Notes
J . Org. Chem., Vol. 61, No. 12, 1996 4183
(87.6), 153.7 (155.2) (diastereomers + rotamers); mass spectrum
characteristic of enecarbamate 5 was obtained.
C4H9). Anal. Calcd for C9H15O2N: C, 63.91; H, 8.88. Found:
C, 63.81; H, 8.89.
N-(ter t-Bu toxyca r bon yl)-3-m eth ylp ip er id in -2-ol. Proce-
dure a was followed which upon purification by MPLC gave 85%
yield of a 64:36 mixture of diastereomers as a colorless oil: IR
(neat) 3429, 1685, cm-1; 1H NMR δ 1.42 (1.44) (d, J ) 8.3 Hz, 3
H), 1.44 (1.36) (br s, 11 H), 1.55-1.72 (m, 2 H), 1.80-1.97 (m, 1
H), 2.91-3.11 (m, 1 H), 3.63-3.72 (m, 1 H), 5.27 (br s, 1 H),
5.44 (br s, 1 H); 13C NMR δ 17.9, 25.3, 25.66 (26.0), 28.3, 35.3,
38.6 (38.7), 74.1, 79.7 (79.8), 155.2 (diastereomers); mass spec-
trum characteristic of enecarbamate 6 was obtained.
N-(ter t-Bu toxyca r bon yl)-1,2,3,4-tetr a h yd r op yr id in e (2).
Procedures A and B gave satisfactory yields (90-95%). Purifica-
tion by FCC gave an analytically pure sample (90%) of 2 as a
colorless oil: IR (neat) 1709, 1659 cm-1 1H NMR δ 1.42 (s, 9
;
H), 1.66-1.80 (m, 2 H), 1.90-2.00 (m, 2 H), 3.41-3.55 (m, 2 H),
4.66-4.77 (4.78-4.90) (m, 1 H), 6.65 (6.77) (br d, J ) 8.0 Hz, 1
H); 13C NMR 21.4 (21.6), 28.2, 41.3, 42.4, 80.3, 105.0 (105.4),
125.2 (125.5), 152.2 (for pair of rotamers); mass spectrum, m/z
(relative intensity) EI 183 (09, M+) 127 (59, M+ - C4H8), 110
(20, M+ - C4H9O), 82 (58, M+ - C4H9O2), 57 (100, C4H9). Anal.
Calcd for C10H17O2N: C, 65.56; H, 9.29. Found C, 65.30; H, 9.29.
N-(ter t-Bu toxyca r bon yl)-3-a llylp yr r olid in -2-ol. Both pro-
cedures a and b gave a colorless oil in 88% yield upon MPLC
purfication (68:32 mixture of diastereomers): IR (neat) 3438,
N-(ter t-Bu toxyca r bon yl)-4,5,6,7-tetr a h yd r oa zep in e (3).
Procedure A was followed, and the reaction mixture was heated
for 1 h. Purification by FCC gave 3 in 77% yield as a colorless
1702, 976, 915 cm-1 1H NMR δ 1.47 (1.44, 1.50) (br s, 11 H),
;
1.97-2.36 (m, 4 H), 3.33-3.50 (m, 2 H), 4.05 (3.16) (br s, 1 H),
5.00-5.14 (m, 2 H), 5.72-5.88 (m, 1 H); 13C NMR δ 27.6, 28.3,
37.2, 44.6 (44.7), 45.2 (45.4), 80.0 (80.3, 81.3), 85.7 (85.9), 116.5
(116.0), 135.9 (136.6), 155.1 (153.3) (diastereomers + rotamers);
mass spectrum characteristic of enecarbamate 7 was obtained.
1
oil: IR (neat) 1702, 1659 cm-1; H NMR δ 1.48 (s, 9 H), 1.63-
1.83 (m, 4 H), 2.13-2.21 (m, 2 H), 3.61-3.70 (m, 2 H), 4.90-
5.00 (m, 1 H), 6.48 (br s, 1 H); 13C NMR 26.1, 28.0, 28.3, 38.9,
46.8, 80.1, 113.9, 130.5, 153.6; mass spectrum, m/z (relative
intensity) EI 197 (13, M+), 141 (78, M+ - C4H8), 124 (15, M+
-
N-(ter t-Bu toxyca r bon yl)-3-a llylp ip er id in -2-ol. Procedure
a was followed which on purification gave a colorless oil in 88%
yield (60:40 mixture of diastereomers): IR (neat) 3435, 1702,
991, 912 cm-1; 1H NMR δ 1.44 (1.47) (br s, 11 H), 1.63-2.22 (m,
4 H), 2.25-2.42 (m, 1 H), 3.10-3.22 (m, 1 H), 3.39-3.58 (m, 1
H), 3.80 (3.08) (s, 1 H), 4.91-5.10 (m, 2 H), 5.20 (5.30) (s, 1H),
5.70-5.88 (m, 1H); 13C NMR δ 27.5, 28.3, 32.7, 43.1, 44.0, 44.9
(45.2), 79.8 (80.1), 81.3, 115.5 (115.7), 136.7 (136.8) 154.9 (153.3)
(diastereomers); mass spectrum characteristic of enecarbamate
8 was obtained.
