An efficient asymmetric aldol reaction of Chan's diene promoted by chiral Ti(IV)-BINOL complex

Article abstract of DOI:10.1016/S0957-4166(01)00150-1

1,3-Bis-(trimethylsilyloxy)-1-methoxy-buta-1,3-diene (Chan's diene) can be conveniently used in asymmetric aldol reaction with aromatic, heteroaromatic, α,β-unsaturated and aliphatic aldehydes in the presence of catalytic amounts (2-8% mol) of chiral Ti(I

Full text of DOI:10.1016/S0957-4166(01)00150-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 959–963
An efficient asymmetric aldol reaction of Chan’s diene promoted
by chiral Ti(IV)–BINOL complex
Annunziata Soriente,* Margherita De Rosa, Marina Stanzione, Rosaria Villano and Arrigo Scettri
Dipartimento di Chimica, Universita` di Salerno, 84081 Baronissi, Salerno, Italy
Received 22 March 2001; accepted 26 March 2001
Abstract—1,3-Bis-(trimethylsilyloxy)-1-methoxy-buta-1,3-diene (Chan’s diene) can be conveniently used in asymmetric aldol
reaction with aromatic, heteroaromatic, a,b-unsaturated and aliphatic aldehydes in the presence of catalytic amounts (2–8% mol)
of chiral Ti(IV)/(R)-BINOL complex. © 2001 Elsevier Science Ltd. All rights reserved.
Rather surprisingly, the masked acetoacetic ester 2
(Chan’s diene),8 easily accessible from commercially
available methyl 3-trimethylsilyloxy-crotonate,9 has
been used only occasionally in stereoselective aldol
condensations, since the presence of a chelating sub-
stituent situated a or b to the carbonyl function seemed
to be a strict prerequisite for attaining high levels of
diastereo- and enantioselectivity.10
1. Introduction
In recent years the development of new procedures for
the enantioselective addition of enolsilanes to aldehydes
under catalytic conditions has been the main target of
several research groups. From a preparative point of
view notable results have been obtained by using O-
silyldienolates of the type 1, since the formation of
polyfunctional C-(5) key intermediates can be achieved
in high yield and enantioselectivity.
2. Results and discussion
As regards the mechanistic aspects, the reported proce-
dures may alternatively involve either the activation of
the aldehydic functionality by chiral catalysts [Ti(IV)1–4
and Cu(II)5,6 complexes] or the formation of a chiral
metalloenolate intermediate.7
In the course of an investigation on the reactivity of
synthetic equivalents of acetoacetate ester dianion4,11
we have found that the enantioselective addition of
Chan’s diene 2 to aldehydes 3 can be performed very
conveniently in the presence of catalytic amounts of
Ti(OiPr)4/(R)-BINOL complex (8 mol%).
As reported in Scheme 1 and Table 1, the reaction
proceeded with good efficiency and enantioselectivity
leading to silylated aldols 4 as the predominant or
exclusive product, while the presence of free aldol 5
could be occasionally detected (entries b, c, e).
Scheme 1.
* Corresponding author. E-mail: titti@chem.unisa.it
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00150-1

960
A. Soriente et al. / Tetrahedron: Asymmetry 12 (2001) 959–963
Table 1. Chiral Ti(IV)/(R)-BINOL-catalyzed asymmetric
aldol condensation
Table 3. Chiral Ti(IV)/(R)-BINOL (2 mol%)-catalyzed
aldol condensation of Chan’s diene
Entry
R
Product
Yield (%)a
E.e. (%)b,c
Entry
R
Product
Yield (%)a
E.e. (%)b
a
b
3-Furyl
C6H5
5a
5b
5b
67
13d
65
7d
68
86
20d
31
92
66
99
99
88
99
91
90
94
92
99
99
a
b
c
3-Furyl
C6H5
C6H4CHꢀCH 5f
n-C9H19 5h
5a
5b
82
94
84
70
99
92
99
98
c
p-CH3OC6H4 5c
d
5c
de
e
p-NO2C6H4
n-C7H15
5d
5e
5e
a All the yields refer to isolated, chromatographically pure com-
pounds and are calculated based on starting materials 3.
