Full Paper
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81
1
4
35.9, 131.3, 128.6, 128.5, 128.3, 128.2, 126.5, 66.5, 50.2, 50.1, 48.8,
(100) [M+H] ( Br); HRMS (FT-MS-ESI): m/z calcd for C H NO Br:
18 23 3
ꢀ
1
+
79
3.9, 25.7, 24.5, 18.9 ppm; IR (KBr): n˜ =1728, 1668 cm ; MS (ESI):
380.0856 [M+H] ( Br); found: 380.0849.
Compound (+)-30h: Colorless oil (63 mg, 18%, >99.5% ee);
+
m/z (%): 324 (100) [M+Na] ; HRMS (FT-MS-ESI): m/z calcd for
C H NO Na: 324.1570 [M+Na] ; found: 324.1562.
+
25
1
1
8
23
3
½aꢁD = +55.78 (c=0.9, CHCl ); H NMR (300 MHz, CDCl ): d=7.37–
3
3
Compound (ꢀ)-30b’: White solid (388 mg, 91%); m.p. 85–868C;
aꢁ =ꢀ68.58 (c=2.0, CHCl ); H NMR (300 MHz, CDCl ): d=7.67 (d,
7.20 (m, 10H), 5.65 (brs, 1H), 5.28 (brs, 1H), 5.19 (dd, J=16.8,
12.0 Hz, 2H), 3.00 (dd, J=58.5, 13.5 Hz, 2H), 2.79–2.73 (m, 1H),
2.51–2.45 (m, 1H), 2.26–2.15 (m, 1H), 2.03–1.92 (m, 1H), 1.79–1.64
2
D
5
1
½
3
3
J=8.3 Hz, 2H), 7.05 (d, J=8.3 Hz, 2H), 5.60–5.51 (m, 2H), 5.46 (brs,
13
1
1
H), 5.32 (brs, 1H), 5.00 (dd, J=62.6, 12.6 Hz, 2H), 2.81–2.75 (m,
(m, 2H), 1.00 ppm (s, 3H); C NMR (75 MHz, CDCl
173.3, 138.0, 135.9, 131.3, 128.6, 128.5, 128.3, 128.2, 126.5, 66.5,
0.2, 50.1, 48.8, 43.9, 25.7, 24.5, 18.9 ppm; IR (KBr): n˜ =1729,
671 cm ; MS (ESI): m/z (%): 352 (100) [M+H] ; HRMS (FT-MS-ESI):
): d=175.2,
3
H), 2.63–2.57 (m, 1H), 2.38–2.19 (m, 2H), 1.94–1.84 (m, 2H), 1.71
13
5
1
(
d, J=4.7 Hz, 3H), 0.91 ppm (s, 3H); C NMR (75 MHz, CDCl ): d=
3
ꢀ
1
+
1
4
73.5, 172.2, 139.0, 137.6, 135.7, 130.0, 125.9, 93.7, 65.4, 55.7, 55.7,
ꢀ1
+
9.8, 24.0, 23.4, 18.1, 13.7 ppm; IR (KBr): n˜ =1729, 1668 cm ; MS
m/z calcd for C22H26NO : 352.1907 [M+H] ; found: 352.1905.
3
+
(
ESI): m/z (%): 450 (100) [M+Na] ; HRMS (FT-MS-ESI): m/z calcd for
+
C H NO NaI: 450.0537 [M+Na] ; found: 450.0529.
1
8
22
3
Preparation of Racemic Esters 30
Compound (ꢀ)-30c: White solid (269 mg, 94%, >99.5% ee); m.p.
26–1278C; ½aꢁ =ꢀ66.08 (c=1.0, CHCl ); H NMR (300 MHz,
A mixture of diamide (1 mmol) in hydrochloric acid (6n, 5 mL) was
heated at 958C until the starting material was consumed. The solu-
tion was basified to pH 5.0 with an aqueous solution of NaOH
2
D
5
1
1
3
CDCl ): d=7.34–7.25 (m, 5H), 5.96 (dd, J=17.4, 10.7 Hz, 1H), 5.70–
3
5
1
.45 (m, 2H), 5.25–5.02 (m, 4H), 2.87–2.80 (m, 1H), 2.67–2.61 (m,
H), 2.39–2.23 (m, 2H), 1.97–1.87 (m, 2H), 0.94 ppm (s, 3H);
(1m). After removal of water, the residue was treated by following
the aforementioned procedure for the esterification of acids from
biotransformations. The following racemic benzyl esters were ob-
tained and they gave identical spectroscopic data to their enan-
tioenriched ones. (ꢂ)-30a: colorless oil (225 mg, 75%); (ꢂ)-30b:
white solid (198 mg, 66%); m.p. 133–1368C; (ꢂ)-30c: white solid
1
3
C NMR (75 MHz, CDCl ): d=173.5, 172.2, 146.0, 135.9, 128.4,
3
1
28.3, 128.2, 115.3, 66.2, 55.6, 55.5, 50.4, 24.2, 23.6, 13.0 ppm; IR
ꢀ1
+
(
KBr): n˜ =1728, 1674 cm ; MS (ESI): m/z (%): 310 (100) [M+Na] ;
+
HRMS (FT-MS-ESI): m/z calcd for C H NO Na: 310.1413 [M+Na] ;
17
21
3
found: 310.1408.
