Rhodium(I)‐Catalyzed Sequential C(sp)?C(sp3) and C(sp3)?C(sp3) Bond Formation through Migratory Carbene Insertion

A Rh^I‐catalyzed three‐component reaction of tert‐propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene‐involving sequential alkyl and alkynyl coupling, in which C(sp) C(sp³) and C(sp³) C(sp³) bonds are built successively on the carbenic carbon atom. The Rh^I‐carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C C bond formations. This reaction provides an efficient and tunable method for the construction of all‐carbon quaternary center.     

Rhodium(I)‐Catalyzed Sequential C(sp)C(sp3) and C(sp3)C(sp3) Bond Formation through Migratory Carbene Insertion

A Rh^I‐catalyzed three‐component reaction of tert‐propargyl alcohol, diazoester, and alkyl halide has been developed. This reaction can be considered as a carbene‐involving sequential alkyl and alkynyl coupling, in which C(sp)? C(sp³) and C(sp³)? C(sp³) bonds are built successively on the carbenic carbon atom. The Rh^I‐carbene migratory insertion of an alkynyl moiety and subsequent alkylation are proposed to account for the two separate C? C bond formations. This reaction provides an efficient and tunable method for the construction of all‐carbon quaternary center.     

Surface oxidation process of a diamond‐like carbon film analyzed by difference X‐ray photoelectron spectroscopy

Difference X‐ray photoelectron spectroscopy (D‐XPS) revealed the surface oxidation process of a diamond‐like carbon (DLC) film. Evaluation of surface functional groups on DLC solely by the C 1s spectrum is difficult because the spectrum is broad and has a secondary asymmetric lineshape. D‐XPS clarified the subtle but critical changes at the DLC surface caused by wet oxidation. The hydroxyl (C―OH) group was dominant at the oxidized surface. Further oxidized carbonyl (C?O) and carboxyl (including carboxylate) (COO) groups were also obtained; however, the oxidation of C?O to COO was suppressed to some extent because the reaction required C―C bond cleavage. Wet oxidation cleaved the aliphatic hydrogenated and non‐hydrogenated sp² carbon bonds (C―H sp² and C―C sp²) to create a pair of C―OH and hydrogenated sp³ carbon (C―H sp³) bonds. The reaction yield for C―H sp² was superior at the surface, suggesting that the DLC film was hydrogen rich at the surface. Oxidation of aromatic sp² rings or polycyclic aromatic hydrocarbons such as nanographite to phenols did not occur because of their resonance stabilization with electron delocalization. Non‐hydrogenated sp³ carbon (C―C sp³) bonds were not affected by oxidation, suggesting that these bonds are chemically inert. Copyright © 2014 John Wiley & Sons, Ltd.     

Copper-Catalyzed Enantioselective Doyle–Kirmse Reaction of Azide-Ynamides via α-Imino Copper Carbenes

[2,3]-Sigmatropic rearrangement reaction involving sulfonium ylide (Doyle–Kirmse reaction) generated from metal carbenes represents one of the powerful methods for the construction of C(sp³)−S and C−C bonds. Although significant advances have been achieved, the asymmetric versions via the generation of sulfonium ylides from metal carbenes have been rarely reported to date, and they have so far been limited to diazo compounds as metal carbene precursors. Here, we describe a copper-catalyzed enantioselective Doyle–Kirmse reaction via azide-ynamide cyclization, leading to the practical and divergent assembly of an array of chiral [1,4]thiazino[3,2-b]indoles bearing a quaternary carbon stereocenter in generally moderate to excellent yields and excellent enantioselectivities. Importantly, this protocol represents a unique catalytic asymmetric Doyle–Kirmse reaction via a non-diazo approach and an unprecedented asymmetric [2,3]-sigmatropic rearrangement via α-imino metal carbenes.     

Copper‐Mediated/Catalyzed Oxyalkylation of Alkenes with Alkylnitriles

A copper‐promoted oxyalkylation of alkenes with alkylnitriles has been developed. The protocol provides rapid access to phthalides (γ‐lactones) or isochromanones (δ‐lactones) via the formation of a C(sp³)?C(sp³) and a C(sp³)?O bond with the generation of up to two quaternary carbon atoms. Mechanistic studies suggest that this reaction is initiated by the formation of the C(sp³)?C(sp³) bond rather than the C(sp³)?O bond. Catalytic conditions were subsequently developed using carboxylic acid as an internal nucleophile.     

