Sonogashira coupling reaction utility

Spiro-linked compounds containing heterocyclic units have been prepared for many apphcations. In general, there are two synthetic pathways to build up heterocyclic spiro compounds. On the one hand, cross-coupling reactions like the Negishi, Kharash, Stille, Suzuki, or Sonogashira coupling reaction can be utilized to connect the heterocychc subunit with the central spiro core [118]. On the other hand, the heterocycle can be built up from spiro precursors containing heteroatoms. 

There are many other examples in the literature where sealed-vessel microwave conditions have been employed to heat water as a reaction solvent well above its boiling point. Examples include transition metal catalyzed transformations such as Suzuki [43], Heck [44], Sonogashira [45], and Stille [46] cross-coupling reactions, in addition to cyanation reactions [47], phenylations [48], heterocycle formation [49], and even solid-phase organic syntheses [50] (see Chapters 6 and 7 for details). In many of these studies, reaction temperatures lower than those normally considered near-critical (Table 4.2) have been employed (100-150 °C). This is due in part to the fact that with single-mode microwave reactors (see Section 3.5) 200-220 °C is the current limit to which water can be safely heated under pressure since these instruments generally have a 20 bar pressure limit. For generating truly near-critical conditions around 280 °C, special microwave reactors able to withstand pressures of up to 80 bar have to be utilized (see Section 3.4.4). 

Another palladium-catalyzed coupling reaction that has been successfully performed on soluble polymers is the Sonogashira coupling. Xia and Wang have presented an approach in which the PEG 4000 utilized simultaneously serves as polymeric support, solvent, and phase-transfer catalyst (PTC) in both the coupling and... 

The applications of microwave chemistry to organic chemistry are too numerous to mention. A few representative examples will be given to illustrate the scope and utility. Microwave chemistry is widely used in synthesis. Examples include the Heck reaction (reaction 13-10)," the Suzuki reaction (reaction 13-12)," the Sonogashira reaction (reaction 13-13)," Ullman type couplings (reaction... 

Muller and coworkers have recently developed a coupling-isomerization reaction, initially identified as a side reaction which occurred under standard Sonogashira conditions [79]. As demonstrated below, the coupling reaction is followed by a shuffling of oxidation states via an alkyne-allene isomerization [80]. The product, a,P-unsaturated ketone 146, is reminiscent of a product which would be obtained from a Heck reaction. The utility of this reaction was further demonstrated when diamine 147 was added to the reaction pot. Following a conjugate addition reaction and imine formation, compound 148 resulted from the three-component, one-pot reaction sequence enabled by the coupling-isomerization reaction. 

Heteroannulation of alkynes is an efficient method for the preparation of complex heterocycles. Preparation of the preannulation substrate is often accomplished via Sonogashira coupling. Indeed, this protocol has been utilized effectively for the preparation of quinazolinones [107] and benzothioazoles [108]. The reactions have been carried out on substituted iodopyrimidines to provide the desired complex heterocycles. 

Numerous works on the optimization of [ F]-fluoridations and the preparation of specific [ F]-labeled radiotracers using diaryliodonium salts have been published. Wiist and coworkers have developed a convenient access to 4-[ F]fiuoroiodobenzene (28) employing 4,4 -diiododiaryliodonium salt 27 as a precursor (Scheme 7.8) [71-73]. 4-[ F]Fluoroiodobenzene (28) has been further utilized in Sonogashira or Stille cross-coupling reactions for the preparation of numerous radiotracers. For example, the Stille reaction with 4-[ F]fiuoroiodobenzene has been used for the synthesis of radiotracers for monitoring COX-2 expression by means of PET. By using optimized reaction conditions F-labeled COX-2 inhibitors 29 and 30 could be obtained in radiochemical yields of up to 94% and 68%, respectively, based upon 4-[ F]fiuoroiodobenzene (28) [72]. 

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