2068
W. Zhang et al. / Tetrahedron Letters 44 (2003) 2065–2068
Trans. 1 2000, 3815; (h) Hodges, J. C. Synlett 2000, 152;
9. Ouari, O.; Polidori, A.; Pucci, B.; Tordo, P.; Chalier, F.
J. Org. Chem. 1999, 64, 3554.
(i) Shuttleworth, S. J.; Allin, S. M.; Wilson, R. D.;
Nasturica, D. Synthesis 2000, 1035; (j) Eames, J.; Watkin-
son, M. Eur. J. Org. Chem. 2001, 1213–1224; (k) Kirschn-
ing, A.; Monenschein, H.; Wittenberg, R. Angew. Chem.,
Int. Ed. Engl. 2001, 40, 650; (l) Yoshida, J.-I.; Itami, K.
Chem. Rev. 2002, 102, 3693.
10. Typical procedure for the reaction of 3a with amines: To
a solution of phenyl isocyanate (0.2 mmol) in CH2Cl2
(0.5–1.0 mL) was added an excess amount of amine (1.5
equiv., 0.3 mmol). The resulting solution was stirred at
60°C for 6–12 h in a capped vial. Upon completion of the
reaction, fluorous isatoic anhydride 1 was added (1.0
equiv., 0.2 mmol) and the reaction mixture was stirred for
2.5 h at 60°C. The reaction mixture was concentrated to
0.2–0.5 mL and loaded onto a 5 g FluoroFlash™ SPE
cartridge12 pre-conditioned with MeOH–H2O (80:20) on
an SPE manifold. The cartridge was eluted with 10 mL of
MeOH–H2O (80:20), then with 100% MeOH to wash off
fluorous compounds from the cartridge. The MeOH–H2O
fraction containing the desired product was evaporated in
a Speedvac to give the corresponding urea in quantitative
yield. The SPE cartridge can be reconditioned by washing
with fluorophilic solvents such as THF or acetone and
equilibrated with MeOH–H2O (80:20) for the next round
of SPE. The cartridge can be reused up to 10 times.
11. Representative analytical data, 3b, 1H NMR (CDCl3) l
3.09 (t, J=5.5 Hz, 2H), 3.98 (t, J=5.5 Hz, 2H), 6.10 (br
s, 1H), 6.80–6.95 (3H), 7.15 (t, J=5.4 Hz, 1H), 7.18–7.26
(4 H), 7.35 (d, J=5.4 Hz, 1H), 7.52 (br s, 1H), 7.60 (d,
J=5.4 Hz, 1H), 8.00 (br s, 1H); MS (EI) m/z (rel.
intensity) 295 (M+, 80), 261 (35), 143 (100), 130 (80). 6d,
1H NMR (CDCl3) l 2.73 (m, 4H), 2.92 (m, 2H), 3.70 (m,
4H), 3.78 (s, 3H), 3.98 (m, 2H), 4.25 (m, 1H), 6.65–6.75
(2H), 6.80–6.70 (4H), 7.51 (t, J=8.2 Hz, 1H), 8.25 (d,
J=4.9 Hz, 1H); MS (CI) m/z (rel. intensity) 344 (M++H,
100).
2. (a) Curran, D. P. Chemtracts-Org. Chem. 1996, 9, 75; (b)
Curran, D. P. Angew. Chem., Int. Ed. Engl. 1998, 37,
1175; (c) Curran, D. P. In Stimulating Concepts in Chem-
istry; Stoddard, F.; Reinhoudt, D.; Shibasaki, M., Eds.;
Wiley-VCH: New York, 2000; p. 25; (d) Curran, D. P.;
Hadida, S.; Studer, A.; He, M.; Kim, S.-Y.; Luo, Z.;
Larhed, M.; Hallberg, M.; Linclau, B. In Combinatorial
Chemistry: A Practical Approach; Fenniri, H., Ed.;
Oxford University Press: Oxford, 2001; Vol. 2, p. 327.
3. Curran, D. P. Synlett 2001, 1488.
4. Zhang, W.; Curran, D.; Chen, C. H.-T. Tetrahedron
2002, 58, 3871.
5. For related fluorous scavenger work, see: (a) Lindsley, C.
W.; Zhao, Z.; Leister, W. H. Tetrahedron Lett. 2002, 43,
4225; (b) Lindsley, C. W.; Zhao, Z.; Leister, W. H.
Strauss, K. A. Tetrahedron Lett. 2002, 43, 6319.
6. Early work on fluorous quenching combined with liquid–
liquid extraction, see: (a) Curran, D. P.; Hadida, S.; Kim,
S. Y.; Luo, Z. Y. J. Am. Chem. Soc. 1999, 121, 6607; (b)
Linclau, B.; Singh, A. K.; Curran, D. P. J. Org. Chem.
1999, 64, 2835; (c) Wipf, P.; Reeves, J. T.; Balachandran,
R.; Giuliano, K. A.; Hamel, E.; Day, B. W. J. Am. Chem.
Soc. 2000, 122, 9391.
7. Polymer-supported isatoic anhydride: Coppola, G. M.
Tetrahedron Lett. 1998, 39, 8233.
8. Polymer-supported isocyanate: (a) Kaldor, S. W.; Siegel,
M. G.; Fritz, J. E.; Dessman, B. A.; Hahn, P. Tetra-
hedron Lett. 1996, 37, 7193; (b) Booth, J. R.; Hodges, J.
C. J. Am. Chem. Soc. 1997, 119, 4882.
12. Fluorous isatoic anhydride 1, isocyanate 2, and Fluo-
roFlash™ SPE cartridges are available from Fluorous