Direct Perfluoroalkylthiolation of Few Chalcogenols

Glenadel, Quentin; Billard, Thierry

doi:10.1002/cjoc.201500913

Cited by 13 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…同时, 他们也发现, 在合成该苯胺骨架的试剂过程中, 当底物的胺含有吸电子取代基时会优先生成一个亚胺中间体, 该中间体可以在三氟乙酸的水解下, 进一步生成活性更高的第二代 Billard 试剂 [64] . 在 2014 年, 他们对该类试剂的反应活性进行了报道, 发现该类试剂相比第一代苯胺结构的试剂有着更为出色的反应活性, 除去上述报道的反应外还可以实现活泼 C-H 键底物 [69] 、杂环底物 C-H 键底物 [70] 、硼酸底物 [71] 剂 [72] (S,O)、活泼卤化物(类卤化物)极性反转的三氟甲硫基化反应 [73] 、炔烃的单、双三氟甲硫基化反应 [74] 以及富电子芳烃、杂芳烃底物的 C-H 键三氟甲硫基化反应 [75] (Scheme 33). [79] 、吲哚 [80] 、苯并呋喃 [81] 、苯并噻吩 [81] 以及苯并吡喃类衍生物 [82] .…”

unclassified

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Zhang¹,

Lü²,

Shen³

2017

Acta Chim. Sinica

View full text Add to dashboard Cite

With a significantly high Hansch's hydrophobicity parameter (π＝1.44), electron-withdrawing trifluoromethylthio group (CF 3 S-) has been considered as one of the most lipophilic substituents and privileged fragments that are able to improve drug molecules' pharmacokinetic and physicochemical properties such as lipophilicity and metabolic stability. It is well-known that incorporation of the trifluoromethylthio group into small molecules greatly enhances its ability to cross lipid membranes and in vivo absorpotion rate. In addition, the high electronegativity of the trifluoromethylthio group significantly improves the small molecule's stablity in acidic environments. Not surprisingly, the trifluoromethylthio group has been of special attention not only from the academia but also from pharmaceutical and agrochemical industry for their use in isostere-based drug design. Development of highly efficient methods for the introduction of the trifluoromethylthio group into small molecules, thereafter, has become a subject of recent focus in the field of organic chemistry. In the early 1960s, a few methods for the formation of trifluoromethylthioethers were reported, which typically involved halogen exchange of the trichloromethyl-substituted compounds and trifluoromethylation of thiolated substrates. However, the conditions of these methods were harsh and incompatible with many common functional groups. Since 2008, new reagents and methods that were able to efficiently incorporate the trifluoromethylthio group under mild conditions have emerged, that pave the way for the facile introduction of trifluoromethylthio group into site-specific positions of the target molecules. In this review, we will first briefly introduce the indirect strategies for trifluoromethylthiolation including halogen exchange and trifluoromethylation of thiolated substrates, and then focus on the direct trifluoromethylthiolation strategies including the transition metal-catalyzed trifluoromethylthiolation reactions, electrophilic trifluoromethylthiolation reactions with electrophilic trifluoromethylthiolating reagents and radical trifluoromethylthiolations. These methods represent the most straightforward and promising approaches for the incorporation of the trifluoromethylthio group into small molecules. At the end, we will discuss the remaining problems and challenges in this particular field.

show abstract

unclassified

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Zhang¹,

Lü²,

Shen³

2017

Acta Chim. Sinica

View full text Add to dashboard Cite

show abstract

“…Next, we assayed the suitability of other nucleophiles to afford N–, O–, and S–SR F bonds. 29 Thus, reaction with benzylamine gave the desired products 11a (93%) and 11b (87%) after 1 h at room temperature, while reaction with 2-mercaptobenzoxazole afforded instantaneously disulfides 12a (99%) and 12b (89%). Unlike phenol, which required a protic acid that activates the electrophilic reagent, preliminary results with alcoholic nucleophiles indicate the necessity of an exogenous base (e.g., Et 3 N) to deprotonate the hydroxyl moiety and deliver the desired products.…”

