Synlett 2011(9): 1303-1307  
DOI: 10.1055/s-0030-1260536
© Georg Thieme Verlag Stuttgart ˙ New York

Transformation of α-Substituted Propanols into γ-Amino Alcohols through Nickel-Catalyzed Amination on the Terminal γ-Carbon of Propanols

Satoshi Ueno*, Kazumi Usui, Ryoichi Kuwano*
Department of Chemistry, Graduate School of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
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Further Information

Publication History

Received 4 January 2011
Publication Date:
20 April 2011 (online)


A nickel-phosphine complex was found to be effective as the catalyst for the transformation of alcohols into β-enaminones, which was successively converted into γ-amino alcohols by a conventional reductant. The sequential transformation is equivalent to the carbon-nitrogen bond formation at the γ-position of saturated alcohols.

    References and Notes

  • 1 For a review on the γ-amino alcohol synthesis, see: Lait SM. Rankic DA. Keay BA. Chem. Rev.  2007,  107:  767 
  • For recent reports on γ-amino alcohol synthesis, see:
  • 2a Rice GT. White MC. J. Am. Chem. Soc.  2009,  131:  11707 
  • 2b Davis FA. Gaspari PM. Nolt BM. Xu P. J. Org. Chem.  2008,  73:  9619 
  • 2c Liang J.-L. Yuan S.-X. Huang J.-S. Yu W.-Y. Che C.-M. Angew. Chem. Int. Ed.  2002,  41:  3465 
  • 3 Espino CG. Wehn PM. Chow J. Du Bois J. J. Am. Chem. Soc.  2001,  123:  6935 
  • Some examples are known as the rhodium-catalyzed nitrene insertion into secondary or tertiary C-H bond at the γ-position. However, multiple steps would be required for the preparation of sulfamate esters and the deprotection of the sulfamoyl group, see:
  • 4a Kang S. Lee H.-K. J. Org. Chem.  2010,  75:  237 
  • 4b Zalatan DN. Du Bois J. J. Am. Chem. Soc.  2008,  130:  9220 
  • 4c Milczek E. Boudet N. Blakey S. Angew. Chem. Int. Ed.  2008,  47:  6825 
  • 4d Brodsky BH. Du Bois J. Chem. Commun.  2006,  4715 
  • 4e Fiori KW. Fleming JJ. Du Bois J. Angew. Chem. Int. Ed.  2004,  43:  4349 
  • 4f Wehn PM. Lee J. Du Bois J. Org. Lett.  2003,  5:  4823 
  • 5 Ueno S. Shimizu R. Kuwano R. Angew. Chem. Int. Ed.  2009,  48:  4543 
  • For examples of reaction involving oxidation of ketones by aryl halides or pseudohalides in the presence of the palladium catalyst, see:
  • 6a Aulenta F. Wefelscheid UK. Brüdgam I. Reißig H.-U. Eur. J. Org. Chem.  2008,  2325 
  • 6b 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 α,β-unsaturated ketones, see: Muzart J. Eur. J. Org. Chem.  2010,  3779 
  • For selected examples of catalytic oxidation of saturated ketones into α,β-unsaturated ketones, see:
  • 8a Zhu J. Liu J. Ma R. Xie H. Li J. Jiang H. Wang W. Adv. Synth. Catal.  2009,  351:  1229 
  • 8b Uyanik M. Akakura M. Ishihara K. J. Am. Chem. Soc.  2008,  131:  251 
  • 8c Tokunaga M. Harada S. Iwasawa T. Obora Y. Tsuji Y. Tetrahedron Lett.  2007,  48:  6860 
  • 8d Shvo Y. Arisha AHI. J. Org. Chem.  1998,  63:  5640 
  • 8e Theissen RJ. J. Org. Chem.  1971,  36:  752 
  • For some examples of oxidation of alcohols by halobenzene in the presence of the nickel or palladium catalyst, see:
  • 9a Berini C. Brayton DF. Mocka C. Navarro O. Org. Lett.  2009,  11:  4244 
  • 9b Bei X. Hagemeyer A. Volpe A. Saxton R. Turner H. Guram AS. J. Org. Chem.  2004,  69:  8626 
  • 9c Guram AS. Bei X. Turner HW. Org. Lett.  2003,  5:  2485 
  • 9d Tamaru Y. Yamada Y. Inoue K. Yamamoto Y. Yoshida Z.-I. J. Org. Chem.  1983,  48:  1286 
  • For some selected examples of reduction of β-enaminones, see:
  • 10a Geng H. Zhang W. Chen J. Hou G. Zhou L. Zou Y. Wu W. Zhang X. Angew. Chem. Int. Ed.  2009,  48:  6052 
  • 10b Neto BAD. Lapis AAM. Bernd AB. Russowsky D. Tetrahedron  2009,  65:  2484 
  • 10c Cimarelli C. Giuli S. Palmieri G. Tetrahedron: Asymmetry  2006,  17:  1308 
  • 10d Zanatta N. Squizani AMC. Fantinel L. Nachtigall FM. Borchhardt DM. Bonacorso HG. Martins MAP. J. Braz. Chem. Soc.  2005,  16:  1255 
  • 10e Harris MINC. Braga ACH. J. Braz. Chem. Soc.  2004,  15:  971 
  • 12 For reactivities of aryl halides on oxidative addition to nickel(0) complexes, see: Tsou TT. Kochi JK. J. Am. Chem. Soc.  1979,  101:  6319 
  • The nickel catalyst might be deactivated in the reaction with 2g because the deprotonated β-enaminone 3p is known to strongly coordinate to the divalent nickel complex.
  • 13a Gerlach DH. Holm RH. J. Am. Chem. Soc.  1969,  91:  3457 
  • 13b Everett GW. Holm RH. Inorg. Chem.  1968,  7:  776 
  • 15 Khurana JM. Kumar S. Nand B. Can. J. Chem.  2008,  86:  1052 
  • 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 

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 µL, 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 β-enaminone 3a (92.9 mg, 86%) as a pale yellow solid. ¹H NMR (400 MHz, CDCl3, TMS): δ = 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): δ = 48.3 (br s), 66.2, 92.4, 127.4, 128.1, 131.1, 140.1, 152.7, 189.1.


We previously demonstrated that the dehydrogenation of β-amino ketones is faster than that of ethyl ketones, see: ref. 5.