Fluorous synthesis microwave-assisted

Abstract Current microwave-assisted protocols for reaction on solid-phase and soluble supports are critically reviewed. The compatibility of commercially available polymer supports with the relatively harsh conditions of microwave heating and the possibilities for reaction monitoring are discussed. Instrmnentation available for microwave-assisted solid-phase chemistry is presented. This review also summarizes the recent applications of controlled microwave heating to sohd-phase and SPOT-chemistry, as well as to synthesis on soluble polymers, fluorous phases and functional ionic liquid supports. The presented examples indicate that the combination of microwave dielectric heating with solid- or soluble-polymer supported chemistry techniques provides significant enhancements both at the level of reaction rate and ease of purification compared to conventional procedures. 

Fluorous Synthesis of Dihydropteridinones by Microwave-Assisted Cyclative Cleavage... 

Fig. 2 A microwave-assisted fluorous synthesis system, microwave reactor (left), plate-to-plate SPE (middle), and a plate centrifuge unit (right)...

In addition to fluorous catalysis, the preparation of fluorous catalyst itself can benefit from microwave-assisted synthesis. The Wood group reported the preparation of rhodium perfluorobutyramide (Rh2(pfm)4), a catalyst for... 

In the synthesis of a compound library of allosteric Akt kinase inhibitors 39, Lindsley and coworkers employed different HTS techniques (Scheme 24) [54]. A polymer-supported base and a fluorous thiol scavenger were used in the alkylation reaction of 40. F-SPE purified intermediate was then used for microwave-assisted cycloaddition of 41. Similar intermediates have been used for generation of an unnatural canthine alkaloid library 42 by performing cycloaddition reactions with an indo-tethered acyl hy-drazide [55]. 

The integration of microwave heating and fluorous technologies has generated a powerful solution to address both the reaction and separation issues in parallel and combinatorial synthesis. With the further development of multimode microwave reactors for plate reactions and F-SPE for plate-to-plate separations, microwave-assisted fluorous synthesis will play an even more important role in compound library synthesis. 

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. 

One early example of microwave-assisted fluorous synthesis involved palladium-catalyzed Stifle couplings of fluorous tin reagents with aryl halides or triflates (Scheme 16.59) [90]. The desired biaryl products were isolated in good yields and purity after a three-phase extraction. Similar results were also achieved by use of so-called F-21 fluorous tags (CFl2CFl2CioF2i) on the tin reagent [91]. 

Abstract The quinoxaline (Qx) nucleus is present in various bioactive molecules. Thus, synthesis of Qxs continues to draw the attention of synthetic oiganic/medici-nal chemists. The contemporary interest in search for newer synthetic methods for this privileged class of compounds rcmains unabated and a vast number of publications continue to appear. The focus of this chapter is on the research woiks pubhshed in this area after the year 2000 with the inherent objective to attain sustainability towards the synthesis. The attention will be on the key sustainable approaches of pharmaceutical industries like the solvent-fiee reactions, use of alternate reaction media (e g., water, fluorous alcohols, polyethylene glycols, and ionic liquids), and alternate modes of synthesis such as microwave-assisted synthesis and flow reactions. 

SCHEME 36 Fluorous synthesis of benzodiazepindione-fused heterocyclic ring systems under microwave (MW) assistance. 

Zhang et al. (2006) have reported an advance fluorous synthesis of hydantoin-, piperazinedione-, and benzodiazepinedione-fused tricyclic and tetracyclic ring systems using a sequence of microwave-assisted, fluorous multicomponent reactions (F-MCRs) and fluorous solid-phase extractions (F-SPEs). They used microwave-assisted one pot, three-component [3+2] cycloaddition of azomethine ylides with... 

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