Fluorous Columns are Superior to Cyclodextrin Columns for Demixing in Fluorous Mixture Synthesis: When and Why to Use Fluorous Silica Gel

Dennis P. Curran; Sivaraman Dandapani; Stefan Werner; Masato Matsugi

doi:10.1055/s-2004-829078

LETTER

Fluorous Columns are Superior to Cyclodextrin Columns for Demixing in Fluorous Mixture Synthesis: When and Why to Use Fluorous Silica Gel

Dennis P. Curran*, Sivaraman Dandapani, Stefan Werner, Masato Matsugi
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
Fax: +1(412)6249861; e-Mail: curran@pitt.edu;

Abstract

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Abstract

Measurements of retention times of assorted fluorous and non-fluorous compounds on both fluorous (FluoroFlash PF-C8) and cyclodextrin (Sumichiral OA 7500) columns show that the fluorous column is superior to the cyclodextrin column for separating fluorous compounds. Guidelines for when and why to use fluorous columns are suggested.

Key words

fluorine - cyclodextrin - chromatography - separation technique - fluorous mixture synthesis

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References

Reviews:

1a Curran DP. Synlett 2001, 1488

1b Curran DP. Handbook of Fluorous Chemistry Wiley-VCH; Weinheim: 2004. Chap. 7. p.101-127

2a Luo ZY. Zhang QS. Oderaotoshi Y. Curran DP. Science 2001, 291: 1766

2b Curran DP. Oderaotoshi Y. Tetrahedron 2001, 57: 5243

2c Curran DP. Furukawa T. Org. Lett. 2002, 4: 2233

2d Zhang W. Luo ZY. Chen CHT. Curran DP. J. Am. Chem. Soc. 2002, 124: 10443

2e Zhang Q. Lu H. Richard C. Curran DP. J. Am. Chem. Soc. 2004, 126: 36

3a Nakamura Y. Takeuchi S. Okumura K. Ohgo Y. Matsuzawa H. Mikami K. Tetrahedron Lett. 2003, 44: 6221

3b Matsuzawa H. Mikami K. Tetrahedron Lett. 2003, 44: 6227

4 Matsuzawa H. Mikami K. Synlett 2002, 1607

5

The fluorous esters (1c, 1d, and 1e) have been already reported by Mikami (ref. 4). The fluorous anilides 3a and 3b are commercially available from Akos or Ambinter. Selected data for the new compounds follow:
3c: colorless oil. ¹H NMR: δ = 7.29 (1 H, t), 7.42 (2 H, t), 7.58 (2 H, d), 7.9 (1 H, br s). ¹⁹F NMR: -124.9 (2 F), -121.5 (2 F), -121.0 (2 F), -120.4 (10 F), -118.0 (2 F), -79.5 (3 F).
6by: colorless oil. ¹H NMR: δ = 0.88 (3 H, t, J = 6.6 Hz), 1.31-1.65 (8 H, m), 2.68 (2 H, t, J = 7.5 Hz), 4.82 (2 H, t, J = 13.3 Hz), 7.32 (2 H, d, J = 8.2 Hz), 7.98 (2 H, d, J = 8.1 Hz). ¹⁹F NMR: -124.9 (2 F), -122.0 (2 F), -121.5 (2 F),
-120.8 (4 F), -118.0 (2 F), -79.5 (3 F). HRMS: Calcd for C₂₁H₁₉F₁₅O₂: 588.1127. Found: 588.1146.
6cz: colorless oil. ¹H NMR: δ = 1.25-1.89 (10 H, m), 2.59 (1 H, br s), 4.80 (2 H, t, J = 13.2 Hz), 7.32 (2 H, d, J = 8.3 Hz), 7.98 (2 H, d, J = 8.2 Hz). ¹⁹F NMR: -124.9 (2 F), -122.0 (2 F), -121.5 (2 F), 120.6 (8 F), -118.0 (2 F), -79.5 (3 F) ppm. HRMS: Calcd for C₂₃H₁₇F₁₉O₂: 686.0921. Found: 686.0925.
6az: colorless oil. ¹H NMR: δ = 1.25-1.89 (10 H, m), 2.59 (1 H, br s), 4.80 (2 H, t, J = 13.2 Hz), 7.32 (2 H, d, J = 8.3 Hz), 7.98 (2 H, d, J = 8.3 Hz) ppm. ¹⁹F NMR: -126.4 (2 F),
-119.1 (2 F), -79.6 (3 F) ppm. HRMS: Calcd for C₁₇H₁₇F₇O₂: 386.1129. Found: 386.1117.

6a

FluoroFlash columns are commercially available from Fluorous Technologies, Inc., www.fluorous.com. Separations are qualitatively similar to Fluofix^® 120E, although FluoroFlash media generally retain fluorous molecules more strongly.

6b

DPC is the Founder and Chief Scientific Advisor of FTI, and holds an equity interest.

7a Syntheses and reactions of these compounds will be reported separately. See: Werner, S.; Curran, D. P., manuscript in preparation

7b For related reactions, see: Werner S. Curran DP. Org. Lett. 2003, 5: 3293

8 Hydrazides 13a-e are described in: Dandapani S. Curran DP. Tetrahedron 2002, 58: 3855

9 Dobbs AP. McGregor-Johnson C. Tetrahedron Lett. 2002, 43: 2807