Reactions that convert carbon–hydrogen (C–H) bonds into carbon–carbon (C–C) or carbon–heteroatom (C–Y) are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study insertion homogeneous metal species unactivated C–H bonds, practical applications this technology chemistry still rare. Only past decade have metal-catalyzed functionalization reactions...

Abstract Katalyse mit Methode : Eine ganze Reihe katalytischer Palladiumsysteme für die C‐H‐Aktivierung/C‐C‐Kupplung (siehe Schema) wurde in jüngerer Zeit entwickelt. Ein besonderer Schwerpunkt ist Pd II ‐katalysierte Kupplung von C‐H‐Bindungen metallorganischen Reagentien durch /Pd 0 ‐Katalysezyklen. Die Vielseitigkeit dieser Katalysemethode wird demonstriert, zudem werden offene Fragen sowie das Entwicklungspotenzial des Gebietes angesprochen. magnified image In den letzten zehn Jahren...

Heck of an Alternative The Mizoroki-Heck reaction is widely used in organic synthesis to link together unsaturated carbon fragments such as olefins and arenes. However, one its drawbacks the need append a reactive group halogen reagents beforehand. Wang et al. (p. 315 , published online 26 November) present alternative palladium-catalyzed that links directly aryl acids. Oxygen added medium concurrently oxidizes C-H bond at linkage site, eliminating for prior halogenation. Introducing amino...

Initial rate studies have revealed dramatic acceleration in aerobic Pd(II)-catalyzed C−H olefination reactions of phenylacetic acids when mono-N-protected amino are used as ligands. In light these findings, systematic ligand tuning was undertaken, which has resulted drastic improvements substrate scope, reaction rate, and catalyst turnover. We present evidence from intermolecular competition kinetic isotope effect experiments that implies the observed increases a result cleavage step....

A visible-light-mediated hydrotrifluoromethylation of unactivated alkenes that uses the Umemoto reagent as CF(3) source and MeOH reductant is disclosed. This effective transformation operates at room temperature in presence 5 mol % Ru(bpy)(3)Cl(2); process characterized by its operational simplicity functional group tolerance.

Systematic ligand development has led to the identification of novel mono-N-protected amino acid ligands for Pd(II)-catalyzed enantioselective C-H activation cyclopropanes. A diverse range organoboron reagents can be used as coupling partners, and reaction proceeds under mild conditions. These results provide a new retrosynthetic disconnection construction enantioenriched cis-substituted cyclopropanecarboxylic acids.

The first Pd(II)-catalyzed sp(3) C-H olefination reaction has been developed using N-arylamide directing groups. Following olefination, the resulting intermediates were found to undergo rapid 1,4-addition give corresponding gamma-lactams. Notably, this method was effective with substrates containing alpha-hydrogen atoms and could be applied effect methylene of cyclopropane substrates.

A novel Pd(II)-catalyzed ortho-C−H olefination protocol has been developed using spatially remote, unprotected tertiary, secondary, and primary alcohols as the directing groups. Mono-N-protected amino acid ligands were found to promote reaction, an array of olefin coupling partners could be used. When electron-deficient alkenes used, resulting olefinated intermediates underwent subsequent oxidative intramolecular cyclization give corresponding pyran products, which converted into...

Pd(0)-catalyzed intermolecular arylation of sp3 C−H bonds has been achieved using PR3/ArI. This protocol can be used to arylate a variety aliphatic carboxylic acid derivatives, including number bioactive drug molecules. The use fluorinated aryl iodides also allows for the introduction fluorine into molecule interest.

A nickel-catalyzed conjunctive cross-coupling between non-conjugated alkenes, aryl iodides, and alkylzinc reagents is reported. Excellent regiocontrol achieved utilizing an 8-aminoquinoline directing group that can be readily cleaved to unmask net β,γ-dicarbofunctionalized carboxylic acid products. Under optimized conditions, both terminal internal alkene substrates provided the corresponding alkyl/aryl difunctionalized products in moderate excellent yields. The methodology developed herein...

An intermolecular 1,2-carboamination of unactivated alkenes proceeding via a Pd(II)/Pd(IV) catalytic cycle has been developed. To realize this transformation, cleavable bidentate directing group is used to control the regioselectivity aminopalladation and stabilize resulting organopalladium(II) intermediate, such that oxidative addition carbon electrophile outcompetes potential β-hydride elimination. Under optimized reaction conditions, broad range nitrogen nucleophiles electrophiles are...

A substrate-directed approach to couple alkylzinc nucleophiles, alkyl halide electrophiles, and non-conjugated alkenes under nickel catalysis is described.

A directed, regiocontrolled hydroamination of unactivated terminal and internal alkenes is reported. The reaction catalyzed by palladium(II) acetate compatible with a variety nitrogen nucleophiles. removable bidentate directing group used to control the regiochemistry, prevent β-hydride elimination, stabilize nucleopalladated intermediate, facilitating protodepalladation event. This method affords highly functionalized γ-amino acids in good yields high regioselectivity.

Reactions that forge carbon–carbon (C–C) bonds are the bedrock of organic synthesis, widely used across chemical sciences. We report a transformation enables C–C to be constructed from two classes commonly available starting materials, alkenes and carbon–hydrogen (C–H) bonds. The reaction employs palladium(II) catalyst utilizes removable directing group both control regioselectivity carbopalladation enable subsequent protodepalladation. A wide range C–H nucleophiles, including...

Earth-abundant metal (EAM) catalysis can have profound impact in the pharmaceutical industry terms of sustainability and cost improvements from replacing precious metals like palladium as well harnessing differential reactivity first-row that allows for novel transformations to enable more efficient routes clinical candidates. The strategy building these capabilities within process group at Bristol Myers Squibb is described herein, with general plan a reaction screening platform,...

A balancing act: Complementary catalytic systems are described, in which the reactivity/selectivity balance PdII-catalyzed ortho-CH olefination can be modulated to enable sequential CH functionalization for rapid preparation of 1,2,3-trisubstituted arenes 1. Additionally, a rare example iterative activation, newly installed functional group directs subsequent activation has been demonstrated (2).

A Pd(II)-catalyzed C–H carbonylation protocol of phenethyl alcohols has been developed using amino acid ligands to promote the reaction. This transformation provides an expedient route 1-isochromanone motifs, which are common structural elements in natural products and other biologically active compounds. concise synthesis a histamine release inhibitor showcases utility this transformation.

Detailed kinetic studies and novel graphical manipulations of reaction progress data in Pd(II)-catalyzed olefinations the presence mono-N-protected amino acid ligands reveal anomalous concentration dependences (zero order o-CF3-phenylacetic concentration, zero oxygen pressure, negative orders both olefin product concentrations), leaving catalyst as sole positive driving force reaction. NMR spectroscopic support proposal that rate inhibition by olefinic substrate is caused formation...