Fluorous Technology

 

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Fluorous Triphasic Systems

Features of Fluorous Triphasic Systems

Fluorous Triphasic Utube
  • Scalable, Continuous All-Liquid Separations
  • Unique FLLE Application

Fluorous Triphasic Systems

Triphasic reactions consist of two organic phases that are separated from each other by a fluorous phase. Accordingly, exchange between the two organic phases is only possible for molecules that can pass through the fluorous phase. This innovative technique intimately couples a separation with a reaction-the reaction in one of the organic phases is used to drive the separation through the fluorous phase in a non-equilibrium fashion.

Consider the U-tube reaction of a 1/1 mixture of fluorous-tagged (S)-2-naphthyl-ethanol and free (R)-2-napthylethanol shown below. To start, the mixture is added to the left side of a U-tube containing organic solvents (both top sides) bridged by FC-72 (bottom). A detagging reagent (here, H2SiF6) is added to the right side of the U-tube. Over time, the tagged (S)-enantiomer migrates through the fluorous phase to the right side, where it is detagged. The resulting free (S)-enantiomer lacks the tag and is now stranded on the right side, whereas the residual tag is highly fluorous and migrates back to the FC-72. The (R)-enantiomer lacks the tag in the first place, so it cannot migrate away from the left side. At the end of the reaction, the (R)-enantiomer remains on the left side, the residual tag is in the middle, and the (S)-enantiomer has migrated to the right side and been detagged.

Fluorous-tagged molecules migrate through triphasic system

Fluorous triphasic reactions are especially useful for removal of fluorous tags because such reactions occur with separation of the tagged product from all untagged impurities. The pairing of an efficient enzymatic or chemical kinetic resolution reaction with a triphasic detagging reaction can result in a rapid and practical separation of enantiomers that does not require any chromatography. As usual, the technique allows for ready recovery of the fluorous tag in a form suitable for reuse. Like fluorous biphasic reactions, volumes of fluorous solvent used are small. However, many fewer fluorines are needed relative to biphasic reactions since the fluorous tagged molecules only needs to transiently pass through the fluorous phase.

Selected References

  • I. Ryu, H. Matsubara, S. Yasuda, H. Nakamura, and D. P. Curran. "Phase-vanishing reactions that use fluorous media as a phase screen, facile, controlled bromination of alkenes by dibromine and dealkylation of aromatic ethers by boron tribromide", J. Am Chem. Soc., in press.
  • Z. Luo, S. M. Swaleh, F. Theil, and D. P. Curran. "Resolution of 1-(2-Naphthyl)ethanol by a combination of an enzyme-catalyzed kinetic resolution with a fluorous triphasic separative reaction", Org. Lett. 2002, 4, 2585. DOI: 10.1021/ol026232f
  • H. Nakamura, B. Linclau, D. P. Curran. "Fluorous triphasic reactions: Transportative deprotection of fluorous silyl ethers with concomitant purification", J. Am. Chem. Soc. 2001, 123, 10119-10120. DOI: 10.1021/ja011716c
  • I. Ryu, H. Matsubara, S. Yasuda, H. Nakamura, D. P. Curran. "Phase-vanishing reactions that use fluorous media as a phase screen. Facile, controlled bromination of alkenes by dibromine and dealkylation of aromatic ethers by boron tribromide", J. Am. Chem. Soc. 2002, 124, 12946.