b E.e.s were determined by HPLC analysis.
f
C6H4CHꢀCH 5f
ge
5g
However, it is noteworthy that greatly improved results
were obtained with Carreira’s procedure7 involving in
situ desilylation of the crude 4b and 5b mixture by
acidic treatment at −78°C. Using this deprotection pro-
tocol, it was found that aldol 5b could be obtained in
94% yield and >99% e.e.
a Yields refer to isolated, chromatographically pure compounds 5
(obtained after desilylation of product 4) and are calculated based
on starting materials 3.
b E.e.s were determined by HPLC analysis of the aldol adduct using
a Chiralpak AD column.
c The absolute configuration of the adducts was established by 1H
NMR analysis (400 MHz) of the corresponding MTPA esters
according to Ref. 12.
Further research, directed at optimizing the level of
catalyst loading, showed that in the presence of reduced
amounts of catalytic species (2 mol%) the condensation
reaction gave 4 as the exclusive product; moreover,
deprotection, performed in situ by acidic treatment at
−78°C, afforded aldols 5 in very good yields and excel-
lent e.e.s. (Table 3).
d Yields refer to free aldol directly obtained by purification of crude
4.
e (S)-(−)-BINOL was used as chiral auxiliary, consequently 5d and 5g
were obtained as predominant (S)-enantiomers.
In every case compounds 4 have been subjected to
deprotection by treatment with CF3COOH (15 equiva-
lents) in aqueous THF solution at 0°C2 to give the
aldols 5 in satisfactory yields and e.e.s.
The result reported in entry d (Table 3) is of particular
synthetic value since addition of masked acetoacetic
esters to aliphatic aldehydes using the reported proce-
dures is known to proceed with low efficiency and/or
enantioselectivity.7
However, free aldols 5b and 5c, obtained directly in
very poor yields by chromatographic purification of
crude reaction mixtures, showed significantly higher
e.e.s than those observed for the corresponding aldols
obtained after cleavage of the trimethylsilyl group of 4.
This suggested the possibility of racemization in the
course of the silyl deprotection reaction.
Finally, a set of experiments, designed to allow a more
careful investigation of the reaction pathway, was com-
pleted. Benzaldehyde 3b was again chosen as the repre-
sentative substrate. Using the optimized conditions,
after desilylation, 5b was isolated in 94% yield and 92%
e.e. (Table 4, entry a). However, when the reaction was
analyzed after stirring for 2 hours at −78°C no forma-
tion of 5b could be detected (entry b). Moreover, 5b
was obtained in poor yield (3%) and an e.e. of 48%
(entry d) when carrying out the reaction in the presence
of 8 mol% Ti(IV)/(R)-BINOL complex over 2 hours at
−78°C, while very high yield of 94% and an e.e of >99%
In order to verify this hypothesis, compounds 4b and 4c
were subjected to treatment with other desilylating
agents and the results reported in Table 2 clearly
showed that both the resulting chemical yields and the
e.e.s could be affected by the type of substrate and the
desilylation procedure employed.
Table 4. Influence of temperature on asymmetric aldol
Table 2. Deprotection of silylated aldols 4 by procedures
condensation
A, B and Ca
Entry
Catalyst
React.
Yield (%)a
94
E.e. (%)b
92
Compound Proc. Ab
Proc. Bc
Proc. Cd
Free aldol
time/temp.
