Direct Synthesis of N-Difluoromethyl-2-pyridones from Pyridines

Abstract

A novel method for the synthesis of N-difluoromethyl-2-pyridones was described. This protocol enables the synthesis of N-difluoromethyl-2-pyridones from readily available pyridines using mild reaction conditions that are compatible with a wide range of functional groups. The preliminary mechanistic study revealed that N-difluoromethylpyridinium salts were the key intermediates to complete this conversion.

Electrochemical meta-C−H Sulfonylation of Pyridines with Nucleophilic Sulfinates

“…By this newly developed method, 8-chloro-3-(phenylsulfonyl)quinoline (48), a key intermediate of the potential Alzheimer's disease drug intepirdine, 42 could be facilely synthesized from inexpensive 8-chloroquinoline, instead of precedents based on transition metal-catalyzed cross-couplings of costly 8-uoro/chloro-3iodoquinoline. [55][56][57] The mild electrochemical route also allows for late-stage modi cation of drug-like molecules such as valdecoxib (34), sildena l (35), as well as nikethamide (40,41) and (S)-cotinine (51), loratadine (52), vismodegib (53), febuxostat (54), abametapir (55), and metyrapone derivatives (56).…”

“…In addition, the resulting meta-sulfonyl pyridine products could serve as a fundamental synthetic platform for subsequent diversi ed transformations. [47][48][49][50][51][52][53][54]…”

Direct Synthesis of N‐Alkyl‐2‐Pyridones Using 2‐Halogenated Pyridines

“…Recently, progress has been reported in the aerobic oxidation of quinolines and isoquinolines. Progress in the aerobic oxidation of pyridine and quinoline salts, using air as the oxidant, has also been reported; for example, Fu, [7] Wang, [8] Luo, [9] and Huang [10] described simple and practical methods utilising air as an oxidant to convert pyridine, isoquinoline, and quinoline salts to ketone products. In addition, Chen et al recently reported that 3-halogenated isoquinoline can be used in a one-pot approach to construct disubstituted isoquinolinone derivatives in aqueous phase.…”

Highly Regioselective Synthesis of N‐β‐trifluoromethyl 2‐pyridones via anti‐Markovnikov Hydroamination of α‐(trifluoromethyl)styrenes with 2‐pyridones

“…In addition, a survey of the literature revealed that examples of the synthesis of Nfluoroalkyl-substituted 2-pryidones are very scarce. [12] α-(Trifluoromethyl)styrenes are remarkably versatile trifluoromethyl-containing building blocks for the synthesis of a variety of structurally diverse fluorine-containing compounds. [13] Currently, various strategies for the preparation of gemdifluoroalkenes from α-(trifluoromethyl)styrenes via defluorination have been well developed.…”