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The atroposelective synthesis of atropisomers with vicinal diaxes remains rare and challenging, due to the steric influence between the two axes and their unique topology. Herein, we disclose a single-step construction of atropisomers with vicinal C-C and C-N chiral diaxes by cyclopentadiene (Cp)-free cobalt-catalyzed intramolecular atroposelective C-H annulation, providing the desired diaxial atropisomers of unique structures with decent stereocontrols of both axes (up to99 % ee and 70 : 1 dr). The optically pure products bearing fluorophores show circular polarized luminescence (CPL) properties, being candidate materials for potential CPL applications. Atropisomerization experiments and density function theory (DFT) calculations are conducted to study the rotational barriers and rotation pathways of the diaxes.

The past decade has witnessed a rapid progress in asymmetric C-H activation. However, the enantioselective C-H alkoxylation and amination with alcohols and free amines remains elusive. Herein, we disclose the first enantioselective dehydrogenative C-H alkoxylation and amination enabled by a simple cobalt/salicyloxazoline (Salox) catalysis. The use of cheap and readily available cobalt(II) salts as catalysts and Saloxs as chiral ligands provides an efficient method to access P-stereogenic compounds in excellent enantioselectivities (up to99 % ee). The practicality of this protocol is demonstrated by gram-scale preparation and further derivatizations of the resulting P-stereogenic phosphinamides, which offering a flexible asymmetric alternative to access P-stereogenic mono- and diphosphine chiral ligands. Preliminary mechanistic studies on the enantioselective C-H alkoxylation reaction suggest that a cobalt(III/IV/II) catalytic cycle might be involved.

A catalytic 1,2-oxyhalogenation method that converts non-conjugated internal alkynes into tetrasubstituted alkenes with high regio- and stereoselectivity is described. Mechanistically, the reaction involves a Pd(II)/Pd(IV) catalytic cycle that begins with a directed oxypalladation step. The origin of regioselectivity is the preference for formation of a six-membered palladacycle intermediate, which is facilitated by a N,N-bidentate 2-(pyridin-2-yl)isopropyl (PIP) amide directing group. Selectivity for C(alkenyl)–X versus –N (X = halide) reductive elimination from the Pd(IV) center depends on the identity of the halide anion; bromide and iodide engage in C(alkenyl)–X formation, while intramolecular C(alkenyl)–N reductive elimination occurs with chloride to furnish a lactam product. DFT calculations shed light on the origins of this phenomenon.

Directing group (DG) assistance provides a good solution to the problems of reactivity and selectivity, two of the fundamental challenges in C(sp3)-H activation. However, the activation of unbiased methylene C(sp3)-H bonds remains challenging due to the high heterolytic bond dissociation energy and substantial steric hindrance. Two main strategies have been developed thus far, that is, use of a strongly coordinating bidentate DG pioneered by Daugulis and use of a weakly coordinating monodentate DG accelerated by pyridine-type ligands, as disclosed by Yu. The seminal work by Daugulis sparked significant interest in the application of the monoanionic bidentate auxiliary in aliphatic C-H activation reactions. Our research has focused on enabling the divergent functionalization and enantiotopic differentiation of unactivated methylene C-H bonds. Inspired by the structure of bidentate 8-aminoquinoline and the accelerating effect of the gem-dimethyl moiety in cyclometalations, we developed a strongly coordinating bidentate 2-(pyridine-yl)isopropyl (PIP) amine DG consisting of a pyridyl group, a gem-dimethyl moiety, and an amino group, which enabled the divergent functionalization of unactivated β-methylene C(sp3)-H bonds to forge C-O, C-N, C-C, and C-F bonds with palladium catalysts. The exclusive β-selectivity was ascribed to the preferential formation of kinetically favored [5,5]-bicyclic palladacycle intermediates. DFT calculations revealed that the well-designed gem-dimethyl group was responsible for the lowered energy and compressed bite angle of the key transition state related to C-H cleavage.More recently, the combination of PIP amine with axially chiral ligands was found to promote asymmetric functionalization of unbiased methylene C(sp3)-H bonds, a challenging research topic in the area of C-H activation that remains to be addressed. Two different types of axially chiral ligands, namely, non-C2-symmetric chiral phosphoric acids (CPAs) and 3,3'-disubstituted BINOLs, have been developed. The former enabled Pd(II)-catalyzed inter- and intramolecular arylation of unbiased methylene C(sp3)-H bonds with high enantioselectivity, whereas the latter promoted a series of asymmetric functionalization reactions, such as alkynylation, arylation, alkenylation/aza-Wacker cyclization, and intramolecular amidation. The unexpectedly high stereocontrol compared with other bidentate DGs might be attributable to steric communication between the ligand and gem-dimethyl moiety of PIP amine. Thus far, the combination of PIP amine DG with 3,3'-disubstituted BINOL ligands is arguably the most general strategy for asymmetric functionalization of unbiased methylene C(sp3)-H bonds. Finally, the ease of installation and removal of PIP under mild conditions and synthetic applications are described.

