Nucleophilic fluoroalkylation of epoxides with fluorinated sulfones

The unprecedented nucleophilic fluoroalkylation of simple epoxides with fluorinated sulfones was achieved to give the beta-fluoroalkyl alcohols in one step. The negative "fluorine effect" in the nucleophilic fluoroalkylation of epoxides with fluorinated carbanions was probed by the reactivity comparison between carbanions PhSO2CF2- (3) and PhSO2CCl2- (4) and between carbanions PhSO2CHF- (7) and PhSO2CHCl- (13). The mediation of this fluorine effect by introducing another electron-withdrawing benzenesulfonyl group was found to be an effective way to significantly increase the nucleophilicity of the fluorinated carbanions, with the reactivity order [(PhSO2)2CF-] (16) > PhSO2CFH- (7) > PhSO2CF2- (3).     

Stereoselective monofluoromethylation of N-tert-butylsulfinyl ketimines using pregenerated fluoro(phenylsulfonyl)methyl anion

Pregeneration of fluoro(phenylsulfonyl)methyl anion (PhSO(2)CHF(-)) paves the way for the efficient and highly stereoselective monofluoromethylation of (R)-N-tert-butylsulfinyl ketimines. The stereocontrol mode of the present diastereoselective monofluoromethylation of ketimines is different from the previously known nucleophilic fluoroalkylation of (R)-N-tert-butylsulfinyl aldimines, which suggests that a cyclic six-membered transition state (rather than a nonchelation controlled one) is involved in the current ketimine reaction.     

Stereoselective synthesis of di- and monofluoromethylated vicinal ethylenediamines with di- and monofluoromethyl sulfones

The diastereoselective nucleophilic (phenylsulfonyl)difluoromethylation and (phenylsulfonyl)monofluoromethylation of alpha-amino N-tert-butanesulfinimines (3) by using PhSO2CF2H and PhSO2CH2F reagents gave products 4 or 5 in high yields (73-99%) and with excellent diastereoselectivity (dr up to >99:1). After subsequent reductive desulfonylation and acid-catalyzed alcoholysis, compounds 4 and 5 could be readily transformed to chiral alpha-difluoromethylated or alpha-monofluoromethylated ethylenediamines in good yields.     

Enantioselective conjugate addition of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones catalyzed by chiral bifunctional organocatalysts

The catalytic enantioselective conjugate addition reaction of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of fluorobis(phenylsulfonyl)methane to α,β-unsaturated ketones under mild reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are useful for the synthesis of chiral monofluoromethylated compounds.     

Preparation of alpha,beta-acetylenic ketones by catalytic heterogeneous oxidation of alkynes

Covalent grafting of iron phthalocyanines onto silica affords active catalysts for selective oxidation of alkynes and propargylic alcohols to alpha, beta-acetylenic ketones, highly valuable precursors in the preparation of fine chemicals.     

Radical (phenylsulfonyl)difluoromethylation with iododifluoromethyl phenyl sulfone

An unprecedented radical (phenylsulfonyl)difluoromethylation of terminal alkenes with PhSO2CF2I has been achieved by using Et3B/air as an initiator. This synthetic methodology was also used in the one-pot regioselective preparation of PhSO2CF2-substituted alkanes, and in the regio- and stereoselective preparation of PhSO2CF2-substituted alkenes with high E/Z ratio (up to > or =100:1).     

A novel nucleophilic substitution of in situ generated 3-tert-butyldimethyl- silyloxyalk-2-enylsulfonium salts with allylindium reagents

[reaction: see text] In situ generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts derived from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf undergo a novel nucleophilic substitution with in situ generated allylindium reagents from indium and allyl halides to give silyl enol ethers of delta,epsilon-unsaturated ketones, which correspond to Michael addition products, in good yields.     

Nickel-Catalyzed Tandem Coupling of alpha,beta-Enones, Alkynes, and Alkynyltins for the Regio- and Stereoselective Synthesis of Conjugated Enynes

The nickel-catalyzed reaction of alpha,beta-enones 2 with alkynes 1, alkynyltins 6, and Me(3)SiCl was carried out by the successive construction of two carbon-carbon bonds to give enol silyl ethers 5, which were then hydrolyzed to conjugated enynes 7, with high regio- and stereoselectivities (isomeric purities: 92-98%).     

