Imashiro and Kuroda
model.21 The aldol product 3a thus obtained was easily
converted to (-)-2 by reduction and cyclization in excel-
lent yield and high optical purity. An efficient preparation
of 5 from inexpensive starting materials has also been
developed. The R,R-dichloro-â-hydroxyesters 3a -f thus
obtained and the corresponding chiral trans glycidates
are useful as versatile chiral building blocks for the
synthesis of other pharmaceutical and biologically active
natural products.22
(10 mL) were added successively to the reaction mixture at
-78 °C and stirred at the same temperature for 7 h (in the
reaction of 4f, the reaction temperature was raised to 0 °C).
The reaction mixture was quenched with saturated NaHCO3
and extracted with AcOEt. The extracts were washed with
brine, dried over MgSO4, and concentrated to dryness under
reduced pressure. To the residue were added THF (40 mL)
and 1 N aqueous HCl (10 mL) at rt. The reaction mixture was
stirred for 0.5 h and extracted with AcOEt. The extracts were
washed with brine and dried over MgSO4. After evaporation
of the solvent, the resulting mixture was purified by silica gel
column chromatography (CHCl3/hexane/AcOEt ) 5:5:1) to give
the aldol product 3a (2.03 g, 73%) with 96% ee as the S
enantiomer. The purity of 3a was upgraded to >99% ee after
recrystallization from hexanes-ether. The aqueous NaHCO3
phase was acidified with aqueous HCl and was extracted with
AcOEt. The extracts were washed with brine and dried over
MgSO4. After evaporation of the solvent, p-toluenesulfonamide
13a was recovered as a colorless solid (2.94 g, 99%).
(3S)-Meth yl 2,2-d ich lor o-3-h yd r oxy-3-(4-m eth oxyp h e-
n yl)p r op ion a te (3a ): yield 73%, 96% ee; mp 53 °C; 1H NMR
(CDCl3, 200 MHz) δ 7.45 (d, J ) 8.68 Hz, 2H), 6.90 (d, J )
8.86 Hz, 2H), 5.38 (s, 1H), 3.91 (s, 3H), 3.18 (br, 1H); IR (KBr)
ν 3047, 2999, 2956, 2900, 2830, 1755, 1746, 1612, 1580, 1514
cm-1; MS (EI) m/z 278 ([M]+), 280 ([M + 2]+), 282 ([M + 4]+).
Anal. Calcd for C11H12Cl2O4: C, 47.33; H, 4.33; Cl, 25.40.
Found: C, 47.32; H, 4.31; C, 25.32.
Exp er im en ta l Section
Gen er a l Meth od s. Reagents were used as received unless
otherwise stated. CH2Cl2 and toluene were redistilled from
CaH2 and were dried over molecular sieves (4 Å). Tetrahydro-
furan (THF) was redistilled from Na and benzophenone, and
was dried over molecular sieves 4 Å. Analytical TLC was
preformed using precoated plates (0.25 mm) followed by
visualization with UV light (254 nm), staining with a solution
of phosphomolybdic acid. Melting points were measured, but
uncorrected. 1H NMR and 13C NMR spectra were recorded with
TMS as an internal standard.
(2,2-Dich lor o-1-m eth oxy)vin yloxytr im eth ylsila n e (5).
To a suspension of methyl trichloroacetate (17.7 g, 100 mmol)
and activated zinc powder (9.8 g, 150 mmol) in anhydrous THF
(100 mL) was added TMSCl (15.2 mL, 120 mmol) at such a
rate to promote gentle refluxing. Stirring was continued at
ambient temperature for 30 min, and then the reaction
mixture was diluted with n-hexane (100 mL) and filtered to
remove the zinc dust. After evaporation of the solvent, the
resulting solution was distilled under reduced pressure to give
4 (18.3 g, 85%): bp 64-65 °C (2 mmHg); 1H NMR (CDCl3, 200
MHz) δ 3.64 (s, 3H), 0.30 (s, 9H); IR (film) ν 3645, 2963, 1749,
1657 cm-1; MS (GCMS) m/z 214 (M+), 216 ([M + 2]+), 218 ([M
+ 4]+).
