Organic Letters
Letter
Table 2. Synthesis of β-Hydroxyamides 4a−p from β-
Notes
a
Ketonitriles 2a−q Catalyzed by Complex 1
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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b
This work was supported by the Spanish MINECO (Projects
CTQ2013-40591-P, CTQ2016-75986-P, and CTQ2014-
51912-REDC) and the Gobierno del Principado de Asturias
(Project GRUPIN14-006).
entry
β-ketonitrile 2
R = 4-C6H4F (2a)
yield of 4 (%)
1
4a, 74
4b, 82
4c, 88
4d, 70
4e, 70
4f, 73
4g, 85
4h, 77
4i, 84
4j, 82
4k, 85
4l, 86
4m, 76
4n, 80
4o, 70
4p, 81
2
R = Ph (2b)
3
R = 4-C6H4Cl (2c)
R = 3-C6H4Cl (2d)
R = 2-C6H4Cl (2e)
R = 3,4-C6H3Cl2 (2f)
R = 4-C6H4Br (2g)
R = 3-C6H4CF3 (2h)
R = 4-C6H4Me (2i)
R = 3-C6H4Me (2j)
R = 4-C6H4OMe (2k)
R = 3,5-C6H3(OMe)2 (2l)
R = 1,2,3,4-tetrahydro-6-naphthyl (2m)
R = 2-furyl (2n)
4
REFERENCES
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(1) See, for example: (a) Meloni, M. M.; Taddei, M. Org. Lett. 2001,
3, 337. (b) Durham, T. B.; Miller, M. J. J. Org. Chem. 2003, 68, 35.
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8
9
10
11
12
13
14
c
15
R = 2-thienyl (2o)
t
16
R = Bu (2p)
a
Reactions were performed under Ar atmosphere starting from
b
1 mmol of the corresponding β-ketonitrile (0.33 M in water). Isolated
yield after chromatographic workup. Reaction time 48 h.
c
Scheme 3. Catalytic Synthesis of the α-Substituted β-
Hydroxyamides 4q−t
(4) Kamal, A.; Khanna, G. B.; Ramu, R. Tetrahedron: Asymmetry
2002, 13, 2039.
(5) For representative examples, see refs 1a−c,g,h and 2 and: Brain,
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(7) See, for example: (a) Touati, R.; Gmiza, T.; Jeulin, S.; Deport, C.;
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̈
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L. Angew. Chem., Int. Ed. 2012, 51, 201.
(8) For enzymatic approaches, see: (a) Mukherjee, C.; Zhu, D.; Biehl,
i.e., the easily accessible ruthenium(II) complex [RuCl2(η6-p-
cymene){P(4-C6H4F)2Cl}].19 Further studies aimed at exploiting
this aqueous protocol for the preparation of related α- and
γ-hydroxyamides, molecules also of high synthetic value in organic
chemistry, from the corresponding ketonitriles are now in progress
in our laboratory and will be the subject of a future contribution.
E. B.; Parmar, R. R.; Hua, L. Tetrahedron 2006, 62, 6150. (b) Kubac
D.; Kaplan, O.; Elisa ova, V.; Patek, M.; Vejvoda, V.; Slamova, K.;
Tothova, A.; Lemaire, M.; Gallienne, E.; Lutz-Wahl, S.; Fischer, L.;
Kuzma, M.; Palentova, H.; van Pelt, S.; Bolte, J.; Kren, V.; Martínkova,
́ ̌
,
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k
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L. J. Mol. Catal. B: Enzym. 2008, 50, 107. (c) Kinfe, H. H.; Chhiba, V.;
Frederick, J.; Bode, M. L.; Mathiba, K.; Steenkamp, P. A.; Brady, D. J.
Mol. Catal. B: Enzym. 2009, 59, 231.
ASSOCIATED CONTENT
* Supporting Information
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(9) For nonenzymatic approaches, see: (a) Vinograd, L. K.; Vul’fson,
N. S. Zh. Obshch. Khim. 1959, 29, 245. (b) Vul’fson, N. S.; Vinograd,
L. K. Zh. Obshch. Khim. 1959, 29, 1147. (c) Goto, A.; Naka, H.;
Noyori, R.; Saito, S. Chem. - Asian J. 2011, 6, 1740. (d) Matsuoka, A.;
Isogawa, T.; Morioka, Y.; Knappett, B. R.; Wheatley, A. E. H.; Saito, S.;
Naka, H. RSC Adv. 2015, 5, 12152.
The Supporting Information is available free of charge on the
Experimental details, characterization data, and NMR
spectra of β-hydroxyamides 4a−t (PDF)
́
(10) For recent works, see: (a) García-Alvarez, R.; Zablocka, M.;
Crochet, P.; Duhayon, C.; Majoral, J.-P.; Cadierno, V. Green Chem.
AUTHOR INFORMATION
Corresponding Authors
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-Mendivil, E.; García-Alvarez, R.; Vidal, C.;
2013, 15, 2447. (b) Tomas
Crochet, P.; Cadierno, V. ACS Catal. 2014, 4, 1901. (c) Tomas
Mendivil, E.; Suarez, F. J.; Díez, J.; Cadierno, V. Chem. Commun. 2014,
50, 9661. (d) Tomas-Mendivil, E.; Menendez-Rodríguez, L.; Francos,
J.; Crochet, P.; Cadierno, V. RSC Adv. 2014, 4, 63466. (e) Tomas
Mendivil, E.; Cadierno, V.; Menendez, M. I.; Lopez, R. Chem. - Eur. J.
2015, 21, 16874. (f) Tomas-Mendivil, E.; Francos, J.; Gonzalez-
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Org. Lett. XXXX, XXX, XXX−XXX