The Journal of Organic Chemistry
Article
mL, 1.17 mmol) by General Procedure A (2.3 equiv on InCl ) was
obtained 20 (19.0 mg, 59%) as a colorless oil.
Modified Radical−Ionic Annulation of N-Acylhydrazones
(General Procedure B). General Procedure A was employed, with
the following modification: The reaction mixture was irradiated for
23−24 h. After filtration of the crude product through silica gel, the
3
18
(
S)-4-Benzyl-3-((R)-2-isopropylpyrrolidin-1-yl)oxazolidin-2-
one (21). From hydrazone 19 (31.8 mg, 0.11 mmol) and 2-
iodopropane (0.11 mL, 1.13 mmol) by General Procedure A (2.2
fraction eluting with 0.8:1 hexane/Et O was concentrated in vacuo and
2
equiv of InCl ) was obtained 21 (27.7 mg, 85%) as colorless crystals.
then heated with NaI (2.5 equiv) in refluxing CH CN (0.3 M) for 1−2
3
3
23
Mp 59−62 °C; [α] +79.3 (c 0.595, CHCl ); IR (film from CDCl )
d. After concentration, the residue was partitioned between Et O and
D
3
3
2
−1 1
3
032, 2950, 2872, 1753, 1213, 1103, 1029 cm ; H NMR (500 MHz,
H O. The organic phase was dried (Na SO ), concentrated, and
2
2
4
CDCl ) δ 7.33−7.15 (m, 5H), 4.12−4.06 (m, 1H), 4.00−3.92 (m,
purified by radial chromatography (hexane/Et O).
3
2
2
H), 3.67 (ddd, J = 3.3, 6.9, 9.2 Hz, 1H), 3.45 (dd, J = 2.7, 13.0 Hz,
H), 3.27 (ddd, J = 8.1, 8.1, 8.1 Hz, 1H), 3.18 (ddd, J = 3.3, 7.5, 10.9
(S)-4-Benzyl-3-((R)-2-ethylpiperidin-1-yl)oxazolidin-2-one
(28a). From hydrazone 1a (28.0 mg, 0.12 mmol) and 1-chloro-4-
iodobutane (0.15 mL, 1.23 mmol) by General Procedure B (2.3 equiv
1
Hz, 1H), 2.53 (dd, J = 10.3, 13.2 Hz, 1H), 1.96−1.81 (m, 3H), 1.75−
.66 (m, 1H), 1.58−1.52 (m, 1H), 0.90 (d, J = 6.8 Hz, 3H), 0.89 (d, J
7.0 Hz, 3H); 13C NMR (125 MHz, CDCl ) δ 156.3, 136.2, 128.9,
1
of InCl
(16.4 mg, 47%) as a yellow oil. [α]
from CDCl ) 3032, 2938, 2848, 1757, 1397, 1230, 1082, 1025 cm ;
H NMR (500 MHz, CDCl ) δ 7.33−7.15 (m, 5H), 4.16 (dd, J = 8.7,
3
, omitting the NEt step from the workup) was obtained 28a
3
24
=
D
+13.3 (c 0.77, CHCl ); IR (film
3
3
−
1
1
28.7, 127.0, 67.4, 65.1, 58.1, 49.3, 39.3, 28.8, 23.0, 22.8, 20.2, 15.2;
3
+
1
HRMS (ESI) m/z calcd for C H N O ([M + H] ) 289.1916, found
3
17
25
2
2
2
89.1916. The structural assignment was confirmed by X-ray
8.7 Hz, 1H), 4.00 (dd, J = 6.7, 8.9 Hz, 1H), 3.92−3.86 (m, 1H), 3.58−
3.54 (m, apparent t, J = 11.5 Hz, 1H), 3.45 (dd, J = 3.7, 13.3 Hz, 1H),
3.35−3.31 (m, 1H), 2.98−2.95 (m, 1H), 2.58 (dd, J = 10.8, 13.2 Hz,
1H), 1.84−1.81 (m, 1H), 1.70−1.63 (m, 3H), 1.60−1.52 (m, 1H),
1.34−1.25 (m, 2H), 1.22−1.08 (m, apparent qd, J = 3.2, 13.2 Hz, 1H),
crystallography.
