The Journal of Organic Chemistry
Page 24 of 42
(d, J = 7.6 Hz, 1H), 6.87 (s, 1H), 6.82 (d, J = 8.1 Hz, 1H), 5.74 J = 10.3, 6.0 Hz, 1H), 5.16 (hept, J = 6.2 Hz, 1H), 5.02 (s, 1H),
1
2
3
4
5
6
7
8
(t, J = 7.5 Hz, 1H), 5.07 – 4.96 (m, 2H), 3.17 – 3.05 (m, 2H),
1.07 (dd, J = 14.4, 6.3 Hz, 6H). 13C{1H} NMR (151 MHz,
CDCl3): δ 171.9, 167.8, 144.2, 138.5, 131.6 (q, 2JCF = 32.0 Hz),
3.81 (dd, J = 13.1, 6.0 Hz, 1H), 2.68 (dd, J = 13.0, 10.6 Hz, 1H),
2.26 (s, 3H), 1.37 (d, J = 6.3 Hz, 3H), 1.13 (d, J = 6.2 Hz, 3H).
13C{1H} NMR (151 MHz, CDCl3): δ 171.9, 167.8, 141.6, 133.5,
129.64, 129.61, 129.0, 128.96, 128.91, 126.6, 125.9, 125.3,
122.2, 121.8, 115.2, 77.4, 71.1, 67.5, 42.2, 21.4, 21.1, 20.2.
HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C25H26NO4
404.1856; found 404.1854. HPLC Analysis: Chiralpak IB, 9%
IP/hexanes, continuous flow at 0.4mL/min, 230 nm; tmajor = 21.8
min, tminor = 20.4 min, ee 80%, er 9.7:90.3; [α]D20 = +4.3 (C = 1,
CHCl3). 24n: Physical State: Pink colored foamy gummy sub-
1
129.8, 128.8, 128.7, 125.4, 124.0 (q, JCF = 272.4 Hz), 118.2,
3
3
116.4 (q, JCF = 3.9 Hz), 111.7 (q, JCF = 3.9 Hz), 78.9, 71.4,
66.0, 39.7, 21.1, 21.0. 19F NMR (471 MHz, CDCl3): δ −61.9
(S). HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C21H21F3NO4
408.1417; found 408.1420. HPLC Analysis: Chiralpak ID, 15%
IP/hexanes, continuous flow at 0.6mL/min, 250 nm; tmajor = 16.1
min, tminor = 12.6 min, ee 93%, er 3.4:96.6; [α]D20 = −4.3 (C = 1,
CHCl3).
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20
21
22
23
24
25
26
27
28
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31
32
33
34
35
36
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stance. Rf = 0.48 (20% EtOAc/hexanes). H NMR (600 MHz,
CDCl3): δ 7.96 – 7.92 (m, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.77 –
7.72 (m, 1H), 7.69 (d, J = 7.0 Hz, 1H), 7.58 – 7.50 (m, 3H), 7.08
(d, J = 7.9 Hz, 2H), 6.67 (d, J = 8.1 Hz, 2H), 6.39 (t, J = 7.3 Hz,
1H), 4.98 (hept, J = 6.3 Hz, 1H), 4.86 (s, 1H), 3.36 (dd, J = 13.7,
8.6 Hz, 1H), 3.09 (dd, J = 13.7, 6.3 Hz, 1H), 2.30 (s, 3H), 1.11
(d, J = 6.2 Hz, 3H), 1.03 (d, J = 6.2 Hz, 3H). 13C{1H} NMR
(151 MHz, CDCl3): δ 173.0, 168.3, 141.3, 134.6, 133.8, 130.0,
129.7, 129.33, 129.30, 128.9, 126.7, 126.0, 125.3, 122.5, 122.2,
116.3, 76.8, 71.1, 66.3, 39.3, 21.35, 21.33, 20.58, 20.57. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C25H26NO4 404.1856; found
404.1857. HPLC Analysis: Chiralpak ID, 85% IP/hexanes, con-
Isopropyl-(3S,5R)-3-((3,5-dimethylphenyl)amino)-5-(naphtha-
len-2-yl)-2-oxotetrahydrofuran-3-carboxylate (24k) and Iso-
propyl-(3R,5R)-3-((3,5-dimethylphenyl)amino)-5-(naphthalen-
2-yl)-2-oxotetrahydrofuran-3-carboxylate (24l). The general
procedure (Method A) was followed using 28f (0.32 g, 0.66
mmol) and TsOH•H2O (0.025 g, 0.13 mmol) as starting materi-
als to afford the diastereomeric mixture of γ-lactones (diastere-
1
omeric ratio = 1.8:1, by crude HNMR) (0.25 g, 90 %) which
were separated by using flash column chromatography. 24k:
Physical State: White foamy solid. Rf = 0.42 (15% EtOAc/hex-
