10.1002/adsc.201900159
Advanced Synthesis & Catalysis
4.9 Hz, 1H), 2.91 (ddd, J = 17.9, 6.2, 4.7 Hz, 1H), 2.77–2.61
(m, 1H), 2.07–1.90 (m, 1H), 1.77 (dddd, J = 14.4, 10.1, 10.1
4.6 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) major
diastereomer: 172.8 (C), 171.0 (C), 136.5 (C), 135.8 (C),
132.8 (q, JC-F =34.3 Hz, 2CF3), 129.5 (2CH), 129.3 (2CH),
128.9 (CH), 128.8 (2CH), 122.8 (q, JC-F = 273.7 Hz, 2CF3),
122.8 (q, JC-F = 3.7 Hz, CH), 77.2 (CH2), 45.9 (CH), 45.5
(CH), 32.2 (CH2), 21.4 (CH2); minor diastereomer: 172.9
(C), 171.1 (C), 136.5 (C), 136.1 (C), 132.8 (q, JC-F = 34.3
Hz, 2CF3), 129.4 (2CH), 129.3 (2CH), 128.7 (2CH), 128.7
(CH), 132.7 (q, JC-F = 272.7 Hz, 2CF3), 122.8 (q, JC-F = 3.7
Hz, CH), 78.0 (CH2), 44.9 (CH), 43.7 (CH), 31.3 (CH2),
20.4 (CH2). 19F{13C} NMR (282 MHz, CDCl3) major
diastereomer: -62.8; minor diastereomer: -62.9. HPLC:
Chiralpak IF eluted with 9:1 heptane/ethanol at 1 mL/min at
25 ºC, UV detection at 210 nm, retention times: major
diastereomer 13.26 min (major enantiomer) and 6.20 min
(minor enantiomer), minor diastereomer 7.38 min (major
enantiomer) and 8.19 min (minor enantiomer).
55.5 (CH3), 45.1 (CH), 42.9 (CH), 31.2 (CH2), 20.4 (CH2).
HPLC: Chiralpak IF eluted with 1:1 heptane/ethanol at 1
mL/min at 25 ºC, UV detection at 260 and 280 nm, retention
time: major diastereomer 31.31 min (major enantiomer) and
16.87 min (minor enantiomer), minor diastereomer 21.34
min (major enantiomer) and 25.29 min (minor enantiomer).
Compound 4k: Following the general procedure, 3k (54 mg,
0.12 mmol, dr > 20:1, er > 200:1) reacted with DPHB (5 mg,
0.026 mmol) for 15 h to provide 4k (37 mg, 69%, dr = 1.8:1,
er = 75:1 and 6.4:1) as a white solid. Rf = 0.30 (petrol
ether/ethyl acetate, 3:1). HRMS (ESI+) m/z calcd for
+
C19H20BrN4O6 [M+NH4]+ = 479.0561, found = 479.0562.
