Configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions: an alternative approach to asymmetric synthesis

Several research groups have recently developed methods to employ configurationally stable, enantioenriched organometallic nucleophiles in stereospecific Pd-catalyzed cross-coupling reactions. By establishing the absolute configuration of a chiral alkyltin or alkylboron nucleophile prior to its use in cross-coupling reactions, new stereogenic centers may be rapidly and reliably generated with preservation of the known initial stereochemistry. While this area of research is still in its infancy, such stereospecific cross-coupling reactions may emerge as simple, general methods to access diverse, optically active products from common enantioenriched organometallic building blocks. This minireview highlights recent progress towards the development of general, stereospecific Pd-catalyzed crosscoupling reactions using configurationally stable organometallic nucleophiles

Simple, efficient protocols for the Pd-catalyzed cross-coupling reaction of aryl chlorides and dimethylamine

Simple and efficient procedures for the Pd-catalyzed cross-coupling reaction of aryl chlorides and dimethylamine are described. At room temperature with a strong base, t-BuXPhos is employed as the supporting ligand; at 110 °C with a weak base, XPhos is employed as the supporting ligand. In each of these cases, commercially available solutions constitute the source of the dimethylamine, and recently disclosed precatalysts constitute the source of the ligand and Pd. This work further expands the utility of these precatalysts in reactions that benefit from an easily activated source of L[subscript 1]Pd(0).National Institutes of Health (U.S.) (GM-058160)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM-F32-75685)Amgen Inc.Merck & Co., Inc.Boehringer Ingelheim PharmaceuticalsMassachusetts Institute of Technology. Undergraduate Research Opportunities Program (Summer Fellowship

Husbandry Of Monodelphis Domestica In The Study Of Mammalian Embryogenesis

Monodelphis domestica, commonly called the laboratory opossum, is a useful laboratory animal for studying marsupial embryogenesis and mammalian development. Females breed year-round and the animals can be sustainably bred indoors. The authors draw on their own laboratory\u27s experience to supplement previously published research on laboratory opossums. They describe a breeding protocol that reliably produces timed-pregnant M. domestica. Additionally, the authors discuss general laboratory opossum husbandry techniques and describe how to collect, handle and culture embryos

Selective Monoarylation of Acetate Esters and Aryl Methyl Ketones Using Aryl Chlorides

Simple, efficient procedures for the monoarylation of acetate esters and aryl methyl ketones using aryl chlorides are presented. Previously, no general method was available to ensure the highly selective monoarylation of these classes of substrates using aryl chlorides. Using palladium precatalysts recently reported by our group, these reactions are easily accomplished under mild conditions that tolerate a wide array of heterocyclic substrates.National Institutes of Health (U.S.) (GM-46059)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM-F32-75685)Merck & Co., Inc.Boehringer Ingelheim Pharmaceutical

A New Class of Easily Activated Palladium Precatalysts for Facile C−N Cross-Coupling Reactions and the Low Temperature Oxidative Addition of Aryl Chlorides

A new class of one-component Pd precatalysts bearing biarylphosphine ligands is described. These precatalysts are air- and thermally stable, are easily activated under normal reaction conditions at or below room temperature, and ensure the formation of the highly active monoligated Pd(0) complex necessary for oxidative addition. The use of these precatalysts as a convenient source of LPd(0) in C−N cross-coupling reactions is explored. The reactivity that is demonstrated in this study is unprecedented in palladium chemistry.National Institutes of Health (U.S.) (GM-058160)National Institutes of Health (U.S.) (postdoctoral fellowship (GM-F32-75685))Boehringer Ingelheim PharmaceuticalsMerck Research LaboratoriesAmgen Inc

Stereospecific Pd-Catalyzed Cross-Coupling Reactions of Secondary Alkylboron Nucleophiles and Aryl Chlorides

We report the development of a Pd-catalyzed process for the stereospecific cross-coupling of unactivated secondary alkylboron nucleophiles and aryl chlorides. This process tolerates the use of secondary alkylboronic acids and secondary alkyltrifluoroborates and occurs without significant isomerization of the alkyl nucelophile. Optically active secondary alkyltrifluoroborate reagents undergo cross-coupling reactions with stereospecific inversion of configuration using this method

Pd-Catalyzed Arylation of Secondary α‑Alkoxytricyclohexylstannanes

We have developed a general process for the formation of α-arylethers via the Pd-catalyzed arylation of secondary α-alkoxytricyclohexylstannanes. Incorporation of cyclohexyl spectator ligands into the alkylstannane and the use of the electron-deficient ligand JackiePhos (1) are critical for achieving selective alkyl transfer in this process. This system circumvents the need for a coordinating/directing oxygen-protecting group to promote selective alkyl transfer and enables α-tetrahydropyran, α-tetrahydrofuran, and open-chain secondary α-alkoxy groups to be employed efficiently in Pd-catalyzed Stille reactions with a broad range of aryl electrophiles. These findings suggest that selective transmetalation of a single marginally activated secondary alkyl unit from Sn to Pd should be broadly achievable provided that unactivated secondary alkyl ligands comprise the other three groups of the tetraalkylstannane

Palladium-Catalyzed Borylation of Primary Alkyl Bromides

A mild Pd-catalyzed process for the borylation of alkyl bromides has been developed using bis­(pinacolato)­diboron as a boron source. This process accommodates the use of a wide range of functional groups on the alkyl bromide substrate. Primary bromides react with complete selectivity in the presence of a secondary bromide. The generality of this approach is demonstrated by its extension to the use of alkyl iodides and alkyl tosylates, as well as borylation reactions employing bis­(neopentyl glycolato)­diboron as the boron source