anes). 1H NMR (600 MHz, CDCl3): δ 7.93 – 7.89 (m, 2H), 7.87
(d, J = 6.3 Hz, 2H), 7.55 – 7.51 (m, 2H), 7.50 (d, J = 7.7 Hz,
1H), 7.50 (d, J = 7.7 Hz, 1H), 6.30 (s, 2H), 5.94 (dd, J = 10.1,
6.4 Hz, 1H), 5.13 (hept, J = 6.1 Hz, 1H), 4.99 (s, 1H), 3.55 (dd,
J = 13.2, 6.3 Hz, 1H), 2.73 (dd, J = 13.1, 10.5 Hz, 1H), 2.22 (s,
6H), 1.34 (d, J = 6.2 Hz, 3H), 1.13 (d, J = 6.2 Hz, 3H). 13C{1H}
NMR (151 MHz, CDCl3): δ 172.1, 167.8, 143.9, 138.8, 135.3,
133.3, 133.0, 128.9, 128.0, 127.7, 126.63, 126.60, 125.0, 122.9,
121.5, 112.9, 80.0, 71.2, 67.2, 42.2, 21.5, 21.3, 21.1. HRMS
(ESI-TOF) m/z: [M+H]+ Calcd for C26H28NO4 418.2013; found
418.2007. HPLC Analysis: Chiralpak IB, 10% IP/hexanes, con-
tinuous flow at 0.6mL/min, 250 nm; tmajor = 13.4 min, tminor
12.6 min, ee 80%, er 10:90; [α]D20 = +0.8 (C = 1, CHCl3).
Isopropyl-(3S,5R)-5-(4-bromophenyl)-3-((3,5-dime-
=
thylphenyl)amino)-2-oxotetrahydrofuran-3-carboxylate (24o)
and Isopropyl-(3R,5R)-5-(4-bromophenyl)-3-((3,5-dime-
thylphenyl)amino)-2-oxotetrahydrofuran-3-carboxylate (24p).
The general procedure (Method A) was followed using 28c
(0.37 g, 0.72 mmol) and TsOH•H2O (0.027 g, 0.14 mmol) as
starting materials to afford the diastereomeric mixture of γ-lac-
tones (diastereomeric ratio = 1.7:1, by crude 1HNMR) (0.277 g,
85 %) which were separated by using flash column chromatog-
raphy. 24o: Physical State: White solid (m.p. 120 – 122 ˚C); Rf
tinuous flow at 0.4mL/min, 230 nm; tmajor = 19.3 min, tminor
=
20
22.9 min, ee 95%, er 97.3:2.6; [α]D = −14.2 (C = 1, CHCl3).
1
= 0.59 (20% EtOAc/hexanes). H NMR (600 MHz, CDCl3): δ
24l: Physical State: Brown colored viscous gummy liquid. Rf =
1
7.54 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 6.47 (s, 1H),
6.24 (s, 2H), 5.70 (dd, J = 10.2, 6.3 Hz, 1H), 5.08 (hept, J = 6.2
Hz, 1H), 4.92 (s, 1H), 3.48 (dd, J = 13.2, 6.3 Hz, 1H), 2.55 (dd,
J = 13.2, 10.3 Hz, 1H), 2.21 (s, 6H), 1.29 (d, J = 6.3 Hz, 3H),
1.08 (d, J = 6.2 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ
171.8, 167.6, 143.8, 138.8, 137.1, 131.9, 127.3, 122.8, 121.6,
112.9, 79.0, 71.2, 67.1, 42.1, 21.4, 21.3, 21.0. HRMS (ESI-
TOF) m/z: [M+H]+ Calcd for C22H25BrNO4 446.0961; found
446.0961. HPLC Analysis: Chiralpak ID, 90% IP/hexanes, con-
0.37 (15% EtOAc/hexanes). H NMR (600 MHz, CDCl3): δ
7.92 (d, J = 8.5 Hz, 1H), 7.87 (t, J = 10.0 Hz, 3H), 7.57 – 7.46
(m, 3H), 6.56 (s, 1H), 6.33 (s, 2H), 5.86 (t, J = 7.5 Hz, 1H), 5.02
(hept, J = 6.4 Hz, 1H), 4.77 (s, 1H), 3.22 (dd, J = 13.7, 8.2 Hz,
1H), 3.15 (dd, J = 13.8, 7.1 Hz, 1H), 2.28 (s, 6H), 1.07 (d, J =
6.2 Hz, 6H). 13C{1H} NMR (151 MHz, CDCl3): δ 172.6, 168.3,
143.6, 138.9, 136.1, 133.1, 132.9, 128.7, 127.9, 127.6, 126.5,
126.4, 124.6, 122.8, 122.0, 113.7, 79.1, 70.9, 66.3, 39.4, 21.4,
21.1, 21.0. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for
C26H28NO4 418.2013; found 418.2017. HPLC Analysis: Chi-
ralpak IC, 20% IP/hexanes, continuous flow at 0.5mL/min, 250
nm; tmajor = 21.3 min, tminor = 17.7 min, ee 95%, er 2.6:97.3;
[α]D20 = −8.2 (C = 1, CHCl3).