Previous methods on Co

The enantioselective desymmetrizing C-H activation of α-gem-dialkyl acyclic amides remains challenging because the availability of four chemically identical unbiased methylene C(sp3)-H bonds and increased rotational freedoms of the acyclic systems add tremendous difficulties for chemo- and stereocontrol. We have developed a method for the synthesis of acyclic aliphatic amides with α,β-contiguous stereogenic centers via PdII-catalyzed asymmetric arylation of unbiased methylene C(sp3)-H, in good yields and with high levels of enantio-, chemo- and diastereoselectivity (up to >99 % ee and >20:1 d.r.). Successive application of this method enables the sequential arylation of the gem-dialkyl groups with two different aryl iodides, giving a range of β-Ar1-β'-Ar2-aliphatic acyclic amides containing three contiguous stereogenic centers with excellent diastereoselectivity.

Herein, we describe an unprecedented cascade reaction to β-stereogenic γ-lactams involving Pd(II)-catalyzed enantioselective aliphatic methylene C(sp3 )-H alkenylation-aza-Wacker cyclization through syn-aminopalladation. Readily available 3,3'-substituted BINOLs are used as chiral ligands, providing the corresponding γ-lactams with broad scope and high enantioselectivities (up to 98 % ee).

A simple and ubiquitously present group, free amine, is used as a directing group to synthesize axially chiral biaryl compounds by PdII -catalyzed atroposelective C-H olefination. A broad range of axially chiral biaryl-2-amines can be obtained in good yields with high enantioselectivities (up to 97 % ee). Chiral spiro phosphoric acid (SPA) proved to be an efficient ligand and the loading could be reduced to 1 mol % without erosion of enantiocontrol in gram-scale synthesis. The resulting axially chiral biaryl-2-amines also provide a platform for the synthesis of a set of chiral ligands.

We present herein our experimental and DFT computational studies on the directing ability of chalcogenoether motifs in Pd-catalyzed atroposelective C-H functionalization. The thioether motif was found to be a superior directing group compared to the corresponding ether and selenoether in terms of reactivity and enantiocontrol. Remarkably, DFT calculation provided a predictive model for the optimization of reaction conditions and the interpretation of the origin of enantioselectivity. Both Pd-catalyzed enantioselective C-H olefination and allylation reactions were successfully developed using chiral phosphoric acids as efficient ligands, providing a broad range of axially chiral biaryls in good yields with excellent enantioselectivities. The highly enantio- and diastereoselective construction of polyaryls bearing multiple stereogenic axes, gram-scale reaction and various chemical transformations make this protocol more attractive and significant.

The atroposelective synthesis of axially chiral styrenes remains a formidable challenge due to their relatively lower rotational barriers compared to the biaryl atropoisomers. Herein, we describe the construction of axially chiral styrenes through PdII -catalyzed atroposelective C-H olefination, using a bulky amino amide as a transient chiral auxiliary. Various axially chiral styrenes were produced with good yields and high enantioselectivity (up to 95 % yield and 99 % ee). Carboxylic acid derivatives of the resulting axially chiral styrenes showed superior enantiocontrol over the biaryl counterparts in CoIII -catalyzed enantioselective C(sp3 )-H amidation of thioamide. Mechanistic studies suggest that C-H cleavage is the enantioselectivity-determining step.

