Mild and Robust Stille Reactions in Water using Parts Per Million Levels of a Triphenylphosphine-Based Palladacycle.

An inexpensive and new triphenylphosphine-based palladacycle has been developed as a pre-catalyst, leading to highly effective Stille cross-coupling reactions in water under mild reaction conditions. Only 500-1000 ppm of Pd suffices for couplings involving a variety of aryl/heteroaryl halides with aryl/hetaryl stannanes. Several drug intermediates can be prepared using this catalyst in aqueous nanoreactors formed by 2 wt % Brij-30 in water.

Chemoselective Reductive Aminations in Aqueous Nanoreactors Using Parts per Million Level Pd/C Catalysis.

Condensation in recyclable water between aldehydes or ketones and amines occurs smoothly within the hydrophobic cores of nanomicelles, resulting in imine formation that is subject to subsequent reduction leading, overall, to reductive amination. This micellar technology enables the synthesis of several types of pharmaceuticals, a new procedure that relies on only 2000 ppm (0.20 mol %) palladium from commercially available Pd/C. A broad range of substrates can be used under mild conditions, leading to high chemical yields of the desired secondary and tertiary amines.

Uncatalyzed conjugate addition of organozinc halides to enones in DME: a combined experimental/computational study on the role of the solvent and the reaction mechanism.

Both aryl and alkylzinc halides prepared by direct insertion of zinc into organic halides in the presence of LiCl underwent the conjugate addition reaction to nonenolizable unsaturated ketones in excellent yield, provided that DME was used instead of THF as the solvent. Diffusion NMR measurements highlighted that the species undergo considerable aggregation under the experimental conditions used in the synthetic procedure, but no substantial differences have been found between the two solvents. Density functional theory calculations, prompted by the experimental aggregation study, revealed an unexpected reaction mechanism, where the coordinating capabilities of DME stabilize a transition state involving two organozinc moieties, lowering the activation energy of the reaction with respect to that seen for THF, enough to explain the fast and quantitative reactions observed experimentally and the different behaviors of the two solvents.