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

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

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 
• 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 

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.