6
P. Borowiecki et al. / Tetrahedron: Asymmetry xxx (2013) xxx–xxx
20A UV detector and Chiralcel OD-H (Diacel) chiral column using
mixtures of n-hexane/isopropyl alcohol as the mobile phase in
appropriate ratios given in the Experimental; HPLC analyses were
carried out in an isocratic manner; flow (f) is given in mL/min;
retention times (tR) are given in minutes under the indicated con-
ditions; racemic alcohols and esters were used as standards. Opti-
cal rotations were measured with a AP-300 automatic polarimeter
(ATAGO) in a 0.5 dm long cuvette. UV–vis absorption spectra were
measured with Cary 3 spectrometer (data were collected on di-
luted solutions in quartz spectroscopy cells). 1H and 13C NMR spec-
tra were measured with a Varian Mercury 400BB spectrometer
operating at 400 MHz for 1H and 100 MHz for 13C nuclei, chemical
shifts (d) are given in parts per million (ppm) related to tetrameth-
ylsilane (TMS) as internal standard; signal multiplicity assignment:
s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; coupling
constant (J) are given in Hertz (Hz). Mass spectra were recorded
with a Micro-mass ESI Q-TOF spectrometer at the Mass Spectrom-
etry Laboratory, Institute of Biochemistry and Biophysics (IBB),
PAN. IR spectra of neat samples were recorded on a PerkinElmer
System 2000 FT-IR Spectrometer equipped with a Pike Technolo-
gies GladiATR™ attenuated total reflectance (ATR) accessory with
a monolithic diamond crystal stage and a pressure clamp. Crystal
data for (S)-(ꢀ)-6, ‘C15H14O’: M = 210.26, crystal dimensions
0.48 ꢂ 0.34 ꢂ 0.28 mm3, trigonal, space group P 32 (no. 145),
a = 13.7423(6) Å, b = 13.7423(6) Å c = 5.1880 Å, U = 848.50(9) Å3,
by silica gel column chromatography with hexane/ethyl acetate
(50/20; v/v) thus obtaining white crystals (12.2 g, 97%). Attention:
the product is extremely air- and light-sensitive and should be
stored in toluene solution at low temperature. Generally a made-
up solution should not be kept for more than 24 h, due to the risk
of decomposition. We postulate the ketone could have been stabi-
lized by storing it as a bisulfite adduct17 or with a small amount
(0.1–0.5%) of hydroquinone as is usually performed in the case of
commercially available compounds of this type. Mp 71–72 °C
(lit.:13 mp 70–72 °C after column chromatography over silica gel
using cyclohexane/ether); Rf (20% ethyl acetate/hexane) 0.84; 1H
NMR (400 MHz, CDCl3): d 1.62 (s, 3H), 4.80 (s, 1H), 7.32–7.38 (m,
2H), 7.43–7.54 (m, 4H), 7.81–7.83 (m, 2H); 13C NMR (100 MHz,
CDCl3): d 25.1, 63.2, 120.2, 124.9 (2C), 127.6, 128.2 (2C), 140.8,
141.9, 206.6; HRMS calculated for [M+H]+: m/z 209.0961; found:
209.0676; FTIR
m
max(neat) cmꢀ1: 3035, 1701, 1611, 1447, 1351,
1298, 1202, 1167, 1001, 917, 733, 662, 619, 560, 459, 416; GC
[150–260 °C (10 °C/min)]: tR = 7.47 min.
4.3. Preparation of 1-(9H-fluoren-9-yl)ethanol ( )-4
In a two-necked round bottomed flask 1-(9H-fluoren-9-yl)etha-
none 3 (11.8 g, 56.7 mmol) was dissolved in methanol (80 mL) and
kept under an atmosphere of nitrogen at ice-water temperature.
Next, sodium borohydride (750 mg, 19.8 mmol) was added por-
tionwise with stirring at a rate sufficient enough to maintain the
internal temperature at 5 °C. The reaction mixture was stirred at
0–5 °C for 3 h. Next, the methyl alcohol was evaporated in vacuo,
and the residue was suspended in distilled H2O (50 mL) and ex-
tracted with EtOAc (3 ꢂ 50 mL). The organic layers were combined
and dried over MgSO4. After filtration through a short silica pad
and solvent evaporation, the crude product was purified by recrys-
tallization from cycohexane/toluene (30/10; v/v) mixture, to afford
a white solid (7.4 g, 62%). Mp 106–108 °C (lit.:13 mp 107 °C after
single recrystallization from petrol ether); Rf (20% ethyl acetate/
hexane) 0.51; 1H NMR (400 MHz, CDCl3): d 0.93 (d, J = 6.19 Hz,
3H), 1.82 (s, 1H), 4.17 (d, J = 4.52 Hz, 1H), 4.56 (qd, J = 6.35,
4.52 Hz, 1H), 7.29–7.48 (m, 4H), 7.52–7.56 (m, 1H), 7.71–7.81 (m,
3H); 13C NMR (100 MHz, CDCl3): d 18.6, 54.5, 70.4, 119.8, 119.9,
124.7, 125.6, 126.9, 126.9, 127.4 (2C), 141.6, 141.8, 143.8, 143.9;
HRMS calculated for [M+H]+: m/z 211.1117; found: 193.0772 (qua-
si-molecular ion decomposed very quickly to the dehydration
Z = 3, F(000) = 336, Dc = 1.234 g m3, T = 100(2) K,
l(Cu-Ka) =
0.588 mmꢀ1
,
SuperNova Agilent diffractometer, hmax = 71.08°,
1864 unique reflections. The structure was solved by direct
methods using the SHELXS 9718 program and was refined by full
matrix least—squares on F2 using the program SHELXL 97.19 All
non-hydrogen atoms were refined with anisotropic displacement
parameters. The hydrogen atoms were introduced at geometrically
idealized coordinates with a fixed isotropic displacement parame-
ter equal to 1.2. Refinement converged at R1 = 0.0482, wR2 = 0.1167
for all data and 147 parameters and 1 restrain (R1 = 0.0435,
wR2 = 0.1133 for 1751 reflections with Io >2r(Io)). The goodness-
of-fit on F2 was equal 1.ꢀ0137.
