Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 7
ARTICLE
Journal Name
after converted into the corresponding trifluoroacetamide: Lux
5u Cellulose-3 (250 × 4.60 mm ), ipa : hex = 1:99, 1.0 mL/min,
230 nm , tR1 = 7.6 min (major), tR2 = 9.0 min (minor); H NMR
Notes and references
1
J. I. Seeman, C. G. Chavdarian and H. DVO. SI:e1c0o.1r0,3J9./CO7rOg.B0C0h4e4m2G.,
1
1985, 50, 5419.
(400 MHz, CDCl3): δ (ppm) 7.29−7.26 (m, 2H), 6.97−6.90 (m,
2H), 3.73−3.69 (m, 1H), 3.14−3.05 (m, 1H), 2.84−2.78 (m, 1H),
1.93−1.88 (m, 1H), 1.80−1.54 (m, 7H); 13C{1H}NMR (100 MHz,
2
(a) B. E. Maryanoff, D. F. McComsey, M. J. Costanzo, P. E.
Setler, J. F. Gardocki, R. P. Shank and C. R. Schneider, J. Med.
Chem., 1984, 27, 943; (b) B. E. Maryanoff, D. F. McComsey, R.
R. Inners, M. S. Mutter, G. P. Wooden, S. L. Mayo and R. A.
Olofson, J. Am. Chem. Soc., 1989, 111, 2487.
1
CDCl3): δ (ppm) 161.6 (d, JC-F = 243.0 Hz), 142.5, 127.9, 127.8,
115.2, 115.0, 64.1, 48.0, 40.0, 30.6, 26.8, 26.0; TOF-HRMS
3
(a) T. D. Penning, G.-D. Zhu, J. Gong, S. Thomas, V. B. Gandhi,
X. Liu, Y. Shi, V. Klinghofer, E. F. Johnson, C. H. Park, E. H. Fry,
C. K. Donawho, D. J. Frost, F. G. Buchanan, G. T. Bukofzer, L.
E. Rodriguez, V. Bontcheva-Diaz, J. J. Bouska, D. J. Osterling,
A. M. Olson, K. C. Marsh, Y. Luo and V. L. Giranda, J. Med.
Chem., 2010, 53, 3142; (b) L. Wang, K. A. Mason, K. K. Ang, T.
Buchholz, D. Valdecanas, A. Mathur, C. Buser-Doepner, C.
Toniatti and L. Milas, Invest. New Drugs, 2012, 30, 2113.
M. C. Bryan, K. Biswas, T. A. N. Peterkin, R. M. Rzasa, L. Arik,
S. G. Lehto, H. Sun, F.-Y. Hsieh, C. Xu, R. T. Fremeau and J. R.
Allen, Bioorg. Med. Chem. Lett., 2012, 22, 619.
calcd for C12H15NF+ [M+H+]: 194.1339, found 194.1342.
Procedure for Synthesis of (+)-(6S,10bR)-McN-4612-Z (3): (R)-
2-phenylpyrrolidine 2a (150 mg, 1.02 mmol, 95% ee), and
styrene oxide (122.6 mg, 1.02 mmol) were combined in 2 mL
of absolute ethanol in 25 mL single port flask and refluxed.
After 19 hours, 2a reacted completed with TLC monitored.
Then the solution was evaporated to yellow oil, which was
combined with PPA (2.0 g), 2 mL toluene and heated at 100 oC
for 4 hours. The reaction was cooled, diluted with ice water,
basified with 40% aqueous potassium hydroxide (PH >11)
under cooling, and extracted with methylene chloride. The
organic layers was washed with water, dried with potassium
carbonate, and evaporated to brown oil. The mixture was
separated by column chromatography (silica gel,
acetate/petroleum ether = 1:5−1:0) to give the (+)-(6S, 10bR)-
4
5
(a) L. E. Burgess and A. I. Meyers, J. Org. Chem., 1992, 57
,
1656; (b) C. J. Dunsmore, R.Carr, T. Fleming and N. J. Turner,
J. Am. Chem. Soc., 2006, 128, 2224; (c) E. J. Cochrane, D.
Leonori, L. A. Hassall and I. Coldham, Chem. Commun., 2014,
50, 9910; (d) S. Hussain, F. Leipold, H. Man, E. Wells, S. P.
France, K. R. Mulholland, G. Grogan and N. J. Turner,
ChemCatChem, 2015, 7, 579; (e) G. A. Aleku, H. Man, S. P.
France, F. Leipold, S. Hussain, L. Toca-Gonzalez, R.
Marchington, S. Hart, J. P. Turkenburg, G. Grogan and N. J.
McN-4612-Z (3 =
) (195 mg, 60%) as yellow oil. 95% ee, [α]20
D
Turner, ACS Catalysis, 2016, 6, 3880; (f) C. Ge, R.-X. Liang, R.-
+18.8 (c = 0.5 in CH3OH) ; SFC conditions: Lux 5u Cellulose-3
(250 × 4.60 mm ), CH3OH : CO2 = 10:90, 2.5 mL/min, 230 nm ,
tR1 = 2.2 min (minor), tR2 = 2.34 min (major); 1H NMR (400 MHz,
CDCl3): δ (ppm) 7.35−7.28 (m, 3H), 7.24−7.14 (m, 4H),
7.10−7.07 (m, 1H), 6.88−6.86 (m, 1H), 4.47−4.41 (t, J = 7.6 Hz,
1H), 3.60−3.56 (m, 1H), 3.51−3.47 (m, 1H), 3.20−3.16 (m, 1H),
2.72−2.67 (m, 1H), 2.54−2.46 (m, 2H), 2.00−1.79 (m, 4H).