(
186 mg, 65%); m.p. 125–1278C; (ꢂ)-30e: colorless oil (211 mg,
Compound (ꢀ)-30e: Colorless oil (271 mg, 90%, >99.5% ee);
70%); (ꢂ)-30 f: colorless oil (196 mg, 68%); (ꢂ)-30g: white solid
(195 mg, 65%); m.p. 108–1108C; (ꢂ)-30h: colorless oil (273 mg,
78%).
2
D
5
1
½
aꢁ =ꢀ8.68 (c=0.7, CHCl ); H NMR (300 MHz, CDCl ): d=7.37–
3
3
7
2
1
3
1
.25 (m, 5H), 5.50 (brd, J=21.0 Hz, 2H), 5.12 (dd, J=21.3, 12.3 Hz,
H), 2.80–2.74 (m, 1H), 2.57–2.51 (m, 1H), 2.22–2.10 (m, 2H), 1.87–
.82 (m, 2H), 1.61–1.32 (m, 4H), 0.90 (t, J=7.1 Hz, 3H), 0.87 ppm (s,
H); C NMR (75 MHz, CDCl ): d=174.9, 173.7, 136.0, 128.5, 128.3,
28.2, 66.2, 53.1, 51.6, 48.5, 42.2, 26.0, 25.3, 18.5, 17.2, 14.6 ppm; IR
Synthesis of 31
1
3
3
A mixture of (+)-30a (151 mg, 0.5 mmol) in dry CH Cl (30 mL) at
2
2
ꢀ1
+
(
KBr): n˜ =1730, 1667 cm ; MS (ESI): m/z (%): 304 (100) [M+H] ;
HRMS (FT-MS-ESI): m/z calcd for C H NO : 304.1907 [M+H] ;
ꢀ788C was bubbled with oxygen for 10 min followed by O until
3
+
18
26
3
the color of solution became pale blue. After removal of O by
3
found: 304.1903.
bubbling with oxygen for 10 min, the mixture was stirred for an-
other 20 min. Dimethyl sulfide (0.11 mL, 1.5 mmol) was added, and
the reaction temperature was increased gradually to room temper-
ature overnight. The solvent was removed on a rotary evaporator,
Compound (ꢀ)-30 f: Colorless oil (262 mg, 91%, >99.5% ee);
2
D
5
1
½
aꢁ =ꢀ17.58 (c=0.6, CHCl ); H NMR (300 MHz, CDCl ): d=7.37–
3
3
7
2
2
.26 (m, 5H), 5.47 (brs, 2H), 5.12 (s, 2H), 2.80–2.75 (m, 1H), 2.58–
.52 (m, 1H), 2.24–2.11 (m, 2H), 1.88–1.82 (m, 3H), 1.73–1.58 (m,
H), 0.97 (t, J=7.4 Hz, 3H), 0.87 ppm (s, 3H); C NMR (75 MHz,
and the residue was dissolved in dry CH Cl2 (6 mL). At ꢀ788C,
2
13
Et SiH (0.12 mL, 0.75 mmol) and BF ·OEt (0.16 mL, 1.25 mmol)
3
3
2
were added consecutively. The reaction mixture was stirred at
CDCl ): d=174.8, 173.7, 136.0, 128.5, 128.2, 128.2, 66.2, 52.3, 50.8,
3
ꢀ
1
ꢀ788C for 3 h and then at room temperature overnight. The reac-
4
8.6, 31.9, 25.9, 25.3, 18.4, 8.3 ppm; IR (KBr): n˜ =1728, 1664 cm ;
+
tion was quenched by adding a saturated solution of NH Cl
MS (ESI): m/z (%): 312 (100) [M+Na] ; HRMS (FT-MS-ESI): m/z calcd
4
+
(20 mL) and extracted with CH Cl (15 mLꢁ3). The combined or-
for C H NO Na: 312.1570 [M+Na] ; found: 312.1563.
