LETTER
Synthesis of b-Amino Ketone O-Alkyl Oximes
1689
concentrated in vacuo. Purification on preparative silica gel
TLC (n-hexane–EtOAc = 4:1 as an eluent) gave 4-[N-(4-
methoxyphenyl)amino]-4-phenyl-2-butanone-O-benzyl
oxime (3a, 35.4 mg, 94%) as a pale brown oil. 1H NMR (270
MHz, CDCl3): d = 1.70 (s, 3 H), 2.41 (dd, J = 5.3, 13.1 Hz,
1 H), 3.20 (dd, J = 8.9, 13.1 Hz, 1H), 3.66 (s, 3 H), 4.30 (br
s, 1 H), 4.51 (dd, J = 5.3, 8.9 Hz, 1 H), 5.11 (d, J = 12.2 Hz,
1 H), 5.17 (d, J = 12.2 Hz, 1 H), 6.26–6.30 (m, 2 H), 6.57–
6.62 (m, 2 H), 7.22–7.46 (m, 10 H). 13C NMR (67.8 MHz,
CDCl3): d = 20.7, 38.8, 55.7, 56.6, 75.8, 114.2, 114.6, 126.2,
127.3, 128.0, 128.4, 128.5, 128.7, 137.7, 141.3, 143.4,
151.7, 156.0.
References and Notes
(1) (a) Reformatsky, S. Ber. Dtsch. Chem. Ges. 1887, 20, 1210.
(b) Shriner, R. L. Org. React. 1942, 1, 1. (c)Garudemar, M.
Organomet. Chem. Rev. A 1972, 8, 183. (d) Harada, T.;
Mukaiyama, T. Chem. Lett. 1982, 161. (e) Kagoshima, H.;
Hashimoto, Y.; Oguro, D.; Saigo, K. J. Org. Chem. 1998, 63,
691. (f) Borah, H. N.; Boruah, R. C.; Sandhu, J. S. Chem.
Commun. 1991, 154. (g) Fukuzawa, S.; Matsuzaka, H.;
Yoshimitsu, S. J. Org. Chem. 2000, 65, 1702.
(h) Kagayama, A.; Igarashi, K.; Shiina, I.; Mukaiyama, T.
Bull. Chem. Soc. Jpn. 2000, 73, 2579.
(2) (a) Fustero, S.; Torre, M. G.; Pina, B.; Fuentes, A. S. J. Org.
Chem. 1999, 64, 5551. (b) Nakamura, E.; Kubota, K.;
Sakata, G. J. Am. Chem. Soc. 1997, 119, 5457. (c) Capriati,
V.; Florio, S.; Luisi, R. Eur. J. Org. Chem. 2001, 2035.
(d) Hou, X. L.; Luo, Y. M.; Yuan, K.; Dai, L. X. J. Chem.
Soc., Perkin Trans. 1 2002, 1487. (e) Lanter, J. C.; Chan,
H.; Zhang, X.; Sui, Z. Org. Lett. 2005, 7, 5905.
(3) (a) Shimizu, M.; Toyoda, T. Org. Biomol. Chem. 2004, 2,
2891. (b) Shimizu, M.; Kobayashi, F.; Hayakawa, R.
Tetrahedron 2001, 57, 9591. (c) Shimizu, M.; Takeuchi, Y.;
Sahara, T. Chem. Lett. 2001, 1196. (d) Shimizu, M.;
Inayoshi, K.; Sahara, T. Org. Biomol. Chem. 2005, 3, 2237.
(e) Shimizu, M.; Sahara, T. Chem. Lett. 2002, 888.
(6) (a) Kotsuki, H.; Hayashida, K.; Shimanouchi, T.; Nishizawa,
H. J. Org. Chem. 1996, 61, 984. (b) Veselovsky, V. V.;
Gybin, A. S.; Lozanova, A. V.; Moiseenkov, A. M.; Smit,
W. A. Tetrahedron Lett. 1988, 29, 175. (c) Weinstein, R.
D.; Renslo, A. R.; Danheiser, R. L.; Tester, J. W. J. Phys.
Chem. B 1999, 103, 2878.
(7) (a) 4-Iodobutanol was obtained from the reaction of THF
with TiI4 (Scheme 3). Confer: (b) Breen, C. C. B.; Bautista,
M. T.; Schauer, C. K.; White, P. S. J. Am. Chem. Soc. 2000,
122, 3952. (c) Dufour, P.; Dartiguenave, M.; Dartiguenave,
Y.; Simard, M.; Beauchamp, A. L. J. Organomet. Chem.
1998, 563, 53.
(f) Hayakawa, R.; Shimizu, M. Org. Lett. 2000, 2, 4079.
