Development of a Traceless Directing Group: Cp*-Free Cobalt-Catalyzed C-H Activation/Annulations to Access Isoquinolinones.

A new traceless directing group, 2-(hydroxymethyl)pyridine, has been reported for the Cp*-free cobalt-catalyzed C-H activation/annulation reaction to synthesize isoquinolinones. The reaction exhibits good functional group tolerance, affording products in good to excellent isolated yields under mild conditions. Notably, the directing group can be removed directly in situ along the catalytic process.

Synthesis of 7-Amido Indolines by Cp*Co(III)-Catalyzed C-H Bond Amidation.

An efficient Cp*Co(III)-catalyzed C-H bond amidation of indolines at the C7-position using dioxazolone as amidating reagents was first reported. N-Methyl-N-(pyrimidin-2-yl)aniline was also found to be a competent coupling partner. This protocol exhibits several unique characteristics, including excellent isolated yields, good functional group tolerance, and operational convenience. Derivatization reactions revealed this method has great potential for applications in synthesis.

Manganese-catalyzed cascade annulations of alkyne-tethered N-alkoxyamides: synthesis of polycyclic isoquinolin-1(2H)-ones.

A strategy for the synthesis of isoxazolidine/1,2-oxazinane-fused isoquinolin-1(2H)-ones from alkyne-tethered N-alkoxyamides is described, in which cheap Mn(acac)2 is used as a catalyst to facilitate a radical cascade annulation. The method features mild conditions, additive-free reaction and broad substrate scope. It is the first example via manganese/air catalytic systems to construct isoquinolin-1(2H)-one heterocycles.

Cobalt-catalyzed peri-selective alkoxylation of 1-naphthylamine derivatives.

A cobalt-catalyzed C(sp2)-H alkoxylation of 1-naphthylamine derivatives has been disclosed, which represents an efficient approach to synthesize aryl ethers with broad functional group tolerance. It is noteworthy that secondary alcohols, such as hexafluoroisopropanol, isopropanol, isobutanol, and isopentanol, were well tolerated under the current catalytic system. Moreover, a series of biologically relevant fluorine-aryl ethers were easily obtained under mild reaction conditions after the removal of the directing group.

Ni(II)-Catalyzed C(sp(2))-H Alkynylation/Annulation with Terminal Alkynes under an Oxygen Atmosphere: A One-Pot Approach to 3-Methyleneisoindolin-1-one.

A nickel(II)-catalyzed alkynylation/annulation cascade via double C-H cleavage has been successfully achieved. This methodology adopted a removable N,O-bidentate directing group with a broad range of amide substrates and terminal alkynes being well tolerated. The catalytic system allowed for atom-economical and environmentally benign one-pot construction of the corresponding 3-methyleneisoindolin-1-one derivatives using O2 as the external oxidant.

Mixed Directing-Group Strategy: Oxidative C-H/C-H Bond Arylation of Unactivated Arenes by Cobalt Catalysis.

A mixed directing-group strategy for inexpensive [Co(acac)3 ]-catalyzed oxidative C-H/C-H bond arylation of unactivated arenes has been disclosed. This strategy enables the arylation of a wide range of benzamide and arylpyridines effectively to afford novel bifunctionalized biaryls, which are difficult to achieve by common synthetic routes. Two different pathways, namely, a single-electron-transmetalation process (8-aminoquinoline-directed) and a concerted metalation-deprotonation process (pyridine-directed), were involved to activate two different inert aromatic C-H bonds. Moreover, the aryl radicals have been trapped by 2,6-di-tert-butyl-4-methylphenol to form benzylated products. This unique strategy should be useful in the design of other arene C-H/C-H cross-couplings as well.

Cobalt-catalyzed C(sp(2))-H alkoxylation of aromatic and olefinic carboxamides.

The cobalt-catalyzed alkoxylation of C(sp(2) )H bonds in aromatic and olefinic carboxamides has been developed. The reaction proceeded under mild conditions in the presence of Co(OAc)2 ⋅4H2 O as the catalyst and tolerates a wide range of both alcohols and benzamide substrates, including even olefinic carboxamides. In addition, this reaction is the first example of the direct alkoxylation of alkenes through CH bond activation.

Cobalt(II)-Catalyzed C(sp2)-H Alkynylation/Annulation with Terminal Alkynes: Selective Access to 3-Methyleneisoindolin-1-one.

A highly efficient cobalt(II)-catalyzed alkynylation/annulation of terminal alkynes assisted by an N,O-bidentate directing group is described. This protocol is characterized by wide substrate scope utilizing cheap cobalt catalysts, and offers a new approach to 3-methyleneisoindolin-1-one, which can be converted into an oxadiazine salt in one step. Moreover, the directing group could be removed in three steps.

