6588
T. Nagashima et al. / Tetrahedron Letters 46 (2005) 6585–6588
6. For other fluorous reagents for amide formation, see:
References and notes
F-CDMT: (a) Markowicz, M. W.; Dembinski, R. Synthe-
sis 2004, 80; (b) , F-carbodiimide:Palomo, C.; Aizpurua, J.
M.; Loinaz, I.; Fernandez-Berridi, M. J.; Irusta, L. Org.
Lett. 2001, 3, 2361.
1. For general reviews on fluorous synthesis, see: (a) Hand-
book of Fluorous Chemistry; Gladysz, J. A., Curran, D. P.,
Horvath, I. T., Eds.; Wiley-VCH: Weinheim, 2004; (b)
Zhang, W. Chem. Rev. 2004, 104, 2531; (c) Zhang, W.
Tetrahedron 2003, 59, 4475; (d) Pozzi, G.; Shepperson, I.
Coord. Chem. Rev. 2003, 242, 115; (e) Tzschucke, C. C.;
Markert, C.; Bannwarth, W.; Roller, S.; Hebel, A. Angew.
Chem., Int. Ed. 2002, 41, 3964; (f) Yoshida, J.; Itami, K.
Chem. Rev. 2002, 102, 3693; (g) Dobbs, A. P.; Kimberley,
M. R. J. Fluorine Chem. 2002, 118, 3; (h) Curran, D. P.
Synlett 2001, 1488; (i) Curran, D. P. In Stimulating
Concepts in Chemistry; Stoddard, F., Reinhoudt, D.,
Shibasaki, M., Eds.; Wiley-VCH: New York, 2000, pp
25–37; (j) Curran, D. P. Angew. Chem., Int. Ed. 1998, 37,
1175.
2. (a) Curran, D. P. Separations with Fluorous Silica Gel
and Related Materials. In Handbook of Fluorous Chemis-
try; Gladysz, J. A., Curran, D. P., Horvath, I. T., Eds.;
Wiley-VCH: Weinheim, 2004, pp 101–127; (b) For
3. (a) Barany, G.; Kempe, M. The Context of Solid-Phase
Synthesis. In A Practical Guide to Combinatorial Chemis-
try; Czarnik, A. W., DeWitt, S. H., Eds.; American
Chemical Society: Washington, DC, 1997, pp 51–97; (b)
Yan, B. Monitoring and Optimizing Organic Reactions
Carried Out on Solid Support. In Polymeric Materials in
Organic Synthesis and Catalysis; Buchmeiser, M. R., Ed.;
Wiley-VCH: Weinheim, 2003, pp 503–526.
7. Available from Fluorous Technologies, Inc. (http://
8. (a) MP-Carbonate and MP-Trisamine are products of
(b) Four to five equiv of MP-Carbonate per each acid
(HOBt, DIEA-HCl, and DIEA-HPF6) was used; (c)
For use of MP-Carbonate in HOBt scavenging, see:
Sauer, D. R.; Kalvin, D.; Phelan, K. M. Org. Lett. 2003,
5, 4721.
9. The reaction time between OBt ester and an amine varies
from within a minute to days depending on sterics and
nucleophilicity of the amine used. Among the amines we
tried, dibenzylamine was especially slow. The reaction
mixture was stirred at room temperature for 3 d to obtain
60% yield of the amide 8. See also Ref. 8c.
10. Typical procedure: To a mixture of carboxylic acid
(0.73 mmol), pyridinium salt (0.79 mmol), and HOBt
(0.79 mmol) in THF (5.0 mL) was added DIEA
(2.5 mmol) at 23 ꢁC. After 5 min, total volume was
adjusted to 6.0 mL by adding THF. After 1/2 h, 1.0 mL
of the solution was added to an amine (0.1 mmol) in THF
(1.0 mL). After 1 h, N-methyl-3-(perfluorononyl)propyl-
amine (0.04 mmol) in THF (0.5 mL) was added to convert
the excess OBt ester to fluorous tagged amide. After 16 h,
MP-Carbonate (loading = 3.4 mmol/g, 0.45 g, 1.5 mmol)
was added to remove HOBt and to neutralize HCl and
HPF6 salts of DIEA, and the mixture was stirred
vigorously for 3 h. The resin was filtered off, and was
rinsed with THF (3 · 2 mL). The filtrate was concentrated,
and the residue was dissolved in DCM (1 mL), and loaded
onto a FluoroFlash SPE cartridge (3 g)7 that was condi-
tioned with 80:20 MeOH–H2O.2b The amide was eluted
with 80:20 MeOH–H2O (10 mL).
4. (a) Mukaiyama, T.; Usui, M.; Shimada, E.; Saigo, K.
Chem. Lett. 1975, 1045; (b) Saigo, K.; Usui, M.; Kikuchi,
K.; Shimada, E.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1977, 50, 1863.
5. (a) Mukaiyama, T. Angew. Chem., Int. Ed. Engl. 1979, 18,
707; (b) Li, P.; Xu, J.-C. Tetrahedron 2000, 56, 8119; (c)
Convers, E.; Tye, H.; Whittaker, M. Tetrahedron Lett.
2004, 45, 3401; (d) Crosignani, S.; Gonzalez, J.; Swinnen,
D. Org. Lett. 2004, 6, 4579; (e) Donati, D.; Morelli, C.;
Taddei, M. Tetrahedron Lett. 2005, 46, 2817.
11. The products were characterized by 1H NMR and low
resolution mass spectral analyses (LC–MS, APCI mode).