Stereoselective Aldol and Michael Additions
(1R)-2-Hydroxy-1,2,2-triphenylethyl (2S,3R,4E)-3-Hydroxy-2,3-di- ethyl acetate. The combined organic layers were dried with MgSO4
FULL PAPER
methyl-4-hexenoate (6): A 50-mL two-necked flask, equipped with
a septum and a magnetic stirrer, was charged with 4c (0.5 g,
and the solvent was removed on a rotary evaporator. The crude
product was submitted to column chromatography (n-hexane/ethyl
1.0 mmol) and connected to the combined nitrogen/vacuum line. acetate, 4:1). After elution of 1,1,2-triphenyl-1,2-ethanediol, com-
After the addition of THF (15 mL), the septum was opened and pound 8 was isolated (Rf ϭ 0.3) in 71% yield (0.17 g) as a colorless
1
nBu4NF·3H2O (0.63 g, 2.0 mmol) was added rapidly while nitrogen oil; [α]2D0 ϭ Ϫ19.8 (c ϭ 1 in chloroform). Ϫ H NMR (300 MHz):
passed through the flask. The flask was closed with the septum,
δ ϭ 0.92 [d, J ϭ 7.1 Hz, 3 H, CH(CH3)], 1.50 [s, 3 H, (CH3)C(OH)],
and the mixture was stirred for 3 h at room temp. After cooling to 1.98Ϫ2.03 (m, 1 H, CHCH3), 3.37 [s, 1 H, CH2(OH)], 3.45Ϫ3.53
0 °C, another portion of nBu4NF·3H2O (0.55 g, 1.75 mmol) was
added and stirring was continued at 0 °C for 12 h. The mixture was
allowed to warm to room temp. and then concentrated on a rotary
evaporator. Deionized water (6 mL) and NaCl (1.4 g) were added,
and the mixture was extracted four times with a total amount of
120 mL of diethyl ether. The combined organic layers were washed
twice with brine and dried with MgSO4. Evaporation of the solvent
on a rotary evaporator and subsequently under an oil-pump va-
cuum afforded a solid crude product which was recrystallized from
petroleum ether to give white, crystalline 6. Yield 0.317 g (74%). Ϫ
(m, 2 H, CH2), 3.89 [s, 1 H, (CH3)C(OH)], 7.20Ϫ7.44 (m, 5 H,
aromatic H). The 1H NMR spectrum is in accordance with that
of racemic (2R*,3R*)-2-methyl-3-phenyl-1,3-butanediol, described
in ref.[22]
Acknowledgments
This work was supported by the Deutsche Forschungsgemeinschaft
and the Fonds der Chemischen Industrie. We would like to thank
Dr. A. Steigel, Mrs. M. Beuer, Mrs. I. Menzel, Dr. G. Broszeit, Mr.
O. Koersgen, and Mr. R. Bürgel for recording the spectra. Special
thanks go to Mrs. S. Houben for carrying out several experiments.
Finally, we would like to thank Dr. W. Poll for assistance with the
crystal structure analyses.
1
[α]2D0 ϭ 66.8 (c ϭ 0.6 in chloroform). Ϫ H NMR (300 MHz): δ ϭ
0.97 [d, J ϭ 7.1 Hz, 3 H, CH(CH3)], 1.09 [s, 3 H, (CH3)C(OH)],
1.35 (d, J ϭ 6.1 Hz, 3 H, 6-H), 2.48 (q, J ϭ 7.1 Hz, 1 H, 2-H), 2.85
[s, 1 H, (C6H5)2COH], 3.19 [s, 1 H, (CH3)C(OH)], 5.31 (dq, Jd
ϭ
14 Hz, Jq ϭ 1.3 Hz, 1 H, 4-H), 5.40 (dq, Jd ϭ 14 Hz, Jq ϭ 6.1 Hz,
1 H, 5-H), 6.66 [s, 1 H, CH(C6H5)], 7.01Ϫ7.57 (m, 15 H, aromatic
H). Ϫ 13C NMR (75 MHz): δ ϭ 11.7 [CH(CH3)], 17.4 (C-6), 24.7
[(CH3)C(OH)], 48.0 (C-2), 72.6 (C-3), 78.7 [CH(C6H5)], 80.3
[(C6H5)COH], 123.8 (C-5), 136.5 (C-4), 175.7 (C-1). Ϫ MS (70 eV,
EI): m/z (%) ϭ 429 (7) [Mϩ]. Ϫ C28H30O4 (430.5): calcd. C 78.11,
H 7.02; found C 77.93, H 7.09. Ϫ Crystal data for 6:[21] orthorhom-
[1]
M. Braun, in Houben Weyl, 4th ed., Vol 21b (Eds.: G.
Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann), Thi-
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B. L. Feringa, J. F. G. A. Jansen, in Houben Weyl, 4th ed.,
[2]
Vol 21b (Eds.: G. Helmchen, R. W. Hoffmann, J. Mulzer, E.