Indium-mediated beta-allylation,beta-propargylation,and beta-allenylation onto alpha,beta-unsaturated ketones: reactions of in-situ-generated 3-tert-butyldimethylsilyloxyalk-2-enylsulfonium salts with in-situ-generated organoindium reagents

3-tert-Butyldimethylsilyloxyalk-2-enylsulfonium salts, generated in situ from the reaction of alpha,beta-enones with dimethyl sulfide in the presence of TBSOTf, underwent a novel nucleophilic substitution with allylindiums to give silyl enol ethers of delta,epsilon-alkenyl ketones in good yields, which correspond to formal Michael addition products. In a similar manner, 1,4-propargylation of propargylindiums onto the sulfonium salts produced the corresponding silyl enol ethers of delta,epsilon-alkynyl ketones in good yields. Organoindium reagents derived from gamma-substituted propargyl bromide and indium afforded the corresponding silyl enol ethers of beta-allenyl ketones in good yields. The reaction proceeds via an addition-substitution mechanism involving the formation of allylic sulfonium salts. The presence of the intermediate sulfonium salt was confirmed by observation of the low-temperature (1)H NMR spectra.     

Synthesis of mono- and geminal dimetalated carbanions of bis(phenylsulfonyl)methane using alkali metal bases and structural comparisons with lithiated bis(phenylsulfonyl)imides

The alpha,alpha'-stabilized carbanion complexes [(PhSO2)2CHLi.THF]1, [(PhSO2)2CHNa.THF]2 and [(PhSO2)2CHK]3 were prepared by the direct deprotonation of bis(phenylsulfonyl)methane I in THF with one molar equivalent of MeLi, BuNa and BnK respectively. The geminal dianionic complexes [(PhSO2)2CLi2.THF]4, [(PhSO2)2CNa2.0.55THF]5 and [(PhSO2)2CK2]6 were similarly prepared by the reaction of I with two molar equivalents of MeLi, BuNa and BnK respectively in THF. NMR and MS solution studies of 1-3 are consistent with the formation of charge-separated species in DMSO media. Solutions studies of 4-6, in conjunction with trapping experiments, indicate that the dianions deprotonate DMSO and regenerate the monoanions 1-3. Crystallographic analysis of 1 revealed a 1D chain polymer in which the metal centers are chelated by the bis(sulfonyl) ligands and connect to neighboring units through Li-O(S) interactions. An unexpected feature of 1 is that the polymeric chains are homochiral, since the chelating ligands of the backbone adopt the same relative configuration. Also, the phenyl substituents of each chelate in 1 are oriented in a cisoid manner. The sodium derivative 2 adopts a related solid-state structure, where enantiomeric pairs of chains combine to give a 1D ribbon motif. The lithium bis(phenylsulfonyl)imides [(PhSO2)2NLi.THF]9 and [(PhSO2)2NLi.Pyr2]10 were also prepared and structurally characterized. In the solid state 9 has a similar connectivity to that found for 1 but with heterochiral chains. In comparison, the more highly solvated complex 10 forms a 1D polymeric arrangement without chelation of the ligands and with the phenyl substituents oriented in a transoid fashion.     

Palladium/acetic acid-catalyzed fluoroalkylation of alkynes with monofluorinated sulfones as pronucleophiles

A facile palladium-catalyzed fluoroalkylation of alkynes with monofluorinated sulfones in the presence of acetic acid has been achieved. By using different α-substituted fluoro(phenylsulfonyl)methane derivatives, a variety of allylated monofluoromethyl compounds were obtained with high regio- and stereoselectivity. Substrate scope and limitation were also examined, and it was found that the reaction was amenable to both 1-aryl-substituted propynes and 3-aryl-substituted propynyl ethers.     

钯催化下全氟碳负离子的产生及其反应

2-三氟甲基-3-氧杂-八氟己酸烯丙酯或2,5-二(三氟甲基)-3,6-二氧杂-十二氟壬酸烯丙酯可在钯的作用下产生相应的全氟碳负离子. 这些碳负离子能够质子化或者对取代苯甲酰氯发生亲核进攻, 后者为芳基氟烷基酮的合成提供了一条简捷途径. 另一方面,上述含氟酸的甲酯和取代苯甲酰氯在钯的作用下同样能发生反应而生成相应的芳基氟烷基酮.     

