G
R. Hertzberg et al.
Paper
Synthesis
Hydrogenation Reactions; General Procedure
References
Raney nickel (4200; aqueous slurry) was activated before use by
treatment with 0.1 M aq NaOH, washing with H2O to a neutral pH,
and finally washing with MeOH (×2).
(1) (a) Gregory, R. J. H. Chem. Rev. 1999, 99, 3649. (b) North, M. Tet-
rahedron: Asymmetry 2003, 14, 147. (c) Moberg, C.;
Wingstrand, E. Synlett 2010, 355.
(2) (a) Ikezaki, M.; Umino, N.; Gaino, M.; Aoe, K.; Iwakuma, T.; Oh-
Ishi, T. Yakugaku Zasshi 1986, 106, 80. (b) Veum, L.; Pereira, S. R.
M.; van der Waal, J. C.; Hanefeld, U. Eur. J. Org. Chem. 2006, 1664.
(3) Ishide, T. Curr. Med. Res. Opin. 2002, 18, 407.
(4) Sacco, E.; Bientinesi, R.; Tienforti, D.; Racioppi, M.; Gulino, G.;
D’Agostino, D.; Vittori, M.; Bassi, P. Expert Opin. Drug Discovery
2014, 9, 433.
A solution of the substrate in 1,4-dioxane was added to the activated
catalyst in an autoclave, which was sealed and flushed once with H2
before increasing the pressure to 20 bar. The mixture was stirred at 80
°C for 3 h, cooled to r.t., filtered over Celite with EtOAc as eluent, and
concentrated. The residue was purified by flash chromatography.
N-[(2R)-2-Hydroxy-2-phenylethyl]-2-phenylacetamide (10a)
(5) (a) Beckmann, M.; Haack, K.-J. Chem. Unserer Zeit 2003, 37, 88.
(b) Breckenridge, C. B.; Stevens, J. T. In Principles and Methods of
Toxicology, 5th ed.; Hayes, A. W., Ed.; CRC Press: Boca Raton,
2007, 727.
The general procedure was followed starting from 4a (73.4 mg, 0.292
mmol) with Raney nickel (129 mg) in 1,4-dioxane (2.2 mL). Flash
chromatography [silica gel, PE–EtOAc (1:2)] gave a pale-yellow solid;
26
yield: 32.7 mg (0.128 mmol, 44%; 98% ee); Rf = 0.32; [α]D –52.5 (c
(6) (a) Lundgren, S.; Wingstrand, E.; Penhoat, M.; Moberg, C. J. Am.
Chem. Soc. 2005, 127, 11592. (b) Lundgren, S.; Wingstrand, E.;
Moberg, C. Adv. Synth. Catal. 2007, 349, 364.
0.83, CH2Cl2).
HPLC [Daicel Chiralpak IC, hexanes–i-PrOH (90:10), 0.7 mL/min; λ =
220 nm]: tR (major): 50.9 min; tR (minor): 63.2 min.
(7) (a) Belokon, Y. N.; Gutnov, A. V.; Moskalenko, M. A.; Yashkina, L.
V.; Lesovoy, D. E.; Ikonnikov, N. S.; Larichev, V. S.; North, M.
Chem. Commun. 2002, 244. (b) Belokon, Y. N.; Carta, P.; Gutnov,
A. V.; Maleev, V.; Moskalenko, M. A.; Yashkina, L. V.; Ikonnikov,
N. S.; Voskoboev, N. V.; Khrustalev, V. N.; North, M. Helv. Chim.
Acta 2002, 85, 3301. (c) Norsikian, S.; Holmes, I.; Lagasse, F.;
Kagan, H. B. Tetrahedron Lett. 2002, 43, 5715. (d) Belokon, Y. N.;
Carta, P.; North, M. Lett. Org. Chem. 2004, 1, 81. (e) Belokon, Y.
N.; Blacker, A. J.; Clutterbuck, L. A.; Hogg, D.; North, M.; Reeve,
C. Eur. J. Org. Chem. 2006, 4609.
IR (neat): 3291, 3029, 2918, 1656, 1545, 701 cm–1
.
1H NMR (500 MHz, CDCl3): δ = 7.26–7.36 (m, 8 H), 7.21 (d, J = 7.1 Hz, 2
H), 5.77 (br s, 1 H), 4.80 (dd, J = 3.4, 7.4 Hz, 1 H), 3.64 (ddd, J = 3.4, 6.6,
14.1 Hz, 1 H), 3.58 (s, 2 H), 3.33 (ddd, J = 5.7, 7.7, 13.8 Hz, 1 H).
13C NMR (125 MHz, CDCl3): δ = 172.7, 141.7, 134.6, 129.6, 129.2,
128.7, 128.0, 127.6, 125.9, 73.8, 47.7, 43.8.
HRMS (ESI-Orbitrap): m/z [M + H]+ calcd for C16H18NO2: 256.1332;
found: 256.1324.
(8) Hertzberg, R.; Monreal Santiago, G.; Moberg, C. J. Org. Chem.
2015, 80, 2937.
