ACCEPTED MANUSCRIPT
6
Tetrahedron
(
75 MHz CDCl
27.8, 131.4, 136.1, 136.8, 137.1, 171.1; m/z (%): 470 (5.5,
M+2), 438(35.5), 352 (40), 209(100), 165(17), 55(13).
3
) 20.1, 22.0, 23.1, 24.7, 39.6, 49.8, 65.3, 124.3,
2 2
13.8, 5.1 Hz, CH Ph), 3.73 (2H, t, J 8.9 Hz, OCH ), 3.93 (2H, t, J
1
8.9 Hz, OCH ), 4.26-4.31 (2H, m, NCH) , 7.12-7.38 (14H, m,
Ph), 7.72 (2H, d, J 7.3 Hz, Ph). δ (75 MHz CDCl ) 20.2, 41.5,
2
C
3
67.8, 71.7, 126.2, 126.8, 126.9, 127.8, 128.4, 129.2, 131.9,
(
S,R,S)-6,6'-Dimethyl-biphenyl-2,2'-dicarboxylic acid bis-[(2-
hydroxy-1-i-butyl-ethyl)-amide] (12d): m.p. 66-71 °C; [Found: C,
1.70; H, 8.55; N, 6.05. C28 requires C, 71.76; H, 8.60;
N, 5.98%]; R (100% EtOAc) 0.35; νmax (KBr) 3400, 3200, 1637,
136.8, 138.4, 139.8, 164.7.
3j
(
S,R,S)-2,2'-Bi-o-tolyl-1,1'-dibenzylbis(oxazoline)
72:28; n-hexane/EtOAc) 0.37; δ (300 MHz CDCl
s, MePh), 2.46 (2H, dd, J 13.7, 8.9 Hz, CH Ph), 2.98 (2H, dd, J
Ph), 3.71 (2H, t, J 8.9 Hz, OCH ), 3.96 (2H, t, J
), 4.26-4.31 (2H, m, NCH), 7.02-7.37 (14H, m, Ph),
.64 (2H, d, J 7.4Hz, Ph); δ (75 MHz CDCl ) 20.2, 41.4, 67.8,
(2b):
R
f
7
40 2 4
H N O
(
H
3
) 2.01 (6H ,
f
-
1
2
1
550, 1434 cm ; δ
H
(300 MHz CDCl
), 0.82 (6H, d, J 5.9 Hz, CHMe
), 1.23-1.27 (2H, m, CHMe ), 1.93 (6H, s, PhMe),
.40-3.45 (2H, dd, J 11.1, 5.6, Hz CH OH), 3.51-3.56 (2H, dd, J
1.1, 3.4 Hz, CH OH), 3.89-4.11 (2H, m, NHCH), 7.34-7.38
(75 MHz CDCl ) 20.3,
2.2, 23.1, 24.7, 39.8, 49.6, 65.3, 124.3, 127.8, 131.4, 136.3,
36.8, 137.3, 171.0; m/z (%): 470 (5.5, M+2), 438(35.5), 352
3
) 0.80 (6H, d, J 5.9 Hz,
1
8
7
7
1
3.7, 5.1 Hz, CH
2
2
CHMe
CH
3
1
(
2
2
), 1.14-1.17 (4H, m,
.9 Hz, OCH
2
2
CHMe
2
2
C
3
2
1.6, 126.2, 126.7, 126.9, 127.8, 128.3, 129.1, 131.7, 137.4,
38.4, 139.5, 164.6.
2
6H, m, Ph), 7.44-7.47 (2H, m, NH); δ
C
3
3
j
2
1
(S,S,S)-2,2'-Bi-o-tolyl-1,1'-di i-propyl bisoxazoline (1c):
(68:32; n-hexane/EtOAc) 0.34; δH (300 MHz CDCl ) 0.69-71
Rf
3
(
40), 209 (100), 165 (17), 55 (13).
(12H, s, CHMe ), 1.43-1.52 (2H, m, CHMe ), 1.99 (6H, s, MePh
2
2
)
, 3.61-3.67 (2H, t, J 7.8 Hz, OCH
2
), 3.77-3.85 (2H, dd, J 16.5,
Step 8: Cyclization of diamides were performed in three methods:
7
.4 Hz, NCH), 4.00-4.06 (t, J 7.8 Hz, 2H, OCH
4H, Ph), 7.61-7.64 (d, J 7.36 Hz, 2H, Ph); δ (100 MHz CDCl
18.1, 18.6, 19.4, 20.2, 32.6, 68.9, 72.4, 126.6, 126.8, 127.9,
31.5, 137.3, 139.6, 164.1,
2
), 7.23-7.32 (m,
Method a: Cyclization procedures of bishydroxylamides 11a-d
C
3
)
3
e, j
and 12a-d were performed according to Andrus procedure.
