Fluorous Subject

The described fluorous-tag strategy has also been applied to the synthesis of biaryl-substituted hydantoins (Scheme 7.81) [94]. 4-Hydroxybenzaldehyde was converted into the corresponding perfluorinated species, which was then subjected to a reductive amination. The resulting amine was treated with an isocyanate to produce the fluorous-tagged urea, which spontaneously cyclized to form the corresponding hydantoin. Finally, the fluorous tag was detached by a Suzuki-type carbon-carbon bond formation to furnish the desired target structure in good yield. 

In a related approach from the same laboratory, the perfluorooctylsulfonyl tag was employed in a traceless strategy for the deoxygenation of phenols (Scheme 7.82) [94], These reactions were carried out in a toluene/acetone/water (4 4 1) solvent mixture, utilizing 5 equivalents of formic acid and potassium carbonate/[l,T-bis(diphe-nylphosphino)ferrocene]dichloropalladium(II) [Pd(dppf)Cl2] as the catalytic system. After 20 min of irradiation, the reaction mixture was subjected to fluorous solid-phase extraction (F-S PE) to afford the desired products in high yields. This new traceless fluorous tag has also been employed in the synthesis of pyrimidines and hydantoins. 

Various other biphasic solutions to the separation problem are considered in other chapters of this book, but an especially attractive alternative was introduced by Horvath and co-workers in 1994.[1] He coined the term catalysis in the fluorous biphase and the process uses the temperature dependent miscibility of fluorinated solvents (organic solvents in which most or all of the hydrogen atoms have been replaced by fluorine atoms) with normal organic solvents, to provide a possible answer to the biphasic hydroformylation of long-chain alkenes. At temperatures close to the operating temperature of many catalytic reactions (60-120°C), the fluorous and organic solvents mix, but at temperatures near ambient they phase separate cleanly. Since that time, many other reactions have been demonstrated under fluorous biphasic conditions and these form the basis of this chapter. The subject has been comprehensively reviewed, [2-6] so this chapter gives an overview and finishes with some process considerations. 

Scheme 16 shows parallel syntheses of cyclic and acyclic amide compounds. Fluorous benzaldehydes were first subjected to reductive amination reactions. The resulting amines were then reacted with isocyanates to form substituted hydantoin rings 14 or with benzoyl chlorides to form amides 15. Purified F-sulfonates were used for palladium-catalyzed cross-coupling reactions to form corresponding biaryl 16 [31] and arylsulfide 17 [32] products, respectively. 

The successful demonstration of the fluorous biphasic concept for performing organometallic catalysis sparked extensive interest in the methodology and it has subsequently been applied to a wide variety of catalytic reactions, including hydrogenation [59], Heck and Suzuki couplings [60, 61] and polymerizations [62]. The publication of a special Symposium in print devoted to the subject [63] attests to the broad interest in this area. 

The reason why fluorous alkanes are immiscible with normal alkanes possibly stems from their different conformations -alkanes exist in well-known zig-zag conformations, whereas perfluoro-n-alkanes adopt more helical conformations because of the larger van der Waals radius of fluorine (r = 135 pm) as compared to that of hydrogen (r = 120 pm). Molecules of fluorous solvents are also subject to very weak van der Waals interactions due to the low polarizability of the electrons of the CF2 groups. As a... 

A different extractive work-up is based on fluorous biphasic systems. This concept was first introduced for fhe recovery of rhodium complexes from hydroformylation processes [13] and was soon extended to separation procedures in combinatorial chemistry [14]. It has been fhe subject of several reviews [15-21]. 

A similar approach of fluorous quasi-racemic synthesis [20] was used to synthesize both enantiomers of mappicine at the same time in a coded mixture. The pyridine derivative 41 was split, and the carbonyl group was reduced enantioselectively by (+)- and (-)-DIP-Cl, respectively. The resulting enantiomerically pure alcohols were subsequently derivatized - the (1 ) enantiomer with BrSi(iPr)2CH2CH2QFi3 to yield (Ji)-4-2 and the (S) enantiomer with BrSi(iPr)2CH2CH2CgFi7 to yield the quasi-enantiomer (S)-43. The mixture of both quasi-enantiomers was then subjected to the reaction sequence leading to the fluorous mappicines (R)-44 and (S)-4S. These were separated by fluorous chromatography and deprotected to yield the two mappicine enantiomers (Scheme 3.21). 

Improvement of organic i liquids has been the subject of nated chain (fluorous ionic hqi lional ionic liquids. Thus emu facilitated. ... 

Improvement of organic reactions by the use of fluorous components and ionic liquids has been the subject of intense research. Imidazolium salts that carry a polyfluori-nated chain (fluorous ionic liquids) are found to act as surfactants when added to conventional ionic liquids. Thus emulsification of fluoroalkanes with the ionic liquid phase is facilitated. ... 

A fluorous chiral organocatalyst (18) promotes the formation of the anti-Mol product (with up to 96% ee) on reaction between aromatic aldehydes with ketones in brine. The enantioselectivity achieved on promotion of aldol and Mannich reactions by another di-diamine-based catalyst (19) can be reversed by the addition of an achiral acid and is to be the subject of further mechanistic investigation. ... 

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