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+66 (c = 1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer. (5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-10-(4-methoxy-
1H NMR (400 MHz, CDCl3): δ = 7.72 (d, J = 7.6 Hz, 2 H), 7.51 (d, J =
7.2 Hz, 1 H), 7.26–7.45 (m, 8 H), 7.06 (t, J = 7.2 Hz, 2 H), 5.95 (t, J =
11.6 Hz, 1 H), 5.20 (d, J = 11.6 Hz, 1 H), 3.91–3.98 (m, 1 H), 3.14 (t,
J = 14.4 Hz, 1 H), 2.40 (s, 3 H), 1.81 (dd, J = 14.4, 4.0 Hz, 1 H), 1.75
(s, 1 H), 1.24 (s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 172.6,
phenyl)-4,6-dimethyl-9-nitro-2-phenyl-2,3-diazaspiro[4.5]dec-
3-en-1-one (4am): Yellow solid, 54 % yield, m.p. 93–96 °C. [α]D20
=
+65.2 (c = 1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer.
1H NMR (400 MHz, CDCl3): δ = 7.68 (d, J = 8.4 Hz, 2 H), 7.40 (t, J =
8.0 Hz, 2 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.4 Hz, 2 H), 7.23
161.2, 137.6, 137.0, 134.2, 133.8, 133.2, 130.2, 129.2, 129.1, 129.0, (t, J = 7.6 Hz, 1 H), 7.13 (d, J = 7.6 Hz, 2 H), 6.67 (d, J = 8.8 Hz, 2 H),
128.2, 128.1, 126.1, 125.3, 119.8, 90.0, 72.5, 66.1, 44.0, 43.1, 40.9, 5.94 (t, J = 11.6 Hz, 1 H), 4.23 (d, J = 12.0 Hz, 1 H), 3.83 (ddd, J =
25.8, 17.8 ppm. HRMS (ESI): m/z calcd. for C28H26BrClN3O4 [M + H]+ 3.2, 11.6, 4.4 Hz, 1 H), 3.68 (s, 3 H), 3.10 (dd, J = 14.4, 13.6 Hz, 1 H),
582.0790; found 582.0782. HPLC analysis (Chiralpak AD-H column, 2.24 (s, 3 H), 1.75 (dd, J = 14.4, 4.4 Hz, 1 H), 1.70 (s, 1 H), 1.21 (s, 3
hexane/2-propanol, 98:2, flow rate: 1.0 mL/min, wavelength: H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 172.7, 160.9, 159.7, 137.8,
220 nm): Rt = 61.35 min (major, major diastereomer).
137.1, 133.7, 129.2 129.0, 128.9, 126.0, 125.1, 119.8, 114.3, 90.4, 72.3,
66.1, 55.1, 46.1, 43.2, 40.9, 26.0, 17.4 ppm. HRMS (ESI): m/z calcd.
for C29H29ClN3O5 [M + H]+ 534.1790; found 534.1798. HPLC analysis
(Chiralpak AD-H column, hexane/2-propanol, 97:3, flow rate: 1.0 mL/
min, wavelength: 220 nm): Rt = 27.48 (major, minor diastereomer)
and 52.76 min (major, major diastereomer).
(5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-4,6-dimethyl-9-
nitro-2-phenyl-10-[2-(trifluoromethyl)phenyl]-2,3-diazaspiro-
[4.5]dec-3-en-1-one (4aj): Pale yellow solid, 54 % yield, m.p. 116–
119 °C. [α]D20 = +54.4 (c = 1.0, CHCl3). >20:1 dr, >99 % ee for the
major diastereomer. 1H NMR (400 MHz, CDCl3): δ = 7.73 (d, J =
7.6 Hz, 2 H), 7.63 (d, J = 7.6 Hz, 1 H), 7.60 (dd, J = 8.0, 0.8 Hz, 1 H),
7.44 (t, J = 8.0 Hz, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 7.26–7.35 (m, 5 H),
6.08 (t, J = 11.6 Hz, 1 H), 5.17 (d, J = 11.6 Hz, 1 H), 3.95 (ddd, J =
12.6, 11.2, 4.4 Hz, 1 H), 3.14 (dd, J = 14.4, 13.2 Hz, 1 H), 2.21 (s, 3
H), 1.81 (dd, J = 14.4, 4.8 Hz, 1 H), 1.73 (s, 1 H), 1.23 (s, 3 H) ppm.