Dibenzocyclooctadiene lignans are an interesting class of molecules because of their unique structure based on an axially chiral biaryl moiety as well as their significant biological activity. Herein, we describe the development of a palladium-catalyzed atroposelective C-H alkynylation and its application in gram-scale, stereocontrolled formal syntheses of (+)-isoschizandrin and (+)-steganone. tert-Leucine was identified as an efficient, catalytic transient chiral auxiliary. A wide range of enantiomerically enriched biaryl compounds were prepared by this approach in good yields (up to 99 %) with excellent enantioselectivity (up to >99 % ee).

Chiral aldehyde catalysis opens new avenues for the activation of simple amines. However, the lack of easy access to structurally diverse chiral aldehyde catalysts has hampered the development of this cutting-edge field. Herein, we report a Pd-catalyzed atroposelective C-H naphthylation with 7-oxabenzonorbornadienes for the preparation of axially chiral biaryls with excellent enantioselectivities (up to >99 % ee). This reaction is scalable and robust, which serves as a key step to provide a rapid access to axially chiral aldehyde catalysts through a three-step C-H functionalization sequence. These chiral aldehydes exhibit better activities and enantioselectivities than the previously reported organocatalysts in the asymmetric activation of glycine derived amides and dipeptides. Moreover, preliminary investigation also discloses that the aldehyde catalyst can effectively override the intrinsic facial selectivity of chiral dipeptide substrates, showcasing the strong chiral induction ability of this type of novel aldehyde catalysts.

Atroposelective synthesis of axially chiral biaryls by palladium-catalyzed C−H olefination, using tert-leucine as an inexpensive, catalytic, and transient chiral auxiliary, has been realized. This strategy provides a highly efficient and straightforward access to a broad range of enantioenriched biaryls in good yields (up to 98 %) with excellent enantioselectivities (95 to >99 % ee). Kinetic resolution of trisubstituted biaryls bearing sterically more demanding substituents is also operative, thus furnishing the optically active olefinated products with excellent selectivity (95 to >99 % ee, s-factor up to 600).

The alkylation of unactivated β-methylene C(sp(3))-H bonds of α-amino acid substrates with a broad range of alkyl iodides using Pd(OAc)2 as the catalyst is described. The addition of NaOCN and 4-Cl-C6H4SO2NH2 was found to be crucial for the success of this transformation. The reaction is compatible with a diverse array of functional groups and proceeds with high diastereoselectivity. Furthermore, various β,β-hetero-dialkyl- and β-alkyl-β-aryl-α-amino acids were prepared by sequential C(sp(3))-H functionalization of an alanine-derived substrate, thus providing a versatile strategy for the stereoselective synthesis of unnatural β-disubstituted α-amino acids.

With the drying up of land resources, the oil and natural gas,power generation equipment, and ocean data is in so great request that the research of the offshore platform is increasingly important.Offshore platform structure and the design of the mooring system both are influenced by the hydrodynamic performance.Then the floating type marine equipment carrier of hydrodynamic being analyzed after doing the frequency domain calculation for the model of floating body by the hydrodynamic software AQWA here.

A general and practical Pd^(II)-catalyzed intermolecular silylation of primary and secondary C−H bonds of α-amino acids and simple aliphatic acids is reported. This method provides divergent and stereoselective access to a variety of optical pure β-silyl-α-amino acids, which are useful for genetic technologies and proteomics. It can also be readily performed on a gram scale and the auxiliary can be easily removed with retention of configuration. The synthetic importance of this method is further demonstrated by the late-stage functionalization of biological small molecules, such as (−)-santonin and β-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this β−C(sp^3)-H silylation process.

Transition metal-catalyzed direct functionalization of C–H bonds has recently emerged as a powerful strategy for the construction of carbon–carbon and carbon–heteroatom bonds. Among various metals employed, base metal copper has attracted significant attention owing to its relatively low cost, abundance, and versatile reactivity. This review aims to comprehensively summarize the recent advances in copper-mediated (both stoichiometric and catalytic) chelation-assisted functionalization of unactivated C–H bonds.

Ni(II)-catalyzed C–H arylation using Ar2I+X− or ArX as the arylating reagent via oxidative addition has been well investigated. However, the analogous cross-coupling of C–H bonds with organoboron reagents via transmetallation remains a great challenge. Here we report the first Ni(II)-catalyzed direct C–H arylation with arylboronic acid esters assisted by a removable bidentate auxiliary. This procedure is scalable and compatible with a wide range of functional groups, providing a complementary protocol for the synthesis of biaryl compounds.