Yield (e.e.) Yield (e.e.) Yield (e.e.) E.e. (%)
%
%
%
a
2
2 h/−78°C+
16 h/rt
4b
4c
65 (88)
69 (91)
78 (88.4)
75 (99)
55 (86)
78 (99)
99
99
b
c
2
8
2 h/−78°C
2 h/−78°C+
16 h/rt
2 h/−78°C
6 h/rt
–
94
–
\99
a Yields refer to isolated, chromatographically pure compounds and
are calculated based on starting materials 3. E.e.s were determined
by HPLC analysis.
d
e
8
8
3
96
48
98
b Procedure A: CF3COOH/H2O/0°C.2
a All the yields refer to isolated, chromatographically pure com-
pounds and are calculated based on starting materials 3.
b Determined by HPLC analysis.
c Procedure B: TBAF/THF/0°C.13
d Procedure C: PPTS/MeOH/rt.14

A. Soriente et al. / Tetrahedron: Asymmetry 12 (2001) 959–963
961
was observed by initially completing the reaction at
−78°C for 2 hours then allowing the mixture to warm to
room temperature and stirring the mixture for 16 hours
(entry c).
NaHCO3 (2 mL) was added until the evolution of gas
ceased (30 min); the reaction mixture was diluted with
ether and the organic layer was washed with brine, dried
over MgSO4 and concentrated in vacuo affording a
yellow oil. The residue was dissolved in THF, cooled to
0°C and treated with TFA (15 equiv.) in water (0.12
mL). After desilylation had proceeded to completion,
the solution was warmed to rt and partitioned between
Et2O and water. The organic layer was washed with a
saturated aqueous solution of NaHCO3 and then dried
over MgSO4 and concentrated in vacuo. Purification by
chromatography on silica gel afforded the aldol adducts
5 (eluent 9:1 CHCl3:Et2O).
The results from this study, reported in Table 4, clearly
showed that the aldol condensation essentially occurred
at room temperature and that the process of
amplification15,16 of the e.e. was involved.
The procedure we have presented can be considered of
enhanced synthetic value as it is highly efficient and
occurs with excellent enantioselectivity. Additionally, all
reactions, including the preparation of the catalytic
species, can be conveniently performed at room temper-
ature with comparable efficiency and virtually no
change in the enantioselectivity (Table 4, entry e).
3.3. Representative procedure for the preparation of
aldol adducts 5 using 2 mol% of catalyst
In a typical experiment, a mixture of Ti(O-i-Pr)4 (0.02
mmol) and R(+)-BINOL (0.02 mmol) and molecular
sieves (77.5 mg) in THF (1 mL) was stirred at rt for 1
h. After cooling the mixture to −78°C the aldehyde (1
mmol) was added dropwise followed, after 30 min, by
silyloxydiene 2 (2 mmol). The resulting solution was
stirred under an inert gas atmosphere at −78°C for 2 h;
after warming at rt the mixture was stirred overnight.
The progress of the reaction was monitored by TLC.
Upon completion, after cooling the mixture to −78°C,
TFA (0.4 mL) was added and the solution was warmed
to rt. After stirring at rt for 1 h, desilylation was
complete and the reaction mixture was diluted with
ether and a saturated aqueous NaHCO3 solution (2 mL)
was added dropwise and the mixture stirred until the
evolution of gas ceased (30 min); the organic layer was
washed with brine, dried over MgSO4 and concentrated
in vacuo affording a yellow oil. Purification by chro-
matography on silica gel using 9:1 CHCl3:Et2O as eluent
afforded the aldol adducts 5.
