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

Abstract

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).

α-Fluoro-α-nitro(phenylsulfonyl)methane as a fluoromethyl pronucleophile: Efficient stereoselective Michael addition to chalcones

“…As mentioned, in the case of enantioselective additions using phenylsulfonylmethane derivatives reported earlier (25,26) strong bases such as CsOH⅐H 2 O, Cs 2 CO 3 , and K 2 CO 3 were required in excessive amounts for the formation of the corresponding phenylsulfonylmethide nucleophile in the medium. However, FNSM is found to be an efficient Michael-type donor in the absence of a base in all reactions performed in our study.…”

“…Reports on highly enantioselective 1,4-addition of monofluoromethylenes to ␣,␤-unsaturated compounds are rare (23,24). Studies by Prakash et al (22) and Ni et al (25) show that conjugate addition of acidic f luoro(phenylsulfonyl)methane (FSM) derivatives to ␣,␤-unsaturated ketones is a suitable example of efficient Michael addition reaction for the C-C bond formation.…”

Reactions of organoboranes with carbanions bearing three potential leaving groups: unusual processes, products and mechanisms

“…26 It was mixed with a trialkylborane (Et3B or Bu3B), the mixture was cooled to -78 °C and lithium bis(trimethylsilyl)amide (LiHMDS), which has previously been used for the deprotonation of 16, 27 was added dropwise. The solution was stirred for 30 minutes at -78 °C and 90 minutes at room temperature and then worked up.…”

Highly Enantioselective Organocatalytic Asymmetric Mukaiyama-aldol Reaction of Difluoroenoxysilanes withβ,γ-Unsaturatedα-Ketoesters

“…手性硫脲催化剂 5 也可催化该反应 [11] , 但是反应进 行缓慢, 在-40 ℃下反应 3 d, 只能以 5%的产率和 5% [14] , 可用他们提出的 "负氟效应", 结合软硬酸碱理论加以说明. 二氟烯醇硅 醚经叔胺活化后形成的二氟取代的碳负离子"硬度"较 高, 因此反应选择性地与"硬度"更高的酮酸酯 2 的 α-酮羰基发生加成反应, 而不是与"硬度"较低的 γ 位发 生共轭加成反应.…”