Section: Resultsmentioning

confidence: 97%

“…Reaction with phenol required the addition of TfOH as a promoter and afforded 10a (97%) and 10b (86%). Next, we assayed the suitability of other nucleophiles to afford N–, O–, and S–SR F bonds . Thus, reaction with benzylamine gave the desired products 11a (93%) and 11b (87%) after 1 h at room temperature, while reaction with 2-mercaptobenzoxazole afforded instantaneously disulfides 12a (99%) and 12b (89%).…”

Section: Resultsmentioning

confidence: 99%

Electrophilic Reagents for the Direct Incorporation of Uncommon SCF₂CF₂H and SCF₂CF₃ Motifs

et al. 2022

View full text Add to dashboard Cite

The introduction of fluoroalkylthioether groups has attracted the attention of the drug-discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds, yet these are often limited to standard SCF 3 and SCF 2 H moieties. Herein, two saccharin-based electrophilic reagents have been disclosed for the incorporation of uncommon SCF 2 CF 2 H and SCF 2 CF 3 motifs. Their reactivity performance, multigram-scale preparation, and divergent derivatization have been thoroughly investigated with a variety of nucleophiles, including natural products and pharmaceuticals.

show abstract

“…Next, we assayed the suitability of other nucleophiles to afford N-, O-, and S-SRF bonds. 28 Thus, reaction with benzylamine gave the desired products 11a (93%) and 11b (87%) after 1 h at room temperature, while reaction with 2-mercaptobenzoxazole afforded instantaneously disulfides 12a (99%) and 12b (89%). Unlike phenol, which required a protic acid that activates the electrophilic reagent, preliminary results with alcoholic nucleophiles indicate the necessity of an exogenous base (e.g., Et3N) to deprotonate the hydroxyl moiety and deliver the desired products.…”

Section: Reaction Scopementioning

confidence: 97%

Shelf-stable electrophilic reagents for the direct incorporation of SCF2CF2H and SCF2CF3 motifs

Mestre

Bernús

Castillón

et al. 2021

Preprint

View full text Add to dashboard Cite

The introduction of fluoroalkylthioether groups has attracted the attention of the drug discovery community given the special physicochemical and pharmacokinetic features they confer to bioactive compounds. Synthetic advances in the field have been capitalized by methods to incorporate SCF3 and SCF2H motifs, however, longer and synthetically more challenging polyfluoroethyl chains are still underdeveloped. Here, two saccharin-based electrophilic reagents have been disclosed for the efficient incorporation of SCF2CF2H and SCF2CF3 motifs. Their reactivity performance has been thoroughly investigated with a variety of nucleophiles such as thiols, alcohols, amines, alkenes, (hetero)aromatics, and organometallic species, including natural products and pharmaceuticals. Finally, multigram-scale preparation and divergent derivatization has been explored from SCF2CF2H derivatives.

show abstract

Direct Perfluoroalkylthiolation of Few Chalcogenols

Cited by 13 publications

References 40 publications

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Electrophilic Reagents for the Direct Incorporation of Uncommon SCF₂CF₂H and SCF₂CF₃ Motifs

Shelf-stable electrophilic reagents for the direct incorporation of SCF2CF2H and SCF2CF3 motifs

Contact Info

Product

Resources

About

Direct Perfluoroalkylthiolation of Few Chalcogenols

Cited by 13 publications

References 40 publications

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Electrophilic Reagents for the Direct Incorporation of Uncommon SCF2CF2H and SCF2CF3 Motifs

Shelf-stable electrophilic reagents for the direct incorporation of SCF2CF2H and SCF2CF3 motifs

Contact Info

Product

Resources

About

Electrophilic Reagents for the Direct Incorporation of Uncommon SCF₂CF₂H and SCF₂CF₃ Motifs