Enantioselective C(sp3)–H Amidation of Thioamides Catalyzed by a CobaltIII/Chiral Carboxylic Acid Hybrid System

Recent advances in Cp^xM^III catalysis (M=Co, Rh, Ir) have enabled a variety of enantioselective C(sp²)?H functionalization reactions, but enantioselective C(sp³)?H functionalization is still largely unexplored. We describe an asymmetric C(sp³)?H amidation of thioamides using an achiral Co^III/chiral carboxylic acid hybrid catalytic system, which provides easy and straightforward access to chiral β‐amino thiocarbonyl and β‐amino carbonyl building blocks with a quaternary carbon stereocenter.     

Ligand‐Enabled Alkynylation of C(sp3)−H Bonds with Palladium(II) Catalysts

The palladium(II)‐catalyzed β‐ and γ‐alkynylation of amide C(sp³)−H bonds is enabled by pyridine‐based ligands. This alkynylation reaction is compatible with substrates containing α‐tertiary or α‐quaternary carbon centers. The β‐methylene C(sp³)−H bonds of various carbocyclic rings were also successfully alkynylated.     

Asymmetric Cycloisomerization of o‐Alkenyl‐N‐Methylanilines to Indolines by Iridium‐Catalyzed C(sp3)−H Addition to Carbon–Carbon Double Bonds

Highly enantioselective cycloisomerization of N ‐methylanilines, bearing o ‐alkenyl groups, into indolines is established. An iridium catalyst bearing a bidentate chiral diphosphine effectively promotes the intramolecular addition of the C(sp³)−H bond across a carbon–carbon double bond in a highly enantioselective fashion. The reaction gives indolines bearing a quaternary stereogenic carbon center at the 3‐position. The reaction mechanism involves rate‐determining oxidative addition of the N ‐methyl C−H bond, followed by intramolecular carboiridation and subsequent reductive elimination.     

β- and γ-C(sp3)−H Heteroarylation of Free Carboxylic Acids: A Modular Synthetic Platform for Diverse Quaternary Carbon Centers

Pd^II-catalyzed C(sp³)−H activation of free carboxylic acids represents a significant advance from conventional cyclopalladation initiated reactions. However, developing a modular synthetic platform for diverse quaternary and tertiary carbon centers based on this reactivity, two challenges remain to be addressed: mono-selectivity in each consecutive C−H functionalization step; compatibility with heteroatoms. While the exclusive mono-selectivity was achieved by β-lactonization/nucleophilic attack, the latter limitation remains to be overcome. Herein, we report the Pd^II-catalyzed β- and γ-C(sp³)−H heteroarylation of free carboxylic acids using pyridine-pyridone ligands capable of overcoming these limitations. A sequence of three consecutive C(sp³)−H activation reactions of pivalic acid provides an unique platform for constructing diverse quaternary carbon centers containing heteroaryls which could serve as an enabling tool for escaping the flat land in medicinal chemistry.     

Enantioconvergent Reductive C(sp)−C(sp3) Cross-Coupling to Access Chiral α-Alkynyl Phosphonates Under Dual Nickel/Photoredox Catalysis

Transition-metal-catalyzed asymmetric carbon−carbon bond formation to forge phosphonates with an α-chiral carbon center through C(sp³)−C(sp³) and C(sp²)−C(sp³) couplings has been successful. However, the enantioselective C(sp)−C(sp³) coupling has not yet been disclosed. Reported herein is an unprecedented enantioconvergent cross-coupling of alkynyl bromides and α-bromo phosphonates to deliver chiral α-alkynyl phosphonates.     

Nickel‐Catalyzed Reductive Allylation of Tertiary Alkyl Halides with Allylic Carbonates

The construction of all C(sp³) quaternary centers has been successfully achieved under Ni‐catalyzed cross‐electrophile coupling of allylic carbonates with unactivated tertiary alkyl halides. For allylic carbonates bearing C1 or C3 substituents, the reaction affords excellent regioselectivity through the addition of alkyl groups to the unsubstituted allylic carbon terminus. The allylic alkylation method also exhibits excellent functional‐group compatibility, and delivers the products with high E selectivity.     

