2
792
Q.-L. Zhao et al. / Tetrahedron: Asymmetry 21 (2010) 2788–2793
by filtration through a pad of silica gel and the solvent was removed
in vacuo. The residue was purified by flash chromatography (tolu-
13C NMR (100 MHz, CDCl
24.3, 10.2. Chiraldex A-TA column (50 m ꢂ 0.25 mm I.D.) at
120 °C constant. = 11.52 min for enantiomer (R), and
= 11.79 min for enantiomer (S).
3
) d 211.2, 46.9, 40.5, 39.8, 29.9, 28.3,
ene, R
f
= 0.63) and furnished ligand 2a as a white foamy solid
t
R
20
(
90 mg, 68% yield), mp 131–132 °C. ½
a
ꢃ
¼ ꢁ255 (c 0.4, CH
2
Cl
) d 139.42 (d, J = 6.1 Hz, 1P), 130.60
) d 7.33 (t, J = 8.0 Hz,
2
).
t
R
D
3
1
P NMR (121 MHz, DMSO-d
6
1
15
(
d, J = 6.1 Hz, 1P). HNMR (400 MHz, DMSO-d
6
4.3.2. 3-Ethylcyclopentanone 4b
1
2
1
4
2
1
1
1
1
2
8
H), 6.94–7.27 (m, 9H), 6.89 (d, J = 8.0 Hz, 1H), 6.67 (d, J = 8.0 Hz,
H NMR (400 MHz, CDCl
3
) d 2.23–2.38 (m, 2H), 2.03–2.16 (m,
H), 5.48 (s, 1H), 4.54 (m, 1H), 4.35 (t, J = 2.8 Hz, 1H), 4.25 (m, 1H),
.21 (d, J = 11.2 Hz, 1H), 3.89 (d, J = 10.0 Hz, 1H), 3.78 (dd, J = 10.0,
.8 Hz, 1H), 2.30–2.83 (m, 12H), 2.08–2.16 (m, 4H), 1.66–1.72(m,
3H), 1.73–1.80 (m, 1H), 1.40–1.50 (m, 3H), 0.92 (t, J = 7.6 Hz, 3H).
1
3
C NMR (100 MHz, CDCl
12.1. Chiraldex A-TA column (50 m ꢂ 0.25 mm I.D.) at 120 °C con-
stant. t = 10.58 min for enantiomer (R), and t = 10.19 min for
3
) d 219.8, 44.9, 38.9, 38.4, 29.1, 28.4,
2H), 1.43–1.51 (m, 4H). 13C NMR (100 MHz, DMSO-d
6
) d 155.9,
R
R
45.5, 145.4, 137.9, 137.2, 137.0, 134.8, 134.7, 133.8, 133.6, 129.6,
29.5, 129.4, 129.2, 128.6, 128.5, 128.4, 127.1, 126.6, 121.8, 118.8,
enantiomer (S).
1
4d
18.7, 118.2, 96.2, 73.9, 73.0, 71.5, 70.1, 69.1, 69.0, 28.4, 28.3, 27.2,
4.3.3. 3-Ethylcycloheptanone 4c
+
1
2.0, 21.9, 21.8. HRMS (ESI) calcd for:
83.3159, found: 883.3148, 1.2 ppm.
C
52
H
53
O
P
9 2
(M+H)
3
H NMR (400 MHz, CDCl ) d 2.36–2.49 (m, 4H), 1.85–1.94 (m,
3H), 1.54–1.67 (m, 2H), 1.22–1.45 (m, 4H), 0.90 (t, J = 7.6 Hz, 3H).
1
3
C NMR (100 MHz, CDCl
28.6, 24.4, 11.4. CP-Chirasil-Dex CB (25 m ꢂ 0.25 mm I.D.) at
120 °C constant. = 13.70 min for enantiomer (R), and
R
t = 13.31 min for enantiomer (S).
3
) d 214.9, 49.6, 43.9, 37.7, 36.5, 30.1,
0
0
4
8
.2.2. 2,4-Bis{[(S)-1,1 -H -binaphthyl-2,2 -diyl] phosphite}-
phenyl 3,6-anhydro-b-
D
-glucopyranoside 2b
t
R
0
0
(
S)-1,1 -H
8
-Binaphthyl-2,2 -diyl-chlorophosphine 6b was syn-
thesized by the same procedure as that for 6a and was used di-
rectly in the following step without further purification.