1H NMR (400 MHz, CDCl3) major diastereomer: 8.32 (d,
J = 8.7 Hz, 2H), 7.52 (d, J = 8.7 Hz, 2H), 7.17 (d, J = 8.8
Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 5.17 (dd, J = 13.5, 7.2 Hz,
1H), 5.04 (dd, J = 13.4, 8.0 Hz, 1H), 4.01 (ddd, J = 7.6, 7.6,
3.6 Hz, 1H), 3.16 (ddd, J = 12.6, 4.9, 3.7 Hz, 1H), 2.98–2.84
(m, 1H), 2.82–2.68 (m, 1H), 2.18–2.11 (m, 1H), 2.08–1.88
(m, 1H); minor diastereomer: 8.32 (d, J = 8.7 Hz, 2H),
7.53 (d, J = 8.7 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 7.13 (d, J
= 8.8 Hz, 2H), 5.12 (dd, J = 13.4, 7.3 Hz, 1H), 4.75 (dd, J =
13.4, 7.6 Hz, 1H), 4.18 (ddd, J = 7.5, 7.5,7.5 Hz, 1H), 3.03
(ddd, J = 10.0, 7.8, 4.8 Hz, 1H), 2.98–2.84 (m, 1H), 2.73 (dd,
J = 12.9, 4.9 Hz, 1H), 2.07–1.90 (m, 1H), 1.76 (dddd, J =
14.7, 10.2, 10.2, 4.7 Hz, 1H). 13C{1H} NMR (100 MHz, d8-
tetrahydrofuran) major diastereomer: 173.3 (C), 171.4 (C),
148.3 (C), 142.7 (C), 137.8 (C), 132.5 (2CH), 131.6 (2CH),
130.9 (2CH), 124.4 (2CH), 122.4 (C), 77.0 (CH2), 44.6
(CH), 45.0 (CH), 33.0 (CH2), 21.4 (CH2); minor
diastereomer: 173.3 (C), 171.4 (C), 148.3 (C), 142.7 (C),
134.5 (C), 132.5 (2CH), 131.5 (2CH), 130.9 (2CH), 124.4
(2CH), 122.4 (C), 78.0 (CH2), 45.3 (CH), 43.3 (CH), 32.0
(CH2), 20.8 (CH2). HPLC: Chiralpak IC eluted with 7:3
heptane/ethanol at 1 mL/min at 25 ºC, UV detection at 280
nm, retention times: major diastereomer 12.64 min (major
enantiomer) and 9.45 min (minor enantiomer), minor
diastereomer 10.38 min (major enantiomer) and 15.81 min
(minor enantiomer).
Compound 4i: Following the general procedure, 3i (65 mg,
0.16 mmol, dr = 26:1, er = 49:1) reacted with DPHB (6 mg,
0.032 mmol) for 48 h to provide 4i (43 mg, 66%, dr = 1.7:1,
er = 12:1 and 19:1) as a white solid. Rf = 0.30 (petrol
ether/ethyl acetate, 2:1). HRMS (ESI+) m/z calcd for C20H20
+
1
N3O6 [M+H]+ = 398.1347, found = 398.1345. H NMR
(400 MHz, CDCl3) major diastereomer: 8.32 (d, J = 8.7
Hz, 2H), 7.25–7.09 (m, 6H), 5.20 (dd, J = 13.3, 7.6 Hz, 1H),
4.99 (dd, J = 13.3, 7.7 Hz, 1H), 4.00 (ddd, J = 7.7, 7.7, 3.6
Hz, 1H), 3.15 (ddd, J = 11.8, 5.2, 3.5 Hz, 1H), 2.82 (ddd, J
= 17.5, 4.4, 4.4 Hz, 1H), 2.72–2.63 (m, 1H), 2.36 (s, 3H),
2.20–2.12 (m, 1H), 2.08–1.94 (m, 1H); minor diastereomer:
8.32 (d, J = 8.7 Hz, 2H), 7.25–7.10 (m, 6H), 5.11 (dd, J =
13.4, 7.4 Hz, 1H), 4.74 (dd, J = 13.4, 7.4 Hz, 1H), 4.13 (ddd,
J = 7.6, 7.6, 7.6 Hz, 1H), 3.04 (ddd, J = 8.7, 7.6, 4.9 Hz, 1H),
2.91 (ddd, J = 18.0, 7.0, 4.7 Hz, 1H), 2.78–2.72 (m, 1H),
2.36 (s, 3H), 2.08–1.94 (m, 1H), 1.77 (dddd, J = 14.0, 9.3,
9.3, 4.8 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3) major
diastereomer: 173.4 (C), 171.4 (C), 148.2 (C), 142.8 (C),
138.2 (C), 135.3 (C), 130.9 (2CH), 130.0 (2CH), 129.4
(2CH), 124.4 (2CH), 77.4 (CH2), 46.7 (CH), 45.3 (CH), 32.9
(CH2), 21.4 (CH2), 20.9 (CH3); minor diastereomer: 173.5
(C), 171.5 (C), 148.2 (C), 142.8 (C), 138.1 (C), 135.1 (C),
130.9 (2CH), 130.0 (2CH), 129.2 (2CH), 124.4 (2CH), 78.5
(CH2), 45.5 (CH), 43.6 (CH), 32.6 (CH2), 20.9 (CH2), 20.8
(CH3). HPLC: Chiralpak ID eluted with 1:1
heptane/ethanol at 1 mL/min at 25 ºC, UV detection at 260
nm, retention time: major diastereomer 17.06 min (major
enantiomer) and 9.31 min (minor enantiomer), minor
diastereomer 13.02 min (major enantiomer) and 11.14 min
(minor enantiomer).