Expeditious copper-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to alpha,beta-cycloalkenones and subsequent transformations

Expeditious CuI-catalyzed conjugate 1,4-addition of bromo[2-(1,3-dioxolan-2-yl)ethyl]magnesium to the five-, six-, seven-, and eight-membered alpha,beta-cycloalkenones is described. The reaction times are decreased dramatically compared to CuBr-(CH(3))(2)S catalysis. The resulting ketoacetals were subsequently cyclized to bicyclic beta-hydroxy ketones and alpha,beta-enones, followed by further transformations.     

Visible Light-Induced Metal-Free Fluoroalkylations

Fluoroalkylation is a crucial synthetic process that enables the modification of molecules with fluoroalkyl groups, which can enhance the properties of compounds and have potential applications in medicine and materials science. The utilization of visible light-induced, metal-free methods is of particular importance as it provides an environmentally friendly alternative to traditional methods and eliminates the potential risks associated with metal-catalyst toxicity. This Account describes our studies on visible light-induced, metal-free fluoroalkylation processes, which include the use of organic photocatalysts or EDA complexes. We have utilized organophotocatalysts such as Nile red, tri(9-anthryl)borane, and an indole-based tetracyclic complex, as well as catalyst-free EDA chemistry through photoactive halogen bond formation or an unconventional transient ternary complex formation with nucleophilic fluoroalkyl source. A variety of π-systems including arenes/heteroarenes, alkenes, and alkynes have been successfully fluoroalkylated under the developed reaction conditions.     

Propargylic oxidations catalyzed by dirhodium caprolactamate in water: efficient access to alpha,beta-acetylenic ketones

Dirhodium(II) caprolactamate (1, Rh 2(cap) 4) with 70% w/w aqueous tert-butyl hydroperoxide (T-HYDRO ) is a highly effective catalytic oxidation protocol for the selective C-H oxidation of alkynes to propargylic ketones. The oxidation occurs readily in aqueous solvent under mild conditions with an inexpensive and easily handled oxidant. Alpha,beta-acetylenic carbonyl compounds are formed in up to 80% isolated yield.     

Copper-catalyzed [4 + 1] cycloadditions of alpha,beta-acetylenic ketones with diazoacetates to form trisubstituted furans

Copper-catalyzed [4 + 1] cycloaddition reaction of alpha,beta-acetylenic ketones with alpha-diazo esters offers an efficient, direct route to highly substituted furans. The reaction conditions and the scope of the process are examined, and a possible mechanism is proposed.     

Broad-spectrum enantioselective diels-alder catalysis by chiral,cationic oxazaborolidines

The cationic chiral Lewis acids 1 and 2, generated by triflic acid protonation of the corresponding neutral oxazaborolidines, serve as excellent catalysts for Diels-Alder addition of cyclopentadiene to a wide variety of dienophiles. Adducts have been obtained in excellent yield and enantioselectivity from alpha,beta-unsaturated esters, lactones, and cyclic ketones. The absolute facial selectivity for each of these substrates follows a common pattern which differs from that observed with alpha,beta-enals. The different reaction channels can be understood in terms of pathways via complexes 3 (for alpha,beta-enals) and 4 (for alpha,beta-enones and esters).     

One-pot three-component reaction for the synthesis of alpha-(aminoethyl)-alpha,beta-enones

[reaction: see text] The synthesis of alpha-substituted alpha,beta-enones by a new metal iodide-promoted one-pot three-component reaction involving commercially available cyclopropyl ketones, aldehydes, and secondary amines followed by base treatment is described.     

Computational insights into the effects of reagent structure and bases on nucleophilic monofluoromethylation of aldehydes

Although fluorobis(phenylsulfonyl)methane(FBSM) and its cyclic analog 2-fluoro-1,3-benzodithiole-1,1,3,3-tetraoxide(FBDT) possess similar physicochemical properties, Shibata et al. found that FBSM failed to undergo nucleophilic monofluoromethylation of aldehydes regardless of the reaction conditions attempted(using various organic and inorganic bases). However, it was later discovered by Hu et al. that the nucleophilic monofluoromethylation could be accomplished by employing lithium hexamethyldi...     

Oxovanadium(V)-induced vicinal dialkylation of cyclic enones with organozinc compounds

Oxovanadium(V) compounds induce nucleophilic alpha,beta-vicinal dialkylation of cyclic alpha,beta-enones with dialkylzinc reagents. Alkylzinc enolates generated from cyclic enones and lithium trialkylzincates were also oxidized by VO(OEt)Cl(2), giving 2, 3-dialkylcycloalkanones.