Palladium-Catalyzed Site-Selective Fluorination of Unactivated C(sp³)–H Bonds

Abstract

The transition-metal-catalyzed direct C-H bond fluorination is an attractive synthetic tool toward the preparation of organofluorines. While many methods exist for the direct sp(3) C-H functionalization, site-selective fluorination of unactivated sp(3) carbons remains a challenge. Direct, highly site-selective and diastereoselective fluorination of aliphatic amides via a palladium-catalyzed bidentate ligand-directed C-H bond functionalization process on unactivated sp(3) carbons is reported. With this approach, a wide variety of β-fluorinated amino acid derivatives and aliphatic amides, important motifs in medicinal and agricultural chemistry, were prepared with palladium acetate as the catalyst and Selectfluor as the fluorine source.

Recent Advances on Amino Acid Modifications via C–H Functionalization and Decarboxylative Functionalization Strategies

“…In a consecutive report, Ge et al. published a similar enantioselective and site‐selective fluorination of amino acids and related systems . Lectka et al.…”

Diastereoselective Substrate-Controlled Transition-Metal-Catalyzed C–H Activation: An Old Solution to a Modern Synthetic Challenge

“…Importantly, a related asymmetric fluorination using Selectfluor as fluorine source was also achieved by using a bicoordinating 2-(pyridin-2-yl)isopropyl-derived DG. 41 …”

Novel Synthesis of Flavones by Regioselective Cyclization of 1‐(2‐Hydroxyphenyl)‐3‐phenyl‐2‐propyn‐1‐ones Derived from 2‐Hydroxybenzoic Acids

“…The 1,4-addition of an excess of secondary amines to O-TBS protected alkynones in CH 3 OH afforded the corresponding enaminoketones, which underwent cyclization and subsequent elimination to produce flavones under reflux conditions. 13 o-(Alkynon-1-yl)phenols obtained from the carbonylative annulation of o-acetoxyiodobenzenes and arylacetylenes in the presence of palladium catalyst also underwent 1,4-addition by diethylamine to yield the corresponding enaminoketones, which were cyclized by substitution to produce flavones after 48 h. 14 Although several methods have been reported for the synthesis of flavones, some suffer from the use of excess reagent, vigorous conditions, and multiple steps. Furthermore, reports on the synthesis of flavones by the cyclization of o-(alkynon-1-yl)phenols are rare, and the scope of the reaction was not fully investigated.…”