The Journal of Organic Chemistry
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4.9.6. Reductive Ring Opening of trans-16a. The reaction was
carried out according to the general procedure described above, starting
with racemic trans-16a (51.9 mg, 0.15 mmol, 1.0 equiv), SmI2 (6.0
equiv), N,N-dimethylethanolamine (0.18 mL, 1.8 mmol, 12.0 equiv),
and dry THF (1.5 mL for SmI2 and 1.5 mL for aziridine, freshly distilled)
held at 0 °C for 1 h. Purification by silica-gel chromatography (18 × 250
mm, 5:1 hexanes/EtOAc as eluent) afforded 20a as a colorless liquid in
88% isolated yield (45.9 mg, 0.132 mmol). Spectral data for 20a: Rf =
0.25 (1:3 EtOAc/hexanes); 1H NMR (CDCl3, 500 MHz) δ 1.10 (t, 3H,
J = 7.2 Hz), 2.35 (s, 3H), 2.72 (dd, 1H, J = 16, 6.0 Hz), 2.81 (dd, 1H, J =
16, 6.0 Hz), 3.94−4.05 (m, 2H), 4.70 (q, 1H, J = 6.7 Hz), 5.67 (d, 1H, J =
7.5 Hz), 7.06−7.11 (m, 2H), 7.12−7.19 (m, 5H), 7.56−7.60 (m, 2H);
13C NMR (CDCl3, 125 MHz) δ 14.0, 21.4, 41.2, 54.3, 60.9, 126.4, 127.1,
127.7, 128.5, 129.4, 137.5, 139.3, 143.2, 170.6. These data match those
41.9, 49.9, 54.5, 61.0, 126.6, 128.2, 128.9, 140.3, 170.5; IR (thin film)
3277 (br, s), 2955 (w), 1736 (s), 1144 (s) cm−1; HRMS (ESI-TOF) m/
z: [M + H]+ calcd for C16H28NO4SiS+, 358.1508; found, 358.1509; [α]2D0
= −21.7 (c 0.87, CH2Cl2) on 98% ee (S)-21a. Spectral data for 25a: 1H
NMR (500 MHz, CDCl3) δ 0.05 (s, 9H), 1.11−1.16 (m, 2H), 1.24 (t,
3H, J = 7.2 Hz), 3.05−3.10 (m, 2H), 3.90 (s, 2H), 4.16 (q, 2H, J = 7.2
Hz), 4.53 (s, 2H), 7.27−7.36 (m, 5H); 13C NMR (CDCl3, 125 MHz) δ
−2.0, 10.3, 14.2, 46.9, 50.0, 51.8, 61.3, 128.1, 128.5, 128.8, 135.5, 169.6;
IR (thin film) 2955 (w), 1746 (s), 1333 (s), 1142 (s) cm−1; HRMS (ESI-
TOF) m/z: [M + H]+ calcd for C16H28NO4SiS+, 358.1508; found,
358.1530.
4.9.10. Reductive Ring Opening of cis-18a. The general procedure
for the reductive ring opening described above was followed, except that
2.5 equiv of Sml2 and 5 equiv of DMEA were used. Starting from cis-18a
(47 mg, 0.19 mmol), purification of the product by silica-gel
chromatography (18 mm × 300 mm, 1:5 EtOAc/hexanes as eluent)
gave 22a as a colorless semisolid in 52% isolated yield (24 mg, 0.1
mmol), along with the α-amino ester resulting from the cleavage of the
N−C3 bond as a colorless semisolid in 13% isolated yield (6 mg, 0.025
mmol). TLC and spectral data for 22a: Rf = 0.15 (1:5 EtOAc/hexane);
1H NMR (CDCl3, 500 MHz) δ 1.12 (t, 3H, J = 7.1 Hz), 1.98 (s, 3H),
2.77 (dd, 1H, J = 15.4, 6.0 Hz), 2.87 (dd, 1H, J = 15.7, 6.0 Hz), 4.04 (q,
2H, J = 7.1 Hz), 5.36−5.43 (m, 1H), 6.60 (d, 1H, J = 8.0 Hz), 7.20−7.32
(m, 5H). The 1H NMR spectral data match those previously reported
for this compound.13b
4.9.11. Reductive Ring Opening of cis-27a. The general procedure
for the reductive ring opening described above was followed, except that
5.0 equiv of Sml2 and 10 equiv of DMEA were used. Starting from cis-
27a18 (19 mg, 0.10 mmol), purification of the product by silica-gel
chromatography (18 mm × 300 mm, 1:1:4 Et2O/CH2Cl2/hexanes as
eluent) gave 31a as a colorless oil in 75% isolated yield (14.4 mg, 0.0746
mmol). Spectral data for 31a: 1H NMR (CDCl3, 300 MHz,) δ 1.25 (t,
3H, J = 7.1 Hz), 3.39 (s, 2H), 3.78 (s, 2H), 4.17 (q, 2H, J = 7.2 Hz),
7.20−7.35 (m, 5H) (N−H proton not located). The 1H NMR spectral
data match those previously reported for this compound.36
4.9.12. Reductive Ring Opening of cis-29a. The general procedure
for the reductive ring opening described above was followed, except that
5.0 equiv of Sml2 and 10 equiv of DMEA were used. Starting from cis-
29a7a (35 mg, 0.10 mmol), purification of the product by silica-gel
chromatography (18 mm × 300 mm, 1:1:4 Et2O/CH2Cl2/hexanes as
eluent) gave 33a as a colorless oil in 69% isolated yield (25 mg, 0.069
mmol). Spectral data for 33a: 1H NMR (300 MHz, CDCl3) δ 1.17 (t,
3H, J = 7.2 Hz), 3.25 (s, 2H), 3.82 (s, 2H), 4.04 (q, 2H, J = 7.2 Hz), 5.27
(s, 1H), 7.15−7.51 (m, 15H); 13C NMR (75 MHz, CDCl3) δ 14.2, 50.3,
54.9, 59.9, 70.3, 127.0, 127.1, 128.28, 128.33, 128.4, 128.7, 139.2, 142.1,
171.6.
