Synthesis of optically active 3-alkoxy-6-hydroxymethyl-6-methyl-2-cyclohexenone

Article abstract of DOI:10.1016/S0957-4166(99)00304-3

Optically active 3-alkoxy-6-hydroxymethyl-6-methyl-2-cyclohexenone and 6-acetoxymethyl-3-alkoxy-6-methyl-2-cyclohexenone were efficiently obtained by lipase-catalyzed kinetic resolution. (R)-6-Acetoxymethyl-3-(methoxymethoxy)-6-methyl-2-cyclohexenone was converted to the synthetic intermediate of cassiol.

Full text of DOI:10.1016/S0957-4166(99)00304-3

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3189–3196
Synthesis of optically active 3-alkoxy-6-hydroxymethyl-
6-methyl-2-cyclohexenone
Hiroaki Miyaoka, Yasuhiro Kajiwara, Miho Hara, Akira Suma and Yasuji Yamada ∗
School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 21 June 1999; accepted 14 July 1999
Abstract
Optically active 3-alkoxy-6-hydroxymethyl-6-methyl-2-cyclohexenone and 6-acetoxymethyl-3-alkoxy-6-
methyl-2-cyclohexenone were efficiently obtained by lipase-catalyzed kinetic resolution. (R)-6-Acetoxymethyl-
3-(methoxymethoxy)-6-methyl-2-cyclohexenone was converted to the synthetic intermediate of cassiol. © 1999
Elsevier Science Ltd. All rights reserved.
1. Introduction
Optically active cyclohexenone I possessing an asymmetric quaternary carbon has been found useful as
a starting material for synthesizing natural products, such as terpenoids. The syntheses of sesquiterpenoid
cassiol1,2 and diterpenoid trisporol B3,4 from cyclohexenone I have been reported, however, only limited
means are available for the synthesis of optically active cyclohexenone I. The authors are presently en-
gaged in the synthesis of sesterterpenoid dysidiolide, a potent inhibitor of protein phosphatase cdc25A,5,6
for optically active cyclohexenones I (R1=H or protecting group, R2=H, R3=alkoxy) are prerequisite to
the synthesis as starting materials. The enzymatic kinetic resolution of the primary alcohol attached
to the asymmetric quaternary carbon appears only slightly in the literature,7,8 although the enzymatic
asymmetrization of prochiral diols has been extensively reported.9 In this study, an efficient method was
established for synthesizing optically active cyclohexenones I (R1=H or Ac, R2=H, R3=OMe or OMOM),
equivalent to (+)-3, (+)-4, (−)-5 and (−)-6, by lipase-catalytic kinetic resolutions. (R)-6-Acetoxymethyl-
3-(methoxymethoxy)-6-methyl-2-cyclohexenone (−)-6, obtained by lipase-catalytic kinetic resolution,
was converted to a synthetic intermediate of cassiol (Fig. 1).
∗
Corresponding author. Tel: +81-426-76-3046; fax: +81-426-76-3069; e-mail: yamaday@ps.toyaku.ac.jp
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00304-3

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Figure 1.
2. Results and discussion
Alcohols (ꢀ)-3 and (ꢀ)-4 were prepared from cyclohexenone 1 and 2,10 respectively, in two steps:
1) methylation with lithium diisopropylamide (LDA) and iodomethane and 2) hydroxymethylation with
LDA and formaldehyde (Scheme 1). Table 1 shows the results of enantioselective acetylation of alcohols
(ꢀ)-3 and (ꢀ)-4. Alcohol (ꢀ)-3 was treated with vinyl acetate in benzene at room temperature in the
presence of lipase AY (from Candida rugosa) to give alcohol (+)-3 and acetate (−)-5, but the reaction rate
and enantiomeric excesses were low (entry 1). Acetylation of (ꢀ)-3 with lipase PS (from Pseudomonas
cepacia) gave alcohol (+)-3 (69% ee) and acetate (−)-5 (90% ee) (entry 2). On using lipase AK (from
Pseudomonas fluorescens), the acetylation of (ꢀ)-3 gave alcohol (+)-3 (96% ee) and acetate (−)-5 (90%
ee) (entry 3). Alcohol (ꢀ)-4 was acetylated with lipase AY, PS and AK (entries 4–6) and satisfactory
results were obtained on using lipase AK. Treatment of (ꢀ)-4 with vinyl acetate in the presence of
lipase AK in benzene at room temperature gave alcohol (+)-4 (99% ee) and acetate (−)-6 (97% ee)
(entry 6). Enantiomeric excesses of (+)-3 and (+)-4 were determined by HPLC analysis, using a column
packed with CHIRALPAK AS (hexane:isopropanol 9:1). Enantiomeric excesses of (−)-5 and (−)-6 were
determined by HPLC analysis of (−)-4, prepared by the methanolysis of (−)-5 and (−)-6 under the above
conditions.
