Palladium-catalyzed (Z)-selective allylation of phosphine oxides with vinylethylene carbonates to construct phosphorus allyl alcohols.

Allylphosphine oxide compounds are important building blocks with broad applications in organic synthesis and pharmaceutical science. Herein, we report an unprecedented palladium-catalyzed allylation of phosphine oxides with vinylethylene carbonates, producing various phosphorus allyl alcohols in excellent yields with high Z-selectivity. In addition, gram-scale synthesis and further functional group transformations demonstrate the practical utility of this synthetic method.

Highly Stereoselective Synthesis of Bis-C-ferrocenyl Glycosides via Palladium-Catalyzed Directed C-H Glycosylation.

Conjugation of carbohydrates to ferrocene scaffolds is of great value in drug design, given the nontoxic and lipophilic nature of ferrocene. However, the efficient and stereoselective synthesis of C-ferrocenyl glycosides remains a challenge. Herein, we developed a Pd-catalyzed stereoselective C-H glycosylation to provide rapid access to sole bis-C-ferrocenyl glycosides in good to high yields (up to 98% yield) with exclusive stereoselectivity. A diverse range of glycosyl chlorides were well tolerated, including d-mannose, d-glucose, l-xylose, l-rhamnose, d-mannofuranose, and d-ribofuranose. Additionally, a mononuclear PdII intermediate was characterized by X-ray single-crystal diffraction, and might participate in the C-H palladation step.

Recent advances in the synthesis of ferrocene derivatives via 3d transition metal-catalyzed C-H functionalization.

In recent years, transition-metal-catalyzed C-H functionalization has gradually developed into a powerful tool for the synthesis of ferrocenes in an atom- and step-economic fashion. However, despite significant achievements, the vast majority of these C-H functionalizations required precious 4d or 5d transition metal catalysts. The use of inexpensive and sustainable 3d metals in the C-H functionalization of ferrocenes remains challenging, especially the development of asymmetric versions. Herein, we summarize the remarkable recent progress in the synthesis of ferrocenes by 3d transition metal-catalyzed C-H activation until December 2021.

Cp*Co(III)-Catalyzed Enantioselective Hydroarylation of Unactivated Terminal Alkenes via C-H Activation.

Enantioselective hydroarylation of unactivated terminal akenes constitutes a prominent challenge in organic chemistry. Herein, we reported a Cp*Co(III)-catalyzed asymmetric hydroarylation of unactivated aliphatic terminal alkenes assisted by a new type of tailor-made amino acid ligands. Critical to the chiral induction was the engaging of a novel noncovalent interaction (NCI), which has seldomly been disclosed in the C-H activation area, arising from the molecular recognition among the organocobalt(III) intermediate, the coordinated alkene, and the well-designed chiral ligand. A broad range of C2-alkylated indoles were obtained in high yields and excellent enantioselectivities. DFT calculations revealed the reaction mechanism and elucidated the origins of chiral induction in the stereodetermining alkene insertion step.

Thioamide-Directed Cp*Co(III)-Catalyzed C-H Allylation of Ferrocenes.

Herein, the first Cp*Co(III)-catalyzed C-H allylation of ferrocene thioamides with allyl carbonates has been developed. This reaction is compatible with a wide range of functional groups, providing various allylated ferrocene derivatives in up to 90% yields. In addition, the C-H allylation protocol is also compatible with the use of vinylcyclopropanes as allylating reagents by merging C-H and C-C activation into one catalytic system. Mechanistic studies revealed that the thiocarbonyl-directing group plays a vital role in C-H activation.

Cp*Co(III)/MPAA-Catalyzed Enantioselective Amidation of Ferrocenes Directed by Thioamides under Mild Conditions.

Cp*Cobalt(III)-catalyzed enantioselective C-H amidation of ferrocenes using monoprotected amino acids (MPAAs) as chiral ligands was developed. The reaction was performed under mild conditions in high yields (up to 97%) with moderate enantioselectivity (up to 77.5:22.5 er), providing a promising strategy to create planar chirality via base-metal-catalyzed enantioselective C-H activation.

Scalable, Stereocontrolled Formal Syntheses of (+)-Isoschizandrin and (+)-Steganone: Development and Applications of Palladium(II)-Catalyzed Atroposelective C-H Alkynylation.

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).

Nickel-catalyzed direct C-H trifluoroethylation of heteroarenes with trifluoroethyl iodide.

