Fluorous Heck couplings

The Heck reaction is another Pdcarbon-carbon bond forming process that is widely employed in organic synthesis and can occur in water. A recent example reported by Cacchi and coworkers was applied to the chemoenzymatic synthesis of (f ) -Rhododendrol (34) and other chiral alcohols (Scheme 4.17) (67]. To aid this work, perfluoro-tagged palladium nanoparticles (Pd p) immobilized on fluorous silica gel or through covalent bonding to silica were used as the catalytic systems. The Heck coupled product could be further treated with (R)-selective LbADH and 2-propanol to address the synthesis of (R)-Rhododendrol in 90% conversion and with 99% ee. 

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. 

This review is divided into four main sections, covering the Heck, Stille, and Suzuki reactions, with miscellaneous reactions being included at the end. Processes featuring alkynes in copper co-catalyzed Sonogashira-type couplings have been included in the section on Heck reactions. This review does not cover carbon-carbon bond formation processes using immobilized catalysts. Similarly, fluorous-phase syntheses " and those on polyethylene glycol " are excluded. 

Another fluorous palladium complex that was applied in a Mizoroki-Heck reaction is the SCS pincer palladium complex 24 (Table 15.1, entry 3) [67]. It was applied under thermal and microwave heating. No fluorous solvent was used and the insoluble catalyst dissolved at the reaction temperature of 140 °C. The catalyst was recovered after 30 to 45 min by solid-phase extraction with a fluorous silica gel. Depending on whether activated or nonactivated substrates were coupled, the yields ranged between 76 and 94%. 

Two new fluorous chiral 2,2 -bis(diphenylphosphino)-1,1 -binaphthyl (BINAP Table 15.1, entries 11 and 12) ligands were synthesized and their efficiency was demonstrated in an asymmetric Mizoroki-Heck reaction (Scheme 15.8) [74-76]. Aryl triflates 38 were coupled with 2,3-dihydrofuran (39) to (i )-40 in up to 93% ee. Either pure fluorous solvents or mixtures of fluorous and nonfluorous solvents were applied. Ligand 34 was compared with conventional BINAP, with the fluorous ligand giving lower reaction rates and a similar level of enantioselectivity in 24-77 h reaction time [74, 75]. The catalyst could not be recovered by reverse-phase silica gel chromatography due to its oxidation. 

Moreno-Manas, M., Pleixats, R. and Villarroya, S. (2(K)1) Fluorous phase soluble palladium nanoparticles as recoverable catalysts for Suzuki cross-coupling and Heck reactions. 

As part of the chemoenzymatic synthesis of (/ )-(-)-rhododendrol, Cacchi and co-workers used perfluorotagged Pd NPs, immobilized on fluorous silica gel in the Mizoroki-Heck reaction of 4-iodophenol and 3-hydro>y-l-butene to synthesize the key intermediate 4-(4-hydro y-phenyl)butan-2-one (more commonly known as raspberiy ketone) in one step. The coupling product was further treated with the Lactobacillus brevis alcohol dehydrogenase (LMDH) in 2-propanol to give (/ )-rhodo-dendrol in 90% conversion and 99% ee (Scheme 4). 

A fluorous nano-paUadium catalyst based on pyrrolidine imide 22 was developed for the Suzuki coupling reaction (Scheme 7.12) [21]. The catalyst 22 promoted the coupling of aryl boronic acid and aryl halide with high yield, and the catalyst was recovered by fluorous liquid-liquid extraction and reused for three times. This fluorous nano-paUadium catalyst 22 was also employed in the Heck reaction in water [22]. The catalyst was recovered by fluorous liquid-liquid phase separation and reused for four times with Utde loss of catalytic activity. 

A fluorous 1,4-disubstituted [l,2,3]-trizole 26 was prepared from fluoroalkyl tosylate to replace the air- and moisture-sensitive phosphine ligand as a recyclable ligand for the palladium-catalyzed Suzuki-Miyaura reaction and Mizoroki-Heck reaction (Scheme 7.23) [36]. As expected, the fluorous ligand, together with palladium acetate, promoted these coupling reactions and the fluorous ligand was conveniently... 

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