ILRI's research—Much more relevant for development

For the November 2011 'liveSTOCK Exchange' event at the International Livestock Research Institute (ILRI), John McDermott, reflects on the evolution of ILRI's research over the past eight years and the future of livestock for development

Palladium Catalyzed Cyclizations of Oxime Esters with 1,2-Disubstituted Alkenes: Synthesis of Dihydropyrroles

Pd-catalyzed cyclizations of oxime esters with 1,2-dialkylated alkenes provide an entry to chiral dihydropyrroles. Substrate and catalyst controlled strategies for selective product formation (vs alternative pyrroles) are outlined

An Umpolung Approach to Alkene Carboamination: Palladium Catalyzed 1,2-Amino-Acylation, -Carboxylation, -Arylation, -Vinylation, and -Alkynylation

Conventional approaches to Pd-catalyzed alkene 1,2-carboamination rely upon the combination of a <i>nucleophilic</i> nitrogen-based component and an internal C-based or external oxidant. In this study, we outline an umpolung approach, which is triggered by oxidative initiation at an <i>electrophilic</i> N-based component and employs “standard” organometallic nucleophiles to introduce the new carbon-based fragment. Specifically, oxidative addition of a Pd(0)-catalyst into the N–O bond of <i>O</i>-pentafluorobenzoyl oxime esters generates imino-Pd­(II) intermediates, which undergo 5-<i>exo</i> cyclization with sterically diverse alkenes. The resultant alkyl-Pd­(II) intermediates are intercepted by organometallic nucleophiles or alcohols, under carbonylative or noncarbonylative conditions, to provide 1,2-carboamination products. This approach provides, for the first time, a unified strategy for achieving alkene 1,2-amino-acylation, -carboxylation, -arylation, -vinylation, and -alkynylation. For carbonylative processes, orchestrated protodecarboxylation of the pentafluorobenzoate leaving group underpins reaction efficiency. This process is likely a key feature in related Narasaka–Heck cyclizations and accounts for the efficacy of <i>O</i>-pentafluorobenzoyl oxime esters in aza-Heck reactions of this type

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Rh-Catalyzed Reactions of 1,4-Benzoquinones with Electrophiles: C–H Iodination, Bromination, and Phenylselenation

Under Rh-catalyzed conditions, typically electrophilic 1,4-benzoquinones exhibit nucleophilic reactivity, such that exposure to appropriate electrophiles generates products of C–H iodination, bromination, and phenylselenation. This provides a mild and general method for direct halofunctionalization, and the first method that can achieve direct C–H phenylselenation of this compound class. The scope and limitations of the new protocols are outlined, and representative derivatizations are highlighted

Branch-Selective, Iridium-Catalyzed Hydroarylation of Monosubstituted Alkenes via a Cooperative Destabilization Strategy

Highly branch-selective, carbonyl-directed hydro­aryl­ations of mono­substituted alkenes are described. The chemistry relies upon a cationic Ir­(I) catalyst modified with an electron deficient, wide bite angle bis­phosphine ligand. This work provides a regio­isomeric alternative to the Murai hydro­aryl­ation protocol

Branch-Selective and Enantioselective Iridium-Catalyzed Alkene Hydroarylation via Anilide-Directed C–H Oxidative Addition

Tertiary benzylic stereocenters are accessed in high enantioselectivity by Ir-catalyzed branch selective addition of anilide <i>ortho</i>-C–H bonds across styrenes and α-olefins. Mechanistic studies indicate that the stereocenter generating step is reversible

Rh-Catalyzed Reactions of 1,4-Benzoquinones with Electrophiles: C–H Iodination, Bromination, and Phenylselenation

Under Rh-catalyzed conditions, typically electrophilic 1,4-benzoquinones exhibit nucleophilic reactivity, such that exposure to appropriate electrophiles generates products of C–H iodination, bromination, and phenylselenation. This provides a mild and general method for direct halofunctionalization, and the first method that can achieve direct C–H phenylselenation of this compound class. The scope and limitations of the new protocols are outlined, and representative derivatizations are highlighted

Branch-Selective, Iridium-Catalyzed Hydroarylation of Monosubstituted Alkenes via a Cooperative Destabilization Strategy

Highly branch-selective, carbonyl-directed hydro­aryl­ations of mono­substituted alkenes are described. The chemistry relies upon a cationic Ir­(I) catalyst modified with an electron deficient, wide bite angle bis­phosphine ligand. This work provides a regio­isomeric alternative to the Murai hydro­aryl­ation protocol

Nucleophilic Aromatic Substitution (S_NAr) as an Approach to Challenging Carbohydrate–Aryl Ethers

A general and practical route to carbohydrate–aryl ethers by nucleophilic aromatic substitution (S_NAr) is reported. Upon treatment with KHMDS, C–O bond formation occurs between carbohydrate alcohols and a diverse range of fluorinated (hetero)­aromatics to provide the targets in good to excellent yields. Commercially available arylating agents, high atom economy, and high regioselectivity are notable features of the protocol. The aryl ether products have potential for wide-ranging applications as exemplified by the synthesis of a novel chiral P,N-ligand