Fluorous solvents, Diels—Alder

Extensions of the triflate catalyst include the use of versions with fluorinated ponytails such as [Sc C(S02C8Fi7)3 3] for use in fluorous phase Diels-Alder reactions (fluorinated solvent.)... 

Bayardon and Sinou have reported the synthesis of chiral bisoxazolines, which also proved to be active ligands in the asymmetric allylic alkylation of l,3-diphenylprop-2-enyl acetate, as well as cyclopropanation, allylic oxidations and Diels-Alder reactions. [62] The ligands do not have a fluorine content greater than 60 wt% and so are not entirely preferentially soluble in fluorous solvents, which may lead to a significant ligand loss in the reaction system and in fact, all recycling attempts were unsuccessful. However, the catalytic results achieved were comparable with those obtained with their non-fluorous analogues. 

Diels-Alder reactions have been performed in most alternative reaction media. For certain substrates this reaction is significantly accelerated in fluorous solvents (Figure 1.9) This has been ascribed to a fluorophobic effect, analogous to the better-known hydrophobic effect where there is an inverse relationship between reaction rate and the solubility of reagents. However, it should be noted that in general cycloaddition reactions (including Diels-Alder reactions) are faster in water and this can be attributed to additional hydrogen bond stabilization of the transition state. 

Other use of the functionalized chiral BINOL includes the 5,5, 6,6, 7, 7, 8,8 -octahydro derivative developed by Chan and coworkers, the titanium complex of which is more effective than BINOL in the enantioselective addition of triethylaluminum and diethylzinc a 4,4, 6,6 -tetrakis(perfluorooctyl) BINOL ligand developed for easy separation of the product and catalyst using fluorous solvents for the same zinc reaction an aluminum complex of 6,6 -disubstituted-2,2 -biphenyldiols used by Harada and coworkers in the asymmetric Diels-Alder reaction a titanium complex of (5 )-5,5, 6,6, 7,7, 8,8 -octafluoro BINOL employed by Yudin and coworkers in the diethylzinc addition, in the presence of which the reaction of the enantiomeric (/f)-BINOL is promoted . 

Lanthanoid salts with non-coordinating anions carrying long perfluoroalkyl chains, Yb[C(SO2CgFi7)3[3 (19) and Sc[C(SO2CgFi7)3[3 (20), have been successfully used as Lewis catalysts for O-acylations, Friedel-Crafts, Diels-Alder, and Mu-kayama aldol reactions in fluorous biphasic media [21] (Scheme 3.6). In these reactions the fluorous medium avoids deactivation of the Lewis acid by solvent coordination. The catalyst can also be recycled and reused. 

There is dramatic acceleration of certain Diels-Alder reactions in fluorous solvents (enhancement approaching those observed in water). 

FIGURE 7.13 Diels-Alder cydoaddition mediated by a hexameric capsule bearing fluorous feet operating in a fluorinated solvent and recycle of the supramolecular catalytic system. 

In another example of catalysis by the hydrogen-bonded hexamers, Shimizu et al. prepared Teflon-footed resorcin[4]arenes [56] (i.e., resorcin[4]arenes with per-fluorinated side chains) that form hexameric capsules in wet fluorous solvents. These capsules, several years later, were used to accelerate a Diels-Alder reaction in abiphasic system [56b]. 

---