Palladium-Catalyzed Synthesis of Aromatic Carboxylic Acids with Silacarboxylic Acids

Aryl iodides and bromides were easily converted to their corresponding aromatic carboxylic acids via a Pd-catalyzed carbonylation reaction using silacarboxylic acids as an <i>in situ</i> source of carbon monoxide. The reaction conditions were compatible with a wide range of functional groups, and with the aryl iodides, the carbonylation was complete within minutes. The method was adapted to the double and selective isotope labeling of tamibarotene

Asymmetric Hydroarylation of Vinylarenes Using a Synergistic Combination of CuH and Pd Catalysis

Detailed in this Communication is the enantioselective synthesis of 1,1-diaryl­alkanes, a structure found in a range of pharmaceutical drug agents and natural products, through the employment of copper­(I) hydride and palladium catalysis. Judicious choice of ligand for both Cu and Pd enabled this hydroarylation protocol to work for an extensive array of aryl bromides and styrenes, including β-substituted vinylarenes and six-membered heterocycles, under relatively mild conditions

Silacarboxylic Acids as Efficient Carbon Monoxide Releasing Molecules: Synthesis and Application in Palladium-Catalyzed Carbonylation Reactions

Silacarboxylic acids have been demonstrated to be easy to handle, air-stable carbon monoxide precursors. Different silacarboxylic acids were synthesized from the corresponding chlorosilanes and carbon dioxide, and their decarbonylation, upon treatment with an array of activators, was evaluated. The release of CO from crystalline MePh₂SiCO₂H proved to be highly efficient, and it was successfully applied in a selection of palladium-catalyzed carbonylative couplings using near-stoichiometric quantities of carbon monoxide precursor. Finally, the synthesis of MePh₂Si¹³CO₂H and its application in carbonyl labeling of two bioactive compounds was demonstrated

Efficient ¹¹C‑Carbonylation of Isolated Aryl Palladium Complexes for PET: Application to Challenging Radiopharmaceutical Synthesis

We describe the successful implementation of palladium-aryl oxidative addition complexes as stoichiometric reagents in carbonylation reactions with ¹¹CO to produce structurally challenging, pharmaceutically relevant compounds. This method enables the first ¹¹C-carbonyl labeling of an approved PET tracer, [¹¹C]­raclopride, for the dopamine D2/D3 receptor by carbonylation with excellent radiochemical purity and yield. Two other molecules, [¹¹C]­olaparib and [¹¹C]­JNJ 31020028, were efficiently labeled in this manner. The technique distinguishes itself from existing methods by the markedly improved purity profiles of the tracer molecules produced and provides access to complex structures in synthetically useful yields, hereby offering a viable alternative to other ¹¹C-labeling strategies