Pd(OAc)2-catalyzed carbonylation of amines.

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.

Synthesis of Phthalideisoquinoline and Protoberberine Alkaloids and Indolo[2,1-a]isoquinolines in a Divergent Route Involving Palladium(0)-Catalyzed Carbonylation(1).

6,7,3',4'-Alkoxy-substituted 1-(2'-bromobenzoyl)-3,4-dihydroisoquinoline methiodides 17 were treated with sodium borohydride in methanol or acetic acid to give erythro-1-(2'-bromo-alpha-hydroxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolines 19. Treatment of 17 with lithium aluminum hydride in tetrahydrofuran gave the threo-isomer 20 in preference to the erythro 19. On the basis of studies on palladium(0)-catalyzed carbonylation of 2-bromo-3,4-dimethoxybenzyl alcohol to 6,7-dimethoxyphthalide, amino alcohol 19 or 20 was treated with a catalytic amount of palladium(II) acetate and triphenylphosphine in an atmosphere of carbon monoxide in the presence of chlorotrimethylsilane and potassium carbonate in boiling toluene to give the corresponding erythro- or threo-types of phthalideisoquinoline alkaloids 1 or 2, respectively. One-pot cyclization of the erythro-amino alcohols 19 was achieved by heating in N,N-dimethylformamide containing potassium carbonate to give 2,3,8,9- or 2,3,9,10-alkoxy-substituted 5,6-dihydroindolo[2,1-a]isoquinolines 3, which have a unique tetracyclic skeleton characteristic of dibenzopyrrocoline alkaloids. Similarly, palladium(0)-catalyzed carbonylation of 1-(2'-bromobenzyl)tetrahydroisoquinolines 21 in the presence of excess potassium carbonate was found to give 8-oxoberbines 22, which on reduction with lithium aluminum hydride can be converted to protoberberine alkaloids 4.