Meta-Selective C_Ar–H Nitration of Arenes through a Ru₃(CO)₁₂-Catalyzed Ortho-Metalation Strategy

The first example of transition metal-catalyzed meta-selective C_Ar–H nitration of arenes is described. With the use of Ru₃(CO)₁₂ as the catalyst and Cu­(NO₃)₂·3H₂O as the nitro source, a wide spectrum of arenes bearing diversified <i>N</i>-heterocycles or oximido as the directing groups were nitrated with meta-selectivity exclusively. Mechanism studies have demonstrated the formation of a new 18e-octahedral ruthenium species as a key <i>ortho</i>-C_Ar–H metalated intermediate, which may be responsible for the subsequent meta-selective electrophilic aromatic substitution (S_EAr). Moreover, this approach provides a fast-track strategy for atom/step economical synthesis of many useful pharmaceutical molecules

Meta-Selective C_Ar–H Nitration of Arenes through a Ru₃(CO)₁₂-Catalyzed Ortho-Metalation Strategy

The first example of transition metal-catalyzed meta-selective C_Ar–H nitration of arenes is described. With the use of Ru₃(CO)₁₂ as the catalyst and Cu­(NO₃)₂·3H₂O as the nitro source, a wide spectrum of arenes bearing diversified <i>N</i>-heterocycles or oximido as the directing groups were nitrated with meta-selectivity exclusively. Mechanism studies have demonstrated the formation of a new 18e-octahedral ruthenium species as a key <i>ortho</i>-C_Ar–H metalated intermediate, which may be responsible for the subsequent meta-selective electrophilic aromatic substitution (S_EAr). Moreover, this approach provides a fast-track strategy for atom/step economical synthesis of many useful pharmaceutical molecules

Cobalt-Catalyzed Carbonylation of C(sp²)–H Bonds with Azodicarboxylate as the Carbonyl Source

A novel and efficient approach for the C­(sp²)–H bond carbonylation of benzamides has been developed using stable and inexpensive Co­(OAc)₂·4H₂O as the catalyst and the commercially available and easily handling azodicarboxylates as the nontoxic carbonyl source. A broad range of substrates bearing diverse functional groups were tolerated. This is the first example where cobalt-catalyzed C­(sp²)–H bond carbonylation occurs with azodicarboxylate as the carbonyl source

Ru(II)-Catalyzed Direct C(sp²)–H Activation/Selenylation of Arenes with Selenyl Chlorides

A new ruthenium catalytic system was developed for the construction of a C­(sp²)–Se bond with the assistance of directing groups. This protocol features mild reaction conditions, wider substrate scope, and convenient late-stage selenylation of bioactive molecules

Highly Stereoselective Assembly of Polycyclic Molecules from 1,6-Enynes Triggered by Rhodium(III)-Catalyzed C–H Activation

An Rh­(III)-catalyzed C–H activation of pyrazolones with 1,6-enynes was investigated. The regioselectivity of the C–H activation/alkyne insertion is readily solved by using symmetric enyne coupling partners, and a C–H activation-triggered cascade reaction is realized, which involves alkyne insertion, tautomerization, and double cyclization to offer a class of structurally complex polycyclic architectures. This cascade reaction tolerates a broad substrate scope in high regioselectivity and stereospecificity and furnishes three new chemical bonds and four chiral centers in a single operation. Various derivatizations of the polycyclic scaffolds are conducted, providing products with ample space for further functional transformations

Difluorination of Furonaphthoquinones

An unprecedented difluorination reaction was developed based on the furonaphthoquinone skeleton of natural products tanshinones and their analogues. By using Selectfluor as the fluorinating source and H₂O as the hydroxyl source, a wide range of unique polycyclic α,α-difluoro β,β-dihydroxyl <i>para</i>-quinone products were achieved with yields up to 90%. The mechanistic studies revealed that the reaction might undergo tandem multiple electrophilic and nucleophilic substitutions, as well as cleavages of C–O and C–C bonds. This approach not only provides a new method to synthesis of α,α-difluoro ketones, but also affords a series of unique chemotypes for biological activity screening

Ligand-Promoted Pd(II)-Catalyzed Functionalization of Unactivated C(sp³)–H Bond: Regio- and Stereoselective Synthesis of Arylated Rimantadine Derivatives

Stereoselective functionalization of the adamantyl bridge methylene C­(sp³)–H bonds is a rather appealing, yet challenging strategy due to the bulky and unactivated nature. Here we present a palladium-catalyzed C­(sp³)–H arylation/hetereoarylation of the antivirus drug rimantadine with the picolinamide moiety as the bidentate directing group and a mono-<i>N</i>-protected amino acid (MPAA) as the ligand. Multisubstituted rimantadine substrates and diverse aryl/heteroaryl iodides are well tolerated, and a series of optically pure arylated rimantadine derivatives have been synthesized in high regio- and diastereoselectivity that provides ample compound space for further pharmaceutical research

Rh(III)-Catalyzed Intermolecular C–H Amination of 1‑Aryl‑1<i>H</i>‑pyrazol-5(4<i>H</i>)‑ones with Alkylamines

An intermolecular C–H amination of 1-aryl-1<i>H</i>-pyrazol-5­(4<i>H</i>)-ones was achieved under mild reaction conditions, using a low catalyst loading and with a broad scope of aminating reagents. This protocol not only provides the first example of rhodium­(III)-catalyzed intermolecular aromatic C–H amination directed by an intrinsic functionality of the substrate/product but also features aminating an existing drug with either primary or secondary <i>N</i>-benzoate alkylamines as the coupling partners

Rh(III)-Catalyzed Intermolecular C–H Amination of 1‑Aryl‑1<i>H</i>‑pyrazol-5(4<i>H</i>)‑ones with Alkylamines

An intermolecular C–H amination of 1-aryl-1<i>H</i>-pyrazol-5­(4<i>H</i>)-ones was achieved under mild reaction conditions, using a low catalyst loading and with a broad scope of aminating reagents. This protocol not only provides the first example of rhodium­(III)-catalyzed intermolecular aromatic C–H amination directed by an intrinsic functionality of the substrate/product but also features aminating an existing drug with either primary or secondary <i>N</i>-benzoate alkylamines as the coupling partners

Substituent-Enabled Oxidative Dehydrogenative Cross-Coupling of 1,4-Naphthoquinones with Alkenes

A Rh-catalyzed oxidative dehydrogenative cross-coupling of 1,4-naphthquinones with alkenes was achieved by using a substituent-enabled C­(sp²)–H functionalization (SEF) strategy. The method shows high functional group tolerance, broad substrate scope, and great potential for further functional transformations