Oxidation of Amino Diols Mediated by TEMPO
FULL PAPERS
28.3 (c2a), 29.1 (c2a), 29.5 (t1a), 31.0 (c1a), 36.6 (t2a), 55.7 (d1a), 56.0
(d2a), 63.2 (t1a), 64.1 (t2a), 72.4 (d1a), 72.7 (d2a), 80.0 (s2a), 80.3
Methyl (2S,3R)-2[N-(tert-Butoxycarbonyl)amino]-3-
hydroxy-3-(4-nitrophenyl)propanoate (4c)
(s1a), 156.0 (s2a), 157.8 (s1a); IR (KBr): n¼3439, 1674 cmÀ1
;
By method A; yield: 38%; by method B (SG-TEMPO-2); yield:
57%; white solid; mp 96 978C; [a]2D5: À23.8 (c 0.8, CHCl3);
1H NMR (400 MHz, CDCl3): d¼1.20 (s, 9H), 3.68 (s, 3H),
4.30 (bs, 1H), 4.50 (d, J¼4.5 Hz, 1H), 5.30 (s, 1H), 5.50 (d,
J¼4.5 Hz, 1H), 7.61 (d, J¼8.6 Hz, 2H), 8.23 (d, J¼8.6 Hz,
2H); 13C NMR (100 MHz, CDCl3): d¼28.0 (c), 52.9 (c), 59.4
(d), 72.9 (d), 80.5 (s), 123.6 (d), 127.6 (d), 147.5 (s), 148.0 (s),
155.8 (s), 171.0 (s); IR (KBr): n¼3436, 2965, 1710, 1665,
1517, 1328 cmÀ1; HRMS (EI): calcd for C15H21N2O7 [M]:
341.1348; found: 341.1353.
HRMS (CI): calcd. for C12H26NO4 [Mþ1]: 248.1861; found:
248.1868.
(2R,3R)-2-[N-(tert-Butoxycarbonyl)amino]-3-(4-
nitrophenyl)-1,3-propanediol (2c)
Yield: 70%; white solid; mp 113 1148C; [a]2D5: À22.0 (c 1,
1
MeOH). H NMR (400 MHz, CDCl3): d¼1.15 (s, 3H), 3.6
(m, 3H), 3.8 (bs, 1H), 4.6 (bs, 1H), 5.1 (s, 1H), 5.3 (s, 1H), 7.4
(d, J¼8 Hz, 2H), 8.05 (d, J¼8 Hz, 2H); 13C NMR (100 MHz,
CDCl3): d¼28.0 (c), 56.7 (d), 62.8 (t), 72.0 (d), 80.1 (s), 123.3
(d), 126.8 (d), 147.0 (s), 149.2 (s), 156.2 (s); IR (KBr): n¼
3422, 2978, 1680, 1520, 1346 cmÀ1; HRMS (CI): calcd. for
C14H21N2O6 [Mþ1]: 313.1399; found: 313.1413.
Acknowledgements
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We are indebted to the Direccion General de Investigacion Cien-
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tÌfico y Tecnica, Spain (Project BQU2003 01756) for financial
support.
Methyl (2R,3R)-3-[N-(tert-Butoxycarbonyl)-N-
(methyl)amino]-2-hydroxyhexanoate (3a)
By method A; yield: 81% (calculated from 1a); colorless oil;
References and Notes
1
[a]2D5: þ25.9 (c 1.83, CHCl3); H NMR (400 MHz, CDCl3):
d¼0.87 (t, J¼7.1 Hz, 3H), 1.23 (m, 2H), 1.41 (s, 9H), 1.70
(m, 2H), 2.71 (s, 3H), 3.63 (s, 3H), 4.37 (m, 1H), 4.71 (d, J¼
5.0 Hz, 1H); 13C NMR (100 MHz, CDCl3): d¼13.5 (q), 19.2
(t), 28.2 (q), 30.7 (t), 31.1 (q), 51.9 (q), 57.2 (d), 58.7 (d), 79.9
[1] a) K. C. Nicolaou, W. M. Dai, R. K. Kuy, Angew. Chem.
Int. Ed. Engl. 1994, 33, 15; b) H. Humezawa, T. Aoyagi,
H. Suda, M. Hamada, T. Takeucii, J. Antibiot. 1976, 29, 9
7; c) S. Shinagawa, T. Kanamaru, S. Harada, M. Asai, H.
Ookazaki, J. Med. Chem. 1987, 30, 1458.
