Umpolung-like Cross-coupling of Tosylhydrazones with 4-Hydroxy-2-pyridones under Palladium Catalysis

Abstract

Tosylhydrazones under palladium catalysis were found to perform cross-coupling reactions with 4-hydroxy-2pyridones. The umpolung-like reactivity, between the α-carbon of tosylhydrazone and the 3-position of the heterocycle, which is observed in the obtained products, indicates the directed sp 3 -CHactivation of an alkylated phenol intermediate by the pendant 3-palladated heterocycle. The reaction and its intercepted variants are surveyed in their scope, allowing the synthesis of inaccessible 3-carbocyclic pyridones in moderate to excellent yields.CH-activation of 2-pyridone heteroaromatic ring has attracted considerable attention in recent years. 1 CH-functionalization at the 3-position is mainly relying on radical mediators, such as nickel, manganese, iron, and iridium complexes, 2 whereas the functionalization of the 5-position is almost exclusively dependent on palladium chemistry (Figure 1). 3 However, the electron Letter pubs.acs.org/OrgLett

Copper-Catalyzed Regioselective Coupling of Tosylhydrazones and 2-Pyridones: A Strategy for the Production of N-Alkylated Compounds

“…All the compound pyridin-2­(1 H )-one derivations and tosylhydrazones are known or commercially available, and data are consistent with the literature . Tosylhydrazones are obtained by condensation of 4-toluenesulfonyl hydrazide with the corresponding ketone .…”

Palladium‐Catalyzed Selective Carbofunctionalization of Inert γ‐C(sp3)−O Bonds with 4‐Hydroxypyridin‐2(1H)‐ones and 4‐Hydroxy‐2H‐pyran‐2‐ones

“…There has been considerable activity focused on the development of efficient and general methods for the construction of 4‐hydroxypyridin‐2( 1H )‐one and 4‐hydroxy‐ 2H ‐pyran‐2‐one because of their comprehensive pharmacological profiles such as anti‐tumor and antivirus activities. Among these, a strategy that uses 4‐hydroxypyridin‐2( 1H )‐one [2a–j] and 4‐hydroxy‐ 2H ‐pyran‐2‐one [2k] as the starting material has been demonstrated as an important strategy ascribed to its bi‐functional character. Consequently, development of efficient methods for the synthesis and structural modifications of 4‐hydroxypyridin‐2( 1H )‐ones and 4‐hydroxy‐ 2H ‐pyran‐2‐ones is still in urgent need.…”

Rh(I)-Catalyzed C6-Selective Decarbonylative Alkylation of 2-Pyridones with Alkyl Carboxylic Acids and Anhydrides

“…Early studies focused on transition-metal-catalyzed cross-coupling reactions of halogenated 2-pyridones to access functionalized derivatives . More recently, catalytic C–H functionalizations with transition metals at the C3, C4, C5, and C6 positions − have gained traction . In particular, advances in the transition-metal-catalyzed C6-selective C–H alkylation of 2-pyridones (Scheme a) have been reported .…”