Secondary-sphere preorganization enables nickel-catalyzed nitrile hydroboration.

Herein, we describe nickel-catalyzed nitrile hydroboration with pinacolborane, wherein a tethered NHC-pyridonate ligand enables efficient catalysis (5 mol% [Ni], ≤6 h reaction time) at room temperature. Mechanistic studies, including isolation of the catalytically relevant intermediates, shed light on the cooperative role of the ligand in activating both reagents simultaneously.

Palladium-Catalyzed Intermolecular Acylative Heck Reactions with Imides as Acyl Electrophiles.

We disclose palladium-catalyzed, intermolecular, acylative Heck reactions that use imides as acyl electrophiles. The catalyst generated from [Pd(allyl)Cl]2 and DPEphos promotes the reaction between N-benzoylglutarimides and norbornene in the presence of silver phosphate. The acylative Heck reaction encompasses an array of N-benzoylglutarimide electrophiles that contain electron-donating, halogenated, and electron-withdrawing substituents to generate α,ß-unsaturated ketones in moderate to high yields (25-82%). The bicylic α,ß-unsaturated ketones are readily transformed into polycyclic architectures via thermal hetero-Diels-Alder reactions that occur by the dimerization of the α,ß-unsaturated ketones.

Ni-Catalyzed Intermolecular Carboacylation of Internal Alkynes via Amide C-N Bond Activation.

The Ni-catalyzed carboacylation of alkynes with amide electrophiles and triarylboroxines is presented. The reaction generates all-carbon tetrasubstituted alkene products in up to 62% yield. NiCl2·glyme is used as an inexpensive precatalyst in the absence of any external reductant or exogenous ligand. Design of Experiment (DoE) was used to achieve the best combination of yield and stereoselectivity in this acylative carbodifunctionalization of alkynes to generate highly substituted enones.

Enantioselective, Palladium-Catalyzed Conjugate Additions of Arylboronic Acids to Form Bis-benzylic Quaternary Stereocenters.

We report enantioselective, palladium-catalyzed conjugate additions of arylboronic acids to ß-aryl, ß,ß-disubstituted enones to generate ketones containing bis-benzylic quaternary stereocenters. A catalyst generated from palladium trifluoroacetate and (S)-4-tert-butyl-2-(2-pyridyl)oxazoline ligand ((S)-t-BuPyOx) promotes conjugate additions of a wide range of arylboronic acids to a variety of ß-aryl, ß,ß-disubstituted enones. Iterative addition of the arylboronic acid to minimize undesired protodeboronation pathways leads to efficient formation of the corresponding ketones containing bis-benzylic quaternary stereocenters in up to 92% yield and up to 93% enantioselectivity.