Palladium‐Catalyzed Cross‐Coupling of Alkenyl Carboxylates

Carboxylate esters have many desirable features as electrophiles for catalytic cross‐coupling: they are easy to access, robust during multistep synthesis, and mass‐efficient in coupling reactions. Alkenyl carboxylates, a class of readily prepared non‐aromatic electrophiles, remain difficult to functionalize through cross‐coupling. We demonstrate that Pd catalysis is effective for coupling electron‐deficient alkenyl carboxylates with arylboronic acids in the absence of base or oxidants. Furthermore, these reactions can proceed by two distinct mechanisms for C?O bond activation. A Pd^0/II catalytic cycle is viable when using a Pd⁰ precatalyst, with turnover‐limiting C?O oxidative addition; however, an alternative pathway that involves alkene carbopalladation and β‐carboxyl elimination is proposed for Pd^II precatalysts. This work provides a clear path toward engaging myriad oxygen‐based electrophiles in Pd‐catalyzed cross‐coupling.     

Palladium‐Catalyzed Three‐Component Cascade Reaction: Facial Access to Densely Functionalized Indolizines

A palladium‐catalyzed three‐component cascade reaction of 2‐(2‐enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.     

Copper‐Catalyzed Borylative Allyl–Allyl Coupling Reaction

Borylative allyl–allyl coupling using allenes, bis(pinacolato)diboron, and allyl phosphates has been developed in the presence of a copper catalyst bearing an N‐heterocyclic carbene ligand. The reaction affords boryl‐substituted 1,5‐diene derivatives in good to high yields with high regioselectivity and Z selectivity.     

A Novel Trypsin‐Catalyzed Three‐Component Mannich Reaction

We found that the trypsin from hog pancreas displayed high activity to promote three‐component Mannich reaction of aromatic aldehydes, aromatic amines, and acetone with moderate‐to‐excellent yields. The reaction tolerates a great range of substrates and extends the application of trypsin in organic synthesis.     

Palladium‐Catalyzed Isomerization and Hydroformylation of Olefins

A novel selective palladium catalyst system based on bidentate 2,2′‐heteroarylarylphosphines and p‐TsOH has been developed for hydroformylation reactions (see scheme). By applying optimal conditions good to excellent regioselectivity is obtained for the hydroformylation of aliphatic and aromatic olefins. It is shown that a low acid concentration is crucial for obtaining high degrees of the linear isomer.

     

Palladium‐Catalyzed Coupling Reaction of Perfluoroarenes with Diarylzinc Compounds

This report describes the first Pd⁰‐catalyzed cross‐coupling of hexafluorobenzene (C₆F₆) with diarylzinc compounds to give a variety of pentafluorophenyl arenes. This reaction could be applied to other perfluoroarenes, such as octafluorotoluene, pentafluoropyridine, and perfluoronaphthalene, to give the corresponding polyfluorinated coupling products. The optimal ligand in this catalytic reaction was PCy₃, and lithium iodide was indispensable as an additive for the coupling reaction. One of the roles of lithium iodide in this catalytic reaction was to promote the oxidative addition of one C?F bond of C₆F₆ to palladium. Stoichiometric reactions revealed that an expected oxidative‐addition product, trans‐[Pd(C₆F₅)I(PCy₃)₂], generated from the reaction of [Pd(PCy₃)₂] with C₆F₆ in the presence of lithium iodide, was not involved in the catalytic cycle. Instead, a transient three‐coordinate, monophosphine‐ligated species, [Pd(C₆F₅)I(PCy₃)], emerged as a potential intermediate in the catalytic cycle. Therefore, we isolated a novel Pd^II complex, [Pd(C₆F₅)I(PCy₃)(py)], in which pyridine (py) acted as a labile ligand to generate the transient species. In fact, in the presence of lithium iodide, this Pd^II complex was found to react smoothly with diphenylzinc to give the desired pentafluorophenyl benzene, whereas the same reaction conducted in the absence of lithium iodide resulted in a decreased yield of pentafluorophenyl benzene, which indicated that the other role of lithium iodide was to enhance the reactivity of the organozinc species during the transmetalation step.     

Palladium‐Catalyzed Hydroamidocarbonylation of Olefins to Imides

Carbonylation reactions allow the efficient synthesis of all kinds of carbonyl‐containing compounds. Here, we report a straightforward synthesis of various imides from olefins and CO for the first time. The established hydroamidocarbonylation reaction affords imides in good yields (up to 90 %) and with good regioselectivity (up to 99:1) when applying different alkenes and amides. The synthetic potential of the method is highlighted by the synthesis of Aniracetam by intramolecular hydroamidocarbonylation.