(
S)-4-Benzyl-3-((R)-2-isobutylpyrrolidin-1-yl)oxazolidin-2-
one (22). From hydrazone 19 (26.4 mg, 0.094 mmol) and 1-iodo-2-
methylpropane (0.11 mL, 0.94 mmol) by General Procedure A (2.3
0.91 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl ) δ 155.2, 136.2,
equiv of InCl ) was obtained 22 (19.0 mg, 67%) as a white solid.
3
3
[
2
α]D25 +80.3 (c 0.63, CHCl ); IR (film from CDCl ) 3023, 2957,
863, 1752, 1392, 1225, 1102, 1033 cm ; H NMR (500 MHz,
128.9, 128.8, 126.9, 66.8, 61.5, 60.5, 54.6, 38.7, 30.8, 26.5, 25.6, 23.8,
3
3
−1
1
+
9.5; HRMS (ESI) m/z calcd for C H N O Na ([M + Na] )
17
24
2
2
+
CDCl ) δ 7.33−7.16 (m, 5H), 4.13 (dd, J = 8.3, 8.3 Hz, 1H), 3.98 (dd,
311.1735, found 311.1728; calcd for C H N O ([M + H] )
3
17 25 2 2
J = 9.1, 9.1 Hz, 1H), 3.94−3.88 (m, 1H), 3.73−3.67 (m, 1H), 3.45
289.1916, found 289.1912.
(
(
2
1
0
dd, J = 3.3, 13.4 Hz, 1H), 3.27 (ddd, J = 8.2, 8.2, 8.2 Hz, 1H), 3.17
ddd, J = 4.1, 8.4, 8.4 Hz, 1H), 2.53 (dd, J = 10.8, 13.2 Hz, 1H), 2.08−
(S)-4-benzyl-3-((R)-2-decylpiperidin-1-yl)oxazolidin-2-one
(28b). From hydrazone 10 (30.5 mg, 0.089 mmol) and 1-chloro-4-
iodobutane (0.11 mL, 0.89 mmol) by General Procedure B (2.3 equiv
.02 (m, 1H), 1.95−1.87 (m, 1H), 1.84−1.77 (m, 1H), 1.64−1.58 (m,
H), 1.53−1.50 (m, 1H), 1.41−1.33 (m, 1H), 1.24−1.18 (m, 1H),
of InCl
(24.9 mg, 70%) as a colorless oil. [α]
(film from CDCl ) 3026, 2925, 2852, 1755, 1396, 1225, 1084, 1022
cm ; H NMR (500 MHz, CDCl ) δ 7.33−7.16 (m, 5H), 4.17 (dd, J
3
, omitting the NEt step from the workup) was obtained 28b
3
13
23.9
.94 (d, J = 6.6 Hz, 3H), 0.91 (d, J = 6.5 Hz, 3H); C NMR (125
D
+4.02 (c 0.82, CHCl ); IR
3
MHz, CDCl ) δ 156.4, 136.5, 129.0, 129.0, 127.1, 67.6, 58.9, 58.1,
3
3
−
1 1
4
8.4, 44.1, 39.7, 29.5, 26.2, 24.5, 22.2, 21.5; HRMS (ESI) m/z calcd for
3
+
C H N O Na ([M + Na] ) 325.1892, found 325.1887; calcd for
C H N O ([M + H] ) 303.2073, found 303.2065.