3. Experimental
3.1. General procedures
All reactions involving air-sensitive materials were per-
formed using oven dried glassware under an atmosphere
of dry nitrogen. THF was distilled from LiAlH4 and
then from sodium and benzophenone. Molecular sieves
,
(4 A) were oven dried at 250°C overnight and stored
under an atmosphere of nitrogen. Thin-layer chro-
matography was performed on Merck Kiesegel 60 F254
plates eluting with the solvents indicated, visualized by
a 254 nm UV lamp or aqueous ceric sulfate solution
followed by heating. Infrared spectra were recorded on
a Bruker 22 series FT-IR spectrometer. NMR spectra
were recorded on a Bruker DRX 400 (400.135 MHz for
1H and 100.03 MHz for 13C) and on a Bruker AM 250
(250.13 MHz for H and 62.89 MHz for 13C) spectrom-
1
eters. Chemical shifts are given in ppm (l) scale; for the
spectra in CDCl3, the CHCl3 signal was used as internal
standard (l 7.26 1H, l 77.0 13C). Coupling constants (J)
are reported in Hz. MS (EI): VG TRIO 2000. Column
chromatographic separations were carried out using
silica gel 60 (70–230 mesh and 230–400 mesh, Merck).
Optical rotations were measured at the sodium D line
(589 nm) at room temperature with a JASCO DIP 1000
polarimeter; concentrations are reported in g/100 mL.
HPLC analysis was performed on a Waters 486
equipped with a variable wavelength detector using a
Chiralpak AD column.
3.4. General procedure for desilylation using TBAF12
(procedure B)
The silylated adduct 4 (1 mmol) was dissolved in anhy-
drous THF (7.5 mL) and the resulting solution was
cooled to 0°C. A solution of TBAF in THF (1 M, 2
mmol) was added and the mixture was stirred until the
deprotection was complete (15–30 min) by TLC.
The reaction mixture was diluted with ether and a
saturated aqueous solution of NaHCO3 (1.5 mL) was
added dropwise until the evolution of gas ceased (30
min); the organic layer was washed with brine, dried
over MgSO4 and concentrated in vacuo affording, after
purification by chromatography, the aldol adduct 5.
3.2. Representative procedure for the preparation of
aldol adducts 5 using 8 mol% of catalyst
In a typical experiment, a mixture of Ti(O-i-Pr)4 (0.08
mmol) and (R)-(+)-BINOL (0.08 mmol) in THF (5 mL)
and molecular sieves (340 mg) was stirred at rt for 1 h.
After cooling the mixture to −78°C the aldehyde (1
mmol) was added dropwise followed, after 30 min, by
silyloxydiene 2 (2 mmol). The resulting solution was
stirred under an inert gas atmosphere at −78°C for 2 h;
after warming at rt the mixture was stirred overnight.
The progress of the reaction was monitored by TLC.
Upon completion, a saturated aqueous solution of
3.5. General procedure for desilylation using PPTS13
(procedure C)
The silylated adduct 4 (1 mmol) was dissolved in anhy-
drous MeOH (3 mL) and treated with pyridinium p-
toluenesulfonate (15 mg).When hydrolysis was complete
(1–3 h) by TLC, the volatiles were removed in vacuo
and the yellow oil obtained was purified by chromatog-
raphy affording the aldol adduct 5.

962
A. Soriente et al. / Tetrahedron: Asymmetry 12 (2001) 959–963
3.6. 5-(R)-(Furan-3-yl)-5-hydroxy-3-oxo-pentanoic acid
Hz, 2H), 6.86 (d, J 8.3 Hz, 2H), 5.12 (dd, J 9.1, 3.2 Hz,
1H), 3.79 (s, 3H), 3.72 (s, 3H), 3.50 (s, 2H), 2.98 (dd, J
17.0, 9.2 Hz, 1H), 2.86 (dd, J 17.0, 3.2 Hz, 1H); lC
(62.89 MHz, CDCl3) 208.2, 169.0, 159.2, 131.7, 129.3,
113.9, 68.4, 50.2, 50.1, 44.4; m/z (EIMS) 252 (M+);
[h]2D5=+48.0 (c 1.0, CHCl3), e.e. 91% (R); HPLC analy-
sis (hexanes:ethanol:trifluoroacetic acid 95:5:0.01), 1
mL/min; (R) enantiomer tr=42.5 min; (S) enantiomer
tr=57.7 min.