1
3
r,s
Method b: A solution of diamide 11a or 12a (236 mg, 0.5
mmol), triphenylphosphane (0.14 g, 5.2 mmol), triethylamine (69
µL, 0.44 mmol) and tetrachloromethane (50 µL, 0.44 mmol) in
dry acetonitrile (3 mL) was stirred over nigh at room temperature
for 19 h. After being concentrated in vacuum, the residue was
dissolved in CH Cl (5 mL), washed with water (3 mL), dried
3
j
(S,R,S)-2,2'-Bi-o-tolyl-1,1'-di i-propyl bisoxazoline (2c):
(68:32; n-hexane/EtOAc) 0.21; δ (300 MHz CDCl ) 0.69-72
(12H, s, CHMe ), 1.43-1.52 (2H, m, CHMe ), 2.00 (6H, s,
MePh), 3.62-3.67 (2H, t, J 7.9 Hz, OCH ), 3.77-3.86 (2H, m,
NCH), 4.00-4.06 (2H, m, OCH ), 7.23-7.33 (4H, m, Ph),7.61-
R
f
H
3
2
2
2
2
2
2
over anhydrous magnesium sulfate and then concentrated in
vacuum. The residue was purified by silica gel column
chromatography (5:30% EtOAc/n-hexanes) to afford light yellow
products 1a (76 mg, 65%) or 2a (71 mg, 60%). Compounds 1b-d
and 2b-d were synthesized in the similar method.
7.64 (2H, s, Ph); δ (75 MHz CDCl ) 18.6, 19.0, 20.6, 36.5, 70.1,
74.9, 124.2, 126.9, 128.2, 129.6, 136.1, 140.5, 164.3.
C
3
(S,S,S)-2,2'-Bi-o-tolyl-1,1'-di i-butyl bisoxazoline (1d): [Found:
C, 77.79; H, 8.35; N, 6.44. C28 requires C, 77.74; H,
36 2 2
H N O
8
.39; N, 6.48%] R (65:35; n-hexane/EtOAc) 0.35; νmax (KBr)
f
-
1
3
k, 3w-y
3417, 3060, 1647, 1542 cm ; δ (300 MHz CDCl ) 0.80-0.87(m,
H
3
Method c:
bar was charged with diamide 11a or 12a (1.77 g, 3.5 mmol), p-
dimethylamino) pyridine (0.043 g, 0.3 mmol) and CH Cl (10
mL) under N . The flask was placed in ice and triethylamine (2.1
mL, 15.4 mmol) and a solution of p-toluensulfonyl chloride (1.34
g, 7 mmol ) in CH Cl (4 mL) was added to the reaction mixture.
The light yellow clear solution was stirred at room temperature
for 18 h. The reaction mixture was diluted with CH Cl (10 mL)
and washing with saturated aqueous NH Cl (10 mL), two layers
were separated and the aqueous layer was extracted with CH Cl
3 × 8 mL). The extracted organic layers were combined and
A flame–dried round–bottom flask with a stirrer
1
2H, CHMe
CH CHMe
.50 (2H, t, J 6.4 Hz, NCH), 4.00-4.10 (4H, m, OCH
4H, m, Ph), 7.57-7.60 (2H, d, J 7.4 Hz, Ph); δ (75 MHz, CDCl
2
), 0.98-1.03(2H, m, CHMe
2
), 1.18-1.36 (2H, m,
2
2
), 1.47-1.52 (2H, m, CH
2
CHMe
2
), 2.01(6H, s, MePh),
), 7.14-7.37
(
2
2
3
(
2
2
C
3
)
20.9, 22.6, 22.9, 25.6, 45.8, 65.3, 73.2, 126.8, 127.6, 128.5,
131.7, 140.9, 164.3; m/z (%) 433 (100, M+1), 418(35), 306 (42),
234 (29), 91(9), 55(23).