Scheme 1.
Absolute configurations of alcohol (+)-3, alcohol (+)-4, acetate (−)-5 and acetate (−)-6 were deter-
mined based on chemical conversions (Scheme 2). Alcohol (+)-4 was reduced with DIBAL-H to give
enone (+)-7 ([α]26 +31.2 (c 0.84, CHCl3)), the antipode of the known enone (−)-7 ([α]26 +28.0 (c 1.85,
D
D
CHCl3), 85% ee).11 Acetylation of (+)-4 gave acetate (+)-6 ([α]26 +66.2 (c 1.25, CHCl3)). Methanolysis
D
of acetates (−)-5 and (−)-6 afforded alcohol (−)-3 in either case. The absolute configurations of (+)-3,
(+)-4, (−)-5 and (−)-6 at C-6 position were thus concluded to be S, S, R and R, respectively.
For assessment of the optically active cyclohexenone derivatives (+)-4 and (−)-6 as potential chiral
building blocks, cyclohexenone derivative (−)-6 was converted to a synthetic intermediate of cassiol
(Scheme 3). Hydrogenation of (−)-6 in the presence of 10% Pd–C and K2CO3 in MeOH gave alcohol 8

H. Miyaoka et al. / Tetrahedron: Asymmetry 10 (1999) 3189–3196
3191
Table 1
Scheme 2.
in 76% yield. The hydroxyl group in 8 was protected as TBDPS ether so as to afford cyclohexanone 9, a
synthetic intermediate of cassiol.3a
Scheme 3.
The lipase-catalyzed method for synthesizing the optically active primary alcohol adjacent to a
quaternary carbon was established. Cyclohexenone derivatives (+)-4 and (−)-6 were clearly shown to
be useful as chiral building blocks in the synthesis of natural products. The total synthesis of dysidiolide
starting from cyclohexenone (+)-4 is now being carried out.
3. Experimental
3.1. General
Optical rotation was measured with a JASCO DIP-360 automatic polarimeter. Infrared (IR) spectra
were recorded with a Perkin–Elmer FT-IR 1710 spectrometer or JASCO FT-IR 620 spectrometer.
1
Ultraviolet (UV) spectra were recorded with a JASCO V-550 spectrophotometer. H and 13C NMR
spectra were recorded with a Bruker DPX-400 or Varian Gemini-300. Chemical shifts were expressed
on a δ (ppm) scale with tetramethylsilane (TMS) as the internal standard (s, singlet; d, doublet; t, triplet;
q, quartet; m, multiplet; br, broad). Electron impact mass spectra (EIMS) and high resolution electron
impact mass spectra (HREIMS) were obtained using Hitachi M-80 or VG Auto Spec spectrometer.
Elemental analysis was conducted using a Perkin–Elmer 242. Column chromatography was carried out
on Merck silica gel 60 (70–230 mesh).

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3.2. (ꢀ)-6-Hydroxymethyl-3-methoxy-6-methyl-2-cyclohexenone (ꢀ)-3
To a cold (−78°C) solution of lithium diisopropylamide [prepared from diisopropylamine (25.6 mL,
182 mmol) and butyllithium (1.48 M in hexane, 104 mL, 154 mmol)] in THF (470 mL) was added
dropwise a solution of the 3-methoxycyclohexenone 1 (17.6 g, 140 mmol) in THF (10 mL). After the
mixture had been stirred at −78°C for 30 min, iodomethane (12.2 mL, 196 mmol) was added and the
mixture was warmed to room temperature over 1 h. The reaction mixture was poured into ether and
saturated NH4Cl solution. The organic layer was washed with water and saturated NaCl solution, dried
over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel
column chromatography (eluted with hexane:AcOEt 1:1) to give methylcyclohexenone derivative (17.6
g, 90% yield) as a colorless oil.
