Nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones: probing the hard/soft nature of fluorinated carbanions.
We have successfully accomplished the nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones. It was found that for acylic alpha,beta-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) approximately = PhSO2CCl2(-) (32) > PhSO2CHF(-) (31) > PhSO2CF2(-) (30). In the case of fluoroalkylation of aryne (35 as the precursor) and alpha,beta-acetylenic ketones 46 with fluorobis(phenylsulfonyl)methane (21), fluorobis(phenylsulfonyl)methylated arenes 36 and beta-fluorobis(phenylsulfonyl)methylated alpha,beta-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 alpha-acyl-beta-fluoroalkylated alpha,beta-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 (alpha,beta-acetylenic ketones).
Ni
Chuanfa
C
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.
Zhang
Laijun
L
Hu
Jinbo
J
D000098:Acetophenones / Q000737:chemistry; D000478:Alkylation; D000480:Alkynes / Q000737:chemistry*; D000838:Anions / Q000737:chemistry; D047188:Chalcones / Q000737:chemistry; D017606:Chlorine Compounds / Q000737:chemistry; D003512:Cyclohexanones / Q000737:chemistry; D017611:Fluorine Compounds / Q000737:chemistry*; D018020:Lithium Compounds / Q000737:chemistry; D008697:Methane / Q000737:chemistry; D008745:Methylation; D015394:Molecular Structure; D013450:Sulfones / Q000737:chemistry*
D000098:Acetophenones; D000480:Alkynes; D000838:Anions; D047188:Chalcones; D017606:Chlorine Compounds; D003512:Cyclohexanones; D017611:Fluorine Compounds; D018020:Lithium Compounds; D013450:Sulfones; C028215:2-cyclohexen-1-one; D008697:Methane; C038699:acetophenone