2
2
2
2
4
(
S,R,S)-2,2'-Bi-o-tolyl-1,1'-di i-butyl bisoxazoline (2d): [Found:
C, 77.77; H, 8.36; N, 6.46. C28 requires C, 77.74; H,
8.39; N, 6.48%]; R (65:35; n-hexane/EtOAc) 0.21; ν (KBr)
2
2
36 2 2
H N O
(
f
max
-
1
3
washed with saturated aqueous NaHCO (10 mL), dried over
Na SO and concentrated. The light yellow oil 1a achieved and
2 4
3
6
406, 3060, 1655, 1625 cm ; δ
.6 Hz, CHMe ), 0.83 (6H, d, J 6.6 Hz, CHMe
H
3
(300 MHz CDCl ) 0.80 (6H, d, J
), 1.15-1.32 (2H,
2
2
purified by column chromatography (5-25% EtOAc/n-hexanes)
to afford pure light yellow products 1a (1.58 g, 96 %) and 2a
2 2 2 2
m, CH CHMe ), 1.45-1.55 (2H, m, CH CHMe ), 2.00 (6H, s,
MePh), 3.50 (2H, t, J 6.4 Hz, NCH), 3.97-4.14 (4H, m, OCH
2
),
(
1.48 mg, 90%). Compounds 1b-d or 2b-d were synthesized in
7
.23-7.36 (4H, m, Ph), 7.58 (2H, d, J 6.8 Hz, Ph); δ (62 MHz
C
the similar method.
CDCl ) 22.5, 22.7, 22.9, 25.2, 45.2, 64.9, 73.2, 125.9, 127.0,
3
3
j
128.7, 129.6, 130.0, 141.0, 165.3; m/z (%): 433 (100, M+1),
(
(
S,S,S)-2,2'-Bi-o-tolyl-1,1'-diphenylbis(oxazoline)
70:30; n-hexane/EtOAc) 0.49; δ (300 MHz CDCl
s, Me), 3.86 (2H, t, J 8.3 Hz, OCH ), 4.39 (2H, dd, J 10.1, 8.3
Hz, OCH ), 5.15 (2H, dd, J 10.1, 8.3 Hz, CH Ph), 7.07-7.42 (14,
m, Ph), 7.88 (2H, dd, J 7.6 Hz, Ph); δ (75 MHz CDCl ) 20.3,
9.8, 74.6, 126.7, 126.9, 127.2, 127.4, 127.6, 128.4, 132.1,
36.9, 140.0, 142.7, 165.6.
(1a):
R
f
4
18(35), 306 (42), 234 (29), 91(9), 55(23).
Synthesis of tert-butyl 4-nitrobenzoperoxoate:
p-Nitrobenzoyl chloride (3.2 g, 17.2 mmol) was dissolved in a
H
3
) 2.04 (6H ,
3
k
2
2
2
C
3
round bottom flask (100 mL) containing CH Cl (35 mL). The
2
2
6
1
o
solution was cooled to –20 C and stirred under nitrogen for 15
min. Pyridine (1.7 mL, 20.0 mmol) was added and the reaction
mixture was stirred for 10 min. Then, tert-butyl hydroperoxide
(3.5 mL, 20.0 mmol) was added dropwise to the reaction at –20
3
j
(
(
S,R,S)-2,2'-Bi-o-tolyl-1,1'-diphenylbis(oxazoline) (2a):
70:30; n-hexane/EtOAc) 0.38; δ (300 MHz, CDCl ) 2.07 (6H,
s, Me), 3.77 (2H, t, J 8.4 Hz, OCH ), 4.43 (2H, dd, J 9.3 Hz,
OCH ) 5.16 (2H, dd, J 9.3, 8.4 Hz, CH Ph), 6.91-7.75 (14H, m,
Ph), 7.75 (2H, d, J 7.3 Hz, Ph). δ (75 MHz CDCl ) 20.3, 69.8,
4.7, 125.4, 126.6, 126.9, 127.2, 127.8, 128.0, 128.4, 128.7,
32.0, 137.5, 165.8.
R
f
H
3
o
C, and was stirred for 4 h. Then the reaction solution was diluted
2
2 2
with CH Cl (20 mL), and washed with water (10 mL). The
2
2
organic layer was separated, dried over MgSO , and evaporated
4
C
3
to obtained crude yellow solid product. Purification using flash
chromatography (n-hexane/EtOAc; 90:10) afforded the light
yellow solid product. (3.9 g, 98%). m.p. 75-78 ºC; δ (300 MHz
H
7
1
3
j
(
(
S,S,S)-2,2'-Bi-o-tolyl-1,1'-dibenzylbis(oxazoline) (1b):
72:28; n-hexane/EtOAc) 0.46; δ (300 MHz CDCl ) 1.99 (6H ,
s, MePh), 2.46 (2H, dd, J 13.8, 8.9 Hz, CH Ph), 2.98 (2H, dd, J
R
f
CDCl ) 1.45 (9H, s, Me), 8.14-8.35 (4H, m, Ph).
3
H
3
3
.3. General Procedure for enantioselective allylic oxidation
2
3k
of cycloolefin using tert-butyl 4-nitrobenzoperoxoate: