Tertiary Amides as Fluoroalkyl Aldehyde Surrogates: Access to meso-Fluorinated Bis(heteroaryl)methanes

Abstract

Tertiary, morpholine-derived, fluoroalkyl amides have been found to be efficient, readily accessible, bench-stable surrogates of fluoroalkyl aldehydes. This discovery is applied to the one-pot synthesis of a symmetrical and, more challengingly, unsymmetrical meso-fluoroalkylated bis(heteroaryl)methanes via a Schwartz's reagent-mediated reductive activation. The usefulness of this approach for the introduction of a fluoromethylated carbon bridge was proven by implementation of the developed methodology in the synthesis of a fluorine-decorated bispyrromethane skeleton and an α-alkylated BODIPY core.

LiBr‐Mediated Cross‐Coupling towards α‐Trifluoromethylamines

“…Owing to the importance of α-trifluoromethyl amines, the synthesis of this class of fluorine-containing compounds has attracted much attention from organic and medicinal chemists. [15][16][17][18] Among different strategies, reductive amina-tion of trifluoromethyl ketones, [19][20][21] trifluoromethylation of imines, [22][23][24] reductive trifluoromethylation of secondary amides, [25] and functionalization of trifluoroacetamides [26,27] are major approaches (Figure 2a). Other elegant methods employing umpolung addition of trifluoromethyl ketimines, [28] hydroamination of trifluoromethylalkenes [29] and cascade reactions using organocatalysts [30] were also developed.…”