The cobalt-catalyzed oxidative annulation of N-arylureas and internal alkynes for the construction of indoles is reported.

An hypervalent iodine-alkyne reagent bearing tert-butyldiphenylsilyl as protecting group instead of triisopropylsilyl is also compatible but gives lower yields (not shown).

The regioselectivity of the acetoxycyclization of N-allylureas to furnish either imidazoles or oxazoles is controlled by choice of the transition-metal catalyst.

A copper-catalyzed oxidative C–H/C–H cross-coupling of benzamides and thiophenes has been developed. This reaction exhibits a broad substrate scope and excellent tolerance of functional groups. The directing group could be readily removed to afford 2-thienylbenzoic acids.

The first examples for Pd(II)-catalyzed direct fluorination of unactivated methylene C(sp3)—H bonds by an inner-sphere mechanism are presented.

Ni(II)-catalyzed dehydrative alkynylation of unactivated C(sp2)–H bonds with terminal alkynes under atmospheric pressure of oxygen was developped. This reaction features the use of catalytic amounts of nickel as the catalyst and O2 as the sole oxidant, providing a user-friendly approach to the synthesis of aryl alkynes.

Using the newly developed bidentate directing group obtained from (pyridin-2-yl)isopropyl amine (PIP-amine), the arylation of (hetero)aryl C—H bonds proceeds via a hypothetical cascade protodecarboxylation/dehydrogenative coupling sequence.

A Pd(II)-catalyzed sulfonylation of both unactivated β-C(sp3)—H and γ-C(sp2)—H bonds with sodium arylsulfinates using an 8-aminoquinoline auxiliary is described.

A copper-catalyzed direct sulfonylation of C(sp2)–H bonds with sodium sulfinates using a removable directing group is described. This reaction tolerates a wide range of functional groups, providing...

The first nickel-catalyzed alkenylation of unactivated C(sp3)–H bonds with vinyl iodides is described. The catalytic system comprises an inexpensive and air-stable Ni(acac)2 as the catalyst and BINOL as the ligand, which is highly efficient for the alkenylation of β-methyl C(sp3)–H bonds of a broad range of aliphatic carboxamides. The resulting olefins can serve as versatile handles for further preparation. Additionally, we also demonstrated the synthesis of functionalized carboxamides bearing α-quaternary carbon centers from simple pivalamide via nickel-catalyzed sequential C(sp3)–H bond functionalization.

The first nickel-catalyzed thiolation of unactivated C(sp3)–H bonds with disulfides was described. This transformation uses (dppp)NiCl2 as a catalyst and BINOL as a ligand, which are efficient for the thiolation of β-methyl C(sp3)–H bonds of a broad range of aliphatic carboxamides. The reaction provides an efficient synthetic pathway to access diverse thioethers.

The direct alkynylation of unactivated aryl C—H bonds employing a removable auxiliary requires only low nickel loadings (0.5 mol%).

The new method is scalable and tolerates a broad range of functional groups and heteroarenes, providing an efficient access to chlorinated arenes and heteroarenes.

Oxazolines are prepared from amides by C—H bond activation, chlorination, and nucleophilic cyclization using palladium catalysis.

The first Ni-catalyzed thiolation of aromatic C—H bonds with disulfides (II) and (IX) employing a 2-(pyridine-2-yl)isopropylamine directing group is reported.

Substrates of type (I) bearing a directing 8-aminoquinoline auxiliary are monoarylated or monoalkylated to afford starting materials such as (IIIa) or (IX).

An efficient synthesis of aryl alkynes using the removable PIP as directing group is developed.

Esters are valuable commodity chemicals widely found in agrochemicals, pharmaceuticals, and advanced materials. They are also important synthetic building blocks for chemical transformation. Recent advances of ester synthesis via transition-metal-catalyzed C–H activation have provided highly efficient and atom-economical alternatives to the traditional methods. Herein, we summarize recent advances on ester synthesis via transition-metal-catalyzed C–H activation. On the basis of the modes of reactivity and the types of C–H bonds, transition-metal-catalyzed alkoxycarbonylation of C–H bonds with various esterification reagents will be discussed in sections 2 and 3. Finally, hydroesterification/hydroacylation of C–C or C–O double bonds via formate C–H activation will be discussed in sections 4 and 5.