PAPER
Endocyclic β-Amino Acids with Two Contiguous Stereocenters
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1H NMR (400 MHz, CDCl3): δ = 7.23 (m, 3 H), 7.16 (m, 2 H), 7.04
(m, 2 H), 6.68 (t, J = 6.9 Hz, 1 H), 6.57 (d, J = 7.5 Hz, 1 H), 4.96 (d,
J = 4.4 Hz, 1 H), 4.40 (br, 1 H), 4.10–4.05 (m, 2 H), 3.25–3.20 (m,
1 H), 2.96–2.83 (m, 2 H), 1.20–1.15 (t, J = 7.1 Hz, 3 H).
Supporting Information for this article is available online at
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References
13C NMR (100 MHz, CDCl3): δ = 172.3, 143.7, 142.3, 129.8, 128.5,
127.9, 127.6, 127.1, 119.1, 117.4, 113.6, 60.8, 56.1, 43.5, 25.1,
14.3.
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2005, 2, 39.
HRMS: m/z [M + H]+ calcd for C18H20NO2: 282.1494; found:
282.1497.
The relative and absolute configurations were tentatively assigned
by comparison with 2b and NOE experiment.
(+)-Methyl 2-Isopropyl-6-methoxy-1,2,3,4-tetrahydroquino-
line-3-carboxylate (2m)
Colorless oil; yield: 49.5 mg (94%), 85% ee; HPLC (Chiracel OD-
H column, 254 nm, 30 C, n-hexane–i-PrOH, 70:30, flow = 0.7
mL/min): tR = 8.2 (major), 9.9 min.
(2) (a) Maison, W.; Kosten, M.; Charpy, A.; Kintscher-
Langenhagen, J.; Schlemminger, I.; Lutzen, A.; Westerhoff,
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(b) Christianson, L. A.; Lucero, M. J.; Appella, D. H.; Klein,
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Nishi, A.; Hosokawa, T. Synlett 2005, 631. (d) Lelais, G.;
Seebach, D. Biopolymers 2004, 76, 206.
[α]D20 +58.4 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 6.61 (d, J = 7.5 Hz, 2 H), 6.52 (d,
J = 8.1 Hz, 1 H), 3.73 (s, 3 H), 3.65 (s, 3 H), 3.10–2.98 (m, 4 H),
1.89–1.84 (m, 1 H), 1.02 (dd, J = 14.8, 6.6 Hz, 6 H).
(3) (a) Miyata, O.; Muroya, K.; Kobayashi, T.; Yamanaka, R.;
Kajisa, S.; Koide, J.; Naito, T. Tetrahedron 2002, 58, 4459.
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Org. Chem. 2003, 1500. (d) O’Brien, P.; Porter, D. W.;
Smith, N. M. Synlett 2000, 1336. (e) Masesane, I. B.; Steel,
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Tetrahedron: Asymmetry 2008, 19, 2135. (b) Basak, R. K.;
Dharuman, S.; Vankar, Y. D. Tetrahedron Lett. 2012, 53,
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2560.
13C NMR (100 MHz, CDCl3): δ = 173.5, 152.5, 138.1, 121.4, 116.3,
114.5, 113.3, 60.3, 55.9, 51.7, 40.0, 30.2, 29.3, 20.5, 19.7.
HRMS: m/z [M + H]+ calcd for C15H22NO3: 264.1600; found:
264.1584.
(+)-Methyl 6-Chloro-2-isopropyl-1,2,3,4-tetrahydroquinoline-
3-carboxylate (2n)
White solid; yield: 50.3 mg (94%); 89% ee; mp 82–84 C; HPLC
(Chiracel OD-H column, 254 nm, 30 C, n-hexane–i-PrOH, 70:30,
flow = 0.7 mL/min): tR = 6.6 (major), 8.6 min.
[α]D20 +58.4 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 6.97–6.91 (m, 2 H), 6.46 (d, J =
8.5 Hz, 1 H), 3.99 (s, 1 H), 3.66 (s, 3 H), 3.10–2.92 (m, 4 H), 1.88–
1.82 (m, 1 H), 1.01 (dd, J = 11.5, 6.6 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 173.1, 142.7, 129.1, 126.9, 122.2,
121.4, 115.8, 59.7, 51.8, 39.6, 30.4, 28.9, 20.4, 19.8.
HRMS: m/z [M + H]+ calcd for C14H19ClNO2: 268.1104; found:
268.1094.
(+)-Methyl 6-Fluoro-2-isopropyl-1,2,3,4-tetrahydroquinoline-
3-carboxylate (2o)
Yellow oil; yield: 47.2 mg (94%); 89% ee; HPLC (Chiracel OD-H
column, 254 nm, 30 C, n-hexane–i-PrOH, 70:30, flow = 0.7
mL/min): tR = 6.4 (major), 7.6 min.
(5) For selected reviews, see: (a) Zhou, Y.-G. Acc. Chem. Res.
2007, 40, 1357. (b) Wang, D.-S.; Chen, Q.-A.; Lu, S.-M.;
Zhou, Y.-G. Chem. Rev. 2012, 112, 2557. (c) Glorius, F.
Org. Biomol. Chem. 2005, 3, 4171. (d) Lu, S.-M.; Han, X.-
W.; Zhou, Y.-G. Chin. J. Org. Chem. 2005, 25, 634.
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2006, 4343.
(8) Ren, L.; Lei, T.; Ye, J. X.; Gong, L.-Z. Angew. Chem. Int.
Ed. 2012, 51, 771.
[α]D20 +23.5 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3): δ = 6.74–6.67 (m, 2 H), 6.48–6.45 (m,
1 H), 3.85 (s, 1 H), 3.66 (s, 3 H), 3.10–2.98 (m, 4 H), 1.93–1.81 (m,
1 H), 1.02 (dd, J = 12.2, 6.6 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 173.3, 156.1 (d, 1JF-C = 234.8 Hz),
140.3, 121.4 (d, 3JF-C = 6.3 Hz), 115.7 (d, 3JF-C = 7.7 Hz), 115.6 (d,
2JF-C = 22.1 Hz), 113.7 (d, 2JF-C = 22.6 Hz), 60.1, 51.7, 39.7, 30.3,
29.2, 20.4, 19.8.
19F NMR (376 MHz, CDCl3): δ = –127.4.
HRMS: m/z [M + H]+ calcd for C14H19FNO2: 252.1400; found:
(9) Shi, L.; Ye, Z.-S.; Cao, L.-L.; Guo, R.-N.; Hu, Y.; Zhou, Y.-
G. Angew. Chem. Int. Ed. 2012, 51, 8286.
(10) For recent examples on hydrogenation of functionalized
quinolines, see: (a) Maj, A. M.; Suisse, I.; Méliet, C.;
Hardouin, C.; Agbossou-Niedercorn, F. Tetrahedron Lett.
2012, 53, 4747. (b) Cai, X.-F.; Chen, M.-W.; Ye, Z.-S.; Guo,
R.-N.; Shi, L.; Li, Y.-Q.; Zhou, Y.-G. Chem. Asian J. 2013,
8, 1381. For selected works on hydrogenation of 2,3-
disubstituted quinolines, see: (c) Wang, T.; Zhuo, L.-G.; Li,
Z.; Chen, F.; Ding, Z.; He, Y.; Fan, Q.-H.; Xiang, J.; Yu, Z.-
X.; Chan, A. S. C. J. Am. Chem. Soc. 2011, 133, 9878.
268.1094.
Acknowledgment
We are grateful to the financial support from National Science
Foundation of China (21125208 & 21032003), National Basic Re-
search Program (2010CB833300) and Chinese Academy of Sci-
ences.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 3239–3244