EIMS m/z (relative intensity) 140 (M+, 80), 98 (100); HREIMS: calcd for C8H12O2 (M+) 140.0837;
1
found: 140.0829; IR (neat) 2962, 1661, 1613 cm−1; UV (EtOH) λmax 246 nm (ε 7900); H NMR (300
MHz, CDCl3) δ 1.14 (3H, d, J=6.9 Hz), 1.70 (1H, m), 2.04 (1H, dq, J=13.2, 4.7 Hz), 2.30 (1H, m), 2.39
(1H, ddd, J=4.6, 5.5, 17.6 Hz), 2.47 (1H, dddd, J=1.2, 5.2, 10.0, 17.6 Hz), 3.67 (3H, s), 5.33 (1H, d,
J=1.2 Hz); 13C NMR (100 MHz, CDCl3) δ 15.3, 28.1, 29.2, 40.1, 55.6, 101.6, 177.7, 201.9.
To a cold (−78°C) solution of lithium diisopropylamide [prepared from diisopropylamine (23.2 mL,
166 mmol) and butyllithium (1.54 M in hexane, 98.2 mL, 151 mmol)] in THF (230 mL) was added
dropwise a solution of the above methylcyclohexenone derivative (6.43 g, 45.9 mmol) in THF (10 mL).
The mixture was stirred at −78°C for 30 min and formaldehyde gas [prepared from paraformaldehyde
(36.7 g) by heating at 180°C] was then introduced during a 30 min period. The reaction mixture was
poured into ether and saturated NH4Cl solution. The organic layer was washed with water and saturated
NaCl solution, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (eluted with hexane:AcOEt 1:2) to give alcohol (ꢀ)-3 (3.73
g, 48% yield) as a colorless oil.
EIMS m/z (relative intensity) 170 (M+, 46), 98 (100); HREIMS: calcd for C9H14O3 (M+) 170.0943;
found: 170.0935; IR (neat) 3419, 2938, 1636, 1606 cm−1; UV (EtOH) λmax 246 nm (ε 13300); 1H NMR
(400 MHz, CDCl3) δ 1.16 (3H, s), 1.44 (1H, ddd, J=3.2, 5.4, 13.4 Hz), 2.03 (1H, ddd, J=5.5, 12.0, 13.4
Hz), 2.39 (1H, ddd, J=3.2, 5.5, 18.0 Hz), 2.61 (1H, dddd, J=1.0, 5.4, 12.0, 18.0 Hz), 3.04 (1H, br t, J=5.5
Hz), 3.70 (3H, s), 3.56 (2H, m), 5.28 (1H, d, J=1.0 Hz); 13C NMR (100 MHz, CDCl3) δ 18.9, 25.5, 29.8,
44.6, 55.8, 69.1, 101.1, 177.8, 205.5.
3.3. (ꢀ)-6-Hydroxymethyl-3-(methoxymethoxy)-6-methyl-2-cyclohexenone (ꢀ)-4
To a cold (−78°C) solution of lithium diisopropylamide [prepared from diisopropylamine (15.5 mL,
110 mmol) and butyllithium (1.56 M in hexane, 66.0 mL, 103 mmol)] in THF (355 mL) was added
dropwise a solution of the 3-(methoxymethoxy)-2-cyclohexenone (2) (11.5 g, 73.4 mmol) in THF
(10 mL). The mixture was stirred at −78°C for 30 min, followed by the addition of iodomethane
(6.40 mL, 103 mmol). The mixture was warmed to room temperature over 1 h. The reaction mixture
was poured into ether and saturated NH4Cl solution. The organic layer was washed with water and
saturated NaCl solution, dried over anhydrous MgSO4 and concentrated under reduced pressure. The
residue was purified by silica gel column chromatography (eluted with hexane:AcOEt 1:1) to give
methylcyclohexenone derivative (12.3 g, 91% yield) as a colorless oil.
EIMS m/z (relative intensity) 170 (M+, 20), 45 (100). Anal. calcd for C9H14O3: C, 63.51; H, 8.29.
Found: C, 63.36; H, 8.21. IR (neat) 2936, 1661, 1614 cm−1; UV (EtOH) λmax 245 nm (ε 9600); 1H NMR
(400 MHz, CDCl3) δ 1.15 (3H, d, J=6.9 Hz), 1.71 (1H, m), 2.06 (1H, dq, J=13.2, 4.8 Hz), 2.28 (1H, m),

H. Miyaoka et al. / Tetrahedron: Asymmetry 10 (1999) 3189–3196
3193
2.42 (1H, dt, J=4.8, 17.4 Hz), 2.50 (1H, dddd, J=1.3, 5.1, 10.3, 17.4 Hz), 3.46 (3H, s), 5.03 (1H, d, J=6.1
Hz), 5.05 (1H, d, J=6.1 Hz), 5.45 (1H, d, J=1.3 Hz); 13C NMR (100 MHz, CDCl3) δ 15.3, 28.0, 29.1,
40.0, 57.0, 94.0, 104.2, 174.5, 201.9.