(4) To a solution of O-benzylhydroxylamine hydrochloride
(2.07 g, 13.0 mmol) in H2O (30.0 mL) was added
I
I
TiI3
+
TiI4
O
O
O
O
TiI3
chloroacetone (0.79 mL, 10.0 mmol) and NaHCO3 (0.84 g,
10.0 mmol) at ambient temperature for 5.0 h. Then, the
mixture was extracted with CH2Cl2 (3 × 10 mL). The
combined organic extracts were dried over anhyd Na2SO4
and concentrated in vacuo to give chloroacetone O-benzyl
oxime (2.08 g, quant., E/Z-mixture) as a colorless oil. Under
an argon atmosphere, to a solution of chloroacetone O-
benzyl oxime (2.00 g, 10.1 mmol) in acetone (30.0 mL) was
added a NaI (2.11 g, 14.1 mmol) at ambient temperature for
14.5 h. The mixture was filtered through a Celite® pad, and
extracted with Et2O (3 × 10 mL). The organic phase was
washed with 10% aq NaHSO3, dried over anhyd Na2SO4,
and concentrated in vacuo. Purification by silica gel column
chromatography (n-hexane–EtOAc = 30:1) gave
H+
TiI4-n
I
I
OH
n
Scheme 3
(8) (a) Shimizu, M.; Goto, H.; Hayakawa, R. Org. Lett. 2002, 4,
4097. (b) Ooi, T.; Miura, T.; Ohmatsu, K.; Saito, A.;
Maruoka, K. Org. Biomol. Chem. 2004, 2, 3312.
(c) Brocchini, S. J.; Eberle, M.; Lawton, R. G. J. Am. Chem.
Soc. 1988, 110, 5211.
iodoacetone O-benzyl oxime (2, 1.90 g, 65%, E:Z = 23:77,
E-isomer: Rf = 0.23; Z-isomer: Rf = 0.29) as a pale brown oil.
E-Isomer: 1H NMR (500 MHz, CDCl3): d = 2.03 (s, 3 H),
3.87 (s, 2 H), 5.15 (s, 2 H), 7.28–7.38 (m, 5 H). 13C NMR
(125.7 MHz, CDCl3): d = 6.0, 13.9, 76.0, 127.9, 128.0,
128.4, 137.6, 154.6. Z-Isomer: 1H NMR (500 MHz, CDCl3):
d = 2.34 (s, 3 H), 3.91 (s, 2 H), 5.10 (s, 2 H), 7.26-7.40 (m, 5
H). 13C NMR (125.7 MHz, CDCl3): d = –7.2, 18.5, 76.0,
127.8, 127.9, 128.3, 137.7, 153.5.
(9) (a) Shimada, T.; Yamamoto, Y. Tetrahedron Lett. 1998, 39,
471. (b) Bayón, P.; March, P.; Espinosa, M.; Figueredo, M.;
Font, J. Tetrahedron: Asymmetry 2000, 11, 1757.
(c) Rigby, J. H.; Fleming, M. Tetrahedron Lett. 2002, 43,
8643. (d) Hayashi, M.; Kohmura, K.; Oguni, N. Synlett
1991, 774. (e) Krohn, K.; Steingröver, K.; Vinke, I. J. Pract.
Chem. 1999, 341, 62.
(10) (a) The formation of the following species 6, 7 may be
excluded. See: Fraile, J. M.; Garcia, J.; Mayoral, J. A.;
Proietti, M. G.; Grazia, M.; Sanchez, M. C. J. Phys. Chem.
1996, 100, 19484. (b) Although there are several arguments
on the role of silica gel, e. g., scavenger of iodine or water,
its acidity may be responsible as part of the imine activation
on the surface (Scheme 4).6
(5) To a solution of TiI4 (69.4 mg, 0.125 mmol) and titanium
tetraisopropoxide (0.125 mL, 0.125 mmol, 1.0 M in CH2Cl2)
in THF (1.0 mL) was added a solution of (Z)-iodoacetone O-
benzyl oxime (2, 72.2 mg, 0.250 mmol) in THF (1.0 mL) at
0 °C under an argon atmosphere. After 30 min stirring, to the
resulting solution was added a THF (1.0 mL) solution of N-
benzylidene-4-methoxyphenylamine (1a, 21.1 mg, 0.100
mmol) and silica gel (dried, 300 mg/mmol) at –78 °C. The
mixture was allowed to warm to ambient temperature with
stirring for 12.0 h. The reaction was quenched with sat. aq
NaHCO3, and EtOAc and 10% aq NaHSO3 were added
successively. The mixture was filtered through a Celite®
pad, and extracted with EtOAc (3 × 10 mL). The combined
organic extracts were dried over anhyd Na2SO4 and
-O-Si-O-Si-O-
-O-Si-O-Si-O-
O
O
O
O
Ti
Ti
iPrO OiPr
I
I
6
7
Scheme 4
Synlett 2006, No. 11, 1687–1690 © Thieme Stuttgart · New York