(Sulfonimidoyl)cyclopropanes have become the subject of special interest since they combine the advantages of two chemical leads (cyclopropane and sulfoximine). However, their synthesis is limited, and the stereoselective synthesis of optically enriched (sulfonimidoyl)cyclopropanes still remains an unsolved task. Here we report the first stereoselective (sulfonimidoyl)cyclopropanation reaction using α,β-unsaturated Weinreb amides and (R)-PhSO(NTs)CH₂Cl [(R)-1]. This reaction possesses a broad substrate scope, and the products can be easily transformed into other useful cyclopropyl-containing and/or sulfonimidoyl-containing compounds. The Weinreb amide group and the counter cation of the base were found to be important for the selective C–Cl bond cleavage.

A copper-mediated deuterotrifluoromethylation of α?diazo esters under the promotion of deuterium oxide (D₂O) has been developed for the synthesis of deuterium-labeled trifluoromethyl compounds. This deuterotrifluoromethylation reaction is of broad scope and can afford the deuterated products with higher than 99% isotopic purity. Moreover, the results of this investigation also provide some experimental evidences to support our previously proposed trifluoromethylation mechanism.

Fluorinated ketones are intriguing compounds in synthetic chemistry and life science-related fields. The development of efficient methodologies to obtain these compounds is of significant importance and has therefore attracted considerable attention. This Minireview highlights recent progress made in the synthesis of fluorine-containing ketones, with an emphasis on those methods in which the construction of carbonyl groups is synergetic with distal (β-, γ-, δ-, etc.) incorporation of fluorine atoms or fluorinated groups.

Described is a one-pot vicinal fluorination-iodination of arynes at room temperature. The diphenyliodonium salt proved to be a privileged catalyst for this nucleophilic fluorination process using CsF as a fluorine source, and a subsequent facile electrophilic iodination with C₄F₉I was also found to be crucial to ensure the efficient fluorination. This new synthetic protocol has a broad substrate scope under mild reaction conditions.

Described is a one-pot vicinal fluorination-iodination of arynes at room temperature. The diphenyliodonium salt proved to be a privileged catalyst for this nucleophilic fluorination process using CsF as a fluorine source, and a subsequent facile electrophilic iodination with C₄F₉I was also found to be crucial to ensure the efficient fluorination. This new synthetic protocol has a broad substrate scope under mild reaction conditions.

A AgF-mediated fluorination with a concomitant cross-coupling between a gem-difluoroolefin and a non-fluorinated olefin is reported. This highly efficient method provides facile access to both α-CF₃ alkenes and β-CF₃ ketones, which otherwise remain challenging to be directly prepared. The application of this method is further demonstrated by the synthesis of bioactive isoxazoline derivatives. This approach represents a conceptually novel route to trifluoromethylated compounds that combines the in situ generation of the CF₃ moiety and a CH functionalization in a single reaction system.

A AgF-mediated fluorination with a concomitant cross-coupling between a gem-difluoroolefin and a non-fluorinated olefin is reported. This highly efficient method provides facile access to both α-CF₃ alkenes and β-CF₃ ketones, which otherwise remain challenging to be directly prepared. The application of this method is further demonstrated by the synthesis of bioactive isoxazoline derivatives. This approach represents a conceptually novel route to trifluoromethylated compounds that combines the in situ generation of the CF₃ moiety and a CH functionalization in a single reaction system.

The selective incorporation of fluorine atoms or fluorinated moieties into organic molecules has become a “hot” research topic in modern organic chemistry. However, selective and efficient synthesis of organofluorine compounds greatly depends on the development of powerful fluorination or fluoroalkylation reagents and reactions. In this context, the past decade has witnessed rapid research progress in the development of α-fluoro sulfoximines as versatile fluoroalkylation reagents. Many efficient nucleophilic, electrophilic and radical fluoroalkylation reactions based on α-fluoro sulfoximine reagents have been developed; among these, several chiral sulfoximine reagents were successfully used in the synthesis of enantiomerically enriched organofluorine compounds. It was found that α-fluoro sulfoximines show unique chemical behaviour characteristics (such as difluorocarbene and fluoroalkyl radical reactivities) significantly different from those of their non-fluorinated counterparts. In addition to the rapid development of fluorinated sulfoximines in organic synthesis, research into their application in materials science has also attracted increasing attention. Sulfoximines are important bioactive substances, and more recently the synthesis and application of fluorinated sulfoximines has attracted much attention in life sciences and the pharmaceutical industry. In this microreview we summarize the preparation, reactions and applications of fluorinated sulfoximines (mainly α-fluoro sulfoximines).

An efficient nucleophilic difluoro(phenylsulfonimidoyl)methylation of unactivated primary alkyl bromides with PhSO(NTBS)CF₂H has been developed. It is particularly remarkable that, when 1.5 equiv. of alkyl bromides are used, the substitution products are obtained in moderate to excellent yields. The prepared difluoro(phenylsulfonimidoyl)methylated alkanes can be readily transformed to gem-difluoroalkenes via base-mediated β-elimination reaction.

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions.