Isopropyl-(3S,5R)-5-(naphthalen-1-yl)-2-oxo-3-(p-tolyla-
mino)tetrahydrofuran-3-carboxylate (24m) and Isopropyl-
(3R,5R)-5-(naphthalen-1-yl)-2-oxo-3-(p-tolylamino)tetrahy-
drofuran-3-carboxylate (24n). The general procedure (Method
A) was followed using 28g (0.42 g, 0.90 mmol) and TsOH•H2O
(0.034 g, 0.18 mmol) as starting materials to afford the diastere-
omeric mixture of γ-lactones (diastereomeric ratio = 1.7:1, by
crude 1HNMR) (0.333 g, 91 %) which were separated by using
flash column chromatography. 24m: Physical State: Yellow
colored foamy gummy substance. Rf = 0.55 (20% EtOAc/hex-
anes). 1H NMR (600 MHz, CDCl3): δ 8.03 (d, J = 8.4 Hz, 1H),
7.92 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 8.2 Hz, 1H), 7.71 (d, J =
7.2 Hz, 1H), 7.62 (t, J = 7.4 Hz, 1H), 7.54 (dt, J = 20.6, 7.6 Hz,
2H), 7.00 (d, J = 8.1 Hz, 2H), 6.61 (d, J = 8.3 Hz, 2H), 6.56 (dd,
tinuous flow at 0.5mL/min, 250 nm; tmajor = 14.4 min, tminor
=
17.3 min, ee 94%, er 97:3; [α]D20 = −12.2 (C = 1, CHCl3). 24p:
Physical State: Beige colored solid (m.p. 145 – 148 ˚C); Rf =
1
0.54 (20% EtOAc/hexanes). H NMR (600 MHz, CDCl3): δ
7.54 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.53 (s, 1H),
6.27 (s, 2H), 5.63 (t, J = 7.5 Hz, 1H), 5.02 (hept, J = 6.2 Hz,
1H), 4.69 (s, 1H), 3.13 (dd, J = 13.8, 8.2 Hz, 1H), 3.00 (dd, J =
13.8, 7.0 Hz, 1H), 2.24 (s, 6H), 1.12 (d, J = 6.3 Hz, 3H), 1.07
(d, J = 6.2 Hz, 3H). 13C{1H} NMR (151 MHz, CDCl3): δ 172.3,
168.2, 143.5, 138.9, 138.0, 131.8, 127.1, 122.4, 122.1, 113.6,
78.2, 71.1, 66.2, 39.4, 21.4, 21.2, 21.0. HRMS (ESI-TOF) m/z:
[M+H]+ Calcd for C22H25BrNO4 446.0961; found 446.0965.
HPLC Analysis: Chiralpak ID, 90% IP/hexanes, continuous
flow at 0.5mL/min, 250 nm; tmajor = 13.8 min, tminor = 12.4 min,
ee 94%, er 3:97; [α]D20 = −5.2 (C = 1, CHCl3).
Isopropyl-(3S,5R)-3-(benzo[d][1,3]dioxol-5-ylamino)-5-(fu-
ran-2-yl)-2-oxotetrahydrofuran-3-carboxylate (24q) and Iso-
propyl-(3R,5R)-3-(benzo[d][1,3]dioxol-5-ylamino)-5-(furan-
23
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