September 2008
1313
1
3
.67 and 3.76—3.84 (each 1H, m, 6-H ), 5.31 (1H, dd, Jꢀ10.8, 7.3 Hz, 3- ylsilyloxy)Butyric Acid (12b) 6.77 g, (78%); colorless oil; H-NMR
2
13
H); C-NMR (CDCl ) d: 20.27 (t), 20.81 (q), 26.23 (t), 27.97 (q), 44.86 (t),
(CDCl ) d: 0.06 and 0.08 (each 3H, s, SiMe ), 0.86 (9H, s, Sit-Bu), 1.55
3 2
3
ꢂ1
6
9.99 (d), 83.40 (s), 152.43 (s), 168.00 (s), 169.96 (s); IR (KBr) cm : 1776, (9H, s, COOt-Bu), 2.49 (2H, d, Jꢀ6.4 Hz, 2-H ), 3.63 and 3.78 (each 1H, dd,
2
ꢃ
1
738, 1722 (CꢀO); MS (EI) m/z: 257 (M ). HR-MS (EI) m/z: 257.1258 Jꢀ13.6, 6.7 Hz and 13.5, 6.6 Hz, 4-H ), 4.30—4.38 (1H, m, 3-H), 9.19 (1H,
2
2
5
13
(
Calcd for C H NO : 257.1263); [a] ꢃ51.4 (cꢀ1.1, CHCl3).
s, CHO), 9.28—10.12 (1H, br, COOH); C-NMR (CDCl ) d: ꢂ5.10 and
tert-Butyl (5R)-5-(tert-Butyldimethylsilyloxy)-2-oxopiperidine-1-carbox- ꢂ4.59 (each s), 17.83 (s), 25.68 (q), 28.06 (q), 40.79 (t), 45.53 (t), 66.59 (d),
ylate (9b): 4.42 g (56%); colorless oil; H-NMR (CDCl ) d: 0.09 (6H, s, 84.53 (s), 152.33 (s), 163.32 (d), 176.54 (s); IR (KBr) cm : 3174 (OH),
SiMe ), 0.89 (9H, s, Sit-Bu), 1.52 (9H, s, COOt-Bu), 1.79—1.88 and 1.92— 1741, 1712, 1697 (CꢀO); MS (FAB) m/z: 362 (MH ); HR-MS (FAB) m/z:
12
19
5
D
3
1
ꢂ1
3
ꢃ
2
2
6
2
.01 (each 1H, m, 4-H ), 2.39—2.47 and 2.67—2.76 (each 1H, m, 3-H ), 362.2002 (Calcd for C H NO Si: 362.1999); [a] ꢂ3.5 (cꢀ1.02, CHCl3).
2 2
16 32 6 D
13
3
.60—3.72 (2H, m, 6-H ), 4.13—4.19 (1H, m, 5-H); C-NMR (CDCl ) d:
(3R)-4-Amino-3-hydroxybutyric Acid (13) A mixture of the imide
(12a, 1 mmol) in 2 M HCl (4 ml) and AcOH (4 ml) was heated at 60 °C under
2
3
ꢂ4.88 (q), 17.99 (s), 25.68 (q), 28.00 (q), 29.00 (t), 31.06 (t), 52.42 (t),
ꢂ1
6
(
4.44 (d), 82.83 (s), 152.49 (s), 170.90 (s); IR (KBr) cm : 1774, 1716 argon atmosphere for 12 h, and concentrated in vacuo. The obtained residue
ꢃ
CꢀO); MS (FAB) m/z: 330 (MH ). HR-MS (FAB) m/z: 330.2103 (Calcd
was desalted by ion-exchange chromatography on a Dowex 50Wꢁ8 (50—
100 mesh, 38 ml, H form) column with 2% NH OH. Concentration of elute
2
4
ꢃ
for C H NO Si: 330.2101); [a] ꢂ8.1 (cꢀ0.95, CHCl3).