methyl ester 5a
Pale yellow oil. [Found: C, 56.48; H, 5.61. C10H12O5
requires: C, 56.60; H, 5.70%]; Rf 0.3 (Et2O:CHCl3 1:9);
wmax (liquid film) 3480, 1740, 1713 cm−1; lH (400 MHz,
CDCl3) 7.34 (s, 1H), 7.32 (d, J 1.5 Hz, 1H), 6.33 (s, 1H),
5.09 (dd, J 8.7, 3.6 Hz, 1H), 3.66 (s, 3H), 3.46 (s, 2H),
2.96 (dd, J 17.2, 8.7 Hz, 1H), 2.85 (dd, J 17.2, 3.6 Hz,
1H); lC (100.03 MHz, CDCl3) 202.5, 167.2, 143.4, 139.0,
127.2, 108.3, 62.8, 52.5, 50.2, 49.5; m/z (EIMS) 212
(M+); [h]D25=+39.1 (c 1.0, CHCl3), e.e. 99% (R); HPLC
analysis (hexanes:ethanol:trifluoroacetic acid 95:5:0.01),
1 mL/min; (R) enantiomer tr=47.05 min; (S) enan-
tiomer tr=58.57 min.
3.11. 5-(S)-p-Nitrophenyl-5-hydroxy-3-oxo-pentanoic
acid methyl ester 5d
Pale yellow oil. [Found: C, 53.83; H, 4.96; N, 5.30.
C12H13NO6 requires: C, 53.93; H, 4.90; N, 5.24%]; Rf 0.2
(Et2O:CHCl3 1:9); wmax (liquid film) 3510, 2987, 2950,
1740, 1646, 1314, 1106 cm−1; lH (400 MHz, CDCl3) 8.12
(d, J 8.6 Hz, 2H), 7.50 (d, J 8.6 Hz, 2H), 5.26 (dd, J 7.3,
4.3 Hz, 1H), 3.69 (s, 3H), 3.50 (s, 2H), 2.93 (m, 2H); lC
(62.89 MHz, CDCl3) 208.2, 169.0, 145.5, 145.6, 129.2,
123.4, 68.4, 50.1, 44.4; m/z (EIMS) 267 (M+); [h]D25=
−39.1 (c 1.0, CHCl3), e.e. 90% (S); HPLC analysis
(hexanes:isopropanol:trifluoroacetic acid 60:40:0.01),
0.3 mL/min; (R) enantiomer tr=23.7 min; (S) enan-
tiomer tr=24.6 min.
3.7. 5-(R)-Phenyl-5-(trimethyl-silyloxy)-3-oxo-pentanoic
acid methyl ester 4b
Pale yellow oil. [Found: C, 61.09; H, 7.59. C15H22O4Si
requires: C, 61.19; H, 7.53%]; Rf 0.8 (Et2O:CHCl3 1:9);
wmax (liquid film) 3508, 2984, 2936, 1740, 1646, 1314,
1106 cm−1; lH (400 MHz, CDCl3) 7.89 (d, J 8.4 Hz, 2H),
7.64 (m, 1H), 7.55 (m, 2H),5.16 (dd, J 9.0, 3.6 Hz, 1H),
3.72 (s, 3H), 3.48 (s, 2H), 3.01 (dd, J 15.1, 9.2 Hz, 1H),
2.67 (dd, J 15.2, 3.8 Hz, 1H), 0.02 (s, 9H); m/z (EIMS)
294 (M+).