Compound 4l: Following the general procedure, 3l (50 mg,
0.12 mmol, dr > 20:1, er = 39:1) reacted with DPHB (5 mg,
0.026 mmol) for 15 h to provide 4l (22 mg, 44%, dr > 20:1,
er = 50:1) as a white solid. Rf = 0.36 (petrol ether/ethyl
25
acetate, 1:1). []D = +21.7 (c = 0.5, CHCl3). HRMS
+
(ESI+) m/z calcd for C19H20N5O8 [M+NH4]+ = 446.1306,
found = 446.1307. 1H NMR (400 MHz, CDCl3): 8.33 (d,
J = 8.8 Hz, 2H), 8.25 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.8
Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 5.17 (dd, J = 10.8, 3.2 Hz,
1H), 5.14 (dd, J = 10.8, 2.8 Hz, 1H), 4.21 (ddd, J = 7.4, 3.8,
3.8 Hz, 1H), 3.23 (ddd, J = 8.6, 4.6, 4.6 Hz, 1H), 2.97 (ddd,
J = 17.7, 4.4, 2.9 Hz, 1H), 2.80 (ddd, J = 17.7, 13.5, 5.3 Hz,
1H), 2.18 (dddd, J = 13.1, 5.1, 5.1, 2.9 Hz, 1H), 1.94 (dddd,
J = 13.3, 13.3, 13.3, 4.5 Hz, 1H). 13C{1H} NMR (100 MHz,
d6-acetone): 173.7 (C), 172.2 (C), 148.5 (C), 148.4 (C),
146.7 (C), 143.2 (C), 131.4 (2CH), 131.1 (2CH), 124.8
(2CH), 124.6 (2CH), 77.2 (CH2), 46.9 (CH), 44.9 (CH), 33.2
(CH2), 21.1 (CH2). HPLC: Chiralpak IC eluted with 2:2:1
heptane/ethanol/chloroforme at 1 mL/min at 25 ºC, UV
detection at 254 nm, retention time: major enantiomer 10.63
min, minor enantiomer 8.03 min.