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C. H. Heathcock, in Modern Synthetic Methods 1992 (Ed.: R.
bic space group; P212121; a ϭ 10.658(3), b ϭ 10.762(4), c ϭ
[3]
3
21.472(6) A; V ϭ 2462.9(13) A ; Z ϭ 4; dcalcd. ϭ 1.161 Mg/m3;
˚
˚
Scheffold), VHCA/VCH, Basel/Weinheim, 1992, pp. 1Ϫ102
µ(Mo-Kα) ϭ 0.076 mmϪ1; F(000) ϭ 920; intensity data 0 Յ h Յ
and references therein.
[4] [4a]
13, Ϫ14 Յ k Յ 0, 0 Յ l Յ 27; 2θmax ϭ 27.56°; R ϭ 0.0408, Rw
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(2S,3S)-3-Hydroxy-2,3-dimethyl-4-hexenoic Acid (7): A mixture of
4c (0.31 g, 0.73 mmol), methanol (85 mL), and water (25 mL) was
stirred in a 250-mL flask at 0 °C. A solution of LiOH·H2O (0.33 g,
8.0 mmol) in 25 mL of water was then added. The mixture was
stirred for 0.5 h at 0 °C and then for 3 days at room temp. Water
(20 mL) was added, and the suspension was extracted three times
with a total amount of 150 mL of diethyl ether in order to remove
1,1,2-triphenyl-1,2-ethanediol. The aqueous layer was cooled in an
ice bath and acidified to pH ϭ 3 by addition of 1 hydrochloric
acid. The solution was saturated with NaCl and extracted five times
with ethyl acetate (150 mL). The combined organic extracts were
dried with Na2SO4 and concentrated on a rotary evaporator to give
colorless, oily 7. Yield 0.075 g (65%). Ϫ [α]2D0 ϭ 25.5 (c ϭ 1 in
B. M. Trost, I. Fleming, C. H. Heathcock), Pergamon Press,
[4e]
Oxford 1991, vol. 2, chapter 1.6. Ϫ
B. Moon Kim, S. F.
Williams, S. Masamune, in Comprehensive Organic Synthesis
(Ed.: B. M. Trost, I. Fleming, C. H. Heathcock), Pergamon
[4f]
Press, Oxford 1991, vol. 2, chapter 1.7. Ϫ
I. Paterson, in
Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Flem-
ing, C. H. Heathcock), Pergamon Press, Oxford 1991, vol. 2,
[4g]
chapter 1.9. Ϫ
335, 653Ϫ668
For reviews, see:
M. Braun, H. Sacha, J. Prakt. Chem. 1993,
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[5a]
M. Sawamura, Y. Ito, in Catalytic Asym-
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[5b]
367Ϫ388. Ϫ
H. Gröger, E. Vogl, M. Shibasaki, Chem. Eur.
1
chloroform). Ϫ H NMR (300 MHz): δ ϭ 1.22 [d, J ϭ 7.2 Hz, 3
J. 1998, 4, 1137Ϫ1141. Ϫ [5c] S. G. Nelson, Tetrahedron: Asym-
H, CH(CH3)], 1.27 [s, 3 H, (CH3)C(OH)], 1.69 (d, J ϭ 6.3 Hz, 3
H, 6-H), 2.57 (q, J ϭ 7.2 Hz, 1 H, 2-H), 3.34 [s, 1 H, (CH3)C(OH)],
5.55 (dq, Jd ϭ 15 Hz, Jq ϭ 1.3 Hz, 1 H, 4-H), 5.40 (dq, Jd ϭ 15 Hz,
Jq ϭ 6.3 Hz, 1 H, 5-H), 7.2 (broad s, 1 H, COOH). Ϫ 13C NMR
(75 MHz): δ ϭ 12.2 [CH(CH3)], 17.7 (C-6), 24.0 [(CH3)C(OH)],
48.2 (C-2), 73.3 (C-3), 124.4 (C-5), 136.2 (C-4), 180.6 (C-1).
metry 1998, 9, 357Ϫ389. Ϫ [5d] R. Mahrwald, Chem. Rev. 1999,
[5e]
99, 1095Ϫ1120. Ϫ
J. S. Johnson, D. A. Evans, Acc. Chem.
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M. Guette, J. Capillon, J.-P. Guette, Tetrahedron 1973, 29,
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E. B. Dongala, D. L. Dull, C. Mioskowski, G. Solladie, Tetra-
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´
C. Mioskowski, G. Solladie, Tetrahedron 1980, 36, 227Ϫ236.
(1R,2R)-1,2-Dimethyl-1-phenyl-1,3-propanediol (8): Under nitrogen,
a solution of 4a (0.70 g, 1.3 mmol) in 5 mL of THF was added
slowly to a vigorously stirred suspension of LiAlH4 (0.88 g,
22 mmol) in THF (50 mL) at room temp. Stirring was continued
overnight. The mixture was cooled in an ice bath and water (5 mL)
was added dropwise. Then, 1 hydrochloric acid was added drop-
wise until the precipitate dissolved. The layers were separated, and
the aqueous phase was extracted three times with chloroform and
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3159