The Formation of Difluoromethylene from Difluoromethyl Phenyl Sulfone and Sodium Methoxide¹

α-(Difluoromethyl)styrene: Improved approach to grams scale synthesis

“…Attempts to improve this synthetic route were not successful. We therefore investigated an alternative strategy to obtain a desired nucleophilic difluoromethylating reagent 3 (Scheme 2, Table 1) [20,21].…”

Nucleophilic, radical, and electrophilic (phenylsulfonyl)difluoromethylations

“…Currently, reagent 1 is commonly prepared via the reaction between PhSH and CHClF 2 in the presence of a base, followed by oxidation (Scheme 2, Eq. (1)) [12,19,20]. In 2003, following a serendipitous discovery of the magnesium metal-mediated reductive tri-and difluoromethylation of chlorosilanes (Eq.…”

“…In this context, selective (phenylsulfonyl)difluoromethylation reactions (the transfer of a PhSO 2 CF 2 group into organic substrates) has been systematically studied in recent years [11]. In retrospect, difluoromethyl phenyl sulfone (1, PhSO 2 CF 2 H) was prepared by Hine and Porter during their study of difluorocarbene chemistry in 1960 [12]. However, the synthetic utility of compound 1 as a nucleophilic (phenylsulfonyl)difluoromethylation reagent was not recognized at that time, although Hine and Porter realized that the (phenylsulfonyl)difluoromethyl anion (PhSO 2 CF 2 À ) was formed by deprotonation of 1 with a base such as sodium methoxide [12].…”

“…In retrospect, difluoromethyl phenyl sulfone (1, PhSO 2 CF 2 H) was prepared by Hine and Porter during their study of difluorocarbene chemistry in 1960 [12]. However, the synthetic utility of compound 1 as a nucleophilic (phenylsulfonyl)difluoromethylation reagent was not recognized at that time, although Hine and Porter realized that the (phenylsulfonyl)difluoromethyl anion (PhSO 2 CF 2 À ) was formed by deprotonation of 1 with a base such as sodium methoxide [12]. In 1972, Edwards and co-workers claimed in a patent that PhSO 2 CF 2 À anion (derived from compound 1 and potassium tert-butoxide in diglyme/Et 2 O at À78 8C) was able to undergo 1,4-addition to a cyclic a,bunsaturated ketone, but the chemical yield was not reported [13,14].…”

Difluoromethyl Phenyl Sulfone as a Selective Difluoromethylene Dianion Equivalent: One‐Pot Stereoselective Synthesis of anti‐2,2‐Difluoropropane‐1,3‐diols

“…It is known that the hydrogen atom of the CF 2 H group in compound 2 is rather acidic, and a common base such as sodium methoxide or even aqueous sodium hydroxide can deprotonate it in an equilibrium mode to generate PhSO 2 CF 2 À (6). [7,8] In 1989, Stahly showed that anion 6, generated in situ, can react with aldehydes to give difluoromethylated carbinols in aqueous NaOH in the presence of a phase-transfer agent. [8] However, he did not observe any SÀC bond cleavage in aqueous NaOH (RT, 4 h).…”