470
P. Bonomi et al. / Tetrahedron: Asymmetry 20 (2009) 467–472
enzymes allows the easy recovery and the reuse of the biocatalyst
with advantages in terms of product purification and process costs.
mixture was heated at 70 °C for 24 h under an N2 atmosphere. The
solution was then cooled to rt and concentrated under reduced
pressure. The resulting residue was triturated with Et2O
(3 ꢁ 100 mL), filtered and the filtrate was evaporated under
reduced pressure. The residue was purified by flash chromatogra-
phy (eluent B) to obtain pure 5-benzyloxy-2-tetralol rac-7b
(1.43 g, 5.6 mmol, 92% yield). TLC (eluent A), Rf = 0.49; 1H NMR
(CDCl3) d: 1.65 (s, 1H, OH), 1.78–1.88 (m, 1H, H-3a), 2.09–2.12
(m, 1H, H-3b), 2.74–2.83 (m, 2H, H-1a, H-4a), 3.00–3.13 (m, 2H,
H-1b, H-4b), 4.14–4.20 (m, 1H, H-2), 5.09 (s, 2H, OCH2), 6.75 (d,
1H, J = 7.6 Hz) and 6.77 (d, 1H, J = 8.0 Hz) (H-6 and H-8), 7.12
(app.t, 1H, J = 7.9 Hz, H-7), 7.33–7.47 (m, 5H, aromatic Hs); 13C
NMR (CDCl3) d: 21.4 (CH2), 31.1 (CH2), 38.5 (CH2), 67.1 (CH), 69.7
(CH2), 108.6 (CH), 121.9 (CH), 125.0 (C), 126.4 (CH), 127.1 (CH),
127.8 (CH), 128.5 (CH), 135.8 (C), 137.4 (C), 156.3 (C); EI MS m/z
(rel. int.) 254 (M+, 10), 236 (7), 162 (5), 144 (5), 91 (100).
4. Experimental
4.1. General experimental
Analytical TLC was performed on silica gel F254 precoated alu-
minium sheets (0.2 mm layer, Merck, Darmstadt, Germany) using
the following eluents: A, hexane/EtOAc (1:1); B, hexane/EtOAc
(2:1); components were detected under an UV lamp and by spray-
ing with a ceric sulfate/ammonium molybdate solution, followed
by heating to ca. 150°. Silica gel 60, 40–63 lm (Merck) was used
for flash chromatography. 1H and 13C NMR spectra were recorded
in CDCl3 at 400.1 and 100.6, respectively, on a Bruker AVANCE
400 Spectrometer equipped with a XWIN-NMR software package
(Bruker, Karlsruhe, Germany). Chemical shifts (d) are given in
ppm, and were referenced to the solvent signals (dH 7.25, dC
77.00 from TMS). EIMS spectra were run on a VG 7070 EQ mass
spectrometer operating at 70 eV. A Merck-Hitachi L-7100 liquid
chromatograph equipped with L-7300 column oven and a L-7400
UV detector was used for analytical HPLC. The OD-Chiralcel col-
umn was from DaicelÒ Chemical Industries Ltd; the S,S-WhelkO1
4.2.4. 8-Benzyloxy-2-tetralol rac-7c
The title compound was prepared from 8-hydroxy-2-tetralol
rac-2c in 88% yield as described for 5-benzyloxy-2-tetralol rac-
7b. TLC (eluent A), Rf = 0.55; 1H NMR (CDCl3) d: 1.61 (s, 1H, OH),
1.80–1.89 (m, 1H, H-3a), 2.02–2.09 (m, 1H, H-3b), 2.67 (dd, 1H,
J = 17.2, 7.8 Hz, H-1a), 2.82–2.90 (m, 1H, H-4a), 2.95–3.02 (m, 1H,
H-4b), 3.22 (dd, 1H, J = 17.2, 5.2 Hz, H-1b), 4.16–4.22 (m, 1H, H-
2), 5.09 (s, 2H, OCH2), 6.76 (d, 1H, J = 8.1 Hz) and 6.77 (d, 1H,
J = 7.9 Hz) (H-5 and H-7), 7.12 (app.t, 1H, J = 8.0 Hz, H-6), 7.33–
7.48 (m, 5H, aromatic Hs); 13C NMR (CDCl3) d: 27.1 (CH2), 31.0
(CH2), 32.6 (CH2), 67.3 (CH), 69.7 (CH2), 108.4 (CH), 121.1 (CH),
123.6 (C), 126.3 (CH), 127.1 (CH), 127.8 (CH), 128.5 (CH), 137.2
(C), 137.4 (C), 156.7 (C); EI MS m/z (rel. int.) 254 (M+, 10), 162
(40), 91 (100).
column was from Regis Technologies Inc. Optical rotations (aD
were measured in MeOH at 25 °C on a Jasco P-1030 polarimeter.
)
All reagents were of commercial quality or purified prior to use
by standard methods. Lipases from T. lanuginosus (TLL), C. rugosa
(CRL), P. pancreas (PPL) were from Sigma–Aldrich (Milano, Italy).
Lipases from P. cepacia (PCL) and P. fluorescens (PFL) were kindly
donated by Amano Enzyme Inc. (Japan). R. miehei lipase (RML)
(ChirazymeÒ L-9, sol.) was from Roche Diagnostics GmbH
(Germany). Octyl agarose (Octyl Sepharose CL-4B) was from Sig-
ma–Aldrich (Milano, Italy).