2
2
1
7
23
3
ganic phase was dried over anhydrous MgSO . After removal of
4
Compound (+)-30g: White solid (63 mg, 21%, >99.5% ee); m.p.
the solvent, the residue was purified by column chromatography
2
D
5
1
1
10–1118C; ½aꢁ = +10.08 (c=1.0, CHCl3); H NMR (300 MHz,
on silica gel by eluting with ethyl acetate to afford (ꢀ)-31 as
CDCl ): d=7.37–7.30 (m, 5H), 5.88 (brs, 1H), 5.78–5.64 (m, 2H),
25
D
3
a white solid (109 mg, 76%, >99.5% ee). m.p. 120–1228C; ½aꢁ
=
5
1
.08 (s, 2H), 4.95–4.90 (m, 2H), 2.64–2.58 (m, 1H), 2.49–2.43 (m,
H), 2.27–2.16 (m, 4H), 1.96–1.91 (m, 2H), 1.34 ppm (s, 3H);
C NMR (75 MHz, CDCl ): d=175.0, 173.9, 135.7, 134.3, 128.6,
1
ꢀ
8.08 (c=1.2, CHCl ); H NMR (300 MHz, CDCl ): d=7.45–7.33 (m,
H), 5.15 (dd, J=19.1, 12.4 Hz, 2H), 3.37–3.33 (m, 2H), 2.72 (t, J=
.2 Hz, 1H), 2.38 (dd, J=12.0, 8.0 Hz, 1H), 2.19–2.10 (m, 3H), 1.92–
.75 (m, 4H), 0.74 ppm (s, 3H); C NMR (75 MHz, CDCl ): d=173.2,
73.0, 137.6, 129.3, 129.2, 128.9, 66.6, 54.7, 53.3, 44.6, 40.4, 35.5,
3.9, 21.7, 14.1 ppm; IR (KBr): n˜ =1731, 1668 cm ; MS (ESI): m/z
%): 288 (100) [M+H] ; HRMS (FT-MS-ESI): m/z calcd for C H NO :
3
3
5
9
1
1
2
1
3
3
1
28.4, 128.3, 117.9, 66.4, 57.8, 54.9, 48.0, 37.0, 27.1, 25.9, 25.4 ppm;
13
ꢀ
1
+
3
IR (KBr): n˜ =1727, 1667 cm ; MS (ESI): m/z (%): 302 (100) [M+H] ;
HRMS (FT-MS-ESI): m/z calcd for C H NO : 302.1751 [M+H] ;
+
18
24
3
ꢀ1
found: 302.1749.
Compound (+)-30g’: White solid (76 mg, 20%); m.p. 118–1198C;
+
(
1
7
22
3
+
288.1594 [M+H] ; found: 288.1592.
2
D
5
1
½
(
(
aꢁ = +58.58 (c=1.5, CHCl3); H NMR (300 MHz, CDCl ): d=7.58
3
d, J=7.9 Hz, 1H), 7.45–7.42 (m, 1H), 7.35–7.30 (m, 1H), 7.23–7.18
m, 1H), 5.88–5.64 (m, 3H), 5.17 (dd, J=17.6, 12.9 Hz, 2H), 4.95–
Synthesis of 32
4
4
.90 (m, 2H), 2.67–2.62 (m, 1H), 2.50–2.44 (m, 1H), 2.28–2.19 (m,
H), 1.98–1.92 (m, 2H), 1.37 ppm (s, 3H); C NMR (75 MHz, CDCl3):
Biotransformation of diamide 17 (210 mg, 1 mmol) followed by
esterification with CH N gave crude product 30a’. Resulting 30a’
13
2
2
d=174.9, 173.6, 135.1, 134.3, 132.9, 130.4, 129.9, 127.5, 123.8,
was mixed with DMF (4 mL) and SOCl (0.4 mL). After stirring at
2
1
1
17.9, 66.0, 57.7, 55.0, 48.0, 36.9, 27.0, 25.8, 25.3 ppm; IR (KBr): n˜ =
728, 1666 cm ; MS (ESI): m/z (%): 380 (100) [M+H] ( Br), 382
room temperature for 3 h, water (4 mL) was added, and mixture
was extracted with ethyl acetate (5 mLꢁ3). The combined organic
ꢀ1
+
79
Chem. Asian J. 2014, 9, 1 – 11
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ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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