Nucleophilic substitution reactions ethers with strong acids

The indan-based a-amino acid derivatives can be synthesized by PTC. Kotha and Brahmachary [11] indicated that solid-liquid PTC is an attractive method that offered an effective way of preparing optically active products by chiral PTC. They found that ethyl isocyanoacetate can be easily bisalkylated in the presence of K2CO3 as the base and tetrabutylammonium hydrogen sulfate as the catalyst. The advantage of isolating water from the reaction medium is to avoid the formation of unwanted hydroxy compounds in the nucleophilic substitution reaction. If liquid-liquid PTC is applied in the system with the strong base NaOH and dichloromethane as the organic solvent, the formation of dihydroxy or cyclic ether can be observed. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

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