Copper-mediated direct alkoxylation of arenes using an N,O-bidentate directing system.

Highly effective CuCl-mediated C-H alkoxylation of arenes and heteroarenes has been developed by using a 2-aminopyridine 1-oxide moiety as an N,O-bidentate directing group. The reaction proceeds smoothly using a broad range of substrates to afford o-alkoxylated benzoic and heteroaromatic amide products. Moreover, the reaction system shows remarkable compatibility when hexafluoroisopropanol is used as a coupling parter; halogen, nitro, ether, alkoxy, ester, and sulfonyl functional groups are all tolerated. The directing group can be easily removed by base hydrolysis, affording o-alkoxylated benzoic acids.

Simultaneous construction of inherent and axial chirality by cobalt-catalyzed enantioselective C-H activation of calix[4]arenes.

The simultaneous construction of multiple stereogenic elements in a single step is highly appealing and desirable in the field of asymmetric synthesis. Furthermore, the catalytic enantioselective synthesis of inherently chiral calix[n]arenes with high enantiopurity has long been a challenging endeavor. Herein, we report an enantioselective cobalt-catalyzed C-H activation/annulation for the efficient construction of inherently chiral calix[4]arenes bearing multiple C-N axially chiral element. By employing the benzamide tethered calix[4]arene as the substrate, the C-H annulation with alkynes can be successfully accomplished, leading to the generation of multiple stereogenic elements. A wide range of calix[4]arenes and alkynes are found to be well compatible, and exhibit good yields, high enantioselectivity and excellent diastereoselectivity. Notably, the gram-scale reaction, catalytic application, synthetic transformations, and chiral recognition further showcase the potential applications of this protocol.

Atroposelective N-N Axes Synthesis via Electrochemical Cobalt Catalysis.

Here, we disclosed an unprecedented cobalt electrocatalyzed atroposelective C-H activation and annulation for the efficient construction of diversely functionalized N-N axes in an undivided cell. A broad range of allene substrates and benzamides bearing different functionalities are compatible with generating axially chiral products with good yields and excellent enantioselectivities (up to 92% yield and 99% ee). A series of synthetic applications and control experiments were also performed, which further expanded the practicality of this strategy.

Chiral bis(imidazolinyl)phenyl NCN pincer rhodium(III) catalysts for enantioselective allylation of aldehydes and carbonyl-ene reaction of trifluoropyruvates.

Chiral NCN pincer rhodium(III) complexes with bis(imidazolinyl)phenyl ligands were found to be effective catalysts for the allylation of a variety of electronically and structurally diverse aldehydes with allyltributyltin, giving the corresponding optically active homoallylic alcohols in high yields with enantioselectivities of up to 97% ee. These complexes were also applied in the carbonyl-ene reaction of ethyl or methyl trifluoropyruvate with various 2-arylpropenes. With the aid of silver trifluoromethanesulfonate, the pincer rhodium(III) catalysts could catalyze the reaction to provide the corresponding chiral α-hydroxy-α-trifluoromethyl esters in good yields with high stereoselectivities (up to 95% ee).

Cobalt-catalyzed atroposelective C-H activation/annulation to access N-N axially chiral frameworks.

The N-N atropisomer, as an important and intriguing chiral system, was widely present in natural products, pharmaceutical lead compounds, and advanced material skeletons. The anisotropic structural characteristics caused by its special axial rotation have always been one of the challenges that chemists strive to overcome. Herein, we report an efficient method for the enantioselective synthesis of N-N axially chiral frameworks via a cobalt-catalyzed atroposelective C-H activation/annulation process. The reaction proceeds under mild conditions by using Co(OAc)2·4H2O as the catalyst with a chiral salicyl-oxazoline (Salox) ligand and O2 as an oxidant, affording a variety of N-N axially chiral products with high yields and enantioselectivities. This protocol provides an efficient approach for the facile construction of N-N atropisomers and further expands the range of of N-N axially chiral derivatives. Additionally, under the conditions of electrocatalysis, the desired N-N axially chiral products were also successfully achieved with good to excellent efficiencies and enantioselectivities.

C-N Axially Chiral Heterobiaryl Isoquinolinone Skeletons Construction via Cobalt-Catalyzed Atroposelective C-H Activation/Annulation.

Herein, the atroposelective construction of isoquinolinones bearing a C-N chiral axis has been successfully developed via a Co-catalyzed C-H bond activation and annulation process. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere to generate the target C-N axially chiral frameworks with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives. Additionally, the current protocol has proved to be an alternative approach for the C-N axial architectures fabrication under electrochemical conditions for cobalt/Salox catalysis, and this strategy allowed the efficient and atom-economical synthesis of various axially chiral isoquinolinones under mild reaction conditions.