(9) (a) Wingstrand, E.; Laurell, A.; Fransson, L.; Hult, K.; Moberg, C.
Chem. Eur. J. 2009, 15, 12107. (b) Fransson, L.; Laurell, A.;
Widyan, K.; Wingstrand, E.; Hult, K.; Moberg, C. ChemCatChem
2010, 2, 683.
(10) Hertzberg, R.; Moberg, C. J. Org. Chem. 2013, 78, 9174.
(11) (a) Hama, T.; Liu, X.; Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc.
2003, 125, 11176. (b) Hama, T.; Culkin, D. A.; Hartwig, J. F. J. Am.
Chem. Soc. 2006, 128, 4976. (c) Hama, T.; Ge, S.; Hartwig, J. F.
J. Org. Chem. 2013, 78, 8250.
(12) (a) Lou, S.; Fu, G. C. J. Am. Chem. Soc. 2010, 132, 1264. (b) Jin, M.;
Nakamura, M. Chem. Lett. 2011, 40, 1012. (c) Mao, J.; Liu, F.;
Wang, M.; Wu, L.; Zheng, B.; Liu, S.; Zhong, J.; Bian, Q.; Walsh, P.
J. J. Am. Chem. Soc. 2014, 136, 17662.
N-[(2R)-2-(3-Chlorophenyl)-2-hydroxyethyl]-2-phenylacetamide
(10i)
The general procedure was followed starting from 4i (61.9 mg, 0.217
mmol) with Raney nickel (95 mg) in 1,4-dioxane (3.4 mL). Flash chro-
matography [silica gel, PE–EtOAc (1:3)] gave a colorless gum; yield:
26
31.9 mg (0.110 mmol, 51%; 90% ee); Rf = 0.37; [α]D –43.5 (c 2.0,
CH2Cl2).
HPLC [Daicel Chiralpak IC, hexanes–i-PrOH (90:10), 0.7 mL/min; λ =
220 nm]: tR (major): 26.5 min; tR (minor): 33.8 min.
IR (neat): 3307, 3064, 3030, 2927, 1646, 1539 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.27–7.37 (m, 4 H), 7.18–7.25 (m, 4 H),
7.12–7.15 (m, 1 H), 5.74 (br s, 1 H), 4.80 (dd, J = 3.2, 7.0 Hz, 1 H), 3.63
(ddd, J = 3.3, 6.6, 14.3 Hz, 1 H), 3.58 (s, 2 H), 3.31 (ddd, J = 5.8, 6.9, 14.1
Hz, 1 H).
(13) Sato, M.; Miyaura, N.; Suzuki, A. Chem. Lett. 1989, 1405.
(14) Gooßen, L. J. Chem. Commun. 2001, 669.
13C NMR (125 MHz, CDCl3): δ = 173.2, 143.9, 134.6, 134.4, 129.9,
(15) (a) Liu, X.-x.; Deng, M.-z. Chem. Commun. 2002, 622. (b) Lu, T.-
Y.; Xue, C.; Luo, F.-T. Tetrahedron Lett. 2003, 44, 1587. (c) Duan,
Y.-Z.; Deng, M.-Z. Tetrahedron Lett. 2003, 44, 3423. (d) Liu, C.;
He, C.; Shi, W.; Chen, M.; Lei, A. Org. Lett. 2007, 9, 5601.
(e) Duan, Y.; Zhang, J.; Yang, J.; Deng, M. Chin. J. Chem. 2009, 27,
179. (f) Peng, Z.-Y.; Wang, J.-P.; Cheng, J.; Xie, X.-m.; Zhang, Z.
Tetrahedron 2010, 66, 8238. (g) Lundin, P. M.; Fu, G. C. J. Am.
Chem. Soc. 2010, 132, 11027. (h) Zimmermann, B.; Dzik, W. I.;
Himmler, T.; Goossen, L. J. J. Org. Chem. 2011, 76, 8107.
(i) Molander, G. A.; Traister, K. M.; Barcellos, T. J. Org. Chem.
2013, 78, 4123.
129.6, 129.3, 128.0, 127.7, 126.2, 124.1, 73.4, 47.8, 43.7.
HRMS (ESI-Orbitrap): m/z [M + H]+ calcd for C16H17ClNO2: 290.0942;
found: 290.0932.
Acknowledgment
Financial support from the Swedish Research Council (Grant 621-
2012-3391) is gratefully acknowledged.
(16) (a) De Joarder, D.; Jennings, M. P. Tetrahedron Lett. 2013, 54,
3990. (b) De Joarder, D.; Jennings, M. P. Eur. J. Org. Chem. 2015,
3303.
(17) (a) Uehling, D. E.; Shearer, B. G.; Donaldson, K. H.; Chao, E. Y.;
Deaton, D. N.; Adkison, K. K.; Brown, K. K.; Cariello, N. F.; Faison,
W. L.; Lancaster, M. E.; Lin, J.; Hart, R.; Milliken, T. O.; Paulik, M.
Supporting Information
Supporting information for this article is available online at
experiments, NMR spectra, HPLC, and computational details are in-
cluded.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–H