Pd(OAc)₂-Catalyzed Carbonylation of Amines

Abstract

A phosphine-free catalytic system [Pd(OAc)2-Cu(OAc)2-air] induced a substrate-specific carbonylation of amines in boiling toluene under CO gas (1 atm). Symmetrical N,N'-dialkylureas were obtained by the carbonylation of primary amines. N,N,N'-Trialkylureas were selectively formed by addition of a secondary amine to the above reaction vessel. Secondary amines did not give tetraalkylureas. However, dialkylamines with a phenyl group on their alkyl chains, such as N-monoalkylated benzylic amine or phenethylamine derivatives, underwent a direct aromatic carbonylation to afford five- or six-membered benzolactams. In the carbonylation, the chelation effect or steric repulsion between Pd(II) and the meta-substituent in the ortho-palladation and the ring sizes of cyclopalladation products that were formed prior to carbonylation were found to generate good site selectivity and increase the reaction rate. In contrast, carbonylation of omega-arylalkylamines with a hydroxyl group gave neither ureas nor benzolactams but instead produced 1,3-oxazolidinones smoothly. Hydrochlorides of amines also underwent carbonylation to afford the corresponding amides under the conditions used. This procedure made it possible to prepare ureas of amino acid esters and N-alkylcarbamates in practical yields.

NH2 As a Directing Group: From the Cyclopalladation of Amino Esters to the Preparation of Benzolactams by Palladium(II)-Catalyzed Carbonylation of N-Unprotected Arylethylamines

“…It should be noted that, in this last case, the corresponding amino ester presents a larger steric hindrance around the amino group. These results are in sharp contrast with those reported by Orito et al 8 for the related carbonylation of secondary amines using Cu(II) as co-oxidant in which the five-membered benzolactams were favored over the six-membered analogues. A greater reactivity of the six-membered palladacycles involved could explain this result.…”

Synthesis of Functionalized Heterocycles via Oxidative Carbonylation

“…Orito and co-workers prepared a variety of five-or six-membered benzolactams by the direct aromatic carbonylation of secondary ω-phenylalkylamines using Pd(OAc) 2 and Cu(OAc) 2 in an atmosphere of CO gas containing air (Scheme 33) [99,100]. In 2007, they applied this methodology to the synthesis of N-protected staurosporinones [101].…”

From Anilines to Isatins: Oxidative Palladium‐Catalyzed Double Carbonylation of CH Bonds

“…Then, coordination and insertion of CO into A affords the carbamoyl intermediate B. [14] Then B undergoes another CO insertion to give the intermediate C. In conclusion, we have developed the first direct oxidative palladium-catalyzed C À H/N À H double carbonylation which introduces adjacent carbonyl groups for the direct synthesis of isatins. This transformation offers a general process for converting readily available substrates into potentially useful compounds.…”