Nickel-Catalyzed Asymmetric Negishi Cross-Couplings of Secondary Allylic Chlorides with Alkylzincs

Complementing previous advances in allylation chemistry, an effective nickel/Pybox catalyst for regioselective asymmetric Negishi cross-couplings of racemic secondary allylic chlorides with readily available organozinc halides has been developed. The method has been applied in two key steps of a formal total synthesis of fluvirucinine A1

Application of a New Chiral Phosphepine to the Catalytic Asymmetric Synthesis of Highly Functionalized Cyclopentenes That Bear an Array of Heteroatom-Substituted Quaternary Stereocenters

Through the design and synthesis of a new chiral phosphepine, the first catalytic asymmetric method for the [3 + 2] cycloaddition of allenes with olefins has been developed that generates cyclopentenes that bear nitrogen-, phosphorus-, oxygen-, and sulfur-substituted quaternary stereocenters. A wide array of racemic γ-substituted allenes can be employed in this stereoconvergent process, which occurs with good enantioselectivity, diastereoselectivity, regioselectivity, and yield. Mechanistic studies, including a unique observation of a (modest) kinetic resolution of a racemic allene, are consistent with addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle

Catalytic Asymmetric Synthesis of Secondary Nitriles via Stereoconvergent Negishi Arylations and Alkenylations of Racemic α-Bromonitriles

The first method for the stereoconvergent cross-coupling of racemic α-halonitriles is described, specifically, nickel-catalyzed Negishi arylations and alkenylations that furnish an array of enantioenriched α-arylnitriles and allylic nitriles, respectively. Noteworthy features of this investigation include: the highly enantioselective synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples of the use of alkenylzinc reagents in stereoconvergent Negishi reactions of alkyl electrophiles; demonstration of the utility of a new family of ligands for asymmetric Negishi cross-couplings (a bidentate bis­(oxazoline), rather than a tridentate pybox); in the case of arylzinc reagents, carbon–carbon bond formation at a remarkably low temperature (−78 °C), the lowest reported to date for an enantioselective cross-coupling of an alkyl electrophile; a mechanistic dichotomy between Negishi reactions of an unactivated versus an activated secondary alkyl bromide

The First Application of a Planar-Chiral Phosphorus Heterocycle in Asymmetric Catalysis: Enantioselective Hydrogenation of Dehydroamino Acids

The First Application of a Planar-Chiral Phosphorus Heterocycle in Asymmetric Catalysis:  Enantioselective Hydrogenation of Dehydroamino Acid

The First Applications of Carbene Ligands in Cross-Couplings of Alkyl Electrophiles: Sonogashira Reactions of Unactivated Alkyl Bromides and Iodides

A Pd/N-heterocyclic carbene-based catalyst achieves the Sonogashira coupling of an array of functionalized, β-hydrogen-containing alkyl bromides and iodides under mild conditions. By furnishing the first example of a nonphosphine-based palladium catalyst for cross-coupling unactivated alkyl electrophiles, this study provides an impetus for future efforts at catalyst development that extend beyond phosphine ligands

Enantioselective Alkenylation via Nickel-Catalyzed Cross-Coupling with Organozirconium Reagents

Enantioselective Alkenylation via Nickel-Catalyzed Cross-Coupling with Organozirconium Reagent

Application of a New Chiral Phosphepine to the Catalytic Asymmetric Synthesis of Highly Functionalized Cyclopentenes That Bear an Array of Heteroatom-Substituted Quaternary Stereocenters

Through the design and synthesis of a new chiral phosphepine, the first catalytic asymmetric method for the [3 + 2] cycloaddition of allenes with olefins has been developed that generates cyclopentenes that bear nitrogen-, phosphorus-, oxygen-, and sulfur-substituted quaternary stereocenters. A wide array of racemic γ-substituted allenes can be employed in this stereoconvergent process, which occurs with good enantioselectivity, diastereoselectivity, regioselectivity, and yield. Mechanistic studies, including a unique observation of a (modest) kinetic resolution of a racemic allene, are consistent with addition of the phosphepine to the allene being the turnover-limiting step of the catalytic cycle

Asymmetric Nickel-Catalyzed Negishi Cross-Couplings of Secondary α-Bromo Amides with Organozinc Reagents

A Ni/Pybox catalyst achieves the asymmetric cross-coupling of secondary α-bromo amides with organozinc reagents. The process tolerates a variety of functional groups and affords the desired product in good yield and in high enantiomeric excess

Nickel/Bis(oxazoline)-Catalyzed Asymmetric Kumada Reactions of Alkyl Electrophiles: Cross-Couplings of Racemic α-Bromoketones

Nickel/Bis(oxazoline)-Catalyzed Asymmetric Kumada Reactions of Alkyl Electrophiles: Cross-Couplings of Racemic α-Bromoketone

Rhodium-Catalyzed Synthesis of Cyclohexenones via a Novel [4 + 2] Annulation

In the presence of a rhodium catalyst, 4-alkynals react with alkynes to furnish cyclohexenones, presumably via metalacycle 1; as far as we are aware, this is the first example of the generation of this class of compounds through such a transformation. In view of the easy accessibility of 4-alkynals (alkynylmetal + α,β-unsaturated aldehyde) and alkynes, this [4 + 2] cyclization constitutes an interesting new approach to functionalized cyclohexenones