Ligandless Nickel-Catalyzed <i>Ortho</i>-Selective Directed Trifluoromethylthiolation of Aryl Chlorides and Bromides Using AgSCF<sub>3</sub>

The direct introduction of the valuable SCF3 moiety into organic molecules has received considerable attention. While it can be achieved successfully for aryl chlorides under catalysis with Ni0(cod)2 and dppf, this report investigates the Ni-catalyzed functionalization of the seemingly more reactive aryl halides ArI and ArBr. Counterintuitively, the observed conversion triggered by dppf/Ni0 is ArCl > ArBr > ArI, at odds with bond strength preferences. By a combined computational and experimental approach, the origin of this was identified to be due to the formation of (dppf)NiI, which favors β-F elimination as a competing pathway over the productive cross-coupling, ultimately generating the inactive complex (dppf)Ni(SCF2) as a catalysis dead end. The complexes (dppf)NiI–Br and (dppf)NiI–I were isolated and resolved by X-ray crystallography. Their formation was found to be consistent with a ligand-exchange-induced comproportionation mechanism. In stark contrast to these phosphine-derived Ni complexes, the corresponding nitrogen-ligand-derived species were found to be likely competent catalysts in oxidation state I. Our computational studies of N-ligand derived NiI complexes fully support productive NiI/NiIII catalysis, as the competing β-F elimination is disfavored. Moreover, N-derived NiI complexes are predicted to be more reactive than their Ni0 counterparts in catalysis. These data showcase fundamentally different roles of NiI in carbon–heteroatom bond formation depending on the ligand sphere.

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“…These in turn can be transformed with a phosphine-based catalyst system, Ni(cod) 2 /dppf, that forms [(dppf)Ni 0 (cod)] in situ. 7,18 …”

Section: Introductionmentioning

confidence: 99%

“…In the context of Ni catalysis, Vicic has shown that a Ni(cod) 2 /bipyridine system allows for functionalization of aryl iodides and selected bromides, but not aryl chlorides. These in turn can be transformed with a phosphine-based catalyst system, Ni(cod) 2 /dppf, that forms [(dppf)Ni 0 (cod)] in situ. , …”

Section: Introductionmentioning

confidence: 99%

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

et al. 2017

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“…图式 10 Ni 催化芳基、烯基类卤化物的三氟甲硫基化反应 Scheme 10 Nickel-Catalyzed coupling of ary, vinyl triflates or nonaflates with NMe 4 SCF 3 此外, 通过官能团化导向的策略, 可以更好地对底物中的 C-Br 键以及 C-Cl 键进行活化, 从而可以更加高效地实现相应的三氟甲硫基化转化. 不列颠哥伦比亚大学的 Love 小组 [21] 发现, 使用不同的含氮导向基, 来使金属镍催化剂形成五元环金属中间体, 无需配体和添加剂的加入, 便可以在温和的条件下实现 C-Br 键、 C-Cl 键到 C-SCF 3 键的转化(Scheme 11).…”

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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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“…1 Therefore, trifluoromethylthiolated compounds are widely used in pharmaceuticals, agrochemicals, and functional materials. 2 Recently, considerable effort has been devoted to the development of new and efficient methods for introducing the CF 3 S group into heteroarenes with different CF 3 S sources. 3 Up to now, a broad range of important heterocycles, such as pyrrole, 4 oxindole, 5 indole, 6 indanone, 7 coumarin, 8 quinone, 9 chromone, 10 and benzofuran(thiophene), 11 have been successfully trifluoromethylthiolated using various nucleophilic, electrophilic, and radical trifluoromethylthiolating reagents.…”

Section: Introductionmentioning

confidence: 99%

Bismuth(III)-Promoted Trifluoromethylthiolation of Pyrazolin-5-ones with Trifluoromethanesulfenamide

et al. 2017

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Ligandless Nickel-Catalyzed Ortho-Selective Directed Trifluoromethylthiolation of Aryl Chlorides and Bromides Using AgSCF₃

Cited by 31 publications

References 51 publications

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Bismuth(III)-Promoted Trifluoromethylthiolation of Pyrazolin-5-ones with Trifluoromethanesulfenamide

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Ligandless Nickel-Catalyzed Ortho-Selective Directed Trifluoromethylthiolation of Aryl Chlorides and Bromides Using AgSCF3

Cited by 31 publications

References 51 publications

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

When Weaker Can Be Tougher: The Role of Oxidation State (I) in P- vs N-Ligand-Derived Ni-Catalyzed Trifluoromethylthiolation of Aryl Halides

Recent Progress on Direct Trifluoromethylthiolating Reagents and Methods

Bismuth(III)-Promoted Trifluoromethylthiolation of Pyrazolin-5-ones with Trifluoromethanesulfenamide

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Product

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Ligandless Nickel-Catalyzed Ortho-Selective Directed Trifluoromethylthiolation of Aryl Chlorides and Bromides Using AgSCF₃