previously reported for this compound.13b The H NMR spectrum of
1
the crude reaction mixture showed the ratio of 20a/24a > 99:1.
4.9.7. Reductive Ring Opening of cis-16b. The general procedure
for the reductive ring opening described above was followed, starting
with aziridine (2R,3R)-16b18 (82% ee, 53.4 mg, 0.15 mmol, 1.0 equiv),
SmI2 (5.0 equiv), N,N-dimethylethanolamine (0.15 mL, 1.5 mmol, 10.0
equiv), and dry THF (1.5 mL for SmI2 and 1.5 mL for aziridine, freshly
distilled) held at 0 °C for 1 h. Purification by silica-gel chromatography
(18 × 250 mm, 5:1 hexanes/EtOAc as eluent) afforded (S)-20b as a
colorless oil in 97% isolated yield (52.1 mg, 0.147 mmol). The optical
purity of (S)-20b was determined to be 84% ee by HPLC analysis
(Chiralcel OD-H column, 98:2 hexanes/iPrOH at 222 nm, flow rate: 1.0
mL/min); retention times: Rt = 12.73 min (major enantiomer (S)-20b)
and Rt = 16.94 min (minor enantiomer (R)-20b). The 1H NMR
spectrum of the crude reaction mixture showed the ratio of 20b/24b >
1
99:1. Spectral data for (S)-20b: Rf = 0.17 (4:1 hexanes/EtOAc); H
NMR (CDCl3, 600 MHz) δ 0.78 (qd, 1H, J = 12.0, 3.2 Hz), 0.87 (qd,
1H, J = 12.0, 3.2), 1.00−1.17 (m, 3H), 1.18 (t, 3H, J = 7.1 Hz), 1.37−
1.45 (m, 1H), 1.54−1.61 (m, 2H), 1.63−1.70 (m, 2H), 1.73−1.81 (m,
1H), 2.25 (dd, 1H, J = 16.0, 5.6 Hz), 2.37 (dd, 1H, J = 16.0, 5.6 Hz), 2.39
(s, 3H), 3.26−3.34 (m, 1H), 4.01 (m, 2H), 5.24 (d, 1H, J = 9.3 Hz), 7.26
(d, 2H, J = 8.1 Hz), 7.72 (d, 2H, J = 8.1 Hz); 13C NMR (CDCl3, 150
MHz) δ 14.1, 21.5, 25.87, 25.93, 26.1, 29.1, 29.3, 35.9, 41.2, 55.5, 60.6,
127.0, 129.6, 138.2, 143.2, 171.6; IR (thin film) 3292 (m), 2928 (vs),
2854 (m), 1734 (vs), 1718 (s), 1456 (m), 1324 (s), 1161 (vs) cm−1;
mass spectrum, m/z (% rel intensity) 354 (MH+) (6.4), 271 (31), 270
(100), 224 (50), 198 (42), 155 (86), 91 (86), 41 (12); Anal. calcd for
C18H27NO4S: C, 61.16; H, 7.70; N, 3.96. Found: C, 61.30; H, 8.12; N,
3.88. [α]2D0 = −10 (c 0.4, EtOAc) on 84% ee (S)-20b.35
4.9.8. Reductive Ring Opening of trans-16b. The reaction was
carried out according to the general procedure described above, starting
with racemic trans-16b (53.3 mg, 0.15 mmol, 1.0 equiv), SmI2 (6.0
equiv), N,N-dimethylethanolamine (0.18 mL, 1.8 mmol, 12.0 equiv),
and dry THF (1.5 mL for SmI2 and 1.5 mL for aziridine, freshly distilled)
held at 0 °C for 1 h. Purification by silica-gel chromatography (18 × 250
mm, 5:1 hexanes/EtOAc as eluent) afforded 20b as a colorless oil in 95%
isolated yield (51.0 mg, 0.144 mmol). The spectral data of 20b are the
same as the product obtained from the reductive ring opening of cis-16b.