A highly selective nickel-catalyzed C-H trifluoroethylation of heteroarenes was developed with the assistance of a monodentate directing group. This protocol provides efficient access to various trifluoroethyl-substituted heteroarenes, including indoles, pyrroles, furans, and thiophenes, with commercially available CF3CH2I as an alkylation reagent. This robust catalytic procedure is scalable and tolerates a broad range of functional groups. Moreover, multifluoroalkylation of indoles is also viable.

Synthesis of Bicyclo[n.1.0]alkanes by a Cobalt-Catalyzed Multiple C(sp3 )-H Activation Strategy.

A cobalt-catalyzed dual C(sp3 )-H activation strategy has been developed and it provides a novel strategy for the synthesis of bicyclo[4.1.0]heptanes and bicyclo[3.1.0]hexanes. A key to the success of this reaction is the conformation-induced methylene C(sp3 )-H activation of the resulting cobaltabicyclo[4.n.1] intermediate. In addition, the synthesis of bicyclo[3.1.0]hexane from pivalamide, by a triple C(sp3 )-H activation, has also been demonstrated.

Divergent and Stereoselective Synthesis of ß-Silyl-α-Amino Acids through Palladium-Catalyzed Intermolecular Silylation of Unactivated Primary and Secondary C-H Bonds.

A general and practical PdII -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 ß-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 ß-cholic acid. Moreover, several key palladacycles were successfully isolated and characterized to elucidate the mechanism of this ß-C(sp3 )-H silylation process.

Site-Selective Alkenylation of δ-C(sp(3))-H Bonds with Alkynes via a Six-Membered Palladacycle.

Most chelation-assisted aliphatic C-H activation proceeds through a kinetically favored five-membered cyclometalated intermediate. Here, we report the first site-selective alkenylation of δ-C(sp(3))-H in the presence of more accessible γ-C(sp(3))-H bonds via a kinetically less favored six-membered palladacycle. A wide range of functional groups are tolerated, and the unique protocol can be applied to the synthesis of chiral piperidines. Moreover, mechanistic insights have been conducted to elucidate the origin of the unusual site-selectivity.

Indole Synthesis via Cobalt(III)-Catalyzed Oxidative Coupling of N-Arylureas and Internal Alkynes.

A mild Co(III)-catalyzed oxidative annulation of N-arylureas and internal alkynes has been developed. The use of less electrophilic ureas other than acetamides as directing groups is crucial for the reaction. A broad range of synthetically useful functional groups are compatible with this reaction, thus providing a new opportunity for the synthesis of diverse indoles.

Cobalt(III)-Catalyzed C2-Selective C-H Alkynylation of Indoles.

A cobalt(III)-catalyzed C-2 selective C-H alkynylation of indoles using hypervalent iodine-alkyne reagents is described. A broad range of synthetically useful functional groups (-F, -Cl, -Br, -CO2Me, -CN) were tolerated, providing an efficient and robust protocol for the synthesis of C-2 alkynylated indoles. The pyrimidyl and silyl protecting groups could be easily removed to give the corresponding 2-ethynyl-1H-indole.

Pd(II)-Catalyzed Direct Sulfonylation of Unactivated C(sp(3))-H Bonds with Sodium Sulfinates.

A Pd(II)-catalyzed sulfonylation of unactivated C(sp(3))-H bonds with sodium arylsulfinates using an 8-aminoquinoline auxiliary is described. This reaction demonstrates excellent functional group tolerance with respect to both the caboxamide starting material and the sodium arylsulfinate coupling partner, affording a broad range of aryl alkyl sulfones. Moreover, the late-stage modification of complex molecules was achieved via this sulfonylation protocol.

Copper-/Silver-Mediated Arylation of C(sp(2))-H Bonds with 2-Thiophenecarboxylic Acids.

A copper/silver-mediated arylation of (hetero)aryl C-H bonds with 2-thiophenecarboxylic acids has been achieved. The protocol features a broad substrate scope and high functional group tolerance. Preliminary mechanistic studies indicate that a cascade protodecarboxylation/dehydrogenative coupling process is likely involved.

Ni(II)/BINOL-catalyzed alkenylation of unactivated C(sp(3))-H bonds.

The first nickel-catalyzed alkenylation of unactivated C(sp(3))-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 ß-methyl C(sp(3))-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(sp(3))-H bond functionalization.

Nickel-catalyzed direct thiolation of unactivated C(sp(3))-H bonds with disulfides.

The first nickel-catalyzed thiolation of unactivated C(sp(3))-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 ß-methyl C(sp(3))-H bonds of a broad range of aliphatic carboxamides. The reaction provides an efficient synthetic pathway to access diverse thioethers.