Fluorous Diels-Alder reaction

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. 

To date, reports have involved palladium catalysts for Suzuki and Sono-gashira coupling reactions [63-66], rhodium catalysts for silylations of alcohols by trialkylsilanes [67,68], and tin-, hafnium-, and scandium-based Lewis acid catalysts for Baeyer-Villiger and Diels-Alder reactions [69]. Regardless of exact mechanism, this recovery strategy represents an important direction for future research and applications development. Finally, a particularly elegant protocol where CO2 pressure is used instead of temperature to desorb a fluorous rhodium hydrogenation catalyst from fluorous silica gel deserves emphasis [28]. 

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.)... 

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. 

More recently, a fluorous organocatalyst has been used to perform selective Diels-Alder reactions of dienes with oc,(3-unsaturated aldehydes in acetonitrile-water. The chiral fluorous imidazolidinone catalyst can be recovered using fluorous silica (80-90% recovery efficiency) and reused. Figure 7.10. Further organocatalytic reactions are presented later in this chapter. 

Figure 7.9 Rate enhancement of a Diels-Alder reaction in fluorous media.

Figure 7.10 Stereo specific Diels-Alder reaction using an organocatalyst and fluorous silica for catalyst recovery.

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 . 

A typical Diels-Alder reaction of acrolein and cyclohexadiene was conducted by Zhang and coworkers using either fluorous imidazolidinone 63 or its standard counterpart 64 as the catalyst (Scheme 5.18) [78]. The product yield (86%), endo j exo ratio (93.4 6.6) and enantioselectivity (93.4% ee for the endo isomer) afforded by 63 were comparable to those of the control experiment with 64. The fluorous catalyst was examined in Diels-Alder reactions of other dienes and a,P-unsaturated aldehydes, providing consistently high enantioselectivities. In addition, 63 could be readily separated from the reaction products by F-SPE and recovered in 80-84% yields with excellent purity. 

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

Fache et al. used fluorous cinchona derivatives in asymmetric Diels-Alder reactions in CHCI3/C5FJ4 (1 1) low enantioselectivity (13%) was obtained [33]. Moreover, due to the low fluorine content of the catalyst (45 wt.% F), the reaction probably occurred in the nonfluorous phase. 

Lanthanide tris(perfluorooctanesulfonyl)methides, such as Sc[C(S02CsFi7)3]3 and Yb[C(S02C8Fi7)3]3, can be immobilized in fluorous phases. These flu-orous Lewis acid catalysts are highly effective for the acylation of alcohols, Friedel-Crafts acylations, Mukaiyama aldol condensations and Diels-Alder reactions (Scheme 18). These reactions proceeded efficiently in an organic/fluorous... 

Shimizu S, Usui A, Sugai M, Suematsu Y, Shirakawa S, Ichikawa H. Hexameric capsule of a resorcinarene bearing fluorous feet as a self-assembled nanoreactor A Diels-Alder reaction in a fluorous biphasic system. Eur J Org Chem 2013 4734-7. 

Fluorous reverse-phase silica gel (FRPSG)-supported Lewis acids are new and effective catalysts of Baeyer-Villiger and Diels-Alder reactions in water. FRPSG-supported Sc[C(S02C4F9)3]3 (5 mol%) catalyzes the Diels-Alder cycloaddition of 2,3-dimethyl-butadiene with methyl vinyl ketone in water at room temperature (16 h, 91%) and can be recycled by simple filtration after the reaction. ... 

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]. 

On the other hand, modified-imidazoHdinones endowed with imidazole (125) [149] or a fluorous tag in the side chain (126) [150] proved to be active in the Diels-Alder cycloaddition in the presence of 5 vol.% water (Figure 24.40). The highly efficient organocatalyst 127 promoted, in the presence ofp-(trifluoromethyl) benzoic acid, the asymmetric Diels-Alder reaction of cyclohexenones with aromatic nitroolefins in seawater and brine with excellent chemo-, regjo-, and stereoselectivities [151], It has been postulated that the cychzation was involved in a concerted addition process and that seawater and brine significantly promoted the... 

A class of perfluorinated bis(dihydrooxazole) copper(ll) (PBDC) complexes immobilized on FSG was developed as catalysts for the enantioselective Diels-TUder reaction (Scheme 7.13) [23]. The perfluorinated bis(dihydrooxazole) copper(II) complexes were synthesized from enantiomericaUy pure 2-aminoethanols, which were then immobilized on FSG to give FSG-PBDG. This catalyst promoted the Diels-Alder reaction with reasonable conversions and enantioselectivities in water or dichloromethane. The fluorous nanoparticle catalysts can be recovered and... 

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. 

Another interesting development is the use of fluorous-based scavengers in conjunction with microwave synthesis and fluorous solid-phase extraction (F-SPE) for purification. This was recently illustrated by Werner and Curran [74] in their investigation of the Diels-Alder cycloaddition of maleic anhydride to diphenylbutadiene (Scheme 11.23). After performing microwave-assisted cycloaddition (160 °C, 10 min) with a 50% excess of the diene, the excess diene reagent was scavenged by a structurally related maleimide fluorous dienophile under the same reaction conditions. Elution of the product mixture from an F-SPE column with Me0H-H20 provided the desired cycloadduct 89 in 79% yield and 90% purity. Subsequent elution with diethyl ether furnished the fluorous Diels-Alder cycloadduct. 

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