Enhancer unreactive halides

In the absence of die polyether, potassium fluoride is insoluble in benzene and unreactive toward alkyl halides. Similar enhancement of solubility and reactivity of other salts is observed in the presence of crown ethers The solubility and reactivity enhancement result because the ionic compound is dissociated to a tightly complexed cation and a naked anion. Figure 4.13 shows the tight coordination that can be achieved with a typical crown ether. The complexed cation, because it is surrounded by the nonpolar crown ether, has high solubility in the nonpolar media. To maintain electroneutrality, the anion is also transported into the solvent. The cation is shielded from interaction with the anion as a... 

The possibility of coupling an aryl halide with an unreactive C - H bond opens a plethora of possibilities in the synthesis of biaryl compounds [171, 172]. A (NHC)Pd(II) complex has recently been used to promote the intramolecular direct arylation of aryl chlorides [173]. Whereas a number of complexes with different NHC were screened, (IPr)Pd(OAc)2 was found to be the pre-catalyst of choice (Scheme 22). The use of IPr HC1 as additive led to an enhancement of reactivity, probably due to the preventive effect on the catalyst decomposition at the high reaction temperature. These conditions... 

In the conversion of 66 to 67, we saw that HMPA was used as an additive. Another useful ingredient in many alkylation reactions is hexamethylphosphorus triamide [HMPT, (Me2N)3P], which coordinates with the enolate anion, diminishing the aggregate state and increasing reactivity. This additive also enhances the polarity of the solvent and thereby enhances the facility of the Sn2 alkylation step (sec. 2.7.A.i). The use of an additive such as HMPA or HMPT is very common when the enolate anion reacts slowly and/or the halide is relatively unreactive. Other acid derivatives such as lactones can react with LDA to give an enolate anion, which then reacts with alkyl halides in the usual manner. 

In the absence of the polyether, potassium fluoride is insoluble in such solvents and unreactive toward alkyl halides. Similar enhancement of the reactivity and solubility of other salts are also observed in the presence of crown ethers. 

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