Palladium-Catalyzed, Multicomponent Approach to β-Lactams via Aryl Halide Carbonylation.

A palladium-catalyzed multicomponent method for the synthesis of β-lactams from imines, aryl halides, and CO has been developed. This transformation proceeds via two tandem catalytic carbonylation reactions mediated by Pd(PBu) and provides a route to prepare these products from five separate reagents. A diverse range of polysubstituted β-lactams can be generated by systematic variation of the substrates.

Computational Study of the Palladium-Catalyzed Carbonylative Synthesis of Aromatic Acid Chlorides: The Synergistic Effect of PtBu and CO on Reductive Elimination.

We describe herein computational studies on the unusual ability of Pd(PtBu ) to catalyze formation of highly reactive acid chlorides from aryl halides and carbon monoxide. These show a synergistic role of carbon monoxide in concert with the large cone angle PtBu that dramatically lowers the barrier to reductive elimination. The tertiary structure of the phosphine is found to be critical in allowing CO association and the generation of a high energy, four coordinate (CO)(PR )Pd(COAr)Cl intermediate.

From Aryl Iodides to 1,3-Dipoles: Design and Mechanism of a Palladium Catalyzed Multicomponent Synthesis of Pyrroles.

A palladium-catalyzed multicomponent synthetic route to polysubstituted pyrroles from aryl iodides, imines, carbon monoxide, and alkynes is described. To develop this reaction, a series of mechanistic studies on the [Pd(allyl)Cl]2/P(t)Bu3 catalyzed synthesis of imidazolinium carboxylates from aryl iodides, imines, and carbon monoxide were first performed, including model reactions for each individual step in the transformation. These show that this reaction proceeds in a concurrent tandem catalytic fashion, and involves the in situ formation of acid chlorides, N-acyl iminium salts, and ultimately 1,3-dipoles, i.

A flexible approach to Pd-catalyzed carbonylations aroyl dimethylaminopyridinium salts.

4-Dimethylaminopyridine (DMAP) is shown to undergo Pd/P Bu catalyzed coupling with aryl halides and carbon monoxide to form electrophilic aroyl-DMAP salts. The reaction is easily scalable to prepare multigram quantities with low catalyst loadings, while the precipitation of these salts as they form leads to products with low impurities. These reagents rapidly react with a variety of nucleophiles, including those that contain potentially incompatible functional groups under standard carbonylative conditions.

Acid Chloride Synthesis by the Palladium-Catalyzed Chlorocarbonylation of Aryl Bromides.

We report a palladium-catalyzed method to synthesize acid chlorides by the chlorocarbonylation of aryl bromides. Mechanistic studies suggest the combination of sterically encumbered PtBu3 and CO coordination to palladium can rapidly equilibrate the oxidative addition/reductive elimination of carbon-halogen bonds. This provides a useful method to assemble highly reactive acid chlorides from stable and available reagents, and can be coupled with subsequent nucleophilic reactions to generate new classes of carbonylated products.