-type
adducts, are kept at a satisfactory level in all cases as
listed in the right column (ca. 90%).
Conclusion
Because both C3 configurations of the major enanti-
omers of syn- and anti-aldols are identical, shown in
Scheme 2, a more convenient method for the preparation
of R-methylene-â-hydroxy esters was investigated (Table
4, method B); that is, mixtures of diastereomeric isomers
are directly converted to the desired olefins without
A new method for the synthesis of optically active
R-methylene-â-hydroxy esters was established using the
consecutive combination of the asymmetric aldol reaction
of a tetra-substituted ketene silyl acetal including an
alkylseleno group with aldehydes and the facile oxidative
deselenization. This protocol provides another way for
producing chiral Morita-Baylis-Hillman adducts with
high ee’s, and the wide range of the substrate generality
(8) Grieco, P. A.; Miyashita, M. J. Org. Chem. 1974, 39, 120-122.
J. Org. Chem, Vol. 70, No. 20, 2005 8105

Shiina et al.
°C was added a 30% aqueous solution of hydrogen peroxide
(6.0 µL, 77 µmol). The mixture was stirred for 2 h at room
temperature, and then quenched with saturated aqueous
NaHCO3. The organic layer was separated and the aqueous
layer was extracted with diethyl ether (three times). The
combined organic layer was washed with water and brine, and
dried over Na2SO4. After evaporation of the solvent, the crude
product was purified by preparative TLC on silica gel to afford
methyl (R)-3-hydroxy-2-methylene-3-phenylpropanoate (7a)
(11.6 mg, 94%, 93% ee).
of this reaction could be applied to the synthesis of many
kinds of R-methylene-â-hydroxy esters having aromatic,
aliphatic and alkenyl substituents on the â-positions.
Experimental Section
General Information. 1H and 13C NMR spectra were
recorded with chloroform (in chloroform-d) or benzene (in
benzene-d6) as an internal standard. Thin-layer chromatog-
raphy was performed on Wakogel B5F. The asymmetric aldol
reaction was carried out under argon atmosphere in dried
glassware. Dichloromethane was distilled from diphosphorus
pentoxide, then calcium hydride, and dried over MS 4 Å.
1-Methoxy-2-methylseleno-1-(trimethylsiloxy)pro-
pene (2). To a solution of diisopropylamine (1.8 mL, 12.8
mmol) in THF (15 mL) at 0 °C was added n-butyllithium in
hexane (1.66 M, 7.8 mL, 12.9 mmol). After the reaction mixture
was stirred for 30 min at 0 °C, a solution of methyl 2-meth-
ylselenopropanoate (2.13 g, 11.8 mmol) in THF (10 mL) was
added at -78 °C. The reaction mixture was stirred for 1 h at
-78 °C and then chlorotrimethylsilane (3.0 mL, 23.7 mmol)
was added. After the reaction mixture was stirred for 1 h at
room temperature, it was concentrated by evaporation of the
solvent. Petroleum ether was added to the residue, and the
suspension was filtered through a small pad of Celite under
argon atmosphere. After evaporation of the solvent, the crude
product was purified by distillation to afford a mixture of KSA
2 (Z/E ) 90/10, 2.22 g, 75%) as a pale yellow oil: bp 31 °C/0.4
mmHg. IR (neat): 1724, 1655, 1439, 1252, 1221, 1178, 1132,
1097, 901, 843 cm-1. HR MS: calcd for C8H18O2SiSe (M + H+)
254.0241, found 254.0240.
Methyl (R)-3-Hydroxy-2-methylene-3-phenylpropanoate
(7a).1f,9 HPLC (CHIRALCEL AS, i-PrOH/hexane ) 1/9, flow
rate ) 0.5 mL/min): tR(R) ) 14.5 min (96.7%), tR(S) ) 23.4
min (3.3%). [R]20D ) -110 (c 0.947, MeOH). 1H NMR (CDCl3):
δ 7.40-7.25 (m, 5H), 6.34 (dd, J ) 1.0, 0.7 Hz, 1H), 5.84 (dd,
J ) 1.3, 1.0 Hz, 1H), 5.53 (dd, J ) 1.3, 0.7 Hz, 1H), 3.72 (s,
1H), 3.00 (br s, 1H). 13C NMR (CDCl3): δ 166.7, 141.9, 141.2,
128.4, 127.8, 126.5, 126.1, 73.2, 51.9.
Typical Procedure for the Synthesis of an Optically
Active r-Methylene-â-hydroxy Ester Using Asymmetric
Aldol Reaction and Successive Deselenization (Method
B, Table 4, Entry 1; 85% combined yield, syn/anti ) 92/
8). Step I. To Sn(OTf)2 (100.5 mg, 0.241 mmol) were added
solutions of (S)-1-methyl-2-(1-naphthylaminomethyl)pyrroli-
dine (74.0 mg, 0.308 mmol) in CH2Cl2 (0.5 mL) and nBu2Sn-
(OAc)2 (92.0 mg, 0.262 mmol) in CH2Cl2 (0.5 mL), respectively.