To a cold (−78°C) solution of lithium diisopropylamide [prepared from diisopropylamine (5.91 mL,
42.0 mmol) and butyllithium (1.56 M in hexane, 89.0 mL, 139 mmol)] in THF (60.0 mL) was added
dropwise a solution of the above methylcyclohexenone derivative (2.04 g, 12.0 mmol) in THF (10 mL).
The mixture was stirred at −78°C for 30 min and formaldehyde gas [prepared from paraformaldehyde (9.0
g) by heating at 180°C] was then introduced during 30 min. The reaction mixture was poured into ether
and saturated NH4Cl solution. The organic layer was washed with water and saturated NaCl solution,
dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was purified by
silica gel column chromatography (eluted with hexane:AcOEt 1:2) to give alcohol (ꢀ)-4 (1.44 g, 60%
yield) as a colorless oil.
EIMS m/z (relative intensity) 200 (M+, 25), 45 (100); HREIMS: calcd for C10H16O4 (M+) 200.1049;
found: 200.1045; IR (neat) 3436, 2934, 1646, 1614 cm−1; UV (EtOH) λmax 247 nm (ε 12000); 1H NMR
(300 MHz, CDCl3) δ 1.15 (3H, s), 1.57 (1H, ddd, J=3.1, 5.4, 13.5 Hz), 2.05 (1H, ddd, J=5.6, 11.6, 13.5
Hz), 2.40 (1H, ddd, J=3.1, 5.6, 18.2 Hz), 2.60 (1H, dddd, J=1.5, 5.4, 11.6, 18.2 Hz), 3.03 (1H, s), 3.45
(3H, s), 3.55 (2H, m), 5.04 (1H, d, J=6.2 Hz), 5.07 (1H, d, J=6.2 Hz), 5.40 (1H, d, J=1.5 Hz); 13C NMR
(75 MHz, CDCl3) δ 18.8, 25.2, 29.5, 44.5, 57.0, 68.8, 94.1, 103.5, 174.6, 205.2.
3.4. Lipase-catalyzed acetylation of alcohols (ꢀ)-3 and (ꢀ)-4
3.4.1. Typical procedure
To a solution of alcohol (ꢀ)-4 (195 mg, 0.988 mmol) and vinyl acetate (270 µL, 2.93 mmol) in benzene
(4.9 mL), lipase AK (99 mg) was added, followed by stirring for one day at room temperature. The
reaction mixture was diluted with Et2O, filtered using a Kiriyama funnel and the filtrate was concentrated
under reduced pressure. The residue was purified by silica gel column chromatography (eluted with
hexane:AcOEt 1:2) to give alcohol (+)-4 (96.4 mg, 48% yield, 99% ee) and acetate (−)-6 (109 mg, 46%
yield, 97% ee) as a colorless oil, respectively.
3.5. (S)-6-Hydroxymethyl-3-methoxy-6-methyl-2-cyclohexenone (+)-3
[α]26 +80.5 (c 1.19, CHCl3).
D
3.6. (R)-6-Acetoxymethyl-3-methoxy-6-methyl-2-cyclohexenone (−)-5
[α]26 −59.5 (c 1.26, CHCl3); EIMS m/z (relative intensity) 212 (M+, 15), 152 (20), 98 (100). Anal.
D
calcd for C9H14O3: C, 62.25; H, 7.60. Found: C, 62.35; H, 7.47. IR (neat) 2942, 1741, 1653, 1611 cm−1;
UV (EtOH) λmax 248 nm (ε 11800); 1H NMR (400 MHz, CDCl3) δ 1.10 (3H, s), 1.72 (1H, dt, J=13.6,
5.1 Hz), 2.02 (3H, s), 2.09 (1H, ddd, J=5.6, 9.9, 13.6 Hz), 2.41 (1H, dt, J=18.0, 5.6 Hz), 2.51 (1H, dddd,
J=0.9, 5.1, 9.9, 18.0 Hz), 3.68 (3H, s), 3.97 (1H, d, J=10.9 Hz), 4.31 (1H, d, J=10.9 Hz), 5.31 (1H, s);
13C NMR (100 MHz, CDCl3) δ 18.9, 25.5, 29.8, 44.6, 55.8, 69.1, 101.1, 177.8, 205.5.