Cobalt-catalyzed enantioselective C-H/N-H annulation of aryl sulfonamides with allenes or alkynes: facile access to C-N axially chiral sultams.

Herein we report a cobalt-catalyzed enantioselective C-H/N-H annulation of aryl sulfonamides with allenes and alkynes, using either chemical or electrochemical oxidation. By using O2 as the oxidant, the annulation with allenes proceeds efficiently with a low catalyst/ligand loading of 5 mol% and tolerates a wide range of allenes, including 2,3-butadienoate, allenylphosphonate, and phenylallene, resulting in C-N axially chiral sultams with high enantio-, regio-, and position selectivities. The annulation with alkynes also exhibits excellent enantiocontrol (up to >99% ee) with a variety of functional aryl sulfonamides, and internal and terminal alkynes. Furthermore, electrochemical oxidative C-H/N-H annulation with alkynes is achieved in a simple undivided cell, demonstrating the versatility and robustness of the cobalt/Salox system. The gram-scale synthesis and asymmetric catalysis further highlight the practical utility of this method.

C-N Axially Chiral Heterobiaryl Skeletons Construction via Cobalt-Catalyzed Atroposelective Annulation.

Herein, the atroposelective construction of five-six heterobiaryl skeleton-based C-N chiral axis has been successfully accomplished via a Co-catalyzed C-H bond activation and annulation process, in which the isonitrile was employed as the C1 source and the 8-aminoquinoline moiety served as both directing group and integral part of C-N atropisomers, respectively. This conversion can be effectively carried out in an environmentally friendly oxygen atmosphere, generating the target axial heterobiaryls with excellent reactivities and enantioselectivities (up to >99% ee) in the absence of any additives, and the obtained 3-iminoisoindolinone products with a five membered N-heterocycle exhibit high atropostability. Additionally, the C-N axially chiral monophosphine backbones derived from this protocol possess the potential to become an alternative ligand platform.

Nickel-Catalyzed anti-Markovnikov Hydrodifluoroalkylation of Unactivated Alkenes.

An efficient Ni-catalyzed hydrodifluoroalkylation of unactivated alkenes with bromodifluoroacetate by using PhSiH3 as hydride source was developed. The transformation affords aliphatic difluorides with anti-Markovnikov regioselectivity. A wide range of highly remote alkenes, simple alkenes, drug molecules, commercially available CF2 precursors, and even nonfluorinated substrates are competent in this reaction under mild conditions, demonstrating the practicability of the strategy. Moreover, mechanistic studies indicated that the difluoroalkyl radical might be a key intermediate to this transformation.

Bis{µ-1-[(2-ethyl-1H-imidazol-1-yl)meth-yl]-1H-benzotriazole}bis-(iodido-cadmium).

The dinuclear title complex, [Cd(2)I(4)(C(12)H(13)N(5))(2)], lies on a crystallographic center of inversion. The Cd(II) atom is four-coordinated by two N atoms from two 1-[(2-ethyl-1H-imidazol-1-yl)meth-yl]-1H-benzotriazole (bmei) ligands and two terminal I atoms in a distorted tetra-hedral coordination environment. The Cd(II) atoms are connected to each other by two bridging bmei ligands. The benzotriazole rings in adjacent mol-ecules are almost parallel, with an average inter-planar distance of 3.3400 (2) Šand a centroid-centroid distance of 4.852 (2) Å.

2,4-Dibromo-6-tert-butyl-benzene-1,3-diol.

In the title compound, C(10)H(12)Br(2)O(2), a multiply substituted bromo-arene, the C-C-C angles within the aromatic ring are in the range 115.7 (7)-122.4 (7)°. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, but no π-π stacking is observed.

O,O'-2-Iodo-1,3-phenyl-ene bis-(diphenyl-phosphinothio-ate).

The title compound, C(30)H(23)IO(2)P(2)S(2), was synthesized by the reaction of 2-iodo-benzene-1,3-diol, chloro-diphenyl-phosphine, Et(3)N and sulfur. The P=S bonds project to opposite sides of the central aromatic ring. The O-P-S and C-P-S bond angles are significantly larger than the O-P-C and C-P-C bond angles, indicating significant distortion of the tetra-hedral geometries of the P atoms. The P=S bond lengths of 1.9311 (13) and 1.9302 (12) Šin the title compound are shorter than that found in Ph(3)P=S [1.950 (3) Å] because the replacement of one C atom attached the P atom by an O atom increases the effective electronegativity of the P atom.