= 8.7, 8.7 Hz, 1H), 4.00 (dd, J = 6.6, 9.0 Hz, 1H), 3.89−3.83 (m, 1H),
3.58−3.54 (m, apparent t, 11.1 Hz, 1H), 3.44 (dd, J = 3.6, 13.2 Hz,
1H), 3.41−3.35 (m, 1H), 2.97−2.95 (m, apparent d, J = 10.7 Hz, 1H),
2.57 (dd, J = 10.8, 13.2 Hz, 1H), 1.84−1.80 (m, 1H), 1.69−1.65 (m,
18
26
2
2
+
18
27
2
2
(
S)-4-Benzyl-3-((S)-2-pentylpyrrolidin-1-yl)oxazolidin-2-one
(
23). From hydrazone 19 (30.9 mg, 0.11 mmol) and iodopentane
(
0.14 mL, 1.07 mmol) by General Procedure A (2.2 equiv of InCl )
2H), 1.61−1.55 (m, 2H), 1.36−1.13 (m, 19H), 0.87 (t, J = 6.9 Hz,
3
23
13
was obtained 23 (19.0 mg, 67%) as a colorless oil. [α]D +79.0 (c
3H); C NMR (125 MHz, CDCl ) δ 155.3, 136.4, 129.1, 129.0,
3
0
1
7
1
.765, CHCl ); IR (film from CDCl ) 3027, 2954, 2925, 2856, 1753,
127.1, 67.0, 60.8, 60.7, 54.8, 38.9, 33.3, 32.0, 31.7, 30.3, 29.9, 29.76,
3
3
−1 1
397, 1217, 1099, 1025 cm ; H NMR (500 MHz, CDCl ) δ 7.26−
29.75, 29.5, 26.7, 25.4, 24.0, 22.8, 14.2; HRMS (ESI) m/z calcd for
3
+
.09 (m, 5H), 4.08 (dd, J = 8.0, 8.0 Hz, 1H), 3.93 (dd, J = 9.1, 9.1 Hz,
H), 3.88−3.82 (m, 1H), 3.58−3.52 (m, 1H), 3.36 (dd, J = 3.5, 13.5
C H N O Na ([M + Na] ) 423.2987, found 423.2988; calcd for
25
40
2
2
+
C H N O ([M + H] ) 401.3168, found 401.3176.
25
41
2
2
Hz, 1H), 3.22 (ddd, J = 8.2, 8.2, 8.2 Hz, 1H), 3.08 (ddd, J = 4.1, 8.0,
(S)-4-Benzyl-3-((R)-2-phenethylpiperidin-1-yl)oxazolidin-2-
one (28c). From hydrazone 11 (32.0 mg, 0.10 mmol) and 1-chloro-4-
iodobutane (0.13 mL, 1.04 mmol) by modified general procedure C
8
1
1
.0 Hz, 1H), 2.46 (dd, J = 10.5, 13.3 Hz, 1H), 2.00−1.94 (m, 1H),
.88−1.80 (m, 1H), 1.76−1.67 (m, 1H), 1.66−1.61 (m, 1H), 1.36−
13
.30 (m, 1H), 1.28−1.13 (m, 7H), 0.82 (t, J = 6.5 Hz, 3H); C NMR
and workup C (2.3 equiv of InCl
as a yellow solid. Mp 78−81 °C; [α]
(film from CDCl ) 3027, 2938, 2856, 1757, 1397, 1225, 1078, 1021
cm ; H NMR (500 MHz, CDCl ) δ 7.30−7.12 (m, 10H), 4.10 (dd, J
3
) was obtained 28c (25.9 mg, 68%)
23
(
125 MHz, CDCl ) δ 156.2, 136.3, 128.8, 128.77, 126.9, 67.4, 60.4,
D
+15.0 (c 1.19, CHCl ); IR
3
3
57.9, 48.5, 39.5, 34.5, 32.3, 28.98, 26.1, 22.7, 21.5, 14.0; HRMS (ESI)
3
+
−1 1
m/z calcd for C H N O Na ([M + Na] ) 339.2048, found 339.2039;
calcd for C H N O ([M + H] ) 317.2229, found 317.2224.