3.12. 5-(S)-5-Hydroxy-3-oxo-dodecanoic acid methyl
ester 5e
3.8. 5-(R)-Phenyl-5-hydroxy-3-oxo-pentanoic acid
methyl ester 5b
Pale yellow oil. [Found: C, 63.84; H, 9.84. C13H24O4
requires: C, 63.91; H, 9.90%]; Rf 0.5 (Et2O:CHCl3 1:9);
wmax (liquid film) 1740, 1616, 1514, 1378, 1106 cm−1; lH
(400 MHz, CDCl3) 4.05 (s, 1H), 3.73 (s, 3H), 3.48 (s,
2H), 2.75–2.60 (m, 2H), 1.53–1.26 (m, 12H), 0.88 (t, 2H,
J 6.1 Hz). lC (100.03 MHz, CDCl3) 208.2, 169.0, 65.2,
50.1, 44.4, 37.4,32.5, 30.6, 30.3, 30.0, 23.8, 23.1, 14.0;
m/z (EIMS) 244 (M+); [h]D25=+25.2 (c 1.0, CHCl3), e.e.
94% (S); HPLC analysis (hexanes:ethanol:trifluoro-
acetic acid 95:5:0.01), 1 mL/min; (S) enantiomer tr 10.3
min; (R) enantiomer tr=11.9 min.
Pale yellow oil. [Found: C, 64.92; H, 6.28. C12H14O4
requires: C, 64.85; H, 6.35%]; Rf 0.4 (Et2O:CHCl3 1:9);
wmax (liquid film) 3508, 2984, 2936, 1740, 1646, 1314,
1106 cm−1; lH (400 MHz, CDCl3) 7.36 (m, 5H), 5.20
(dd, J 9.1, 3.1 Hz, 1H), 3.51 (s, 3H), 3.46 (s, 2H), 3.01
(dd, J 17.4, 9.1 Hz, 1H), 2.91 (dd, J 17.4, 3.2 Hz, 1H);
lC (100.03 MHz, CDCl3) 208.2, 169.0, 139.4, 128.3,
125.7, 68.4, 50.2, 50.1, 44.4; m/z (EIMS) 222 (M+);
[h]2D5=+57.1 (c 1.0, CHCl3), e.e. 99% (R); HPLC (hex-
anes:ethanol:trifluoroacetic acid 95:5:0.01), 1 mL/min;
(R) enantiomer tr=25.7 min; (S) enantiomer tr=37.7
min.
3.13. 5-(R)-5-Hydroxy-3-oxo-7-phenyl-hept-6-enoic acid
methyl ester 5f
3.9. 5-(R)-p-Methoxyphenyl-3-oxo-5-(trimethyl-silyl-
oxy)-pentanoic acid methyl ester 4c
Pale yellow oil. [Found: C, 67.72; H, 6.56. C14H16O4
requires: C, 67.63; H, 6.50%]; Rf 0.4 (Et2O:CHCl3 1:9);
wmax (liquid film) 3478, 3026, 2953, 1712, 1651, 1494
cm−1; lH (400 MHz, CDCl3) 7.18 (m, 5H), 6.6–6.61 (dd,
J 15.9, 1.1 Hz, 1H), 6.24–6.15 (dd, J 15.9, 6.1 Hz, 1H),
4.80 (m, 1H), 3.74 (s, 3H), 3.52 (s, 2H), 2.86 (d, J 6.1 Hz,
2H); lC (100.03 MHz, CDCl3) 202.7, 169.0, 136.5, 130.7,
130.2, 128.8, 128.0, 126.7, 68.5, 52.6, 49.8, 43.2; m/z
(EIMS) 248 (M+); [h]D25=+20.2 (c 1.0, CHCl3), e.e. 99%
(R); HPLC analysis (hexanes:ethanol:trifluoroacetic
acid 95:5:0.01), 1 mL/min; (R) enantiomer tr=28.2 min;
(S) enantiomer tr=36.1 min.
