Efficient Difluoromethylation of sp<sup>3</sup> Carbon Nucleophiles by Bromodifluoromethylation Reagents with Organic Bases

Liu, Guokai; Wang, Xin; Xu, Lu; Xu, Xiu‐Hua; Tokunaga, Etsuko; Shibata, Norio

doi:10.1002/open.201200033

Cited by 39 publications

(21 citation statements)

References 76 publications

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“…270 With some nucleophiles, such as amines, sulfonium salts can form donor–acceptor complexes (EDA complexes), able to generate CF 3 -radicals which can be used for the trifluoromethylation of arenes. 271…”

Section: Sulfonium Saltsmentioning

confidence: 99%

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

et al. 2019

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Organosulfur compounds have long played a vital role in organic chemistry and in the development of novel chemical structures and architectures. Prominent among these organosulfur compounds are those involving a sulfur(IV) center, which have been the subject of countless investigations over more than a hundred years. In addition to a long list of textbook sulfur-based reactions, there has been a sustained interest in the chemistry of organosulfur(IV) compounds in recent years. Of particular interest within organosulfur chemistry is the ease with which the synthetic chemist can effect a wide range of transformations through either bond formation or bond cleavage at sulfur. This review aims to cover the developments of the past decade in the chemistry of organic sulfur(IV) molecules and provide insight into both the wide range of reactions which critically rely on this versatile element and the diverse scaffolds that can thereby be synthesized.

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Section: Sulfonium Saltsmentioning

confidence: 99%

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

et al. 2019

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“…Most of these reactions are focused on the difluoromethylation of heteroatoms, such as O, S, N, P, and Se nucleophiles, and [2+1] cycloaddition with alkenes or alkynes. However, examples of the difluoromethylation of C−H nucleophiles are sparse, with limited success being reported …”

Section: Methodsmentioning

confidence: 99%

“…β‐Ketoesters and malonates are the most studied C−H nucleophiles, and their efficient difluoromethylation with high C/O selectivity was reported very recently by the research groups led by Shibata, Shen, and Liu . However, the reactivity of many other C−H nucleophiles, such as common esters, amides, fluorenes, and alkynes, towards difluorocarbene is largely underexplored or unknown.…”

Section: Methodsmentioning

confidence: 99%

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br

Xie

Zhu

et al. 2019

Angew Chem Int Ed

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An efficient method for the selective C‐difluoromethylation of carbon acids with the reagent TMSCF2Br has been developed. A variety of structurally diverse sp3‐ and sp‐hybridized carbon nucleophiles, including esters, amides, fluorenes, terminal alkynes, β‐ketoesters, malonates, and other activated C−H nucleophiles, could be efficiently and selectively transformed into the corresponding C‐difluoromethylated products under mild conditions. This protocol is also effective for the late‐stage difluoromethylation of pharmaceutically relevant molecules and can be readily scaled up. Moreover, ambident substrates with more than one reactive site towards difluorocarbene can be difluoromethylated orthogonally using TMSCF2Br.

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“…While reagents for electrophilic difluoromethylation of carbon and heteroatom nucleophiles have been reported,6, 7h,i,k,u, 8a the difluoromethylation of C

_{sp^{3}}

‐centered nucleophiles remains an area of limited success. Recently, we reported shelf‐stable reagents, S ‐(bromodifluoromethyl)diaryl sulfonium salts,7p for electrophilic difluoromethylation of C

_{sp^{3}}

‐centered nucleophiles including β‐ketoesters and dicyanoalkylidenes. We also reported the difluoromethylation of β‐ketoesters using a difluoromethylsulfoxinium salt 7o.…”

Section: Methodsmentioning

confidence: 99%

“…We also reported the difluoromethylation of β‐ketoesters using a difluoromethylsulfoxinium salt 7o. In contrast to the monofluoromethylation11 and trifluoromethylation,12 all the β‐ketoesters gave a mixture of C‐ and O‐difluoromethylation products in good yields with poor to modest regioselectivities (C/O=6:4 to 8:2, Scheme ) 7o,p. For the reaction of 1,3‐diones, only O‐difluoromethylation products were selectively obtained 7s.…”

Section: Methodsmentioning

confidence: 99%

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones, and Dicyanoalkylidenes

Wang

Liu

et al. 2014

Angewandte Chemie

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S‐((Phenylsulfonyl)difluoromethyl)thiophenium salts were designed and prepared by a triflic acid catalyzed intramolecular cyclization of ortho‐ethynyl aryldifluoromethyl sulfanes. The thiophenium salts were found to be efficient as electrophilic difluoromehtylating reagents for introduction of a CF2H group to sp3‐hybridized carbon nucleophiles such as of β‐ketoesters and dicyanoalkylidenes. The (phenylsulfonyl)difluoromethyl group can be readily transformed into CF2H under mild reaction conditions. Enantioselective electrophilic difluoromethylation was also achieved in the presence of bis(cinchona) alkaloids.

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Efficient Difluoromethylation of sp³ Carbon Nucleophiles by Bromodifluoromethylation Reagents with Organic Bases

Cited by 39 publications

References 76 publications

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones, and Dicyanoalkylidenes

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Efficient Difluoromethylation of sp3 Carbon Nucleophiles by Bromodifluoromethylation Reagents with Organic Bases

Cited by 39 publications

References 76 publications

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

Bond-Forming and -Breaking Reactions at Sulfur(IV): Sulfoxides, Sulfonium Salts, Sulfur Ylides, and Sulfinate Salts

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF2Br

S‐((Phenylsulfonyl)difluoromethyl)thiophenium Salts: Carbon‐Selective Electrophilic Difluoromethylation of β‐Ketoesters, β‐Diketones, and Dicyanoalkylidenes

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Efficient Difluoromethylation of sp³ Carbon Nucleophiles by Bromodifluoromethylation Reagents with Organic Bases

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br