16
32
4
D
4
tert-Butyl (3R)-3-(tert-Butyldimethylsilyloxy)-2-oxopiperidine-1-carbox- to dryness to give the crude w-acid, which was recrystallized from
1
28)
ylate (10b): 0.79 g (10%); colorless oil; H-NMR (CDCl ) d: 0.15 and 0.17 water–EtOH. 96 mg (80% from 12a); colorless prisms, mp 211 °C (lit. mp
3
1
(
6H, each s, intensity ratio 9 : 11, SiMe ), 0.90 and 0.91 (9H, each s, inten-
211—213 °C); H-NMR (D O) d: 2.38 (2H, d, Jꢀ6.5 Hz, 2-H ), 2.91 and
2 2
2
sity ratio 4 : 5, Sit-Bu), 1.51 and 1.56 (9H, each s, intensity ratio 4 : 5, COOt- 3.12 (each 1H, dd, Jꢀ13.1, 9.4 Hz and 13.1, 3.2 Hz, 4-H ), 4.11—4.21 (1H,
2
1
3
Bu), 1.71—2.13 (4H, m, 4- and 5-H ), 6-H [2.57—2.66 and 2.84—2.93 m, 3-H); C-NMR (D O) d: 43.19 (t), 44.99 (t), 66.39 (d), 179.42 (s); IR
1H, each m, intensity ratio 2 : 3), 3.58—3.72 (1H, m)], 4.17 and 4.33 (1H, (KBr) cm : 3413 (OH, NH), 1577 (CꢀO); MS (FAB) m/z: 120 (MH );
2
2
2
ꢂ1
ꢃ
(
1
3
25
28)
28
each dd, intensity ratio 2 : 3, Jꢀ8.2, 5.6 and 7.4, 4.6 Hz, 3-H); C-NMR
[a]D ꢂ21.1 (cꢀ0.79, H O)(lit. [a]D ꢂ20.7 (cꢀ1.0, H O)). 102 mg (85%
2
2
(
(
(
CDCl ) d: ꢂ5.56, ꢂ5.41, ꢂ4.77 and ꢂ4.59 (each q), 18.22 and 18.32 from 12b).
3
each s), 19.91 and 26.56 (each t), 25.63 and 25.77 (each q), 27.46 and 28.00
each q), 28.70 and 30.46 (each t), 45.54 (t), 68.74 and 71.54 (each d), 82.72
Acknowledgements This work was partially supported by The Specific
and 86.31 (each s), 148.61 and 152.74 (each s), 169.63 and 171.98 (each s); Research Found of Hokuriku University (2007).
ꢂ1
ꢃ
IR (KBr) cm : 1778, 1707 (CꢀO); MS (FAB) m/z: 330 (MH ). HR-MS
(
(
2
4
FAB) m/z: 330.2102 (Calcd for C H NO Si: 330.2101); [a] ꢃ16.2 References and Notes
16 32 4 D
cꢀ1.02, CHCl ).
1) Lee D. G., van den Engh M., “Oxidation in Organic Chemistry,” ed. by
Trahanovsky W. S., Academic Press, New York, 1973.
3
tert-Butyl (3R)-3-Acetoxy-1,2,3,4-tetrahydropyridine-1-carboxylate
11a) To a solution of the lactam (9, 2.57 g, 10 mmol) in toluene (20 ml) at
2)
3)
4)
Plieker B., Synthesis, 2005, 2453—2472 (2005).
(
Sheehan J. C., Tulis R. W., J. Org. Chem., 39, 2264—2267 (1974).
Carlsen P. H. J., Katsuki T., Martin V. S., Sharpless K. B., J. Org.
Chem., 46, 3936—3938 (1981).