Nickel-Catalyzed C−I-Selective C(sp2)−C(sp3) Cross-Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides

Despite several methodologies established for C(sp²)−I selective C(sp²)−C(sp³) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a C(sp²)−I selective manner is rare. Here we report a general Ni-catalyzed C(sp²)−I selective cross-electrophile coupling (XEC) reaction, in which, beyond 3° alkyl bromides (for constructing arene-flanked quaternary carbons), 2° and 1° alkyl bromides are also demonstrated to be viable coupling partners. Moreover, this mild XEC displays excellent C(sp²)−I selectivity and functional group compatibility. The practicality of this XEC is demonstrated in simplifying the routes to several medicinally relevant and synthetically challenging compounds. Extensive experiments show that the terpyridine-ligated Ni^I halide can exclusively activate alkyl bromides, forming a Ni^I−alkyl complex through a Zn reduction. Attendant density functional theory (DFT) calculations reveal two different pathways for the oxidative addition of the Ni^I−alkyl complex to the C(sp²)−I bond of bromo(iodo)arenes, explaining both the high C(sp²)−I selectivity and generality of our XEC.     

A Tunable and Enantioselective Hetero‐Diels–Alder Reaction Provides Access to Distinct Piperidinoyl Spirooxindoles

The active complexes of chiral N,N′‐dioxide ligands with dysprosium and magnesium salts catalyze the hetero‐Diels–Alder reaction between 2‐aza‐3‐silyloxy‐butadienes and alkylidene oxindoles to selectively form 3,3′‐ and 3,4′‐piperidinoyl spirooxindoles, respectively, in very high yields and with excellent enantioselectivities. The exo ‐selective asymmetric cycloaddition successfully regaled the construction of sp³‐rich and highly substituted natural‐product‐based spirooxindoles supporting many chiral centers, including contiguous all‐carbon quaternary centers.     

Lewis Acid Catalyzed Transfer Hydromethallylation for the Construction of Quaternary Carbon Centers

The design and gram‐scale synthesis of a cyclohexa‐1,4‐diene‐based surrogate of isobutene gas is reported. Using the highly electron‐deficient Lewis acid B(C₆F₅)₃, application of this surrogate in the hydromethallylation of electron‐rich styrene derivatives provided sterically congested quaternary carbon centers. The reaction proceeds by C(sp³)?C(sp³) bond formation at a tertiary carbenium ion that is generated by alkene protonation. The possibility of two concurrent mechanisms is proposed on the basis of mechanistic experiments using a deuterated surrogate.     

C(sp3)−H Functionalizations Promoted by the Gold Carbene Generated from Vinylidenecyclopropanes

The gold carbene generated from vinylidenecyclopropanes (VDCPs) can smoothly perform a C(sp³)?H bond insertion reaction, stereoselectively affording the intramolecular C(sp³)?H bond functionalized product, benzoxepine, with syn‐configuration in moderate to good yields under mild conditions. The KIE investigation on this bond functionalization partially revealed that the carbene insertion step might be rate‐determining. Using a chiral gold(I) catalyst, the first example on the asymmetric variant of gold carbene insertion into C(sp³)?H bond has been disclosed, giving the desired products with excellent results.     

Transition‐metal‐free Chemoselective Oxidative C−C Coupling of the sp3 C−H Bond of Oxindoles with Arenes and Addition to Alkene: Synthesis of 3‐Aryl Oxindoles,and Benzofuro‐ and Indoloindoles

A transition‐metal (TM)‐free and halogen‐free NaOt Bu‐mediated oxidative cross‐coupling between the sp³ C−H bond of oxindoles and sp² C−H bond of nitroarenes has been developed to access 3‐aryl substituted and 3,3‐aryldisubstituted oxindoles in DMSO at room temperature in a short time. Interestingly, the sp³ C−H bond of oxindoles could also react with styrene under TM‐free conditions for the practical synthesis of quaternary 3,3‐disubstituted oxindoles. The synthesized 3‐oxindoles have also been further transformed into advanced heterocycles, that is, benzofuroindoles, indoloindoles, and substituted indoles. Mechanistic experiments of the reaction suggests the formation of an anion intermediate from the sp³ C−H bond of oxindole by tert ‐butoxide base in DMSO. The addition of nitrobenzene to the in‐situ generated carbanion leads to the 3‐(nitrophenyl)oxindolyl carbanion in DMSO which is subsequently oxidized to 3‐(nitro‐aryl) oxindole by DMSO.     

