Light fluorous

Curran DP, Luo ZY (1999) Fluorous Synthesis with Fewer Fluorines (Light Flu-orous Synthesis) Separation of Tagged from Untagged Products by Solid-Phase Extraction with Fluorous Reverse-Phase Silica Gel. J Am Chem Soc 121 9069-9072... 

All NMR samples were dissolved in chloroform. The fluorous tin hydride is only slightly soluble in chloroform. Therefore it is necessary to saturate this NMR sample. The NMR spectrum must be recorded quickly since the tin hydride reduces chloroform on standing in the light. 

Fig. 17. Fluorous patches direct the pairing of protein segments in lipid micelles. The hydrophobic peptides partition into lipid micelles, forming a-helices. Then, the superhydrophobic hexafluoroleucine residues seek each other, causing self-association into dimers and higher order aggregates. Fluorine is light, while the backbone of the a-helices is dark. From Ref. [81], with permission.

Another elegant technique in fluorous synthesis is the use of reverse-phase fluorinated silica gel as a solid separation phase. Such fluorinated solids allow the separation of fluorous from nonfluorous materials by selective adsorption, and can even be used for chromatographic separations by degree of fluorination (Kainz et al., 1998). These techniques require a considerably lower content of fluorine for efficient separation and have been referred to as light fluorous synthesis (Curran and Luo, 1999). 

Interestingly, the first experiments demonstrating the fluorous biphasic concept were actually made in 1991 by M. Vogt, a German PhD student at the Rheinisch-Westfalischen Technischen Hochschule in Aachen. Unfortunately, Vogt (and his supervisor ) never published these results except as a PhD thesis hidden at the technical school library in Aachen, so their work remained secret. It came to light only some years after the field of fluorous biphasic chemistry was established internationally [151]. 

An elegant way out of the problem of low solubility was the advent of light fluorous chemistry (usually employing a fluoricity of below 40% w and fluo-... 

A traceless perfluoroalkylsulfonyl linker for the deoxygenation of phenols has been reported by Holmes. A more lightly fluorous variant has also been presented by Zhang, where microwave heating was applied to increase the speed of the reaction. The traceless tag was exemplified in syntheses of triaryl-substituted pyrimidines and hydantoins (Reaction Scheme 10). 

Curran, D. P. (2006) Organic synthesis with light-fluorous reagents, reactants, catalysts, and... 

Curran, D. P. (2004) Light fluorous chemistry - A user s guide, in The Handbook of Fluorous Chemistry (eds J. A. Gladysz, D. P. Curran and I. T. Horvath), Wiley-VCH Verlag GmbH, Weinheim, pp. 128-156. 

According to a loose convention, heavy fluorous (F > 60%) and light fluorous ... 

Fluorous scavengers do not necessarily need to form a covalent bond with the species they have to remove into the fluorous phase. For example, lightly fluorous N,N -dialkyl ureas can bind to perfluorocarboxyl ic acids by hydrogen... 

Scheme 3.26 Lightly fluorous N.N -dialkyl urea (Rp = QFn) has a relatively low partition coefficient of 30 70 in a C-Fp/CHjCIj biphasic system. After addition of perfluoroheptanoic acid, the partition coefficient of the resulting hydrogen bonded complex is 99 1, and the urea is completely removed from the organic into the fluorous phase [29].

While it is instructive to view BTF as a potential substitute for other types of solvents, chemical common sense and experience teach us that no one solvent is an exact substitute for another. Indeed, some applications where BTF is advantageous are already beginning to emerge. For example, in our group BTF has displaced benzene as the solvent of first choice for many kinds or radical reactions. And the unique features of BTF and related lightly fluorinated solvents for fluorous synthesis techniques cannot be substituted for by any traditional organic solvent. 

Stuart and co-workers reported the first synthesis of a light fluorous BINAP, (R)-6,6 -bis(lH,lH,2H,2H-perfluorooctyl)-2,2 -bis(diphenylphosphino)-l,l -bi-naphthyl (F content = 38%), and its application to a Ru complex catalyzed asymmetric hydrogenation of dimethyl itaconate [Eq. (2)] [10). The reaction was carried out at ambient temperature under the same reaction conditions as those reported by Noyori [11). The chemical yield (83%) and enantioselectivity (95.7% ee) were similar to those reported (88% and 95.4% ee, respectively). However, there was no description of the recovery of the catalyst or ligand. 

CH2)mRfn and serve a like dissolves like function. When such phase labels are present in sufficient length or quantity, the fluorous phase affinity (fluorophilicity) of the compound can be extremely high. This characteristic is used in the design of dyes that adhere strongly to Teflon. Molecules that have large numbers of such fluorine atoms - typically from 39 to > 100 - are called heavy fluorous compounds. However, for certain applications moderate fluorous phase affinities suffice, and for the compounds used in such applications, the term light fluorous is sometimes utilized (Table 3.1). 

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