Copper-Mediated Regioselective C-H Sulfenylation and Selenation of Phenols with Phenanthroline Bidentate Auxiliary.

A copper-mediated, phenanthroline-directed highly ortho-selective C-H sulfenylation of phenols with diaryl disulfides proceeds to form the corresponding unsymmetrical diaryl sulfides in good yield. The key to success is the introduction of a phenanthroline directing group of the bidentate-chelating nature, which is easily attachable, detachable, and even recyclable. Moreover, the same strategy is applicable to the C-H selenation, giving the diaryl selenides with high efficiency and regioselectivity.

Synthesis of Seven-Membered Benzolactones by Nickel-Catalyzed C-H Coupling of Benzamides with Oxetanes.

A NiCl2 (PEt3 )2 -catalyzed regioselective C-H coupling of 8-aminoquinoline-derived benzamides with oxetanes has been developed. The reaction proceeds with concomitant removal of the 8-aminoquinoline auxiliary to directly form the corresponding seven-membered benzolactones, which frequently occur in natural products and bioactive molecules. Additionally, no stereochemical erosion is observed during the course of the reaction, and the use of enantioenriched and substituted oxetane thus provides a new avenue to the optically active benzolactone.

Nickel-Catalyzed Stereospecific C-H Coupling of Benzamides with Epoxides.

A Ni(OAc)2 -catalyzed C-H coupling of 8-aminoquinoline-derived benzamides with epoxides has been developed. The reaction proceeds with concomitant removal of the 8-aminoquinoline auxiliary to form the corresponding 3,4-dihydroisocoumarins directly. Additionally, the nickel catalysis is stereospecific, and the cis- and trans-epoxides are converted into the corresponding cis- and trans-dihydroisocoumarins with retention of configuration, which is complementary to previously reported palladium catalysis. Moreover, while still preliminary, the Csp3 -H functionalization is also achieved in the presence of modified NiCl2 catalysts.

A Divergent Approach to Indoles and Oxazoles from Enamides by Directing-Group-Controlled Cu-Catalyzed Intramolecular C-H Amination and Alkoxylation.

A directing-group-controlled, copper-catalyzed divergent approach to indoles and oxazoles from enamides has been developed. The picolinamide-derived enamides undergo the intramolecular aromatic C-H amination in the presence of a Cu(OPiv)2 catalyst and an MnO2 oxidant to form the corresponding indoles in good yields. On the other hand, simpler aryl- or alkyl-substituted enamides are converted to the 2,4,5-trisubstituted oxazole frameworks via vinylic C-H alkoxylation under identical conditions. The copper catalysis can provide uniquely divergent access to indole and oxazole heteroaromatic cores of great importance in medicinal and material chemistry.

Copper-Mediated Decarboxylative Coupling of Benzamides with ortho-Nitrobenzoic Acids by Directed C-H Cleavage.

A copper-mediated decarboxylative coupling of benzamides with ortho-nitrobenzoic acids by 8-aminoquinoline-directed C-H cleavage has been developed. This reaction proceeds smoothly with only a copper salt to produce the corresponding biaryl compounds in good yields. The products can be easily transformed into various nitrogen-containing heterocyclic compounds. Moreover, the combination of copper and a suitable base promotes a decarboxylative C-H arylation and cyclization sequence to deliver phenanthridinone derivatives in one pot.

Copper-Catalyzed Intramolecular Benzylic C-H Amination for the Synthesis of Isoindolinones.

A copper-catalyzed intramolecular amination occurs at the benzylic C-H of 2-methylbenzamides to deliver the corresponding isoindolinones of great interest in medicinal chemistry. The mild and abundant MnO2 works well as a terminal oxidant, and the reaction proceeds smoothly under potentially explosive organic peroxide-free conditions. Additionally, the directing-group-dependent divergent mechanisms are proposed: 8-aminoquinoline-containing benzamides include a Cu-mediated organometallic pathway whereas an aminyl radical-promoted Hofmann-Loffler-Freytag (HLF)-type mechanism can be operative in the case of N-naphthyl-substituted substrates.

Copper-Catalyzed Formal [4 + 1] Cycloaddition of Benzamides and Isonitriles via Directed C-H Cleavage.

A copper-catalyzed formal [4 + 1] cycloaddition of benzamides and isonitriles via 8-aminoquinoline-directed C-H cleavage has been developed. The reaction proceeds well even in the presence of a base metal catalyst, CuBr·SMe2, alone to deliver the corresponding 3-iminoisoindolinones in good yields. Moreover, the unique acceleration effects of diphenyl sulfide are also disclosed.

Synthesis of indolines by copper-mediated intramolecular aromatic C-h amination.

A Cu(OAc)2-mediated intramolecular aromatic C-H amination proceeds with the aid of a picolinamide-type bidentate coordination group to deliver the corresponding indolines in good yields. The reaction occurs smoothly even under noble-metal-free conditions, and in some cases the use of an MnO2 terminal oxidant renders the process catalytic in Cu. The mild oxidation aptitude of Cu(OAc)2 and/or MnO2 accommodates the formation of electron-rich thiophene- and indole-fused indoline analogues. The Cu-based system can provide an effective approach to various indolines of potent interest in pharmaceutical and medicinal chemistry.

Synthesis of carbazoles by copper-catalyzed intramolecular C-H/N-H coupling.

A Cu-catalyzed intramolecular C-H amination for the synthesis of carbazoles has been developed. The key to success is the installation of the picolinamide-based directing group, which is spontaneously removed after the coupling event. The Cu catalysis proceeded smoothly under Pd- and I(III)-free conditions, and its mild oxidation aptitude enables the rapid and concise construction of heteroatom-incorporated carbazole core π-systems.