Deh yd r a t ion of La ct a m ols in H MP A.17 P r oced u r e A.
The reaction was carried out by modification of Monson’s
procedure. HMPA (5.0 mL) was added via syringe to a dry 25
mL flask containing lactamol (1.0 mmol) under N2. The flask
was heated in an oil bath at 160-180 ˚C for 1-5 h depending
upon the type of lactamol. Increasing the oil bath temperature
to >210 ˚C may lead to undesired decomposition products. The
progress of the reaction is accompanied by a color change from
colorless to a pale or dark yellow solution, and the reaction can
be monitored by TLC (10% ethyl acetate/petroleum ether). After
the mixture was cooled to rt, saturated NH4Cl was added and
the aqueous layer was extracted with ether (4 × 10 mL). The
combined organic phase was washed with saturated NH4Cl (4
× 20 mL) to remove residual HMPA, dried over K2CO3, and
concentrated in vacuo. Purification of enecarbamates by silica
gel chromatography gave analytically pure samples.
Deh yd r a t ion of La ct a m ols w it h MsCl/DMAP /E t3N.14
P r oced u r e B. To a stirred solution of lactamol (1.0 mmol) in
CH2Cl2 (5 mL) were added triethylamine (3.0 mmol) and DMAP
(5 mg, 4 mol %). The mixture was cooled to -5 ˚C in an ice
bath, and MsCl (1.5 mmol) was added dropwise to the solution.
The mixture was stirred for 1-4 h depending upon the type of
substrate. The reaction was quenched with saturated NH4Cl
solution and extracted with CH2Cl2. The organic phase was
washed with saturated NH4Cl (4 × 10 mL), water, dried over
K2CO3, and concentrated in vacuo.
Deh yd r a tion in Ac2O/DMAP /ba sic Al2O3.16 P r oced u r e
D. To a stirred solution of lactamol (1.0 mmol) in dry ether (10
mL) at rt under N2 were added anhydrous acetic anhydride (15.0
mmol) and catalytic amount of DMAP. The reaction mixture
was stirred for 3 h. After removal of solvent in vacuo, the crude
acetate was dissolved in CH2Cl2 and treated with DMAP (1.5
mmol)/basic alumina (0.3 g) and heated to reflux for 10 h. The
alumina was then filtered off and the organic layer washed with
water, dried over K2CO3, and concentrated in vacuo. Purifica-
tion by silica gel column chromatography gave an analytically
pure sample.
C4H9O) 96 (17, M+ - C4H9O2), 57 (100, C4H9). Anal. Calcd for
C
11H19O2N: C, 67.00; H, 9.65. Found: C, 66.75; H, 9.75.
Eth yl N-(ter t-Bu toxyca r bon yl)-(S)-(-)-2-p yr r olin e-5-ca r -
boxyla te (4). Procedure A gave crude material in 80% yield
which upon FCC afforded pure 4 in 70% yield as a colorless oil:
1
IR (neat) 2987 (s), 1761 (s), 1719 (s) 1634 (m) cm-1; H NMR δ
1.18 (t, J ) 6.0 Hz, 3 H), 1.34 (1.39) (s, 9 H), 2.58 (t, J ) 15.0
Hz, 1 H), 2.98 (q, J ) 15.0 Hz, 1 H), 4.20 (q, J ) 6.9 Hz, 1 H),
4.41-4.61 (m, 1 H), 4.86 (d, J ) 13.2 Hz, 1 H), 6.55 (6.42) (br s,
1 H); 13C NMR δ 13.9 (14.0), 27.9 (28.1), 34.1 (35.3), 57.7 (58.2),
60.9, 80.6 104.8, 129.8 (129.9), 151.2, 171.4 (171.7) (pair of
rotomers); mass spectrum m/z (relative intensity) EI 241 (1.6,
M+), 185 (M+ - C4H8), 168 (M+ - C4H9O), 141 (9, M+ - C5H8O2),
112 (5, M+ - C7H13O2), 96 (M+ - C7H13O3), 68 (100, M+
-
C8H13O4). Anal. Calcd for C12H19O4: C, 59.75; H, 7.88.
Found: C, 59.86: H, 7.98.