Asymmetric Tandem 1,5‐Hydride Shift/Ring Closure for the Synthesis of Chiral Spirooxindole Tetrahydroquinolines

The direct functionalization of sp³ C?H bonds through a tandem 1,5‐hydride shift/ring closure is described. Various optically active spirooxindole tetrahydroquinoline derivatives bearing contiguous quaternary or tertiary stereogenic carbon centers were readily synthesized. A chiral scandium complex of N,N′‐dioxide promoted the reactions in good yields (up to 97 %) with excellent diastereoselectivities (>20:1) and enantioselectivities (up to 94 % ee). Kinetic isotope effect (KIE) experiments and internal redox reactions of chiral substrates were conducted, and the results provided intriguing information that helped clarify the mechanism of the reaction.     

Enantioselective palladium-catalyzed C(sp2)–C(sp2) σ bond activation of cyclopropenones by merging desymmetrization and (3 + 2) spiroannulation with cyclic 1,3-diketones

Catalytic asymmetric variants for functional group transformations based on carbon–carbon bond activation still remain elusive. Herein we present an unprecedented palladium-catalyzed (3 + 2) spiro-annulation merging C(sp²)–C(sp²) σ bond activation and click desymmetrization to form synthetically versatile and value-added oxaspiro products. The operationally straightforward and enantioselective palladium-catalyzed atom-economic annulation process exploits a TADDOL-derived bulky P-ligand bearing a large cavity to control enantioselective spiro-annulation that converts cyclopropenones and cyclic 1,3-diketones into chiral oxaspiro cyclopentenone–lactone scaffolds with good diastereo- and enantio-selectivity. The click-like reaction is a successful methodology with a facile construction of two vicinal carbon quaternary stereocenters and can be used to deliver additional stereocenters during late-state functionalization for the synthesis of highly functionalized or more complex molecules.

An unprecedented palladium-catalyzed (3 + 2) spiro-annulation merging C–C bond activation and desymmetrization was developed for the enantioselective construction of synthetically versatile and value-added oxaspiro products with up to 95% ee.     

Visible‐Light‐Driven Palladium‐Catalyzed Radical Alkylation of C−H Bonds with Unactivated Alkyl Bromides

Reported herein is a novel visible‐light photoredox system with Pd(PPh₃)₄ as the sole catalyst for the realization of the first direct cross‐coupling of C(sp³)−H bonds in N‐aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra‐ and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp³)−C(sp³) and C(sp²)−C(sp³) bonds in moderate to excellent yields. These redox‐neutral reactions feature broad substrate scope (>60 examples), good functional‐group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible‐light photocatalyst and radicals are involved in the process.     

Photoredox Nickel-Catalysed Stille Cross-Coupling Reactions

The Stille cross-coupling reaction is one of the most common strategies for the construction of C−C bonds. Despite notable strides in the advancement of the Stille reaction, persistent challenges persist in hindering its greener evolution. These challenges encompass multiple facets, such as the high cost of precious metals and ligands, the demand for various additives, and the slow reaction rate. In comparison to the dominant palladium-catalysed Stille reactions, cost-effective nickel-catalysed systems lag behind, and enantioconvergent Stille reactions of racemic stannanes remain undeveloped. Herein, we present a pioneering instance of nickel-catalysed enantioconvergent Stille cross-coupling reactions of racemic stannane reagents, resulting in the formation of C−C bonds in good to high yields with excellent stereoselectivity. This strategy provides a practical, scalable, and operationally straightforward method for the synthesis of C(sp³)−C(sp³), C(sp³)−C(sp²), and C(sp³)−C(sp) bonds under exceptionally mild conditions (without additives and bases, ambient temperature). The innovative use of synergistic photoredox/nickel catalysis enables a novel single-electron transmetalation process of stannane reagents, providing a new research paradigm of Stille reactions.