ꢂ70 °C Super-Hydride (1.0 M in THF, 10.6 ml) was added dropwise. After
stirring at ꢂ70 °C for 30 min, DIPEA (10 ml, 57 mmol), dimethylamino-
pyridine (24 mg) and TFAA (1.7 ml, 12 mmol) were added. The mixture
was warmed to room temperature and stirred for 2 h, and water (20 ml)
was added to the mixture. Organic layer was separated and washed with
brine (30 mlꢁ3), dried over anhydrous Na SO , and evaporated to furnish
the crude product which was purified by chromatography (silica gel,
AcOEt–hexane, 1 : 5). 1.71 g (71%); colorless oil; H-NMR (CDCl ) d: 1.47
and 1.49 (9H, each s, intensity ratio 4 : 6, t-Bu), 2.06 (3H, s, OAc), 2.12—
.18 and 2.36—2.43 (each 1H, m, 4-H ), 3.56—3.74 (2H, m, 2-H ), 4.69—
.87 (1H, m, 3-H), 5.08—5.21 (1H, br, 5-H), 6.76 and 6.88 (1H, each d, in-
tensity ratio 3 : 2, Jꢀ8.2 and 7.1 Hz, 6-H); C-NMR (CDCl ) d: 21.17 (q),
7.22 and 27.35 (each t), 28.28 (q), 44.15 and 45.14 (t), 65.76 and 65.92 11) Tanaka K., Yoshifuji S., Nitta Y., Chem. Pharm. Bull., 35, 364—369
5)
6)
7)
Desai M. C., Chawla H. P. S., Dev S., Tetrahedron, 38, 379—382 (1982).
Torii S., Inokuchi T., Kondo K., J. Org. Chem., 50, 4980—4982 (1985).
Yoshifuji S., Arakawa Y., Nitta Y., Chem. Pharm. Bull., 33, 5042—
2
4
5
047 (1985).
8
9
)
Yoshifuji S., Tanaka K., Kawai T., Nitta Y., Chem. Pharm. Bull., 33,
5515—5521 (1985).
Yoshifuji S., Tanaka K., Kawai T., Nitta Y., Chem. Pharm. Bull., 34,
3873—3878 (1986).
1
3
)
2
2
2
4
10) Yoshifuji S., Tanaka K., Nitta Y., Chem. Pharm. Bull., 33, 1749—1751
1
3
3
(1985).
2
(
1
each d), 81.08 (s), 101.27 and 101.73 (each d), 125.42 and 125.77 (each d),
(1987).
ꢂ1
52.35 and 152.67 (each s), 170.40 (s); IR (KBr) cm : 1739, 1705 (CꢀO);
12) Yoshifuji S., Tanaka K., Nitta Y., Chem. Pharm. Bull., 35, 2994—3001
(1987).
13) Yoshifuji S., Matsumoto H., Tanaka K., Nitta Y., Tetrahedron Lett., 21,
ꢃ
MS (EI) m/z: 241 (M ). HR-MS (EI) m/z: 241.1312 (Calcd for C H NO :
2
1
2
19
4
2
3
41.1314); [a] ꢃ18.4 (cꢀ1.06, CHCl3).
D
2
963—2964 (1980).
tert-Butyl (3R)-3-(tert-Butyldimethylsilyloxy)-1,2,3,4-tetrahydropyri-
1
4) Tanaka K., Yoshifuji S., Nitta Y., Chem. Pharm. Bull., 34, 3879—3884
dine-1-carboxylate (11b) This compound was prepared from 9b in a simi-
lar manner to that described for 11a. 2.57 g (82%); colorless oil; H-NMR
1
(1986).
1
1
1
1
5) Kaname M., Yoshifuji S., Tetrahedron Lett., 33, 8103—8104 (1992).
6) Yoshifuji S., Kaname M., Chem. Pharm. Bull., 43, 1302—1306 (1995).
7) Yoshifuji S., Kaname M., Chem. Pharm. Bull., 43, 1617—1620 (1995).
8) Kaname M., Yoshifuji S., Sashida H., Tetrahedron Lett., 49, 2786—
(
(
[
CDCl ) d: 0.08 and 0.09 (each 3H, s, SiMe ), 0.88 (9H, s, Sit-Bu), 1.49
3
2
9H, s, COOt-Bu), 1.96—2.06 and 2.19—2.29 (each 1H, m, 4-H ), 2-H
2
2
3.06—3.19 (1H, m), 3.73 and 3.84 (1H, each d, intensity ratio 3 : 7, Jꢀ11.7
and 12.0 Hz)]. 3.95—4.04 (1H, m, 3-H), 4.66—4.88 (1H, m, 5-H), 6.67 and
6
2
788 (2008).
