安定で取り扱いの容易な求核的フッ素化剤 (FLUOLEAD^R)

4-tert-ブチル-2,6-ジメチルフェニルサルファートリフルオリド (FLUOLEAD^R)は，梅本らによって開発された新規な求核的フッ素化剤です。高い熱安定性を有する結晶で，DASTなどの既存の求核的フッ素化剤よりも安定で，取り扱いが容易です。種々の基質をフッ素化することが可能で，良好な収率で対応するフッ素化合物を与えます。

“Discovery of 4-tert-Butyl-2,6-dimethylphenylsulfur Trifluoride as a Deoxofluorinating Agent with High Thermal Stability as Well as Unusual Resistance to Aqueous Hydrolysis, and Its Diverse Fluorination Capabilities Including Deoxofluoro-Arylsulfinylation with High Stereoselectivity”

T. Umemoto, R. P. Singh, Y. Xu, N. Saito, J. Am. Chem. Soc. 2010, 132, 18199. DOI: 10.1021/ja106343h

Versatile, safe, shelf-stable, and easy-to-handle fluorinating agents are strongly desired in both academic and industrial arenas, since fluorinated compounds have attracted considerable interest in many areas, such as drug discovery, due to the unique effects of fluorine atoms when incorporated into molecules. This article describes the synthesis, properties, and reactivity of many substituted and thermally stable phenylsulfur trifluorides, in particular, 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead, 1k), as a crystalline solid having surprisingly high stability on contact with water and superior utility as a deoxofluorinating agent compared to current reagents, such as DAST and its analogues. The roles of substiuents on 1k in thermal and hydrolytic stability, fluorination reactivity, and the high-yield fluorination mechanism it undergoes have been clarified. In addition to fluorinations of alcohols, aldehydes, and enolizable ketones, 1k smoothly converts non-enolizable carbonyls to CF2 groups, and carboxylic groups to CF3 groups, in high yields. 1k also converts C(═S) and CH3SC(═S)O groups to CF2 and CF3O groups, respectively, in high yields. In addition, 1k effects highly stereoselective deoxofluoro-arylsulfinylation of diols and amino alcohols to give fluoroalkyl arylsulfinates and arylsulfinamides, with complete inversion of configuration at fluorine and the simultaneous, selective formation of one conformational isomer at the sulfoxide sulfur atom. Considering the unique and diverse properties, relative safety, and ease of handling of 1k in addition to its convenient synthesis, it is expected to find considerable use as a novel fluorinating agent in both academic and industrial arenas.