(s), 156.3 (s), 172.5 (s); IR (KBr): n¼3350, 1700, 1657 cmÀ1
;
HRMS (CI): calcd. for C13H26NO5 [Mþ1]: 276.1811; found:
¬
[2] a) M. Pasto, A. Moyano, M. A. Pericas, A. Riera, Tetra-
276.1814.
hedron: Asymmetry 1996, 7, 243; b) G. C. G. Pais, M. E.
Maier, J. Org. Chem. 1999, 64, 4551.
[3] A. E. J. De Nooy, A. C. Besemer, H. van Bekkum, Syn-
thesis 1996, 1153.
Methyl (2R,3R)-2-[N-(tert-Butoxycarbonyl)-N-
(methyl)amino]-3-hydroxyhexanoate (4a)
[4] a) F. J. Aladro, F. M. Guerra, F. J. Moreno-Dorado, J. M.
Bustamante, Z. D. Jorge, G. M. Massanet, Tetrahedron
Lett. 2000, 41, 3209; b) P. M. Wovkulich, K. Shankaran,
J. Kiegiel, R. Uskokovic, J. Org. Chem. 1993, 58, 832;
c) N. J Davis, S. L. Flitsch, Tetrahedron Lett. 1993, 34,
1181.
By method A; yield: 78% (calculated from 2a); colorless oil;
1
[a]2D5: À40.3 (c 2.73, CHCl3); H NMR (400 MHz, CDCl3):
d¼0.84 (t, J¼7.1 Hz, 3H), 1.12 1.22 (m, 4H), 1.42 (s, 9H),
2.70 (s, 3H), 3.69 (s, 3H), 4.44 (c, J¼7.0 Hz, 1H), 4.75 (d, J¼
7.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): d¼13.8 (c), 18.2
(t), 28.1 (c), 34.4 (c), 35.0 (t), 52.1 (c), 65.4 (d), 69.7 (d), 80.7
[5] M. Ikunaka, J. Matsumoto, Y. Nishimoto, Tetrahedron:
Asymmetry 2002, 13, 1201.
(s), 154.6 (s), 172.9 (s); IR (KBr): n¼3425, 1735, 1675 cmÀ1
;
HRMS (CI): calcd. for C13H26NO5 [M]: 276.1811, found
276.1810.
[6] Amixture of regioisomers (75:25) was obtained by
Sharpless epoxidation of trans/2-hexenol, reaction with
methylamine-Ti(O-i-Pr)4 and protection of the methyl-
amino group with Boc2O as described in: C. Hajji,
M. L. Testa, R. Salud-Bea, E. Zaballos-GarcÌa, J. Serv-
Methyl (2S,3R)-2-[N-(Dichloroacetyl)amino]-3-
hydroxy-3-(4-nitrophenyl)propanoate (4b)
¬
¬
er-Carrio, J. Sepulveda-Arques, Tetrahedron 2000, 56,
8173.
By methods Aand B, yields are reported in Table 2; white solid;
mp 160 1618C; [a]2D5: þ16.4 (c 0.73, MeOH); 1H NMR
(300 MHz, DMSO-d6): d¼3.79 (s, 3H), 4.82 (dd, J¼9.2 and
2.7 Hz, 1H), 5.45 (dd, J¼4.5 and 2.7 Hz, 1H), 6.50 (d, J¼
4.5 Hz, 1H, exchanged with D2O), 6.61 (s, 1H), 7.74 (d, J¼
8.6 Hz, 2H), 8.23 (d, J¼8.6 Hz, 2H), 9.03 (d, J¼9.2 Hz, 1H, ex-
changed with D2O); 13C NMR (75 MHz, DMSO-d6): d¼53.7
(c), 60.2 (d), 67.3 (d), 73.5 (d), 124.7 (d), 128.6 (d), 149.2 (s),
150.1 (s), 166.9 (s), 171.3 (s); IR (KBr): n¼3402, 2954, 1689,
1647, 1540, 1317 cmÀ1; HRMS (EI): calcd for C12H13N2O6Cl2
[Mþ1]: 351.0150; found: 351.0142.
[7] R. Ciriminna, C. Bolm, T. Fey, M. Pagliaro, Adv. Synth.
Catal. 2002, 344, 159. The catalytic sol-gel silica matrices
organically modified (ormosils) were prepared through
reductive amination of 4-oxo-TEMPO with 3-aminopro-
pyltrimethoxysilane in the presence of NaBH3CN in
methanol followed by the sol-gel polycondensation proc-
ess of suitable silicon alkoxide percursors.
[8] D. Brunel, F. Fajula, B. Nagy, B. Deroide, L. Veum, J. A.
Peters, H. van Bekkum, Appl. Catal. A: General 2001,
213, 73.
Adv. Synth. Catal. 2004, 346, 655 660
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