Final answer:
Nucleophilic aromatic substitution reactions with aryl diazonium salts are promoted by electron-withdrawing groups and facilitated by catalytic cross-coupling methods, such as Suzuki and C-H activation, to modify nucleosides and aromatic rings.
Step-by-step explanation:
Nucleophilic aromatic substitution reactions using aryl diazonium salts involve the replacement of a good leaving group by a nucleophile on an aromatic ring. When electron-withdrawing groups are present on the ring, such as nitro groups or carbonyl moieties, they stabilize the negative charge that develops during the reaction, making the substitution possible. The use of metal catalysts, such as palladium or iridium, in cross-coupling reactions has enabled the efficient formation of carbon-carbon and carbon-heteroatom bonds in the modification of nucleosides and aromatic compounds.
For example, Suzuki coupling reactions have been employed to attach arylboronic acids to halogenated nucleoside derivatives, forming arylated nucleosides which are biologically significant. Similarly, direct aroylation methods, such as those catalyzed by Pd(OH)2/C (Pearlman's catalyst), have been developed to achieve C-H activation and aroylation of nucleoside bases.
Another example includes the regioselectivity ortho mono-phenylation of 6-arylpurine nucleosides made possible through (N1 purine nitrogen atom)-directed C-H activation. Moreover, C-H activation strategies have been extended to the modification of 7-deazapurines, providing insights into potential therapies and the study of carcinogenesis mechanisms.