LETTER
Transformation of a-Substituted Alcohols into g-Amino Alcohols
1307
Blakey, S. Angew. Chem. Int. Ed. 2008, 47, 6825.
(11) Typical Procedure for the Transformation of 1a into 3a:
In a nitrogen-filled drybox, a 4-mL screw-capped vial was
charged with Ni(cod)2 (5.5 mg, 0.02 mmol), K3PO4 (636.8
mg, 3.0 mmol), and dioxane (0.3 mL). After a magnetic stir
bar was added, the vial was fitted with a septum cap, and
removed from the drybox. A solution of trimethylphosphine
(60 mL, 1 M THF solution, 0.06 mmol), chlorobenzene (0.3
mL, d 1.106 g/mL, 2.95 mmol), morpholine (2a), and 1-
phenyl-1-propanol (1a) was added. The resulting mixture
was heated at 100 °C. The progress of the reaction was
confirmed by GC analysis. After complete consumption of
the starting material, the reaction mixture was quenched
with H2O (1 mL) and extracted with EtOAc (3 × 1 mL). The
organic layer was concentrated, and purified by silica gel
column chromatography (hexane–EtOAc = 3:1 → 1:8),
which gave the b-enaminone 3a (92.9 mg, 86%) as a pale
yellow solid. 1H NMR (400 MHz, CDCl3, TMS): d = 3.27–
3.53 (m, 4 H), 3.63–3.93 (m, 4 H), 5.88 (d, J = 12.6 Hz, 1 H),
7.33–7.56 (m, 3 H), 7.74 (d, J = 12.6 Hz, 1 H), 7.83–8.00 (m,
2 H). 13C{1H} NMR (100 MHz, CDCl3): d = 48.3 (br s),
66.2, 92.4, 127.4, 128.1, 131.1, 140.1, 152.7, 189.1.
(12) For reactivities of aryl halides on oxidative addition to
nickel(0) complexes, see: Tsou, T. T.; Kochi, J. K. J. Am.
Chem. Soc. 1979, 101, 6319.
(13) The nickel catalyst might be deactivated in the reaction with
2g because the deprotonated b-enaminone 3p is known to
strongly coordinate to the divalent nickel complex.
(a) Gerlach, D. H.; Holm, R. H. J. Am. Chem. Soc. 1969, 91,
3457. (b) Everett, G. W.; Holm, R. H. Inorg. Chem. 1968, 7,
776.
(14) We previously demonstrated that the dehydrogenation of b-
amino ketones is faster than that of ethyl ketones, see: ref. 5.
(15) Khurana, J. M.; Kumar, S.; Nand, B. Can. J. Chem. 2008, 86,
1052.
(d) Brodsky, B. H.; Du Bois, J. Chem. Commun. 2006,
4715. (e) Fiori, K. W.; Fleming, J. J.; Du Bois, J. Angew.
Chem. Int. Ed. 2004, 43, 4349. (f) Wehn, P. M.; Lee, J.;
Du Bois, J. Org. Lett. 2003, 5, 4823.
(5) Ueno, S.; Shimizu, R.; Kuwano, R. Angew. Chem. Int. Ed.
2009, 48, 4543.
(6) For examples of reaction involving oxidation of ketones by
aryl halides or pseudohalides in the presence of the
palladium catalyst, see: (a) Aulenta, F.; Wefelscheid, U. K.;
Brüdgam, I.; Reißig, H.-U. Eur. J. Org. Chem. 2008, 2325.
(b) Terao, Y.; Kametani, Y.; Wakui, H.; Satoh, T.; Miura,
M.; Nomura, M. Tetrahedron 2001, 57, 5967.
(7) For a review on the palladium-mediated dehydrogenation of
saturated ketones into a,b-unsaturated ketones, see: Muzart,
J. Eur. J. Org. Chem. 2010, 3779.
(8) For selected examples of catalytic oxidation of saturated
ketones into a,b-unsaturated ketones, see: (a) Zhu, J.; Liu,
J.; Ma, R.; Xie, H.; Li, J.; Jiang, H.; Wang, W. Adv. Synth.
Catal. 2009, 351, 1229. (b) Uyanik, M.; Akakura, M.;
Ishihara, K. J. Am. Chem. Soc. 2008, 131, 251.
(c) Tokunaga, M.; Harada, S.; Iwasawa, T.; Obora, Y.; Tsuji,
Y. Tetrahedron Lett. 2007, 48, 6860. (d) Shvo, Y.; Arisha,
A. H. I. J. Org. Chem. 1998, 63, 5640. (e) Theissen, R. J.
J. Org. Chem. 1971, 36, 752.
(9) For some examples of oxidation of alcohols by halobenzene
in the presence of the nickel or palladium catalyst, see:
(a) Berini, C.; Brayton, D. F.; Mocka, C.; Navarro, O. Org.
Lett. 2009, 11, 4244. (b) Bei, X.; Hagemeyer, A.; Volpe, A.;
Saxton, R.; Turner, H.; Guram, A. S. J. Org. Chem. 2004, 69,
8626. (c) Guram, A. S.; Bei, X.; Turner, H. W. Org. Lett.
2003, 5, 2485. (d) Tamaru, Y.; Yamada, Y.; Inoue, K.;
Yamamoto, Y.; Yoshida, Z.-I. J. Org. Chem. 1983, 48, 1286.
(10) For some selected examples of reduction of b-enaminones,
see: (a) Geng, H.; Zhang, W.; Chen, J.; Hou, G.; Zhou, L.;
Zou, Y.; Wu, W.; Zhang, X. Angew. Chem. Int. Ed. 2009, 48,
6052. (b) Neto, B. A. D.; Lapis, A. A. M.; Bernd, A. B.;
Russowsky, D. Tetrahedron 2009, 65, 2484. (c) Cimarelli,
C.; Giuli, S.; Palmieri, G. Tetrahedron: Asymmetry 2006,
17, 1308. (d) Zanatta, N.; Squizani, A. M. C.; Fantinel, L.;
Nachtigall, F. M.; Borchhardt, D. M.; Bonacorso, H. G.;
Martins, M. A. P. J. Braz. Chem. Soc. 2005, 16, 1255.
(e) Harris, M. I. N. C.; Braga, A. C. H. J. Braz. Chem. Soc.
2004, 15, 971.
(16) The compound 3n was characterized as the Z-isomer by
an observing of the small coupling constant (J = 7.5 Hz)
between two vinyl protons; see supporting information for
details. The 1H NMR and 13C NMR spectroscopic data are in
agreement with the previously reported literature, see: Haak,
E. Eur. J. Org. Chem. 2007, 2815.
Synlett 2011, No. 9, 1303–1307 © Thieme Stuttgart · New York