3
1
9
28
2
2
+
= 8.9, 8.9 Hz, 1H), 3.97 (dd, J = 6.4, 9.0 Hz, 1H), 3.88−3.82 (m, 1H),
3.60−3.56 (m, 1H), 3.52−3.48 (m, 1H), 3.42 (dd, J = 3.6, 13.2 Hz,
1H), 2.99−2.97 (m, 1H), 2.71 (ddd, J = 5.0, 12.2, 13.5 Hz, 1H), 2.59−
2.54 (m, 2H), 1.97−1.90 (m, 2H), 1.71−1.66 (m, 2H), 1.63−1.56 (m,
19
29
2
2
(
S)-4-Benzyl-3-((S)-2-(4-chlorobutyl)pyrrolidin-1-yl)-
oxazolidin-2-one (24). From hydrazone 19 (39.7 mg, 0.14 mmol)
and 1-chloro-4-iodobutane (0.17 mL, 1.41 mmol) by General
1
3
Procedure A (2.2 equiv of InCl ) was obtained 24 (19.5 mg, 41%)
2H), 1.37−1.24 (m, 2H); C NMR (125 MHz, CDCl ) δ 155.1,
3
3
as a yellow oil. [α]D24 +70.2 (c 0.50, CHCl ); IR (film from CDCl )
142.2, 136.0, 128.9, 128.8, 128.4, 128.2, 126.9, 125.8, 66.7, 60.5 (2C),
3
3
−1 1
3021, 2938, 2868, 1757, 1221, 1086, 1029 cm ; H NMR (500 MHz,
54.6, 38.7, 35.0, 31.7, 31.6, 26.4, 23.8; HRMS (ESI) m/z calcd for
+
CDCl ) δ 7.33−7.16 (m, 5H), 4.13 (dd, J = 8.1, 8.1 Hz, 1H), 3.98 (dd,
C H N O Na ([M + Na] ) 387.2048, found 387.2046; calcd for
23 29 2 2
3
23 28
2
2
+
J = 8.5, 8.5 Hz, 1H), 3.95−3.89 (m, 1H), 3.69−3.63 (m, 1H), 3.55 (m,
apparent t, J = 6.6 Hz, 2H), 3.44 (dd, J = 3.5, 13.4 Hz, 1H), 3.24 (ddd,
J = 8.2, 8.2, 8.2 Hz, 1H), 3.18 (ddd, J = 4.1, 8.1, 8.1 Hz, 1H), 2.53 (dd,
J = 10.5, 13.3 Hz, 1H), 2.09−2.02 (m, 1H), 1.96−1.88 (m, 1H), 1.85−
C H N O ([M + H] ) 365.2229, found 365.2221.
(R)-1-(2-Phenethylpyrrolidin-1-yl)ethanone (29). A mixture of
14 (110.9 mg, 0.316 mmol) and BH ·THF (1 M solution in THF,
3
9.49 mL, 9.49 mmol) was heated to reflux and sealed under a
coldfinger condenser. After heating at reflux for 48 h, additional BH3·
THF (6.3 mL, 6.3 mmol) was added and heating was continued for 72
h. After cooling to rt, 2 M HCl was cautiously added until gas
evolution ceased. The mixture was then made basic by addition of
aqueous 1.25 M KOH and concentrated, and the aqueous residue was
extracted with CH Cl . The organic phase was dried (Na SO ) and
13
1
.70 (m, 4H), 1.56−1.37 (m, 3H), 1.31−1.19 (m, 1H); C NMR
(
125 MHz, CDCl ) δ 156.2, 136.1, 128.9, 128.8, 127.0, 67.4, 60.1,
3
57.9, 48.5, 45.0, 39.4, 33.7, 32.8, 28.9, 23.7, 21.5; HRMS (ESI) m/z
+
37
(
relative intensity) calcd for C H N O ClNa ([M + Na] , Cl)
18 25 2 2
3
61.1473, found 361.1477 (5%); calcd for C H N O ClNa ([M +
18 25 2 2
+
35
Na] , Cl) 359.1502, found 359.1500 (17%); calcd for C H N O Cl
18
26
2
2
2
2
2
4
+
37
(
[M + H] , Cl) 339.1654, found 339.1646 (33%); calcd for
concentrated. After azeotropic removal of moisture by concentration
+
35
C H N O Cl ([M + H] , Cl) 337.1683, found 337.1685 (100%).
from benzene solution, CH Cl (1.46 mL) and acetic anhydride (1.86
18
26
2
2
2
2
6
438
J. Org. Chem. 2015, 80, 6432−6440