1
3
.81 (1H, each d, intensity ratio 7 : 3, Jꢀ8.1 and 7.8 Hz, 6-H); C-NMR
1
2
2
9) Yu J., Truc V., Riebel P., Hierl E., Mudryk B., Tetrahedron Lett., 46,
4011—4013 (2005).
0) Oliveira D. F., Miranda P. C. M. L., Correia C. R. D., J. Org. Chem.,
(
2
8
CDCl ) d: ꢂ4.76 and ꢂ4.68 (each q), 18.06 and 18.12 (each s), 25.78 (q),
3
8.32 (q), 31.71 and 31.85 (each t), 47.54 and 48.72 (each t), 64.83 (d),
0.56 and 80.69 (each s), 102.37 and 102.94 (each d), 125.08 and 125.40
6
4, 6646—6652 (1999).
ꢂ1
(
each d), 152.29 and 152.65 (each s); IR (KBr) cm : 1705 (CꢀO); MS (EI)
1) Schumacher K. K., Jiang J., Joullié M. M., Tetrahedron Asymmetry, 9,
ꢃ
m/z: 313 (M ); HR-MS (EI) m/z: 313.2070 (Calcd for C H NO Si:
47—53 (1998).
1
6
31
3
2
5
3
13.2073); [a] ꢂ16.5 (cꢀ1.18, CHCl3).
22) Dormoy J. R., Synthesis, 1982, 753—756 (1982).
3R)-3-Acetoxy-4-(N-tert-butoxycarbonyl-N-formylamino)butyric 23) Rossen K., Kolarovi cˇ A., Baskakov D., Kiesel M., Tetrahedron Lett.,
Acid (12a) The enamine (11, 24 mmol) was oxidized and worked up as de-
45, 3023—3025 (2004).
D
(
scribed above for the general procedure for RuO oxidation of N-protected 24) Ferrari R., Di Mauro S., Sherwood G., “L-Carnitine and its Role in
4
1
cyclic ene-carbamates. 5.57 g (80%); colorless oil; H-NMR (CDCl ) d:
Medicine: from Function to Therapy,” Academic, San Diego, 1992.
5) De Simone C., Famularo G., “Carnitine Today,” Springer Verlag, Hei-
delberg, 1997.
26) Jain R. P., Williams R. M., Tetrahedron, 57, 6505—6509 (2001) and
references cited therein.
27) Irie T., Ikota N., Fukushi K., Japan Patent 002637 (2001) [Chem.
Abstr., 18, 945 (2001)].
28) Kamal A., Ramesh Khanna G. B., Krishnaji T., Ramu R., Tetrahedron
3
2
1
3
3
2
1
1
.56 (9H, s, t-Bu), 2.01 (3H, s, OAc), 2.64 (2H, d, Jꢀ6.7 Hz, 2-H ), 3.81 and
2
.95 (each 1H, dd, Jꢀ14.2, 3.8 and 14.2, 6.9 Hz, 4-H ), 5.42—5.48 (1H, m,
-H), 6.81—7.28 (1H, br, COOH), 9.17 (1H, s, CHO); C-NMR (CDCl ) d:
0.87 (q), 27.95 (q), 36.75 (t), 42.47 (t), 67.90 (d), 84.87 (s), 152.13 (s),
63.44 (d), 170.53 (s), 174.48 (s); IR (KBr) cm : 3482 (OH), 1743, 1711,
693 (CꢀO); MS (FAB) m/z: 290 (MH ). HR-MS (FAB) m/z: 290.1242
2
1
3
3
ꢂ1
ꢃ
2
3
(Calcd for C H NO : 290.1240); [a] ꢃ10.0 (cꢀ1.99, CHCl3).
12 20 7 D
Asymmetry, 17, 1281—1289 (2006).
(
3R)-4-(N-tert-Butoxycarbonyl-N-formylamino)-3-(tert-butyldimeth-