Nucleophilic Fluoroalkylation of α,β-Enones, Arynes, and Activated Alkynes with Fluorinated Sulfones: Probing the Hard/Soft Nature of Fluorinated Carbanions

We have successfully accomplished the nucleophilic fluoroalkylation of α,β-enones, arynes, and activated alkynes with fluorinated sulfones. It was found that for acylic α,β-enones, although the reaction medium and the structure of the enones can all influence the regioselectivity of the nucleophilic alkylation reactions, the hard/soft nature of the carbanions played a major role. By using the 1,4- and 1,2-addition product ratio as a probe to determine the hard/soft nature of the above-mentioned four halogenated carbanions, the order of the softness of these carbanions can be given as follows: [(PhSO2)2CF−] (20) ≈ PhSO2CCl2− (32) > PhSO2CHF− (31) > PhSO2CF2− (30). In the case of fluoroalkylation of aryne (35 as the precursor) and α,β-acetylenic ketones 46 with fluorobis(phenylsulfonyl)methane (21), fluorobis(phenylsulfonyl)methylated arenes 36 and β-fluorobis(phenylsulfonyl)methylated α,β-enones 47 were obtained as the corresponding products in good yields. During the reaction between 2-fluoro-2-(phenylsulfonyl)acetophenone (34) and arynes or activated alkynes 46, an intramolecular tandem reaction process leads to the formation of acyl-fluoroalkylated arenes 43 or α-acyl-β-fluoroalkylated α,β-enones 48. It turned out that the softness of a fluorine-bearing carbanion (such as 20 or 33 derived from 21 or 34) plays a crucial role for the success of the nucleophilic fluoroalkylation reactions with arynes and some activated alkynes (α,β-acetylenic ketones).