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Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp.sup.3-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners.sup.1,2. Although the use of native functional groups (for example, carboxylic acids, alkenes and alcohols) has improved the overall efficiency of such transformations by expanding the range of potential feedstocks.sup.3-5, the direct functionalization of carbon-hydrogen (C-H) bonds--the most abundant moiety in organic molecules--represents a more ideal approach to molecular construction. In recent years, an impressive range of reactions that form C(sp.sup.3)-heteroatom bonds from strong C-H bonds has been reported.sup.6,7. Additionally, valuable technologies have been developed for the formation of carbon-carbon bonds from the corresponding C(sp.sup.3)-H bonds via substrate-directed transition-metal C-H insertion.sup.8, undirected C-H insertion by captodative rhodium carbenoid complexes.sup.9, or hydrogen atom transfer from weak, hydridic C-H bonds by electrophilic open-shell species.sup.10-14. Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp.sup.3)-H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp.sup.3) arylation of a diverse set of aliphatic, C-H bond-containing organic frameworks through the combination of light-driven, polyoxometalate-facilitated hydrogen atom transfer and nickel catalysis. This dual-catalytic manifold enables the generation of carbon-centred radicals from strong, neutral C-H bonds, which thereafter act as nucleophiles in nickel-mediated cross-coupling with aryl bromides to afford C(sp.sup.3)-C(sp.sup.2) cross-coupled products. This technology enables unprecedented, single-step access to a broad array of complex, medicinally relevant molecules directly from natural products and chemical feedstocks through functionalization at sites that are unreactive under traditional methods.Direct coupling of aliphatic C-H nucleophiles to aryl electrophiles is described, through the combination of light-driven polyoxometalate hydrogen atom transfer and nickel catalysis., Author(s): Ian B. Perry [sup.1] , Thomas F. Brewer [sup.1] , Patrick J. Sarver [sup.1] , Danielle M. Schultz [sup.2] , Daniel A. DiRocco [sup.2] , David W. C. MacMillan [...]

The addition of a methyl group to a drug molecule can greatly alter the drug's pharmacological properties. A catalyst has been developed that enables this 'magic methyl effect' to be rapidly explored for drug discovery. Late-stage functionalization of complex organic molecules., Author(s): Emily B. Corcoran, Danielle M. Schultz Author Affiliations: Manganese catalyst enables exploration of the magic methyl effect Developing a small-molecule drug requires iterations of building and testing new compounds [...]

The beneficial properties of many medicines, materials and consumer products composed of small organic molecules are greatly influenced by the locations and types of chemical groups within those molecules--especially 'functional' [...]

Aliphatic amines, oxygenated at remote positions within the molecule, represent an important class of synthetic building blocks to which there are currently no direct means of access. Reported herein is an efficient and scalable solution that relies upon decatungstate photocatalysis under acidic conditions using either H2O2 or O2 as the terminal oxidant. By using these reaction conditions a series of simple and unbiased aliphatic amine starting materials can be oxidized to value-added ketone products. Lastly, NMR spectroscopy using in situ LED-irradiated samples was utilized to monitor the kinetics of the reaction, thus enabling direct translation of the reaction into flow. [ABSTRACT FROM AUTHOR]

A new gold(I)-catalyzed multicomponent synthesis of β-alkoxy ketones from aldehydes, alcohols, and alkynes is described. This atom economical synthesis was achieved through the use of the gold complex (SPhos)AuNTf2 as a catalyst, and allows for the preparation of a diverse array of β-alkoxy ketone products. Mechanistic studies illustrate that these reactions proceed via gold(I)-catalyzed hydrolysis of the alkyne to an aryl ketone, which then undergoes an aldol reaction with an oxocarbenium ion generated in situ from the aldehyde and alcohol components. [ABSTRACT FROM AUTHOR]

This short review describes new developments in palladium-catalyzed aminoarylation reactions between aryl halides and alkenes bearing pendant nitrogen nucleophiles. These transformations provide a novel and powerful method for accessing numerous three-, five-, six-, and seven-membered nitrogen heterocycles. 1 Introduction 2 Synthesis of Pyrrolidines via Palladium-Catalyzed Alkene Aminoarylation Reactions 2.1 Palladium(0)-Catalyzed Alkene Aminoarylation Reactions 2.1.1 Synthesis of trans-2,5-Disubstituted Pyrrolidines 2.1.2 Transformations of Aryl Chloride Electrophiles 2.1.3 Synthesis of Hexahydro-3H-pyrrolizin-3-ones 2.1.4 Enantioselective Synthesis of Monosubstituted Pyrrolidines 2.1.5 Asymmetric Total Synthesis of (+)-Aphanorphine 2.2 Palladium(II)-Catalyzed Arene C-H Activation/Alkene Aminoarylation 3 Synthesis of Other Five-Membered Heterocycles via Palladium-Catalyzed Alkene Aminoarylation 3.1 Synthesis of Pyrazolidines 3.2 Synthesis of Isoxazolidines 4 Aminoarylation Reactions for the Synthesis of Three-, Six-, and Seven-Membered Heterocycles 4.1 Synthesis of Aziridines 4.2 Synthesis of Morpholines 4.3 Synthesis of Saturated 1,4-Benzodiazepines 5 Palladium-Catalyzed Synthesis of Fused-, Bridged-, and Spiro-Polycyclic Heterocycles 5.1 Cascade Alkene Difunctionalization Reactions 5.2 Tandem N-Arylation/Alkene Aminoarylation Reactions 5.3 Intramolecular Alkene Aminoarylation Reactions 5.3.1 Synthesis of Tropane Derivatives 5.3.2 Synthesis of Spirooxindoles 5.3.3 Cascade C-H Functionalization/Intramolecular Alkene Aminoarylation Reactions 6 Conclusions [ABSTRACT FROM AUTHOR]

A new method for the synthesis of tricyclic nitrogen heterocycles from N,2-diallylaniline derivatives is described. These transformations proceed via sequential alkene aminopalladation of an intermediate LnPd(Ar)(NRR′) species followed by alkene carbopalladation of the resulting LnPd(Ar)(R) complex. Both alkene insertion steps occur in preference to C−N or C−C bond-forming reductive elimination. An unusual 1,3-palladium shift occurs when 2-Allyl-N-(2-vinylphenyl)aniline is employed as substrate, which yields a tetracyclic molecule with three contiguous stereocenters. [ABSTRACT FROM AUTHOR]

Abstract: A strategy for the stereoselective preparation of enantiomerically enriched cis-2,6-disubstituted piperazines from amino acid precursors is described. The target compounds are generated in 95–99% ee with good to excellent levels of diastereoselectivity (usually 14:1 to >20:1) using Pd-catalyzed carboamination reactions between aryl or alkenyl halides and substituted ethylenediamine derivatives to form the heterocyclic rings. The synthesis requires only 4–5 steps from commercially available amino acids, and allows for the modular construction of piperazines bearing different substituents at N1, N4, C2, and C6. The use of this strategy for the construction of 2,3-disubstituted piperazines, fused bicyclic piperazines, and tetrahydroquinoxalines is also reported. In addition, the mechanism of the key carboamination reactions is discussed, and new models that predict and explain the stereochemical outcome of these transformations are presented. [Copyright &y& Elsevier]

An improved method for the Pd-catalyzed synthesis of 2,2′-bipyrazine ligand (IIa) is developed. [ABSTRACT FROM AUTHOR]

A new method for the construction of β-alkoxy ketones from readily available precursors is reported and a mechanism for the Au(I)-catalyzed reaction is proposed. [ABSTRACT FROM AUTHOR]