N-(ter t-Bu toxyca r bon yl)-3-m eth yl-2-p yr r olin e (5). Pro-
cedure A was followed, and the reaction mixture was heated for
1 h. Purification by FCC gave 5 in 85% yield as a colorless oil:
IR (neat) 1702 (s), 1628 (m) cm-1; 1H NMR δ 1.42 (s, 9 H), 1.65
(s, 3 H), 2.38-2.55 (m, 2 H), 3.58-3.75 (m, 2 H), 6.11 (6.23) (s,
1 H); 13C NMR δ 13.5, 28.4, 33.1 (34.1), 45.2 (45.7), 79.6, 118.1,
124.1, 151.4 (151.7) (for pair of rotamers); mass spectrum, m/z
(relative intensity) EI 183 (15, M+) 127 (63, M+ - C4H8), 110
(21, M+ - C4H9O), 82 (57, M+ - C4H9O2), 57 (100, C4H9). Anal.
Calcd for C10H17O2N: C, 65.57; H, 9.28; N, 7.65. Found: C.
65.44; H, 9.29; N, 7.55.
N-(ter t-Bu toxyca r bon yl)-3-m eth yl-2-p ip er id in e (6). Pro-
cedure A gave 6 as a colorless oil in 80% yield, and an
analytically pure sample was obtained by passing the crude
product through silica gel contained in a pipette (petroleum
ether): IR (neat) 1702 (s), 1675 (sh, m) cm-1; 1H NMR δ 1.43 (s,
9 H), 1.61 (s, 3 H), 1.72-1.83 (m, 2 H), 1.91 (t, J ) 6.0 Hz, 2 H),
3.36-3.50 (m, 2 H), 6.45 (6.60) (s, 1 H); 13C NMR δ 21.8, 26.7
(26.9), 28.3, 40.8, 41.8, 79.9 (80.0), 113.9 (114.3), 120.0 (120.3),
152.2 (152.7) (for pair of rotamers); mass spectrum, m/z (relative
intensity) EI 197 (16, M+) 141 (100, M+ - C4H8), 124 (17, M+
-
OC4H9), 96 (21, M+ - O2C5H9), 82 (65, M+ - O2C6H11), 57 (64,
C4H9). Anal. Calcd for C12H19O2N: C, 67.00; H, 9.64; N, 7.10.
Found: C, 66.83; H, 9.81; N, 6.84.
N-(ter t-Bu toxyca r bon yl)-3-a llyl-2-p yr r olin e (7). Proce-
dure A was followed and upon purification gave 7 in 80% yield
as a colorless oil: IR (neat) 1702 (s), 1680 (sh, m), 1030 (s), 919
1
(m) cm-1; H NMR δ 1.42 (s, 9 H), 2.41-2.55 (m, 2 H), 2.75 (d,
J ) 6.0 Hz, 2 H), 3.61-3.77 (m, 2 H), 5.05 (br d, J ) 16.5 Hz, 2
H), 5.66-5.86 (m, 1 H), 6.14 (6.29) (s, 1 H); 13C NMR δ 28.4,
32.9, 45.1 (45.6), 79.7, 116.0, 120.7, 124.4, 135.3, 151.5 (151.7)
(for pair of rotamers); mass spectrum, m/z (relative intensity)
EI 209 (14, M+), 194 (2.0, M+), 153 (71, M+ - C4H8), 124 (3.0,
M+ - OC5H9), 108 (34, M+ - O2C5H9), 80 (20, M+ - O2C7H12),
57 (100, C4H9). Anal. Calcd for C12H19O2N: C, 68.89; H, 9.09;
N, 6.69. Found: C, 68.78; H, 9.15; N, 6.63.
N-(ter t-Bu toxyca r bon yl)-2-p yr r olin e (1). Procedure D
was followed, and the reaction mixture was heated at reflux for
16-20 h. Workup and concentration in vacuo followed by
purification via FCC gave a pure analytical sample (40%) of 1
as a colorless oil: IR (neat) 1702, 1628 cm-1; 1H NMR δ 1.44 (s,
9 H), 2.53-2.66 (m, 2 H), 3.61-3.66 (m, 2 H), 4.95 (br d, J )
12.6 Hz, 1 H), 6.41 (6.54) (br s, 1 H); 13C NMR δ 28.2 (28.4),
29.5, 44.6 (45.0), 79.7, 107.3, 129.6, 151.4 (pair of rotamers); mass
spectrum, m/z (relative intensity) EI 169 (10, M+), 113 (36, M+
- C4H8), 96 (22, M+ - C4H9O), 68 (63, M+ - C5H9O2), 57 (100,
N-(ter t-Bu toxyca r bon yl)-3-a llyl-2-p ip er id in e (8). Proce-
dure A was followed, and the reaction mixture was heated for 1
h. An analytically pure sample was obtained by passing the
crude product through pipette filled silica gel column (petroleum