1
4d
4.3.4. 3-Methylcyclohexanone 4d
1
Treatment of compound
1
2
5
(72 mg, 0.3 mmol), 6b (430 mg,
.2 mmol) and DMAP (8 mg, 0.066 mmol) as described for ligand
a afforded ligand 2b, which was purified by flash chromatography
= 0.45) to produce a white foamy solid (120 mg, 45%
H NMR (300 MHz, CDCl
3
) d 2.18–2.41 (m, 3H), 2.01–2.09 (m,
2H), 1.83–1.95 (m, 2H), 1.59–1.74 (m, 1H), 1.24–1.40 (m, 1H),
1.02 (d, J = 6.3 Hz, 3H). C NMR (75 MHz, CDCl
41.1, 34.2, 33.3, 25.3, 22.1. CP-Chirasil-Dex CB (25 m ꢂ 0.25 mm
I.D.) at 70 °C constant. t = 37.36 min for enantiomer (R), and
= 39.01 min for enantiomer (S).
1
3
3
) d 212.0, 50.0,
(
toluene, R
f
2
D
0
31
yield), mp 136 °C;
(
(
2
1
½
a
ꢃ
¼ þ230 (c 0.4, CH
2
Cl
) d 136.75 (s, 1P), 136.30 (s, 1P). H NMR
) d 7.31 (t, J = 7.8 Hz, 2H), 7.25 (t, J = 7.5 Hz,
H), 6.90–7.07 (m, 7H), 6.83 (d, J = 8.1 Hz, 1H), 6.73 (d, J = 7.8 Hz,
H), 5.46 (d, J = 1.2 Hz, 1H), 4.36 (s, 2H), 4.20–4.24 (d, 2H), 3.87
2
);
P
NMR
R
1
121 MHz, DMSO-d
300 MHz, DMSO-d
6
t
R
6
1
5
4.3.5. 3-Phenylcyclohexanone 4e
1
H NMR (400 MHz, CDCl
3
) d 7.31–7.35 (m, 2H), 7.21–7.25 (m,
(
2
d, J = 10.2 Hz, 1H), 3.68 (d, J = 8.1 Hz, 1H), 2.56–2.76 (m, 12H),
3H), 2.97–3.05 (m, 1H), 2.34–2.59 (m, 4H), 2.06–2.18 (m, 2H),
1.79–1.91 (m, 2H). C NMR (100 MHz, CDCl ) d 211.2, 144.4,
3
128.7, 126.7, 126.6, 49.0, 44.8, 41.2, 32.8, 25.6. HPLC (Daicel Chiral-
1
3
13
.06–2.17 (m, 4H), 1.63–1.71 (m, 12H), 1.35–1.51 (m, 4H).
) d 156.2, 145.4, 137.9, 136.9, 134.7,
33.7, 129.5, 129.2, 129.1, 128.6, 128.5, 127.1, 126.9, 122.1,
18.8, 118.2, 116.3, 97.0, 75.0, 74.9, 72.7, 72.1, 70.3, 69.8, 28.4,
C
NMR (75 MHz, DMSO-d
6
1
1
2
8
cel OD-H 25 cm ꢂ 4.6 mm I.D., Hexane/i-PrOH = 99.2/0.8, flow
R
rate = 0.5 mL/min at 20 °C, detected at 209 nm): t = 36.98 min
+
7.2, 27.1, 21.9, 21.8. HRMS (ESI) calcd for: C52
83.3159, found: 883.3140, 2.2 ppm.
H
53
O
9
P
2
(M+H)
R
for enantiomer (R), and t = 34.29 min for enantiomer (S).