A
weighting scheme
2
w ¼ ½
r
2F2o þ ð0:0418PÞ þ 3:1964Pꢁ where P ¼ ðFo2 þ 2F2c Þ=3 was
used in the final stage of refinement. The residual electron den-
sity = +0.28/ꢀ0.41 eÅꢀ3. Crystallographic data (excluding structure
factors) for the structure reported in this paper have been depos-
ited with the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-931578. Copies of the data can be
obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: +44 1223 336 033; e-mail: depos-
it@ccdc.cam.ac.uk). Three-dimensional X-ray diffraction data were
collected from single crystals of (S)-(ꢀ)-6, which were isolated by
crystallization from a hexane solution at ambient temperature.
Crystals of chiral alcohol (S)-(ꢀ)-6 were grown in Glass Vials PTFE
Lined Cap Clear (V = 4 mL) with a small hole (prepared by a needle)
in silicone septa. ORTEP drawings were made using Ortep3 for
Windows.20
product, 9-ethylidene-9H-fluorene); FTIR
m
max(neat) cmꢀ1: 3403,
3347, 2981, 2894, 1446, 1366, 1320, 1293, 1240, 1074, 949, 867,
736, 659, 637, 560, 540, 431; UV/vis: kmax = 254 nm; HPLC (5% i-
PrOH/hexane; f = 0.7 mL/min; T = 30 °C): tR = 17.694, 20.350 min;
GC [150–260 °C (10 °C/min)]: tR = 7.83 min.
4.4. Preparation of 1-(9H-fluoren-9-yl)ethyl acetate ( )-5
To a solution of 1-(9H-fluoren-9-yl)ethanol ( )-4 (500 mg,
2.38 mmol) and a catalytic amount of 4-(dimethylamino)pyridine
(DMAP, 5 mg) in dry CH2Cl2 (15 mL), acetic anhydride (267 mg,
2.62 mmol) was added with stirring at ice-bath temperature. The
reaction mixture was stirred at RT for 24 h, after which the solvent
residue was evaporated off under reduced pressure, and the reac-
tion was quenched with a saturated NaHCO3 solution (8 mL) and
extracted with CH2Cl2 (3 ꢂ 10 mL). The organic phases were com-
bined, dried over Na 2SO4, and after filtration of the drying agent,
condensed using a rotary evaporator. The crude product was puri-
fied by gradient column chromatography using hexane/ethyl ace-
tate (50/10, 50/20; v/v) as an eluent to afford a yellow oil
(580 mg, 97%). Rf (20% ethyl acetate/hexane) 0.80; 1H NMR
(400 MHz, CDCl3): d 0.74 (d, J = 6.19 Hz, 3H), 2.24 (s, 3H), 4.33 (d,
J = 4.28 Hz, 1H), 5.73 (dd, J = 6.31, 4.17 Hz, 1H), 7.32–7.49 (m,
4H), 7.58–7.61 (m, 1H), 7.71–7.84 (m, 3H); 13C NMR (100 MHz,
4.2. Preparation of 1-(9H-fluoren-9-yl)ethanone 3
9H-Fluorene 1 (10 g, 60 mmol), tert-BuOK (12.15 g, 108 mmol),
and tert-BuONa (1.33 g, 13.8 mmol) were powdered with a mortar
and dissolved in dry diethyl ether (100 mL). Next, ethyl acetate 2
(9 g, 102.1 mmol) was added dropwise and the resulting mixture
was stirred at reflux for 3 h, then cooled to room temperature
and poured into a 2% solution of acetic acid (100 mL). The aqueous
phase was subsequently extracted with diethyl ether (3 ꢂ 50 mL),
and the combined organic phases were washed with saturated
NaHCO3 (50 mL), H2O (50 mL), and dried over anhydrous MgSO4.
After filtering off the drying agent and evaporation of the residue
of solvents under reduced pressure, the crude product was purified