Unlike the facile synthesis of β-monofluoromethyl alcohols by nucleophilic monofluoromethylation of epoxides, the synthesis of β-difluoromethyl alcohols by nucleophilic difluoromethylation of epoxides still remains a challenge. Herein, studies on tackling this problem with PhSO(NTBS)CF₂H (2; TBS=tert-butyldimethylsilyl) are reported. The preorganization of 2 and epoxides with BF₃⋅Et₂O was found to be crucial for the reaction. The reaction shows excellent regioselectivity and has a broad substrate scope. The facile transformation of the ring-opened products to β-difluoromethyl, γ-difluoromethyl, and β-difluoromethylenyl alcohols demonstrates the synthetic utility of the reaction.

An unprecedented silver-catalyzed formal insertion of arynes into R_fI (R_f=CF₃, C₂F₅) bonds has been developed. This protocol provides easy access to various ortho-perfluoroalkyl iodoarenes under mild conditions. In this insertion reaction, an ionic atom-transfer reaction of R_fI occurs, and a silver-mediated metathesis process is involved in the efficient transfer of the electropositive iodine atom.

The direct conversion of diaryl ketones and enolizable aliphatic aldehydes into gem-difluoroalkenes has been a long-standing challenge in organofluorine chemistry. Herein, we report efficient strategies to tackle this problem by using difluoromethyl 2-pyridyl sulfone as a general gem-difluoroolefination reagent. The gem-difluoroolefination of diaryl ketones proceeds by acid-promoted Smiles rearrangement of the carbinol intermediate; the gem-difluoroolefination is otherwise difficult to achieve through a conventional Julia–Kocienski olefination protocol under basic conditions due to the retro-aldol type decomposition of the key intermediate. Efficient gem-difluoroolefination of aliphatic aldehydes was achieved by the use of an amide base generated in situ (from CsF and tris(trimethylsilyl)amine), which diminishes the undesired enolization of aliphatic aldehydes and provides a powerful synthetic method for chemoselective gem-difluoroolefination of multi-carbonyl compounds. Our results provide new insights into the mechanistic understanding of the classical Julia–Kocienski reaction.

Although many methods are available for the synthesis of optically enriched monofluoromethyl secondary alcohols, synthesizing optically enriched monofluoromethyl tertiary alcohols remains a challenge. An efficient and easy-to-handle nucleophilic fluoromethylation protocol was developed. The current monofluoromethylation showed much higher facial selectivity than the corresponding difluoromethylation and proceeded via a different type of transition state. Excellent stereoselective control at the fluorinated carbon chiral center was found, an effect believed to be facilitated by the dynamic kinetic resolution of the chiral α-fluoro carbanions.

A highly stereoselective synthesis of tetrasubstituted monofluoroalkenes with aldehydes and fluorobis(phenylsulfonyl)methane (FBSM) in one pot has been developed. The reaction was amenable to para- and meta-substituted aryl aldehydes, 2-naphthaldehyde, and cinnamaldehyde, giving phenylsulfonyl-substituted monofluoroalkenes in 40%–86% yields with 98/2–99/1 Z/E ratios. The presence of the sulfonyl group enables the further transformation of the products into more useful monofluoroalkenes.

A detailed investigation of the reactions of PhSO₂CF₂H and PhSO₂CH₂F with (E)-chalcone (=(E)-1,3-diphenylprop-2-en-1-one) at low temperatures revealed that these two reactions were kinetically controlled, and the ratios of 1,2- vs. 1,4-adducts, which did not change much over time at these temperatures, reflect the relative rates of the two reaction pathways. The controlled experiments of converting the PhSO₂CF₂- and PhSO₂CHF-substituted 1,2-adducts to 1,4-adducts showed that these isomerizations are not favored due to the low stability and hard-soft nature of PhSO₂CF and PhSO₂CHF⁻ anions. Moreover, taking advantage of the remarkable stability and softness of (PhSO₂)₂CF⁻ anion, an efficient thermodynamically controlled isomerization of (PhSO₂)₂CF-substituted 1,2-adduct to 1,4-adduct was achieved for the first time.

Monofluorinated epoxides were successfully prepared through the O-cyclization reaction between α-fluorosulfoximines and ketones. The obtained fluoroepoxides were found to readily undergo an interesting ring-opening process (involving both a CF bond cleavage and another CF bond formation) in the presence of titanium tetrafluoride or pyridinium poly(hydrogen fluoride) to afford α-fluorinated ketones. The later process constitutes a formal catalytic 1,2-fluorine shift reaction.

The first highly efficient and stereoselective difluoromethylation of structurally diverse N-tert-butylsulfinyl ketimines has been achieved with an in situ generated PhSO₂CF₂⁻ anion, which provides a powerful synthetic method for the preparation of a variety of structurally diverse homochiral α-difluoromethyl tertiary carbinamines, including α-difluoromethyl allylic amines and α-difluoromethyl propargylamines. The stereocontrol mode of the present diastereoselective difluoromethylation of ketimines was found to be different from that of other known fluoroalkylations of N-tert-butylsulfinyl aldimines, which suggests that a cyclic six-membered transition state may be involved in the reaction.