The 1H NMR spectrum of the crude reaction mixture showed the ratio
of 20b/24b > 99:1
4.9.13. Reductive Ring Opening of cis-29b. The general procedure
for the reductive ring opening described above was followed, starting
with cis-29b7a (44 mg, 0.12 mmol). Purification of the product by silica-
gel chromatography (18 mm × 300 mm, 1:5 EtOAc/hexanes as eluent)
gave a 1:1.4 mixture of β-amino ester 30b (22% NMR yield) and
1
unreacted cis-29b (31% NMR yield). The H NMR spectrum of the
crude reaction mixture indicated the formation of amine 34 in 39% yield.
Extending the reaction time from 40 min to 2 h for the ring-opening
reaction of cis-29b (42 mg, 0.12 mmol) at room temperature gave 30b
(8.6 mg, 0.024 mmol) in 22% isolated yield and amine 34 in 52%
isolated yield. The unreacted cis-29b was isolated with a 20% recovery.
4.9.9. Reductive Ring Opening of cis-17a. The general procedure
for the reductive ring opening described above was followed, starting
with aziridine cis-17a (53.4 mg, 0.15 mmol, 1.0 equiv), SmI2 (4.0 equiv),
N,N-dimethylethanolamine (0.12 mL, 1.2 mmol, 8.0 equiv), and dry
THF (2.0 mL for SmI2 and 1.5 mL for aziridine, freshly distilled) held at
1
Spectral data for 30b: H NMR (600 MHz, CDCl3) δ 0.90−1.04 (m,
1
2H), 1.05−1.23 (m, 2H), 1.20 (t, 3H, J = 7.1 Hz), 1.45−1.54 (m, 1H),
1.60−1.80 (m, 6H), 2.34 (dd, 1H, J = 14.5, 7.0 Hz), 2.47 (dd, 1H, J =
14.5, 5.3 Hz), 2.77 (dt, 1H, J = 7.0, 5.3 Hz), 4.03−4.14 (m, 2H), 4.94 (s,
1H), 7.15−7.19 (m, 2H), 7.23−7.28 (m, 4H), 7.35−7.41 (m, 4H) (N−
H proton not located); 13C NMR (150 MHz, CDCl3) δ 14.2, 26.5, 26.6,
26.7, 28.4, 29.5, 36.0, 40.9, 56.8, 60.2, 64.1, 126.89, 126.91, 127.4, 127.6,
128.33, 128.34, 144.2, 144.4, 172.9; HRMS (ESI-TOF) m/z: [M + H]+
calcd for C24H32NO2, 366.2433; found, 366.2431. Spectral data for 34:
1H NMR (600 MHz, CDCl3) δ 1.84 (bs, 2H), 5.20 (s, 1H), 7.18−7.23
(m, 2H), 7.26−7.32 (m, 4H), 7.33−7.37 (m, 4H); 13C NMR (150 MHz,
0 °C for 1 h. The H NMR spectrum of the crude reaction mixture
showed that 21a and 25a were present in a ratio of 23:1. Purification by
silica-gel chromatography (18 × 250 mm, 5:1 hexanes/EtOAc as eluent)
afforded (S)-21a as a white solid in 84% isolated yield (45.2 mg, 0.126
mmol) and 25a as a colorless oil in 4% isolated yield (2.0 mg, 0.0056
mmol). Spectral data for 21a: white solid; mp 60−61 °C; 1H NMR (500
MHz, CDCl3) δ −0.14 (s, 9H), 0.75 (td, 1H, J = 14, 4.5 Hz), 0.84 (td,
1H, J = 14, 4.0 Hz), 1.17 (t, 3H, J = 7 Hz), 2.52 (td, 1H, J = 14, 4.5 Hz),
2.63 (td, 1H, J = 14, 4.0 Hz), 2.79−2.90 (m, 2H), 4.08 (qd, 2H, J = 7.2,
1.5 Hz), 4.81−4.90 (m, 1H), 5.57 (d, 1H, J = 8 Hz), 7.24−7.30 (m, 1H),
7.30−7.39 (m, 4H); 13C NMR (CDCl3, 125 MHz) δ −2.2, 10.2, 14.0,
1
CDCl3) δ 59.7, 126.88, 126.92, 128.4, 145.6. The H and 13C NMR
I
dx.doi.org/10.1021/jo501694h | J. Org. Chem. XXXX, XXX, XXX−XXX