Pale yellow oil. [Found: C, 59.15; H, 7.54. C16H24O5Si
requires: C, 59.23; H, 7.46%]; Rf 0.8 (Et2O:CHCl3 1:9);
wmax (liquid film) 3500, 2988, 2940, 1740, 1616, 1514,
1378, 1106 cm−1; lH (400 MHz, CDCl3) 7.25 (d, J=8.5
Hz, 2H), 6.84 (d, J 8.5 Hz, 2H), 5.10 (dd, J 8.9, 3.9 Hz,
1H), 3.79 (s, 3H), 3.72 (s, 3H), 3.50 (s, 2H), 3.00 (dd, J
15.0, 8.9 Hz, 1H), 2.65 (dd, J 15.0, 3.9 Hz, 1H), 0.03 (s,
9H); m/z (EIMS) 324 (M+).
3.10. 5-(R)-p-Methoxyphenyl-5-hydroxy-3-oxo-pen-
tanoic acid methyl ester 5c
Pale yellow oil. [Found: C, 61.96; H, 6.32. C13H16O5
requires: C, 61.90; H, 6.39%]; Rf 0.3 (Et2O:CHCl3 1:9);
wmax (liquid film) 3500, 2988, 2940, 1740, 1616, 1514,
1378, 1106 cm−1; lH (400 MHz, CDCl3) 7.26 (m, J 8.3
3.14. 5-(S)-5-Hydroxy-3-oxo-7-phenyl-hept-6-enoic acid
methyl ester 5g
See above; [h]2D5=−18.5 (c 1.0, CHCl3), e.e. 99% (S).

A. Soriente et al. / Tetrahedron: Asymmetry 12 (2001) 959–963
963
3.15. 5-(S)-5-Hydroxy-3-oxo-tetradecanoic acid methyl
3. De Rosa, M.; Dell’Aglio, R.; Soriente, A.; Scettri, A.
Tetrahedron: Asymmetry 1999, 10, 3659–3662.
4. De Rosa, M.; Soriente, A.; Scettri, A. Tetrahedron:
Asymmetry 2000, 11 (15), 3187–3195.
ester 5h
Pale yellow oil. [Found: C, 66.25; H, 10.44. C15H28O4
requires: C, 66.14; H, 10.36%]; Rf 0.5 (Et2O:CHCl3 1:9);
wmax (liquid film) 1740, 1616, 1514, 1378, 1106 cm−1; lH
(400 MHz, CDCl3) 4.06 (s, 1H), 3.77 (s, 3H), 3.46 (s,
2H), 2.75–2.64 (m, 2H), 1.51–1.25 (m, 16H), 0.87 (t,
2H, J=6.2 Hz). lC (100.03 MHz, CDCl3) 208.2, 169.0,
65.2, 50.1, 44.4, 37.4, 32.5, 30.6, 30.3, 30.0, 23.8, 23.1,
14.0; m/z (EIMS) 272 (M+); [h]D25=+26.2 (c 1.0,
CHCl3), e.e. 98% (S); HPLC analysis (hex-
anes:ethanol:trifluoroacetic acid 95:5:0.01), 1 mL/min;
(S) enantiomer tr=9.7 min; (R) enantiomer tr=11.1
min.
5. Evans, D. A.; Murry, J. A.; Kozlowski, C. J. Am. Chem.
Soc. 1996, 118, 5814–5815.
6. Pagenkopf, B. L.; Kruger, J.; Stojanovic, A.; Carreira, E.
M. Angew. Chem., Int. Ed. 1998, 37, 3124–3126.
7. Kruger, J.; Carreira, E. M. J. Am. Chem. Soc. 1998, 120,
837–838.
8. Chan, T. H.; Brownbridge, P. J. Chem. Soc., Chem.
Commun. 1979, 578–579.
9. Brownbridge, P.; Chan, T. H.; Brook, M. A.; Kang, G. J.
Can. J. Chem. 1983, 61, 688–693.
10. (a) Evans, D. A.; Black, W. C. J. Am. Chem. Soc. 1993,
115, 4497; (b) Evans, D. A.; Kozlowski, C.; Murry, J. A.;
Burgey, C. S.; Campos, K. R.; Connell, B. T.; Staples, R.
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Acknowledgements
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