13C{1H}NMR (100 MHz, CDCl3): δ (ppm) 144.26, 139.27, 137.64,
129.13, 129.09, 128.38, 126.44, 126.22, 126.12, 125.10, 63.89,
58.15, 52.98, 45.27, 30.42, 21.95. The analytical data are
consistent with the literature.19, 20
R. Liu, B. Xiang and Y.-X. Jia, Tetrahedron Lett., 2017, 58, 142.
(a) T. C. Nugent and M. El-Shazly, Adv. Synth. Catal., 2010,
6
7
352, 753; (b) W. Tang and X. Zhang, Chem. Rev., 2003, 103
,
3029; (c) J.-H. Xie, S.-F. Zhu and Q.-L. Zhou, Chem. Rev., 2011,
111, 1713.
(a) C. A. Willoughby and S. L. Buchwald, J. Am. Chem. Soc.,
1992, 114, 7562; (b) C. A. Willoughby and S. L. Buchwald, J.
Org. Chem., 1993, 58, 7627; (c) C. A. Willoughby and S. L.
Buchwald, J. Am. Chem. Soc., 1994, 116, 11703.
M. Chang, W. Li, G. Hou and X. Zhang, Adv. Synth. Catal.,
2010, 352, 3121.
8
9
C. Li and J. Xiao, J. Am. Chem. Soc., 2008, 130, 13208.
10 F. Chen, Z. Ding, J. Qin, T. Wang, Y. He and Q.-H. Fan, Org.
Lett., 2011, 13, 4348.
11 C. Guo, D.-W. Sun, S. Yang, S.-J. Mao, X.-H. Xu, S.-F. Zhu and
Q.-L. Zhou, J. Am. Chem. Soc., 2015, 137, 90.
Conclusions
12 (a) Chiral Amine Synthesis, ed. P. G. Andersson, Wiley-VCH
Weinheim 2010, pp. 179-223; (b) S. J. Roseblade and A. Pfaltz,
Acc. Chem. Res., 2007, 40, 1402; (c) D.-S. Wang, Q.-A. Chen,
S.-M. Lu and Y.-G. Zhou, Chem. Rev., 2012, 112, 2557; (d) J. J.
Verendel, O. Pàmies, M. Diéguez and P. G. Andersson, Chem.
Rev., 2014, 114, 2130.
In conclusion, a highly enantioselective Ir−(R,R)-spiroPhos
catalyzed asymmetric hydrogenation of 2-aryl cyclic imines in
absence of any additives has been developed. Under mild
reaction conditions a variety of 2-aryl cyclic imines were
smoothly hydrogenated to afford the corresponding chiral free
cyclic amines in high yields and excellent enantioselectivities
(up to 98%). This approach provided a straightforward access
to chiral free cyclic amines and could be successfully applied to
the synthesis of a biological active molecular skeleton, (+)-
(6S,10bR)-McN-4612-Z.
13 (a) T. Yamagata, H. Tadaoka, M. Nagata, T. Hirao, Y. Kataoka,
V. Ratovelomanana-Vidal, J. P. Genet and K. Mashima,
Organometallics, 2006, 25, 2505; (b) G. Zhu and X. Zhang,
Tetrahedron: Asymmetry, 1998, 9, 2415.
14 (a) Privileged Chiral Ligands and Catalysts, ed. Q.-L. Zhou,
Wiley-VCH, Weinheim, 2011; pp. 137-170; (b) J.-H. Xie and
Q.-L. Zhou, Acc. Chem. Res., 2008, 41, 581; (c) K. Ding, Z. Han
and Z. Wang, Chem. −Asian J., 2009, 4, 32; (d) J.-H. Xie and
Q.-L. Zhou, Acta Chim. Sinica, 2014, 72, 778.
Acknowledgements
15 (a) Q. Yan, D. Kong, M. Li, G. Hou and G. Zi, J. Am. Chem. Soc.,
2015, 137, 10177; (b) D. Kong, M. Li, R. Wang, G. Zi and G.
Hou, Org. Biomol. Chem., 2016, 14, 1216; (c) D. Kong, M. Li,
G. Zi and G. Hou, Org. Biomol. Chem., 2016, 14, 4046; (d) D.
We are grateful for the financial support from the National
Natural Science Foundation of China (grant nos. 21672024,
21272026, and 21472013), Program for Changjiang Scholars
and Innovative Research Team in University, and Beijing
Municipal Commission of Education.
Kong, M. Li, G. Zi, G. Hou and Y. He, J. Org. Chem., 2016, 81
,
6640; (e) Q. Yan, D. Kong, W. Zhao, G. Zi and G. Hou, J. Org.
Chem., 2016, 81, 2070.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins