1694
T. Govender, P. I. Arvidsson / Tetrahedron Letters 47 (2006) 1691–1694
4.4. (R)-3-[(9H-Fluoren-9-ylmethoxycarbonyl)-isopropyl-
amino]-butyric acid (2c)
References and notes
1
. (a) Fairlie, D. P.; Abbenante, G.; March, D. R. Curr.
Med. Chem. 1995, 2, 654; (b) Cody, W. L.; He, J. X.;
Reily, M. D.; Haleen, S. J.; Walker, D. M.; Reyner, E. L.;
Stewart, B. H.; Doherty, A. M. J. Med. Chem. 1997, 40,
2
5
25
546
Amorphous solid; yield 94%; ½aꢀ +0.35 and ½aꢀ +0.50.
589
ꢁ1 1
IR (KBr): 3167, 1731, 1697, 1147 cm . H NMR
300 MHz, CDCl , rotamers): 0.60 (d, J = 6.7 Hz, 1.5H);
.73 (d, J = 5.9 Hz, 1.5H); 0.86 (d, J = 5.9 Hz, 1.5H);
.96 (d, J = 6.7 Hz, 1.5H); 1.39 and 1.86 (m, 1H); 2.09–
.38 (m, 1H); 2.50–2.70 (m, 1); 2.77 (s, 1.5H); 2.80
s, 1.5H); 4.01–4.26 (m, 2H); 4.33–4.67 (m, 2H); 7.22–
.42 (m, 4H); 7.60 (m, 2H); 7.75 (m, 2H); 10.10 (br s,
.5H). C NMR (75 MHz, CDCl ): 19.5 (q), 19.8 (q),
0.1 (d), 20.1 (d), 30.6 (q), 30.8 (q), 35.9 (t), 36.1 (t), 47.5
d), 47.6 (d), 60.5 (d), 67.3 (t), 67.4 (t), 120.0 (d), 120.0
d), 120.1 (d), 125.0 (d), 125.0 (d), 125.2 (d), 125.3 (d),
27.2 (d), 127.4 (d), 127.7 (d), 127.8 (d), 127.8 (d), 141.5
s), 141.5 (s), 141.6 (s), 144.1 (s), 144.3 (s), 144.5 (s),
56.8 (s), 156.9 (s), 176.8 (s), 177.2 (s). MS (ESI) m/z
(
3
2
228; (c) Haviv, F.; Fitzpatrick, T. D.; Swenson, R. E.;
0
0
2
Nichols, C. J.; Mort, N. A.; Bush, E. U.; Diaz, G.;
Bammert, G.; Nguyen, A.; Nellans, H. N.; Hoffman, D. J.;
Johnson, E. S.; Greer, J. J. Med. Chem. 1993, 36, 363; (d)
Vitoux, B.; Aubry, A.; Cung, M. T.; Marraud, M. Int. J.
Pept. Protein Res. 1986, 27, 617.
(
7
0
2
1
3
2. For reviews see: (a) Gellman, S. H. Acc. Chem. Res. 1998,
31, 173; (b) Cheng, R. P.; Gellman, S. H.; DeGrado, W. F.
Chem. Rev. 2001, 101, 3219; (c) Seebach, D.; Beck, A. K.;
Bierbaum, D. J. Chem. Biodiv. 2004, 1, 1111; For a recent
biologically relevant example see: (d) Stephens, O. M.;
Kim, S.; Welch, B. D.; Hodson, M. E.; Kay, M. S.;
Schepartz, A. J. Am. Chem. Soc. 2005, 127, 13126.
3
(
(
1
(
1
3
3
. Schmitt, M. A.; Choy, S. H.; Guzei, I. A.; Gellman, S. H.
J. Am. Chem. Soc. 2005, 127, 13130.
+
68.3 [M+H] .
4
. See: Enantioselective Synthesis of b-Amino Acids; 2nd ed.;
Juaristi, E., Soloshonok, V., Eds., John Wiley & Sons:
Hoboken, NJ, 2005.
4.5. (S)-3-Carboxymethyl-3,4-dihydro-1H-isoquinoline-2-
carboxylic acid 9H-fluoren-9-ylmethyl ester (7b)
5
. (a) Seebach, D.; Ciceri, P. E.; Overhand, M.; Jaun, B.;
Rigo, D.; Oberer, L.; Hommel, U.; Amstutz, R.; Widmer,
H. Helv. Chim. Acta 1996, 79, 2043; (b) Gademann, K.;
Ernst, M.; Seebach, D.; Hoyer, D. Helv. Chim. Acta 2000,
2
5
25
546
Amorphous solid; yield 88%; ½aꢀ
+45.7 and ½aꢀ
589
+
54.7. IR (KBr): 3065, 1731, 1698, 1422, 1120,
40 cm . H NMR (300 MHz, CDCl ): 2.35 (m, 2H);
.80 (m, 1H); 3.08 (m, 1H); 4.17–5.05 (m, 5H); 7.05–
.90 (m, 13H). C NMR (75 MHz, CDCl ): 33.1 (t),
7.0 (t), 43.4 (t), 43.7 (t), 47.4 (d), 47.5 (d), 67.8 (t),
20.2 (d), 125.1 (d), 125.2 (d), 125.3 (d), 126.3 (d),
26.5 (d), 126.9 (d), 127.0 (d), 127.3 (d), 127.9 (d),
29.3 (d), 129.6 (d), 132.1 (s), 132.4 (s), 132.5 (s), 132.7
8
3, 16.
ꢁ
1 1
7
2
8
3
1
1
1
3
6. (a) Aurelio, L.; Brownlee, R. T. C.; Hughes, A. B. Chem.
Rev. 2004, 104, 5823; (b) Aurelio, L.; Box, J. S.; Brownlee,
R. T. C.; Hughes, A. B.; Sleebs, B. E. J. Org. Chem. 2003,
68, 2652.
7. (a) Freidinger, R. M.; Hinkle, J. S.; Perlow, D. S.; Arison,
B. H. J. Org. Chem. 1983, 48, 77; (b) Aurelio, L.;
Brownlee, R. T. C.; Hughes, A. B.; Sleebs, B. E. Aust. J.
Chem. 2000, 53, 425.
1
3
3
(
1
s), 141.6 (s), 144.0 (s), 155.5 (s), 155.8 (s), 176.9 (s),
77.5 (s). MS (ESI) m/z 414.3 [M+H] .
+
8. Zhang, S.; Govender, T.; Norstr o¨ m, T.; Arvidsson, P. I. J.
Org. Chem. 2005, 70, 6918.
9
. Tantry, S. J.; Kantharaju; Babu, V. V. S. Tetrahedron
Lett. 2002, 43, 9461.
3
1
1
0. No oxazinanes from Fmoc-b -amino acids seems to have
been described in the literature; the only example found
was formation of the Boc-protected oxazinanes from
aspartic acid: Burtin, G.; Corringer, P.; Young, D. W. J.
Chem. Soc., Perkin Trans. 1 2000, 20, 3451.
1. (a) Harrison, J. R.; O’Brien, P.; Porter, D. W.; Smith, N.
M. J. Chem. Soc., Perkin Trans. 1 1999, 3623; (b)
Salvadori, S.; Guerrini, R.; Balboni, G.; Bianchi, C.;
Bryant, S. D.; Cooper, P. S.; Lazarus, L. H. J. Med. Chem.
1999, 42, 5010.
Acknowledgements
We are grateful to Vetenskapsr a˚ det (The Swedish
Research Council) for financial support, and to the
Wenner-Gren Foundation for a postdoctoral fellowship
to T.G. We would also like to acknowledge the Taka-
sago International Corporation for a kind gift of the
3
b -amino acids used.