1
4d
4
.3.6. 1,3-Diphenyl-1-pentanone 4f
1
4
.3. Representative procedure for the 1,4-addition of
H NMR (400 MHz, CDCl
J = 7.2 Hz, 1H), 7.53 (d, J = 7.6 Hz, 2H), 7.16–7.30 (m, 5H), 3.22–
.30 (m, 3H), 1.76–1.84 (m, 1H), 1.60–1.70 (m, 1H), 0.80 (t,
3
) d 7.90 (d, J = 7.2 Hz, 2H), 7.53 (d,
diethylzinc to 2-cyclohexenone 3a
3
1
3
A solution of (CuOTf)
0.02 mmol, 17.7 mg) in THF (4 mL) was stirred for 1 h at rt under
nitrogen. After the solution was cooled to 0 °C, 2-cyclohexenone
0.5 mmol, 0.048 mL) was added and the solution was stirred for
0 min at 0 °C. Then ZnEt (1.2 mmol, 1.2 mL of 1.0 M solution in
hexane) was added dropwise using a syringe within 2 min. After
h, the reaction was quenched by H O (2 mL) and 2 M HCl (2 mL),
and extracted with ethyl acetate (5 mL ꢂ 3). The combined organic
layer was washed with saturated NaHCO solution, brine, and then
dried over anhydrous Na SO , filtered and concentrated in vacuo
ꢀC
2 6
H
6
(0.005 mmol, 2.5 mg) and ligand 2a
3
J = 7.6 Hz, 3H). C NMR (100 MHz, CDCl ) d 199.2, 144.7, 137.3,
(
132.9, 128.5, 128.4, 128.0, 127.6, 126.3, 45.6, 43.0, 29.2, 12.1. HPLC
(Daicel Chiralcel AD-H 25 cm ꢂ 4.6 mm I.D., Hexane/i-PrOH = 95/5,
flow rate = 0.5 mL/min at 25 °C, detected at 254 nm):
(
1
2
t
R
R
= 16.75 min for enantiomer (R), and t = 14.90 min for enantio-
mer (S).
4
2
1
0e
4.3.7. 3-(4-Chlorophenyl)-1-phenylpentanone 4g
1
3
3
H NMR (400 MHz, CDCl ) d 7.89 (d, J = 7.2 Hz, 2H), 7.54 (d,
2
4
J = 7.6 Hz, 1H), 7.43 (d, J = 7.6 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H),
7.16 (d, J = 8.4 Hz, 2H), 3.24 (s, 3H), 1.74–1.81 (m, 1H), 1.57–1.64
to obtain the crude product. The conversion and the yield were
determined by GC equipped with a SE-30 column (30 m ꢂ 0.32 mm
I.D.) using dodecane as an internal standard. The enantiomeric ex-
cess was determined by GC analysis with a Chiraldex A-TA column
1
3
3
(m, 1H), 0.80 (t, J = 7.6 Hz, 3H). C NMR (100 MHz, CDCl ) d
198.8, 143.1, 137.1, 133.0, 131.9, 129.0, 128.6, 128.5, 128.0, 45.4,
42.4, 29.2, 12.0. HPLC (Daicel Chiralcel AD-H 25 cm ꢂ 4.6 mm
I.D., Hexane/i-PrOH = 95/5, flow rate = 0.5 mL/min at 25 °C, de-
(
50 m ꢂ 0.25 mm I.D.). The absolute configuration was determined
by comparison with authentic samples. The crude product was
purified by column chromatography on silica gel (200–300 mesh)
tected at 254 nm):
R
t = 18.49 min for enantiomer (R), and
t
R
= 14.79 min for enantiomer (S).
(
4
Petroleum ether/EtOAc, 20/1)and the product3-ethylcyclohexanone
a was obtained as a colorless oil. The characterization data and
analytic conditions of the 1,4-adducts are as follows.
1
4d
4.3.8. 3-(4-Methoxyphenyl)-1-phenylpentanone 4h
1
3
H NMR (400 MHz, CDCl ) d 7.89 (d, J = 7.2 Hz, 2H), 7.52 (d,
J = 7.2 Hz, 1H), 7.42 (d, J = 7.6 Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H),
6.82 (d, J = 8.4 Hz, 2H), 3.77 (s, 3H), 3.18–3.24 (m, 3H), 1.73–1.79
(m, 1H), 1.58–1.64 (m, 1H), 0.80 (t, J = 7.6 Hz, 3H). C NMR
4
.3.1. 3-Ethylcyclohexanone 4a15
1
13
H NMR (400 MHz, CDCl
3
) d 2.15–2.38 (m, 3H), 1.82–2.01 (m,
3
H), 1.52–1.69 (m, 2H), 1.19–1.34 (m, 3H), 0.84 (t, J = 7.6 Hz, 3H).
3
(100 MHz, CDCl ) d 199.4, 157.9, 137.3, 136.7, 132.9, 128.5,