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Open accessJournal ArticleDOI: 10.1038/S41467-021-21633-2

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

02 Mar 2021-Nature Communications (Nature Publishing Group)-Vol. 12, Iss: 1, pp 1-8
Abstract: 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. Site-selective C–H functionalization still faces some challenges, such as the introduction and removal of an appropriate directing group. Here, the authors introduce a temporary directing group for selective meta-C–H functionalization of 2-arylbenzaldehydes via reversible imine formation.

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Topics: Imine (51%)

11 results found

Open access
Yongbing Liu1, Haibo Ge1Institutions (1)
01 Jan 2017-
Abstract: Transition-metal-catalysed direct C(sp3)−H functionalization of primary aliphatic amines is an attractive – but elusive – process that could provide efficient access to biologically and pharmaceutically important compounds. Now, a palladium-catalysed γ-arylation of primary alkylamines is achieved using an inexpensive, catalytic and transient directing group.

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152 Citations

Journal ArticleDOI: 10.1126/SCIENCE.ABD5992
14 May 2021-Science
Abstract: Transition metal-catalyzed aryl C-H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal ortho-C-H activation, distal (meta- and/or para-) C-H activation remains more challenging due to the inaccessibility of these sites in the formation of energetically favorable organometallic pretransition states. Directing the catalyst toward the distal C-H bonds requires judicious template engineering and catalyst design, as well as prudent choice of ligands. This review aims to summarize the recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, and catalyst and/or ligand selection to control distal C-H activation.

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30 Citations

Journal ArticleDOI: 10.1021/ACS.JOC.1C00646
Yangyang Wang1, Gaorong Wu1, Xiaobo Xu1, Binghan Pang1  +2 moreInstitutions (1)
Abstract: The direct arylation of aliphatic ketones has been developed via Pd-catalyzed β-C(sp3)-H bond functionalization with 2-(aminooxy)-N,N-dimethylacetamide as a novel transient directing group (TDG), which showed remarkable directing ability to generate arylated products in moderate to good yields. Furthermore, the reaction can tolerate abundant substrate of ketones and aryl iodides. This study expands the scope of applications for TDGs.

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Topics: Aryl (51%)

1 Citations

Journal ArticleDOI: 10.1039/D1CC04121E
Chaolumen Bai1, Bao Chao1, Tegshi Muschin1, Agula Bao1  +3 moreInstitutions (1)
Abstract: The regiodivergent catalytic dehydrogenative cross-coupling reactions at both sp2 and sp3 hybridized carbons of aromatic compounds are particularly challenging. Herein, we report the finding of transient directing group controlled regiodivergent C(sp3)-C(sp2) and C(sp2)-C(sp2) cross-coupling in the o-methyl benzaldehyde frameworks. Catalyzed by palladium, using K2S2O8 or [F+] reagents as by-standing oxidants and unactivated arenes as substrates/solvents, various benzyl benzaldehydes or phenyl benzaldehydes were prepared. A mechanism study indicated that the regiospecificity is dominated by the [5,6]-fused palladacycle or [6,5]-fused palladacycle intermediates, which are generated from Pd-chelation with specified transient directing groups and further C-H activations.

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Topics: Benzaldehyde (51%)


47 results found

Journal ArticleDOI: 10.1038/NCHEM.1607
Joanna Wencel-Delord1, Frank Glorius2Institutions (2)
01 May 2013-Nature Chemistry
Abstract: The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry.

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1,615 Citations

Journal ArticleDOI: 10.1021/AR000209H
Abstract: Several novel synthetic reactions of arenes and alkanes discovered and investigated in our laboratory are summarized here. These include olefin arylation, hydroarylation of alkynes, hydroxylation of arenes, carboxylation of arenes and alkanes, and aminomethylation and acetoxylation of alkanes. Most of these reactions are catalyzed by highly electrophilic transition metal cationic species generated in situ in an acid medium, involving electrophilic metalation of C−H bonds of arenes and alkanes which lead to the formation of aryl−metal and alkyl−metal σ-complexes.

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Topics: Metalation (52%)

1,178 Citations

Journal ArticleDOI: 10.1038/366529A0
Shinji Murai1, Fumitoshi Kakiuchi1, S. Sekine1, Yasuo Tanaka1  +3 moreInstitutions (1)
08 Jul 1993-Nature
Abstract: The selective cleavage of carbon–hydrogen bonds in organic compounds is a critical step in many organic syntheses, and is particularly important in the conversion of hydrocarbons to useful organic compounds. An organometallic ruthenium complex can cleave C–H bonds in a variety of aromatic systems, leading to addition to alkenes by C–C bond formation. The catalyst operates with a degree of efficiency, selectivity and generality that will make it extremely valuable in organic synthesis.

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Topics: Organic synthesis (60%), Catalysis (51%)

1,050 Citations

Journal ArticleDOI: 10.1126/SCIENCE.1067074
Jian Yang Cho1, Man Kin Tse1, Daniel Holmes1, Robert E. Maleczka1  +1 moreInstitutions (1)
11 Jan 2002-Science
Abstract: Arylboron compounds have intriguing properties and are important building blocks for chemical synthesis. A family of Ir catalysts now enables the direct synthesis of arylboron compounds from aromatic hydrocarbons and boranes under "solventless" conditions. The Ir catalysts are highly selective for C-H activation and do not interfere with subsequent in situ transformations, including Pd-mediated cross-couplings with aryl halides. By virtue of their favorable activities and exceptional selectivities, these Ir catalysts impart the synthetic versatility of arylboron reagents to C-H bonds in aromatic and heteroaromatic hydrocarbons.

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Topics: Aryl (54%), Organic synthesis (50%), Borylation (50%)

839 Citations