Selenide‐Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes

Wu, Jingzhi; Xu, Jia; Zhao, Xiaodan

doi:10.1002/chem.201603975

Cited by 48 publications

(18 citation statements)

References 99 publications

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“…另外, 他们采用官能团导向的策略实现了 Rh(III)催化吲哚 2 位 C-H 键的三氟甲硫基化反应 [114] (Scheme 60). [117] . 他们也对该体系下的手性硫醚、硒醚催化剂进行了考察.…”

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Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Zhang¹,

Lü²,

Shen³

2017

Acta Chim. Sinica

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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.

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Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Zhang¹,

Lü²,

Shen³

2017

Acta Chim. Sinica

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“…Trifluoromethanesulfonic acid (1.4 equiv) was added to 4-chlorophenylethyne 27 (1.3 equiv) in CH 2 Cl 2 . 17 After 10 min at rt, the solvent was removed and THF, NHC-borane 8 (0.1 mmol), and iPr 2 NEt (0.1 mmol) were added. Heating at 70 °C for 1 h, followed by cooling, concentration, and chromatography, provided 10a in 41% yield.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…So we next studied several one-pot reactions where the alkenyl triflate was generated in situ and then directly converted to an α-NHC-boryl ketone. Two convenient ways to make alkenyl triflates are base-promoted triflation of ketones and addition of triflic acid to alkynes, so one-pot variants of each where studied.…”

Section: Resultsmentioning

confidence: 99%

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Facile Synthesis of α-N-Heterocyclic Carbene-Boryl Ketones from N-Heterocyclic Carbene-Boranes and Alkenyl Triflates

2019

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Reactions of readily available alkenyl triflates with Nheterocyclic carbene (NHC)-boranes in the presence of diisopropyl ethyl amine provided about three dozen stable α-NHC-boryl ketones. Isolated yields were typically 40−56% for B-unsubstituted NHCboranes (NHC-BH 3 ), and somewhat lower for NHC-boranes with Bsubstituents (NHC-BH 2 R). The requisite alkenyl triflates can be made separately or prepared in situ from either ketones or alkynes. The experimental evidence supports a radical chain mechanism that involves the following: (1) addition of an NHC-boryl radical to the alkenyl triflate, (2) fragmentation to give the α-NHC-boryl ketone, SO 2 , and trifluoromethyl radical, and (3) hydrogen abstraction by trifluoromethyl radical from the starting NHC-borane to return the NHC-boryl radical along with trifluoromethane. Reactions 1 and 3 are both new and evidently rather fast.

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“…Lowering the reaction temperature led to only a moderate yield (entry 14). It is noted that the desired product was generated in only 44% yield in the absence of chalcogenide catalyst, which indicated a significant role of the Lewis basic catalyst in this transformation (entry 15) . Without acid, the reaction did not occur (entry 16).…”

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Chalcogenide-Catalyzed Intermolecular Electrophilic Thio- and Halofunctionalization of gem-Difluoroalkenes: Construction of Diverse Difluoroalkyl Sulfides and Halides

et al. 2020

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Thio- and halodifluoromethylated compounds are an important class of compounds in medicinal chemistry and organic synthesis. Herein, we report a facile method for the construction of these compounds via chalcogenide-catalyzed intermolecular electrophilic thio- and halofunctionalization of gem-difluoroalkenes. Simple treatment of gem-difluoroalkenes with electrophilic sulfur/halogen reagents and various O- or N-nucleophiles affords diverse multifunctionalized thio- and halodifluoromethylated compounds. This reaction features a relatively broad substrate scope, good functional group tolerance, and mild reaction conditions.

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Selenide‐Catalyzed Stereoselective Construction of Tetrasubstituted Trifluoromethylthiolated Alkenes with Alkynes

Cited by 48 publications

References 99 publications

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Facile Synthesis of α-N-Heterocyclic Carbene-Boryl Ketones from N-Heterocyclic Carbene-Boranes and Alkenyl Triflates

Chalcogenide-Catalyzed Intermolecular Electrophilic Thio- and Halofunctionalization of gem-Difluoroalkenes: Construction of Diverse Difluoroalkyl Sulfides and Halides

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