(3S)-Meth yl 2,2-dich lor o-3-h ydr oxy-3-ph en ylpr opion ate
(3b): yield 69%, 95% ee; mp 53 °C; 1H NMR (CDCl3, 200 MHz)
δ 7.51-7.54 (m, 2H), 7.38-7.40 (m, 2H), 5.43 (d, J ) 5.2 Hz,
1H), 3.92 (s, 3H), 3.23 (d, J ) 5.2 Hz, 1H); IR (KBr) ν 3533,
2963, 1747 cm-1; MS (EI) m/z 249 ([M]+), 251 ([M + 2]+), 253
([M + 4]+). Anal. Calcd for C10H10Cl2O3: C, 48.22; H, 4.05; Cl,
28.47. Found: C, 48.01; H, 4.25; C, 28.5.
(3S,4E)-Meth yl 2,2-d ich lor o-3-h yd r oxy-5-p h en yl-4-p en -
1
ten oa te (3c): yield 62%, 92% ee; mp 49 °C; H NMR (CDCl3,
P r ep a r a tion of Su lfon a m id es. Gen er a l P r oced u r e. To
a solution of D-valine (10.0 g, 85.4 mmol) in aqueous 1 N NaOH
(171 mL, 176 mmol) was added dropwise a solution of p-
toluenesulfonyl chloride (16.3 g, 85.4 mmol) in THF (85 mL)
under ice-cooling, and the reaction mixture was stirred
overnight. After evaporation of THF, the solution was washed
with CHCl3. The aqueous solution was acidified with aqueous
2 N HCl and extracted with AcOEt. The extracts were washed
with saturated aqueous NaHCO3 and dried over MgSO4. The
solvent was evaporated to give the sulfonamide 13a as a
colorless solid (15.7 g, 68%).
Typ ica l P r oced u r e for Asym m etr ic Mu k a iya m a -Ald ol
Rea ction of Ald eh yd es (4a -f) w ith Keten e Silyl Aceta l
(5) Ca ta lyzed by Oxa za bor olid in on es (12a -i). To a solu-
tion of p-toluenesulfonamide 13a (11 mmol, 2.98 g) in CH2Cl2
(100 mL) was added dropwise 1 M BH3‚THF complex in THF
solution (10 mmol) at 0 °C under N2 atmosphere. The solution
was stirred at 0 °C for 0.5 h and cooled to -78 °C. A solution
of aldehyde 4a (10 mmol, 1.36 g) in CH2Cl2 (10 mL) and a
solution of ketene silyl acetal 5 (11 mmol, 2.37 g) in CH2Cl2
200 MHz) δ 7.44 (d, J ) 8.68 Hz, 2H), 7.37-7.29 (m, 3H), 6.83
(d, J ) 15.6 Hz, 1H), 6.36 (dd, J ) 6.29 Hz, 15.9 Hz, 1H), 4.96
(d, J ) 6.00 Hz, 1H), 3.94 (s, 3H), 2.84 (br, 1H); IR (KBr) ν
3509, 3029, 2957, 1775, 1750 cm-1; MS (EI) m/z 274 (M+), 275
([M + 1]+), 276 ([M + 2]+), 277 ([M + 3]+), 278 ([M + 4]+).
Anal. Calcd for C12H14Cl2O5: C, 52.39; H, 4.40; Cl, 25.77.
Found: C, 52.01; H, 4.33; Cl, 25.82.
(3S)-Meth yl 2,2-dich lor o-3-h ydr oxy-5-ph en ylpen tan oate
1
(3d ): yield 38%, 94% ee; H NMR (CDCl3, 200 MHz) δ 7.33-
7.20 (m, 5H), 4.22 (dd, J ) 1.54 Hz, 6.44 Hz, 1H), 3.89 (s, 3H),
2.97 (m, 1H), 2.7 (br, 1H), 2.75 (dt, J ) 8.16 Hz, 13.8 Hz, 1H),
2.20 (m,1H), 1.97 (m, 1H); MS (EI) m/z 276 (M+), 277 ([M +
1]+), 278 ([M + 2]+), 279 ([M + 3]+), 280 ([M + 4]+); IR (film)
ν 3511, 3029, 2958, 1749, 1766 cm-1. Anal. Calcd for C12H14
-
Cl2O5: C, 52.01; H, 5.09; Cl, 25.58. Found: C, 51.59; H, 5.01;
Cl, 25.21.
