Studies on synthetic strategies of biorelevant nitrogen-containing privileged scaffolds

Abstract

Part 1. Bifunctionalization of Unactivated Alkenes Using with N-alkenoxypyridinium Salts N-alkenoxypyridinium salts have been used as synthetic units for the polarity-inversion reaction of enolates for the production of α-functionalized carbonyl compounds. In this dissertation, a strategy with N-alkenoxypyridinium salts that allows simultaneous difunctional groups incorporation of α-keto and γ-pyridyl groups into unactivated alkenes is considered. The photocatalytic system breaks the N-O bond of the N-alkenoxypyridinium salt and generates an α-carbonyl radical. The resulting α-carbonyl radical combines with the deactivated alkene to form an alkyl radical intermediate and is subsequently added to the pyridinium salt. Through this transformation, it is possible to ultimately obtain various γ-pyridyl ketones under mild reaction conditions. This strategy is characterized by a wide substrate scope and excellent functional group compatibility and is expected to be useful for pharmaceutical applications due to the late-stage functionalization of complex biologically related molecules.

Part 2. C-H Functionalization of N-alkenoxyheteroarenium Salts by a Traceless Nucleophile N-alkenoxyheteroarenium salts have been used as synthetic units for polar reversal reactions with nucleophilic heteroarenes. In this thesis, in order to overcome the electron deficit inherent in heteroarenium salts, A strategy for regioselective C-H functionalization leveraged by traceless nucleophile is considered. The quinolinium ring converts into a dearomatized intermediate and is site-selectively functionalized at the C8 position of the quinoline at room temperature. This transformation has wide versatility in other electron-deficient heteroarenes such as phenanthridine, isoquinoline and pyridine N-oxide. The role of nucleophiles enabling the conversion of N-alkenoxyheteroarenium salts, which was previously limited, was investigated through experimental and computational studies. This strategy allows for the subsequent functionalization of complex biologically relevant molecules and is expected to be a practical tool in drug development.