Phosphonium Ylide-Mediated Programmable Fluorination to Access Mono- and Difluoromethylarenes

Abstract

Compounds bearing fluorinated moieties are pervasive in a wide range of pharmaceuticals and agrochemicals. The installation of fluorinated units is a persistently vital task in synthetic chemistry, where facile and manipulable assays are highly demanding. Herein, we establish a general and programmable fluorination strategy for the modular assembly of mono- and difluoromethylarenes through the controllable deprotonation and fluorination of phosphonium ylides. Moreover, the rational combination of the reaction sequence allows the rapid construction of diversified fluorine-containing arenes.

Synthesis of gem‐Difluorinated Keto‐Sulfoxides from Sulfoxonium Ylides

“…In summary, our work unveils a novel facet of sulfoxonium ylide reactivity, [33] enabling the direct and mild synthesis of 21 gem-difluorinated sulfoxides in 14-80 %. Compared to previous methods to make these compounds and derivatives, this onepot methodology is of practical importance, even considering that some examples are synthesized in moderate yields.…”

Phosphine-Mediated Morita–Baylis–Hillman-Type/Wittig Cascade: Access to E-Configured 3-Styryl- and 3-(Benzopyrrole/furan-2-yl) Quinolinones

“…Notably, this type of biheterocycle based on quinolinone scaffolds has been proved to exhibit a wide range of bioactivities . Given our long-standing interest in organocatalysis and heterocycle chemistry, we herein report our efforts in the exploration of the metal-free, phosphine-mediated MBH-type/Wittig cascade sequence of benzaldehydes, enabling the facile assembly of a range of 3-styryl-quinolinoes with high structural complexity and diversity (Scheme b, bottom, path a). Furthermore, a one-pot sequence for the synthesis of 3-(benzopyrrole/furan-2-yl)­quinolinones was also successfully accomplished (Scheme b, bottom, path b), further expanding the potential of this phosphine-mediated platform.…”

Soft Fluorination of 4-Alkylpyridines

“…are prevalent in druglike molecules, and accordingly methods for their fluorination have been the subject of considerable research. Pyridylic fluorination is typically achieved using prefunctionalized substrates and usually involves replacement of oxygen or another halogen − or decarboxylation . The direct lateral fluorination of pyridines has recently received significant attention (Figure b).…”