Efficient Nucleophilic Fluoromethylation and Subsequent Transformation of Alkyl and Benzyl Halides Using Fluorobis(phenylsulfonyl)methane

Abstract

An efficient methodology for the nucleophilic fluoromethylation of alkyl and benzyl halides using alpha-fluoro-alpha-(phenylsulfonyl)methane (1) as a highly versatile reagent is reported. Using benzyl halides, stereospecific one-pot synthesis of alpha-fluorovinyl compounds such as alpha-fluorostyrylsulfones, alpha-fluorocinnamates, and alpha-fluorochalcones has been achieved. The methodology has been extended toward the synthesis of alpha-substituted fluoroalkane derivatives using selective reductive desulfonylation conditions.

Divergent Regio‐ and Stereoselective Gold‐catalyzed Synthesis of α‐Fluorosulfones and β‐Fluorovinylsulfones from Alkynylsulfones

“…This result can be attributed to the presence of a reactive benzylic C−H in close proximity to the generated gold carbene intermediate . Nucleophilic fluoromethylation and subsequent sulfone elimination of 3 n gives fluoroalkene 7 in very good yield . 3 n also reacts with an in situ generated aryne to furnish 8 in excellent yield .…”

“…Given fluorine's pre‐eminence in medicinal chemistry and the sulfonyl group's importance as an organic building block, their juxtaposition on a vinyl or carbonyl template (fluoro‐ A or fluoro ‐B in Scheme ) should lead to desirable motifs in medicinal or synthetic chemistry but their syntheses are quite challenging. For examples, Hu and Prakash have demonstrated the fluoro‐ A type compounds were versatile fluorinated building blocks. In fact, the synthesis of fluoro‐ A type compounds has only been reported via the electrophilic fluorination of precursor C, using expensive, low‐atom economic reagents and harsh conditions that often give rise to difluorination byproducts .…”

Einführung von Fluor und fluorhaltigen funktionellen Gruppen

“…Da die nucleophile Substitution das Erhitzen in siedendem Acetonitril erfordert, zersetzen sich die Ausgangsverbindungen häufig, bevor die Substitution stattfindet. [192] Die nucleophile Reaktivität resonanzstabilisierter Fluormethyl-Anionen wurde in der Mitsunobu-Reaktion von Alkoholen [193] sowie in Substitutionsreaktionen mit Alkylhalogeniden [194] zur Synthese von Monofluoralkenen genutzt. Anzumerken ist, dass a-Fluormethylsulfide unter Normalbedingungen leicht zu den entsprechenden a-Fluormethylsulfoxiden oxidiert werden.…”

“…[504] Außerdem wurde die Einführung der Monofluormethingruppe durch Aldolkondensationen beschrieben. [194] Die dabei auftretende E-Selektivität ist vermutlich auf den Nachbargruppeneffekt der Arylgruppe im Eliminierungsschritt zurückzuführen. [194] Die dabei auftretende E-Selektivität ist vermutlich auf den Nachbargruppeneffekt der Arylgruppe im Eliminierungsschritt zurückzuführen.…”

Synthetic Methods for Fluorinated Olefins

“…[57] www.eurjoc. Cr II -mediated reduction of 2,2-dibromo-2-fluoroethyl silyl ethers is a unique synthetic methodology for fluorinated vinyl compounds (Scheme 33).…”