13C NMR (100.6 MHz, CDCl3): δ = 172.1, 160.4, 137.4, 136.7, 134.5,
133.9, 129.5, 129.2, 129.0, 128.9, 126.2, 125.9, 119.7, 89.7, 72.3, 65.8,
46.5, 43.1, 40.8, 25.9, 17.4 ppm. HRMS (ESI): m/z calcd. for
(5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-10-(2-methoxy-
phenyl)-4,6-dimethyl-9-nitro-2-phenyl-2,3-diazaspiro[4.5]dec-
3-en-1-one (4an): Yellow solid, 62 % yield, m.p. 171–174 °C. [α]D20
=
+48.8 (c = 1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer.
1H NMR (400 MHz, CDCl3): δ = 7.65 (d, J = 7.6 Hz, 2 H), 7.39 (t, J =
7.6 Hz, 2 H), 7.29–7.37 (m, 5 H), 7.22 (t, J = 7.6 Hz, 1 H), 7.13 (dt, J =
8.0, 1.6 Hz, 1 H), 6.80 (d, J = 8.0 Hz, 1 H), 6.71 (t, J = 7.6 Hz, 1 H),
5.94 (t, J = 11.6 Hz, 1 H), 5.16 (d, J = 12.0 Hz, 1 H), 3.87 (dt, J = 12.4,
4.4 Hz, 1 H), 3.84 (s, 3 H), 3.14 (t, J = 14.0 Hz, 1 H), 2.28 (s, 3 H), 1.78
(dd, J = 14.4, 4.4 Hz, 1 H), 1.73 (s, 1 H), 1.22 (s, 3 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 173.0, 161.6, 156.8, 137.9, 137.0, 133.6,
129.7, 129.1, 129.0, 128.8, 127.6, 125.9, 121.7, 120.9, 120.0, 111.4,
90.2, 72.3, 66.3, 55.6, 43.3, 41.0, 36.8, 25.9, 16.7 ppm. HRMS (ESI):
m/z calcd. for C29H29ClN3O5 [M + H]+ 534.1790; found 534.1794.
HPLC analysis (Chiralpak AD-H column, hexane/2-propanol, 97:3,
flow rate: 1.0 mL/min, wavelength: 220 nm): Rt = 28.07 (major, mi-
nor diastereomer) and 45.190 min (major, major diastereomer).
C
29H26ClF3N3O4 [M + H]+ 572.1558; found 572.1563. HPLC analysis
(Chiralpak OD-H column, hexane/2-propanol, 98:2, flow rate:
1.0 mL/min, wavelength: 220 nm): Rt = 102.62 min (major, major
diastereomer).
(5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-4,6-dimethyl-9-
nitro-2-phenyl-10-(p-tolyl)-2,3-diazaspiro[4.5]dec-3-en-1-one
(4ak): Yellow solid, 65 % yield, m.p. 114–117 °C. [α]D20 = +78 (c =
1
1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer. H NMR
(400 MHz, CDCl3): δ = 7.68 (dd, J = 8.4 Hz, 2 H), 7.41 (t, J = 7.6 Hz,
2 H), 7.35 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.4 Hz, 2 H), 7.24 (t, J =
7.2 Hz, 1 H), 7.09 (br. s, 2 H), 6.95 (d, J = 7.6 Hz, 2 H), 5.97 (t, J =
11.6 Hz, 1 H), 4.25 (d, J = 12.0 Hz, 1 H), 3.83 (dt, J = 12.0, 4.0 Hz, 1
H), 3.10 (t, J = 13.6 Hz, 1 H), 2.25 (s, 3 H), 2.20 (s, 3 H), 1.75 (dd, J =
13.6, 3.6 Hz, 1 H), 1.73 (s, 1 H), 1.20 (s, 3 H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 172.7, 161.0, 138.6, 137.8, 137.0, 133.7,
130.1, 129.6, 129.1, 129.0, 128.9, 126.0, 119.9, 90.3, 72.2, 66.0, 46.4,
43.2, 40.8, 25.9, 21.0, 17.4 ppm. HRMS (ESI): m/z calcd. for
(5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-4,6-dimethyl-9-
nitro-2-phenyl-10-(thiophen-2-yl)-2,3-diazaspiro[4.5]dec-3-en-
1-one (4ao): Yellow solid, 62 % yield, m.p. 173–175 °C. [α]D20 = +65.2
1
(c = 1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer. H
NMR (400 MHz, CDCl3): δ = 7.75 (dd, J = 8.4, 1.2 Hz, 2 H), 7.42 (t,
J = 7.6 Hz, 2 H), 7.30–7.34 (m, 4 H), 7.24 (t, J = 7.6 Hz, 1 H), 7.10 (d,
J = 5.2 Hz, 1 H), 6.91 (dd, J = 3.6, 1.2 Hz, 1 H), 6.79 (dd, J = 4.8,
3.6 Hz, 1 H), 5.91 (t, J = 11.6 Hz, 1 H), 4.61 (d, J = 11.2 Hz, 1 H), 3.81
(ddd, J = 13.2, 11.6, 4.4 Hz, 1 H), 3.04 (dd, J = 14.4, 13.6 Hz, 1 H),
2.28 (s, 3 H), 1.80 (s, 1 H), 1.73 (dd, J = 14.4, 4.4 Hz, 1 H), 1.22 (s, 3
H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 172.2, 160.8, 137.5, 137.1,
135.1, 133.8, 129.2, 129.0, 128.9, 127.2, 127.0, 126.0, 125.9, 119.7,
91.4, 72.3, 66.2, 43.1, 41.9, 40.6, 26.0, 17.3 ppm. HRMS (ESI): m/z
calcd. for C26H25ClN3O4S [M + H]+ 510.1249; found 510.1253. HPLC
analysis (Chiralpak AD-H column, hexane/2-propanol, 98:2, flow
rate: 1.0 mL/min, wavelength: 220 nm): Rt = 34.13 (major, minor
diastereomer), 43.11 (minor, minor diastereomer), 76.68 (minor, ma-
jor diastereomer) and 112.23 min (major, major diastereomer).