Compound 4j: Following the general procedure, 3j (50 mg,
0.12 mmol, dr = 15:1, er > 200:1) reacted with DPHB (5 mg,
0.026 mmol) for 18 h to provide 4j (38 mg, 76%, dr = 2.2:1,
er = 40:1 and 37:1) as a white solid. Rf = 0.28 (petrol
ether/ethyl acetate, 3:1). HRMS (ESI+) m/z calcd for C20H20
+
1
N3O7 [M+H]+ = 414.1296, found = 414.1300. H NMR
(400 MHz, CDCl3) major diastereomer: 8.31 (d, J = 8.7
Hz, 2H), 7.17 (d, J = 8.7 Hz, 2H), 7.16 (d, J = 8.7 Hz, 2H),
6.89 (d, J = 8.7 Hz, 2H), 5.18 (dd, J = 13.3, 7.5 Hz, 1H),
5.00 (dd, J = 13.3, 7.8 Hz, 1H), 3.97 (ddd, J = 7.7, 7.7, 3.6
Hz, 1H), 3.82 (s, 3H), 3.14 (ddd, J = 11.8, 5.1, 3.6 Hz, 1H),
2.82 (ddd, J = 17.4, 4.3, 4.3 Hz, 1H), 2.72 (dddd, J = 12.6,
9.0, 5.8, 5.8 Hz, 1H), 2.22–2.08 (m, 1H), 2.07–1.93 (m, 1H);
minor diastereomer: 8.31 (d, J = 8.7 Hz, 2H), 7.24 (d, J =
8.7 Hz, 2H), 7.14 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz,
2H), 5.09 (dd, J = 13.3, 7.4 Hz, 1H), 4.73 (dd, J = 13.3, 7.5
Hz, 1H), 4.13 (ddd, J = 7.6, 7.6, 7.6 Hz, 1H), 3.81 (s, 3H),
3.02 (ddd, J = 9.0, 9.0, 4.9 Hz, 1H), 2.91 (ddd, J = 17.9, 6.8,
4.8 Hz, 1H), 2.72 (dddd, J = 12.6, 9.0, 5.8, 5.8 Hz, 1H),
2.07–1.93 (m, 1H), 1.77 (dddd, J = 14.1, 9.5, 9.0, 4.8 Hz,
1H). 13C{1H} NMR (100 MHz, CDCl3) major diastereomer:
172.8 (C), 171.1 (C), 159.9 (C), 147.8 (C), 140.8 (C),
130.0 (2CH), 129.9 (C), 127.7 (2CH), 124.6 (2CH), 114.7
(2CH), 77.7 (CH2), 55.5 (CH3), 45.5 (CH), 45.4 (CH), 32.4
(CH2), 21.7 (CH2); minor diastereomer: 172.9 (C), 171.2
(C), 159.8 (C), 147.8 (C), 140.8 (C), 130.0 (2 CH), 129.4
(C), 127.9 (2CH), 124.6 (2CH), 114.9 (2CH), 78.1 (CH2),
Compound 4m: Following the general procedure, 3m (60
mg, 0.16 mmol, dr = 28:1, er = 100:1) reacted with DPHB
(6 mg, 0.032 mmol) for 15 h to provide 4m (41 mg, 68%, dr
= 2.4:1, er = 39:1 and 5.5:1) as a white solid. Rf = 0.30
(petrol ether/ethyl acetate, 3:1). HRMS (ESI+) m/z calcd for
C17H19N4O6S+ [M+NH4]+ = 407.1020, found = 407.1019.
1H NMR (400 MHz, CDCl3) major diastereomer: 8.33 (d,
J = 8.7 Hz, 2H), 7.33–7.30 (m, 1H), 7.24 (d, J = 8.7 Hz, 2H),
7.04–6.94 (m, 2H), 5.23 (dd, J = 13.5, 7.3 Hz, 1H), 4.99 (dd,
J = 13.5, 7.4 Hz, 1H), 4.32 (ddd, J = 7.4, 7.4, 3.3 Hz, 1H),
3.20 (ddd, J = 12.4, 5.2, 3.3 Hz, 1H), 3.01–2.85 (m, 1H),
2.83–2.73 (m, 1H), 2.22–2.14 (m, 1H), 2.08–2.00 (m, 1H);
minor diastereomer: 8.32 (d, J = 8.7 Hz, 2H), 7.33–7.30
(m, 1H), 7.22 (d, J = 8.7 Hz, 2H), 7.04–6.94 (m, 2H), 5.03
(dd, J = 13.1, 8.3 Hz, 1H), 4.83 (dd, J = 10.2, 6.8 Hz, 1H),
4.69 (dd, J = 14.6, 6.5 Hz, 1H), 3.08–3.02 (m, 1H), 3.00–
2.88 (m, 1H), 2.83–2.73 (m, 1H), 2.13–2.09 (m, 1H), 1.95–
7
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