3.7. (S)-6-Hydroxymethyl-3-(methoxymethoxy)-6-methyl-2-cyclohexenone (+)-4
[α]27 +91.8 (c 1.36, CHCl3).
D

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3.8. (R)-6-Acetoxymethyl-3-(methoxymethoxy)-6-methyl-2-cyclohexenone (−)-6
[α]26 −63.6 (c 1.33, CHCl3); EIMS m/z (relative intensity) 242 (M+, 10), 138 (18), 45 (100). Anal.
D
calcd for C12H18O5: C, 59.49; H, 7.49. Found: C, 59.19; H, 7.51. IR (neat) 2940, 1740, 1655, 1614 cm−1;
UV (EtOH) λmax 248 nm (ε 16300); 1H NMR (300 MHz, CDCl3) δ 1.12 (3H, s), 1.75 (1H, dt, J=13.5,
5.5 Hz), 2.04 (3H, s), 2.12 (1H, ddd, J=5.5, 9.6, 13.5 Hz), 2.44 (1H, dt, J=18.3, 5.5 Hz), 2.55 (1H, dddd,
J=1.1, 5.5, 9.6, 18.3 Hz), 3.47 (3H, s), 3.98 (1H, d, J=10.9 Hz), 4.32 (1H, d, J=10.9 Hz), 5.05 (1H, d,
J=5.7 Hz), 5.07 (1H, d, J=5.7 Hz), 5.31 (1H, s); 13C NMR (100 MHz, CDCl3) δ 19.6, 20.9, 25.3, 29.5,
43.7, 57.1, 68.2, 77.2, 94.1, 103.7, 173.8, 200.6.
3.9. (R)-4-Hydroxymethyl-4-methyl-2-cyclohexenone (+)-7
To a cold (−78°C) solution of cyclohexenone (+)-4 (52.7 mg, 264 µmol, 99% ee) in toluene (2.6 mL),
DIBAL-H (0.95 M in hexane, 584 µL, 555 µmol) was added dropwise and the mixture was stirred at the
same temperature for 30 min. The reaction mixture was diluted with Et2O, treated with saturated NaCl
solution and stirred for 6 h at room temperature. The organic layer was dried over anhydrous MgSO4
and concentrated under reduced pressure. The residue was purified by silica gel column chromatography
(eluted with hexane:AcOEt 1:1) to give cyclohexenone (+)-7 (25.3 mg, 69% yield) as a colorless oil.
[α]26 +31.2 (c 0.84, CHCl3); EIMS m/z (relative intensity) 240 (M+, 10), 110 (100); HREIMS: calcd
D
for C8H12O2 (M+) 140.0837; found: 140.0817; IR (neat) 3427, 2931, 1676 cm−1; UV (EtOH) λmax 227
nm (ε 6400); 1H NMR (300 MHz, CDCl3) δ 1.14 (3H, s), 1.74 (1H, dddd, J=1.0, 5.6, 6.8, 13.7 Hz), 2.08
(1H, ddd, J=6.8, 8.3, 13.7 Hz), 2.48 (2H, m), 3.48 (1H, d, J=10.5 Hz), 3.56 (1H, d, J=10.5 Hz), 5.94
(1H, d, J=10.2 Hz), 6.73 (1H, dd, J=1.0, 10.2 Hz); 13C NMR (75 MHz, CDCl3) δ 21.9, 30.8, 33.9, 38.2,
69.8, 129.0, 156.1, 199.8.
3.10. Acetylation of alcohol (+)-4 to acetate (+)-6
To a solution of alcohol (+)-4 (14.6 mg, 73.0 µmol, 99% ee) in pyridine (1.0 mL), Ac2O (1.0 mL) was
added and stirred at room temperature for 10 h. The reaction mixture was concentrated under reduced
pressure. The residue was purified by silica gel column chromatography (eluted with hexane:AcOEt 1:2)
to give acetate (+)-6 (16.5 mg, 93% yield) as a colorless oil.
[α]26 +66.2 (c 1.25, CHCl3).
D
3.11. Methanolysis of acetate (−)-5 to alcohol (−)-3
To a solution of acetate (−)-5 (32.9 mg, 155 µmol, 90% ee) in MeOH (1.55 mL), K2CO3 (107 mg, 775
µmol) was added, followed by stirring at room temperature for 3 h. The reaction mixture was diluted with
AcOEt, filtered through silica gel. The filtrate was concentrated under reduced pressure to give alcohol
(−)-3 (22.9 mg, 87% yield) as a colorless oil.