C
29H29ClN3O4 [M + H]+ 518.1841; found 518.1843. HPLC analysis
(Chiralpak OD-H column, hexane/2-propanol, 95:5, flow rate:
1.0 mL/min, wavelength: 220 nm): Rt = 20.24 (minor, major dia-
stereomer) and 26.28 min (major, major diastereomer).
(5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-4,6-dimethyl-9-
nitro-2-phenyl-10-(o-tolyl)-2,3-diazaspiro[4.5]dec-3-en-1-one
(4al): Yellow solid, 46 % yield, m.p. 95–98 °C. [α]D20 = +54.8 (c = 1.0,
CHCl3). >20:1 dr, 98 % ee for major diastereomer. 1H NMR (400 MHz,
CDCl3): δ = 7.75 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 7.6 Hz, 2 H), 7.39 (d,
J = 8.0 Hz, 2 H), 7.32 (d, J = 8.4 Hz, 2 H), 7.26–7.31 (m, 2 H), 7.06–
7.11 (m, 2 H), 6.95 (t, J = 7.2 Hz, 1 H), 6.01 (t, J = 11.2 Hz, 1 H), 4.83
(d, J = 11.6 Hz, 1 H), 3.88 (dt, J = 12.0, 4.0 Hz, 1 H), 3.15 (t, J = (5S,6R,8S,9S,10S)-8-(4-Chlorophenyl)-6-hydroxy-6-methyl-9-
14.0 Hz, 1 H), 2.47 (s, 3 H), 2.23 (s, 3 H), 1.82 (s, 1 H), 1.78 (dd, J =
14.4, 4.4 Hz, 1 H), 1.23 (s, 3 H) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 173.1, 160.7, 137.8, 137.1, 136.4, 133.7, 132.0, 131.6, 129.1, 129.0,
128.9, 128.4, 126.6, 126.3, 126.0, 119.9, 90.5, 72.7, 66.2, 43.6, 41.1,
40.9, 25.9, 19.6, 17.0 ppm. HRMS (ESI): m/z calcd. for C29H29ClN3O4
nitro-2,10-diphenyl-4-propyl-2,3-diazaspiro[4.5]dec-3-en-1-one
(4ap): Yellow solid, 48 % yield, m.p. 170–173 °C. [α]D20 = +51.6 (c =
1
1.0, CHCl3). >20:1 dr, >99 % ee for the major diastereomer. H NMR
(400 MHz, CDCl3): δ = 7.67 (d, J = 8.0 Hz, 2 H), 7.40 (t, J = 7.6 Hz, 2
H), 7.36 (d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.4 Hz, 2 H), 7.16–7.26 (m,
[M + H]+ 518.1841; found 518.1849. HPLC analysis (Chiralpak OD-H 6 H), 5.98 (t, J = 11.6 Hz, 1 H), 4.29 (d, J = 11.6 Hz, 1 H), 3.84 (dt,
column, hexane/2-propanol, 95:5, flow rate: 1.0 mL/min, wave- J = 11.6, 4.0 Hz, 1 H), 3.13 (t, J = 14.4 Hz, 1 H), 2.63–2.72 (m, 1 H),
length: 220 nm): Rt = 20.14 (minor, major diastereomer) and
31.56 min (major, major diastereomer).
2.43–2.51 (m, 1 H), 1.76 (dd, J = 14.4, 4.4 Hz, 1 H), 1.67–1.74 (m, 1
H), 1.66 (s, 1 H), 1.38–1.47 (m, 1 H), 1.22 (s, 3 H), 0.93 (t, J = 7.6 Hz,
Eur. J. Org. Chem. 2016, 1165–1172
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim