Fluorous-Tagged Thiols

Fluorous-Tagged Scavengers 8.3.3.1 Fluorous-Tagged Thiols 

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Zhang and coworkers have reported the synthesis of two fluorous DCT reagents for parallel synthesis. TCT was allowed to react with a fluorous-tagged alcohol as well as a fluorous-tagged thiol to produce the two reagents shown in Scheme 8.23 [34]. 

Scheme 8.52 Removal of alkylation reagents utilizing a fluorous-tagged thiol scavenger.

Curran, D. P. and Oderaotoshi, Y. (2001) Thiol additions to acrylates by fluorous mixture synthesis Relative control of elution order in demixing by the fluorous tag and the thiol substituent. Tetrahedron, 57, 5243-5253. 

Lindsley and coworkers have reported the synthesis of a suite of fluorous-tagged scavengers for parallel solution phase synthesis (Figure 8.4) [32]. These scavengers have been applied towards the synthesis of various libraries in high efficiency and exceptional purity (>96%). Of particular note is the use of a tagged-epoxide for removal of alkoxide and thiols (Scheme 8.21). 

Use as Tag for Substituted Heterocycles. The fluorous thiol has been used as a phase tag to facilitate purification in the synthesis of disubstituted pyrimidines (eq 3). Using a catch and release strategy, the fluorous thiol is first attached to 2,4-dichloro-6-methylpyrimidine. Tagged pyrimidine 3 is then reacted with 3-trifluoromethylpyrazole to give 4. After the fluorous tag is activated by oxidation with Oxone, it is displaced by nucleophiles such as amines and thiols to give a variety of disubstituted pyrimidines. In this multi-step synthesis, the intermediates and the final product are purified by F-SPE. The fluorous intermediates are collected in the second fraction eluted with MeOH, while the final product is collected in the first fraction eluted with 80 20 Me0H H20. 

Milton et al. have demonstrated the preparation of substrates for the Pummerer reaction by the addition of thiols to glyoxalates. Procter et al have extended this methodology to include fluorous phase tag thiols which then led to Pummerer intramolecular cyclative capture under the appropriate reaction conditions. The methodology efficiently resulted in tagged heterocyclic frameworks which could be further modified in a number of... 

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