4.2.5. 5-Benzyloxy-2-tetralyl butyrate rac-8b
A solution of 5-benzyloxy-2-tetralol rac-7b (510 mg, 2.0 mmol),
triethylamine (0.30 mL, 2.1 mmol) and a catalytic amount of DMAP
in dry CH2Cl2 (10 mL) was treated dropwise with butyryl chloride
(0.3 mL, 2.6 mmol). The reaction mixture was stirred at rt under an
N2 atmosphere until the complete disappearance of the starting
material (TLC analysis, eluent B). Usual work-up afforded 5-benzyl-
oxy-2-tetralyl butyrate rac-8b, pure by TLC, which was used for the
next step without further purification (600 mg, 1.85 mmol, 93%
yield). Rf = 0.76 (eluent B); 1H NMR (CDCl3) d: 0.97 (t, 3H,
J = 7.3 Hz), 1.63–1.73 (m, 2H) and 2.31 (t, 2H, J = 7.5 Hz) (Hs of
CH3CH2CH2 moiety), 1.93–2.09 (m, 2H, H2-3), 2.79–2.00 (m, 3H,
H2-4 and H-1a), 3.14 (dd, 1H, J = 16.6, 4.80 Hz, H-1b), 5.10 (s, 2H,
OCH2), 5.21–5.26 (m, 1H, H-2), 6.74 (d, 1H, J = 8.2 Hz) and 6.77
(d, 1H, J = 7.7 Hz) (H-6 and H-8), 7.1 (app.t, 1H, J = 8.0 Hz, H-7),
7.35–7.48 (m, 5H, aromatic Hs); 13C NMR (CDCl3) d: 13.6 (CH3),
18.5 (CH2), 20.8 (CH2), 27.4 (CH2), 34.7 (CH2), 36.5 (CH2), 69.3
(CH), 69.8 (CH2), 108.6 (CH), 121.7 (CH), 124.9 (C), 126.4 (CH),
127.1 (CH), 127.8 (CH), 128.5 (CH), 135.3 (C), 137.4 (C), 156.2 (C),
173.4 (C); EI MS m/z (rel. int.) 324 (M+, 1), 236 (20), 91 (100).
4.2. Synthesis of substrates
5-Hydroxy-2-tetralone 6b and 8-hydroxy-2-tetralone 6c were
prepared from 6-methoxy- 4b and 7-methoxy-1-tetralone 4c,
respectively, as described in Ref. 15. 1-Methylphenethyl butyrate
9 and 2-tetralyl butyrate 1a were prepared as reported in Ref. 22.
4.2.1. Racemic 5-hydroxy-2-tetralol rac-2b
To a solution of 5-hydroxy-2-tetralone 6b (1.35 g, 8.3 mmol) in
anhydrous MeOH (100 mL) at 0 °C under N2, NaBH4 (600 mg,
15.9 mmol) was added portion wise. The reaction mixture was
allowed to warm to rt, stirred for 3 h (TLC control) and then
quenched by the addition of acetone (3 mL), water (100 mL) and
a few drops of concd HCl. After removal of MeOH under reduced
pressure, the remaining aqueous phase was extracted with EtOAc
(3 ꢁ 100 ml). The organic extracts were dried (Na2SO4), evaporated
under reduced pressure, and the residue was purified by flash
chromatography (eluent A) to give racemic 5-hydroxy-2-tetralol
rac-2b as a white solid (1.28 g, 7.8 mmol, 94% yield). TLC (eluent
A), Rf = 0.32; 1H NMR, 13C NMR and EI MS as in Ref. 15.
4.2.6. 8-Benzyloxy-2-tetralyl butyrate rac-8c
The title compound was prepared from 8-benzyloxy-2-tetralol
rac-7c in 94% yield as described above for 5-benzyloxy-2-tetralyl
butyrate rac-8b. Rf = 0.78 (eluent B); 1H NMR (CDCl3) d: 0.94
(t, 3H, J = 7.1 Hz), 1.59–1.71 (m, 2H) and 2.25 (t, 2H, J = 7.3 Hz)
(Hs of CH3CH2CH2 moiety), 1.90–2.03 (m, 2H, H2-3), 2.77 (dd,
1H, J = 17.5 and 6.6 Hz, H-1a), 2.82–2.97 (m, 2H, H2-4), 3.11 (dd,
1H, J = 17.5 and 5.4 Hz, H-1b), 5.06 (s, 2H, OCH2), 5.24–5.29 (m,
1H, H-2), 6.73 (d, 1H, J = 8.1 Hz) and 6.74 (d, 1H, J = 7.7 Hz) (H-5
and H-7), 7.12 (app.t, 1H, J = 7.9 Hz, H-6), 7.30–7.46 (m, 5H, aro-
matic Hs); 13C NMR (CDCl3) d: 13.4 (CH3), 18.3 (CH2), 26.3 (CH2),
27.3 (CH2), 28.8 (CH2), 36.4 (CH2), 69.1 (CH), 69.5 (CH2), 108.2
4.2.2. Racemic 8-hydroxy-2-tetralol rac-2c
The title compound was prepared by NaBH4 reduction of 8-hy-
droxy-2-tetralone 6c in 91% yield as described above for 5-hydro-
xy-2-tetralol rac-2b. TLC (eluent A), Rf = 0.29; 1H NMR, 13C NMR
and EI MS as in Ref. 15.
4.2.3. 5-Benzyloxy-2-tetralol rac-7b
To a stirred solution of 5-hydroxy-2-tetralol rac-2b (1.0 g,
6.1 mmol) in dry CH3CN (100 mL), K2CO3 (840 mg, 6.1 mmol) and
benzyl bromide (0.73 mL, 6.1 mmol) were added, and the reaction