[α]27 −76.1 (c 1.45, CHCl3).
D
3.12. Methanolysis of acetate (−)-6 to alcohol (−)-3
To a solution of acetate (−)-6 (11.8 mg, 48.4 µmol, 97% ee) in MeOH (500 µL), K2CO3 (33.4 mg, 242
µmol) was added and stirred at room temperature for 3 h. The reaction mixture was diluted with AcOEt

H. Miyaoka et al. / Tetrahedron: Asymmetry 10 (1999) 3189–3196
3195
and filtered through silica gel. The filtrate was concentrated under reduced pressure to give alcohol (−)-3
(7.5 mg, 91% yield) as a colorless oil.
[α]24 −64.4 (c 0.63, CHCl3).
D
3.13. (R)-2-Hydroxymethyl-2-methylcyclohexanone 8
A solution of cyclohexenone (−)-6 (419 mg, 1.73 mmol, 97% ee) in MeOH (30.0 mL) in the
presence of 10% Pd–C (164 mg) and K2CO3 (196 mg) was stirred at room temperature for 1 h under
H2 atmosphere and then diluted with Et2O and filtered through Celite. The filtrate was concentrated
under reduced pressure. The residue was purified by silica gel column chromatography (eluted with
hexane:AcOEt 4:1) to give cyclohexanone 8 (184 mg, 76% yield) as a colorless oil.
[α]26 −98.4 (c 1.06, CHCl3); EIMS m/z (relative intensity) 142 (M+, 3), 124 (60), 82 (100); HREIMS:
D
1
calcd for C8H14O2 (M+) 142.0994; found: 142.0995; IR (neat) 3422, 2936, 1700 cm−1; H NMR (400
MHz, CDCl3) δ 1.18 (3H, s), 1.57 (1H, m), 1.65 (1H, m), 1.75 (1H, m), 1.81 (1H, m), 2.03 (1H, m),
2.27 (1H, dddd, J=1.4, 3.2, 4.6, 14.4 Hz), 2.51 (1H, ddd, J=6.1, 12.9, 14.4 Hz), 2.56 (1H, t, J=7.1 Hz),
3.47 (1H, dd, J=6.7, 11.4 Hz), 3.51 (1H, dd, J=7.3, 11.4 Hz); 13C NMR (100 MHz, CDCl3) δ 20.2, 20.7,
27.3, 35.6, 39.0, 50.1, 69.1, 218.1.
3.14. (R)-2-(tert-Butyldiphenylsiloxymethyl)-2-methylcyclohexanone 9
To a solution of alcohol 8 (77.9 mg, 550 µmol) in DMF (600 µL) was added imidazole (112 mg,
1.65 mmol) and tert-butyldiphenylsilyl chloride (357 µL, 1.38 mmol). The mixture was stirred at room
temperature for 1 h and diluted with ether. The organic layer was washed with water and saturated
NaCl solution, dried over anhydrous MgSO4 and concentrated under reduced pressure. The residue was
purified by silica gel column chromatography (eluted with hexane:AcOEt 5:1) to give TBDPS ether 9
(139 mg, 66% yield) as a colorless oil.
[α]27 +10.9 (c 1.39, CHCl3); EIMS m/z (relative intensity) 323 (M+−tBu, 100); HREIMS: calcd for
D
1
C20H23O2Si (M+−tBu) 323.1467; found: 323.1474; IR (neat) 2932, 2858, 1709 cm−1; H NMR (300
MHz, CDCl3) δ 1.04 (9H, s), 1.14 (3H, s), 1.6–2.0 (6H, m), 2.30 (1H, dt, J=6.5, 14.5 Hz), 2.37 (1H, dt,
J=6.9, 14.5 Hz), 3.69 (1H, d, J=9.8 Hz), 3.71 (1H, d, J=9.8 Hz), 7.35–7.45 (6H, m), 7.66 (4H, m); 13
C
NMR (75 MHz, CDCl3) δ 19.3, 20.8, 21.2, 26.8, 27.0, 36.0, 39.2, 50.8, 68.8, 127.6, 129.6, 133.3, 135.7,
214.5.
Acknowledgements
The authors express appreciation to Amano Pharmaceutical Co. Ltd for kindly providing Lipase AY,
PS and AK. This work was supported in part by a Grant-in-Aid for Scientific Research (Grant No.
09672165) from the Ministry of Education, Science, Sports and Culture of Japan.
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