N. Gaggero et al. / Tetrahedron: Asymmetry 22 (2011) 1231–1233
1233
Table 3
used throughout the work. NMR spectra were recorded on a Bruker
AC 300 operating at 300.13 MHz for 1H NMR and 75.3 MHz for 13
HPLC analysis of Michael adducts 11–19
C
Columna
Eluant
tR Major (min)
tR Minor (min)
NMR. Chemical shifts were reported by using CHCl3 as the external
standard (7.24 ppm for 1H NMR and 77.0 for 13C NMR). Optical
rotations were measured with a Perkin Elmer 241 polarimeter;
11a
11b
11c
11d
11e
11g
11h
11i
12a
13a
16a
17a
18a
19a
A
A
A
B
A
A
A
A
A
A
B
B
A
A
1% i-PrOH
1% i-PrOH
1% i-PrOH
1% i-PrOH
1% i-PrOH
2% i-PrOH
1% i-PrOH
1% i-PrOH
2% i-PrOH
2% i-PrOH
1% i-PrOH
1% i-PrOH
1% i-PrOH
1% i-PrOH
11.0
12.0
12.1
25.2
9.0
17.2
9.0
8.5
13.1
13.2
17.1
27.2
10.1
18.1
18.1
9.4
the [a]
values are reported in 10ꢀ1 deg cmꢀ2 gꢀ1, concentration
D
(c) is reported in g per 100 mL. Chiral HPLC separations were per-
formed on a Agilent HP 1100 apparatus, equipped with a diode ar-
ray detector, using mixtures of hexane/2-propanol as eluant,
detection at 230 nm unless otherwise stated. The flux was set to
1 ml minꢀ1 and the volume of injection was 20
lL.
14.2
5.7
17.0
6.1
24.6
38.6
15.2
62.5
18.6
31.4
16.8
59.4
4.2. General procedure for BSA-catalyzed thio-Michael addition
The synthesis of (S)-1,3-diphenyl-3-(p-methoxyphenylsulfa-
nyl)-propan-1-one 11d is typical.
a
A = Chiralcel OD-H; B = Lux cellulose 2.
At first, trans-chalcone 1 (0.208 g, 1 mmol) was added to a mag-
netically stirred solution of BSA (3.30 g, 0.05 mmol) in 12.5 mL of
20 mM sodium tetraborate buffer solution (pH 9). The mixture
was stirred for 30 min, then 4-methoxythiopenol 10d (0.14 g,
1 mmol) was added. The reaction was stirred at room temperature
for 18 h, then extracted with ethyl acetate (4 x 20 mL) and the or-
ganic phase dried (MgSO4) and concentrated under vacuum. The
crude product 11d (0.35 g, yield 99%) obtained was chemically
pure (by 1H NMR). HPLC (Lux Cellulose 2, iPrOH-hexane 1–99) tR
(S) 25.2 min, tR (R) 27.2, ee 70%. The adduct 11d was crystallized
from n-hexane/dichloromethane; concentration of the mother li-
quor allowed us to recover 11d (0.23 g, 66% yield) in 86% ee,
J2 = 8.5 Hz), 6.82 (m, 2H), 7.13–7.53 (m, 10H), 7.86 (d, 2H,
J = 7.3 Hz). 13C NMR (75 MHz, CDCl3): 44.9 (CH2), 46.1 (CH), 55.7
(CH3), 110. 8 (CH), 120.9 (CH), 121.2 (CH), 127.0 (CH), 128.0
(CH), 128.3 (CH), 128.5 (CH), 129.1 (CH), 136.9 (C), 141.2 (C),
159.0 (C), 197.1 (C). ESI-MS m/z 348 (M+Na)+.
References
1. Jacob, C. Nat. Prod. Rep. 2006, 23, 851–863.
2. Jacob, C.; Anwar, A. Physiol. Plant. 2008, 133, 469–480.
3. Inoue, H.; Takeo, S.; Kawazu, M.; Kugita, H. Yakugaku Zasshi 1973, 93, 729–732.
4. Chatgilialoglu, C.; Asmus, K. D. Sulfur-Centered Reactive Intermediates in
Chemistry and Biology; Springer: New York, 1991.
5. Metzner, P.; Thuillier, A. Sulfur Reagents in Organic Synthesis; Academic Press:
New York, 1994.
½
a 2D0
ꢁ
¼ ꢀ100:6 (c 1, CH2Cl2).
All Michael adducts 11–19 are known compounds (except for
11e whose data are reported below) and have been isolated in pure
form (as revealed by NMR comparison to data reported in the liter-
ature) following the general procedure described above. Determi-
nation of ee’s has been performed by HPLC by using Chiralcel
OD-H or Lux Cellulose 2 columns (Table 3).
6. Enders, D.; Lüttgen, K.; Narine, A. A. Synthesis 2007, 959–980.
7. Dai, L.; Wang, S.-X.; Chen, F.-E. Adv. Synth. Catal. 2010, 352, 2137–2141.
8. Suresh, P.; Pitchumani, K. Tetrahedron Asymmetry 2008, 19, 2037–2044.
9. Dzyuba, S. V.; Klibanov, A. Tetrahedron: Asymmetry 2004, 15, 2771–2777.
10. Colonna, S.; Gaggero, N.; Manfredi, A.; Spadoni, M.; Casella, L.; Carrea, G.; Pasta,
P. Tetrahedron 1988, 44, 5169–5178.
_
11. Colonna, S.; Gaggero, N.; Drabowicz, J.; Łyzwa, P.; Mikołajczyyk, M. Chem.
4.2.1. 1,3-Diphenyl-3-(o-methoxyphenylsulfanyl)-propan-1-one
Commun. 1999, 1787–1788.
11e
_
12. Skarzewski, J.; Zielin´ ska-Błajet, M.; Turowska-Tyrk, I. Tetrahedron Asymmetry
Yield 85%, mp >400 °C, ½a D25
ꢁ
¼ ꢀ6:0 (c 0.2, CHCl3). 1H NMR
2001, 12, 1923–1928.
13. Nishimura, K.; Tomioka, K. J. Org. Chem. 2002, 67, 431–435.
(300 MHz, CDCl3): 3.58 (dd, 1H, J1 = 5.6 Hz, J2 = 17.0 Hz), 3.69 (dd,
1H, J1 = 8.5 Hz, J2 = 17.0 Hz), 3.82 (s, 3H), 5.09 (dd, 1H, J1 = 5.6 Hz,