Ruthenium‐Catalyzed <i>para</i>‐Selective C−H Alkylation of Aniline Derivatives

Leitch, Jamie A.; McMullin, Claire L.; Paterson, Andrew J.; Mahon, Mary F.; Bhonoah, Yunas; Frost, Christopher G.

doi:10.1002/ange.201708961

Cited by 32 publications

(9 citation statements)

References 79 publications

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“…However, remote C–H functionalization still remains a great challenge. Compared with recently developed meta -selective C–H functionalization 10 – 26 , para -selective C–H functionalization is less explored; 27 – 34 only a few examples, such as steric-hindered arenes 35 , 36 , electron-rich arenes 37 – 43 , and substrates with a directing group 44 , have been reported to date. For instance, Zhang and co-workers reported in 2011 a Pd(II)-catalyzed para -selective amination of ortho -methoxy-substituted anilide.…”

Section: Introductionmentioning

confidence: 99%

“…Despite such major advances, most para -selective C–H functionalizations suffer from serious drawbacks such as limited substrate scope and relatively poor regioselectivity, which significantly restrict their applications (Fig. 1a ) 27 – 34 . Therefore, a catalyst-controlled strategy for para -selective C–H functionalization of arenes is highly desired.…”

Section: Introductionmentioning

confidence: 99%

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Ruthenium(II)-enabled para-selective C–H difluoromethylation of anilides and their derivatives

et al. 2018

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Transition-metal-catalyzed direct site-selective functionalization of arene C–H bonds has emerged as an innovative approach for building the core structure of pharmaceutical agents and other versatile complex compounds. However, para-selective C–H functionalization has seldom been explored, only a few examples, such as steric-hindered arenes, electron-rich arenes, and substrates with a directing group, have been reported to date. Here we describe the development of a ruthenium-enabled para-selective C–H difluoromethylation of anilides, indolines, and tetrahydroquinolines. This reaction tolerates various substituted arenes, affording para-difluoromethylation products in moderate to good yields. Results of a preliminary study of the mechanism indicate that chelation-assisted cycloruthenation might play a role in the selective activation of para-CAr–H bonds. Furthermore, this method provides a direct approach for the synthesis of fluorinated drug derivatives, which has important application for drug discovery and development.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ruthenium(II)-enabled para-selective C–H difluoromethylation of anilides and their derivatives

et al. 2018

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“…Remote selective functionalization is more challenging than the ortho ‐functionalization reactions that have been extensively studied . In recent years, para ‐selective functionalization reactions of aromatic compounds have undergone great progress for acetoxylation, alkylation, arylation, difluoromethylation, and olefinization . Meanwhile, the para ‐C–H selective functionalization of various aromatic amides has been reported in detail.…”

Section: Para‐c–h Functionalization Of Aromatic Amidesmentioning

confidence: 99%

C–H Functionalization of Aromatic Amides

et al. 2020

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Since the beginning of the 21st century, significant progress has been made in transition metal‐catalyzed C–H functionalization of aromatic amides. The achievements in this field have mainly focused on ortho (proximal) functionalization, there have been far fewer reports on remote C–H functionalization, and para‐ and meta‐selective functionalizations remain a major challenge. Interestingly, there are few related comments in this field. In a few published cases, the scope of the report is relatively narrow, either to comment on the functionalization of a specific directing group or to summarize the functionalization of a specific reaction site. Herein, for the first time, we have comprehensively summarized the C–H functionalization of aromatic amides. This review is divided into three parts: ortho‐, para‐ and meta‐C–H functionalization of aromatic amides, and is subdivided according to the type of catalyst. The directing groups, reaction types, conditions, mechanism and applications of the corresponding reactions are discussed in detail.

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“…In addition, a high molecular weight scaffold comprising of significant number of chemically equivalent C-H bonds is prone to deliver less selective functional group incorporation. Alternative approach by overruling the extra-steps associated with covalently linked template-based assembly is highly desirable [16][17][18][19][20][21][22][23][24][25][26][27] . We envisioned the development of a temporary DG, which can be designed to bind substrate reversibly and can also accommodate a metal center via strong coordination (Fig.…”

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confidence: 99%

Imine as a linchpin approach for meta-C–H functionalization

et al. 2021

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Despite the widespread applications of C–H functionalization, controlling site selectivity remains a significant challenge. Covalently attached directing groups (DGs) served as ancillary ligands to ensure ortho-, meta- and para-C–H functionalization over the last two decades. These covalently linked DGs necessitate two extra steps for a single C–H functionalization: introduction of DG prior to C–H activation and removal of DG post-functionalization. Here we report a temporary directing group (TDG) for meta-C–H functionalization via reversible imine formation. By overruling facile ortho-C–H bond activation by imine-N atom, a suitably designed pyrimidine-based TDG successfully delivered selective meta-C–C bond formation. Application of this temporary directing group strategy for streamlining the synthesis of complex organic molecules without any necessary pre-functionalization at the meta position has been explored.

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Ruthenium‐Catalyzed para‐Selective C−H Alkylation of Aniline Derivatives

Cited by 32 publications

References 79 publications

Ruthenium(II)-enabled para-selective C–H difluoromethylation of anilides and their derivatives

Ruthenium(II)-enabled para-selective C–H difluoromethylation of anilides and their derivatives

C–H Functionalization of Aromatic Amides

Imine as a linchpin approach for meta-C–H functionalization

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