(3S)-Meth yl 2,2-dich lor o-3-h ydr oxyh exan oate (3e): yield
42%, 89% ee; bp 72-73 °C (1.2 mmHg); 1H NMR (CDCl3, 200
MHz) δ 4.07 (d, J ) 4.03 Hz, 1H), 3.91 (s, 3H), 2.54 (br, 1H),
2.18 (m,1H), 1.08 (d, J ) 6.74 Hz, 3H), 1.05 (d, J ) 6.94 Hz,
3H); IR (film) ν 3492, 2962, 2879, 1767, 1749 cm-1. Anal. Calcd
for C7H12Cl2O5: C, 39.09; H, 5.62; Cl, 32.97. Found: C, 38.58;
H, 5.45; Cl, 31.57.
(20) For a theoretical study on the coordination of aldehydes to
N-sulfonyloxazaborolidine see: Salvatella, L.; Ruiz-Lo´pez, M. F. J . Am.
Chem. Soc. 1999, 121, 10722-10780 and references therein.
(21) (a) Corey, E. J .; Rohde, J . J . Tetrahedron Lett. 1997, 38, 37-
40. (b) Corey, E. J .; Barness-Seeman, D.; Lee, T. W. Tetrahedron Lett.
1997, 38, 4351-4354.
(22) (a) Rague, B.; Chapleur, Y.; Castro, B. J . Chem. Soc., Perkin
Trans. 1 1982, 2063-2066. (b) Shono, T.; Kise, N. Chem. Lett. 1987,
697-700. (c) Yamamoto, T.; Ishibuchi, S.; Ishizuka, T.; Haratake, M.;
Kunieda, T. J . Org. Chem. 1993, 58, 1997-1998. (d) Flisak, J . R.;
Gombatz, K. J .; Holmes, M. M.; J armas, A. A.; Lantos, I.; Mendelson,
W. L.; Novack, V. J .; Remich, J . J .; Snyder, L. J . Org. Chem. 1993, 58,
6247-6254. (e) Boger, D. L.; Patane, M. A.; Zhou, J . J . Am. Chem.
Soc. 1994, 116, 8544-8556. (f) Adger, B. M.; Barkley, J . V.; Bergeron,
S.; Cappi, M. W.; Flowerdew, B. M.; J ackson, M. P.; McCague, R.;
Nugent, T. C.; Roberts, S. M. J . Chem. Soc., Perkin Trans. 1 1997,
3501-3507. (g) Ruano, J . L. G.; Paredes, C. G. Tetrahedron Lett. 2000,
41, 5357-5361.
(3S)-Meth yl 2,2-d ich lor o-3-h yd r oxy-3-cycloh exylp r o-
1
p ion a te (3f): yield 27%, 62% ee; bp 102 °C (0.8 mmHg); H
NMR (CDCl3, 200 MHz) δ 4.05 (d, J ) 4.79 Hz, 1H), 3.90 (s,
3H), 2.5 (br, 1H), 1.76-1.15 (m, 11H); IR (film) ν 3491, 2930,
2855, 1768, 1749 cm-1. Anal. Calcd for C10H16Cl2O5: C, 47.08;
H, 6.32; Cl, 27.79. Found: C, 46.76; H, 6.30; Cl, 27.41.
(2R,3S)-Meth yl 3-(4-Meth oxyp h en yl)glycid a te ((-)-2).
To a solution of 3a (1.50 g, 5.37 mmol, 96% ee) in AcOH (5.4
mL) was added activated Zn powder (387 mg, 5.91 mmol) at
rt. After being stirred for 1.5 h at rt, the reaction mixture was
quenched with H2O (50 mL) and extracted with AcOEt. The
extracts were washed with brine, dried over MgSO4 and
concentrated under reduced pressure. The residue was purified
978 J . Org. Chem., Vol. 68, No. 3, 2003