Highly <i>ortho</i>‐Selective Trifluoromethylthiolation Reactions using a Ligand Exchange Strategy

Yin, Weiyu; Wang, Zhaofeng; Huang, Yong

doi:10.1002/adsc.201400362

Cited by 77 publications

(16 citation statements)

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“…随后, 华东理工大学的曹松小组 [27] [28] 通过对氧化剂的考察, 发现在一价铜盐的催化下, 使用过氧化物作为氧化剂, 可以实现苄位 C-H 键无官能团导向的三氟甲硫基化反应. 北京大学的黄湧小组 [29] 报道了官能团导向芳基 C-H 键的氧化三氟甲硫基化反应. 该过程中, 氧化剂的作用可能是将转金属后的 Pd(II)-SCF 3 中间体氧化成 Pd(IV)中间体, 从而促进还原消除过程.…”

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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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“…6 In this context, several C-H trifluoromethylthiolation reactions were reported using electrophilic trifluoromethylthiolating reagents 7,8 or oxidative conditions. 9,10 Daugulis and co-workers reported a C-H trifluoromethylthiolation using toxic and volatile (CF 3 S) 2 and a substoichiometric amount of Cu(OAc) 2 , but only ditrifluoromethylthiolated products were obtained (Scheme 1a (5) AgSbF6 (5) Solvent ( earth-abundant inexpensive first-row transition metal catalyst, 11 and here we report a Cp*Co III -catalyzed C-H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines (Scheme 1e). 12 We previously reported that Cp*Co III catalysts act as alternatives to expensive Cp*Rh III catalysts 13 improved the yield probably due to the instability of the highly reactive reagent 2b towards water (entry 11).…”

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Cp*Co^III-catalyzed directed C–H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines

et al. 2017

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“…[15] In this process,S electfluor was used as as tandaloneo xidant. We wondered whether this ligandexchange strategyc ould be exploited for inert sp 3 C À Hb ondf unctionalization (Scheme 2).…”

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confidence: 99%

Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp³ CH Fluorination

et al. 2016

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Thed irect functionalization of inert sp 3 C À Hb onds is limited to afew bond types. Although the activation of sp 3 C À Hb onds can be accomplished under mild conditions using palladium catalysts,t he subsequent functionalization is not trivial due to the high energy required to convert palladium(II) to palladium(IV). We have systematicallys tudied the palladium oxidation using computation-guided experiments for reactions involving strong chelation control. We find that amild external ligand could significantly accelerate the oxidation of palladium(II) to palladium(IV) for strong bidentated irecting groups. Thea ccelerationi sb elieved to be ar esult of ligand stabilization of both the palladium(II) and palladium(IV)intermediates.

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Highly ortho‐Selective Trifluoromethylthiolation Reactions using a Ligand Exchange Strategy

Cited by 77 publications

References 77 publications

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Cp*Co^III-catalyzed directed C–H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines

Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp³ CH Fluorination

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Highly ortho‐Selective Trifluoromethylthiolation Reactions using a Ligand Exchange Strategy

Cited by 77 publications

References 77 publications

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Cp*CoIII-catalyzed directed C–H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines

Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp3 CH Fluorination

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About

Cp*Co^III-catalyzed directed C–H trifluoromethylthiolation of 2-phenylpyridines and 6-arylpurines

Ligand‐Assisted Palladium(II)/(IV) Oxidation for sp³ CH Fluorination