The mixture was stirred for 5 min at room temperature, and
then was cooled to -78 °C. To the reaction mixture were added
solutions of KSA 2 (65.0 mg, 0.257 mmol) in CH2Cl2 (0.5 mL)
and benzaldehyde (22.8 mg, 0.215 mmol) in CH2Cl2 (0.5 mL)
at -78 °C, successively. The mixture was further stirred for 1
h, and then quenched with saturated aqueous NaHCO3. The
organic layer was separated and the aqueous layer was
extracted with CH2Cl2 (three times). The combined organic
layer was washed with water and brine, and dried over Na2-
SO4. After evaporation of the solvent, the crude product was
purified by preparative TLC on silica gel to afford a mixture
of methyl (2S,3R)-3-hydroxy-2-methyl-2-methylseleno-3-phe-
nylpropanoate (6a) and its anti-(2R,3R)-isomer (52.4 mg, 85%,
syn/anti ) 92/8).
(Z)-1-Methoxy-2-methylseleno-1-(trimethylsiloxy)pro-
pene (Z-2). 1H NMR (C6D6): δ 3.30 (s, 3H), 2.13 (s, 3H), 1.87
(s, 3H), 0.30 (s, 9H). 13C NMR (C6D6): δ 152.8, 84.0, 56.0, 17.4,
4.5, 0.2.
Typical Procedure for the Synthesis of an Optically
Active r-Methylene-â-hydroxy Ester Using Asymmetric
Aldol Reaction and Successive Deselenization (Method
A, Table 1, Entry 3; Table 2, Entry 1; Table 3, Entry 1;
86% combined yield, syn/anti ) 92/8). Step I. To Sn(OTf)2
(217.4 mg, 0.516 mmol) were added solutions of (S)-1-methyl-
2-(1-naphthylaminomethyl)pyrrolidine (143.1 mg, 0.615 mmol)
in CH2Cl2 (1.1 mL) and nBu2Sn(OAc)2 (197.2 mg, 0.556 mmol)
in CH2Cl2 (1.1 mL), respectively. The mixture was stirred for
5 min at room temperature, and then was cooled to -78 °C.
To the reaction mixture were added solutions of KSA 2 (123.5
mg, 0.511 mmol) in CH2Cl2 (1.1 mL) and benzaldehyde (48.0
mg, 0.452 mmol) in CH2Cl2 (1.27 mL) at -78 °C, successively.
The mixture was further stirred for 1 h, and then quenched
with saturated aqueous NaHCO3. The organic layer was
separated and the aqueous layer was extracted with CH2Cl2
(three times). The combined organic layer was washed with
water and brine, and dried over Na2SO4. After evaporation of
the solvent, the crude product was purified by preparative TLC
on silica gel to afford methyl (2S,3R)-3-hydroxy-2-methyl-2-
methylseleno-3-phenylpropanoate (6a) (102.8 mg, 79%, 93%
ee) and its anti-(2R,3R)-isomer (9.0 mg, 7%, 59% ee).
Step II. To a solution of the mixture of syn-R-methyl-R-
methylseleno-â-hydroxy ester (6a) and its anti-(2R,3R)-isomer
(26.5 mg, 92.3 µmol) in THF (1.85 mL) at 0 °C was added a
30% aqueous solution of hydrogen peroxide (10.0 µL, 129 µmol).
The mixture was stirred for 3 h at room temperature, and then
quenched with saturated aqueous NaHCO3. The organic layer
was separated and the aqueous layer was extracted with
diethyl ether (three times). The combined organic layer was
washed with water and brine, and dried over Na2SO4. After
evaporation of the solvent, the crude product was purified by
preparative TLC on silica gel to afford methyl (R)-3-hydroxy-
2-methylene-3-phenylpropanoate (7a) (15.4 mg, 87%, 90% ee).
Methyl (2S,3R)-3-Hydroxy-2-methyl-2-methylseleno-3-
phenylpropanoate (6a). HPLC (CHIRALCEL AS, i-PrOH/
hexane ) 1/9, flow rate ) 1.0 mL/min): tR ) 6.1 min (3.4%),
Acknowledgment. This work was partially sup-
ported by a Grant-in-Aid for Scientific Research from
the Ministry of Education, Science, Sports and Culture,
Japan.
tR ) 7.0 min (96.6%). IR (neat): 3479, 1716 cm-1 1H NMR
.
(CDCl3): δ 7.40-7.23 (m, 5H), 5.16 (s, 1H), 3.70 (s, 3H), 3.28
(br s, 1H), 2.16 (s, 3H), 1.32 (s, 3H). 13C NMR (CDCl3): δ 172.9,
137.8, 127.9, 127.9, 127.7, 73.2, 52.5, 52.2, 16.4, 4.6. HR MS:
calcd for C12H16O3SeNa (M + Na+) 311.0163, found 311.0160.
Methyl (2R,3R)-3-Hydroxy-2-methyl-2-methylseleno-3-
phenylpropanoate. HPLC (CHIRALCEL AS, i-PrOH/hexane
Supporting Information Available: Spectra for products
6b-6h and 7b-7h. This material is available free of charge
via the Internet at http://pubs.acs.org.
) 1/9, flow rate ) 1.0 mL/min): tR ) 8.8 min (20.6%), tR
)
JO051276Y
10.4 min (79.4%). 1H NMR (CDCl3): δ 7.40-7.25 (m, 5H), 5.13
(s, 1H), 3.74 (s, 3H), 3.47 (br s, 1H), 1.96 (s, 3H), 1.43 (s, 3H).
Step II. To a solution of pure syn-R-methyl-R-methylseleno-
â-hydroxy ester (18.5 mg, 64.4 µmol) in THF (0.64 mL) at 0
(9) Drewes, S. E.; Emslie, N. D. Tetrahedron: Asymmetry 1992, 3,
255-260.
8106 J. Org. Chem., Vol. 70, No. 20, 2005