Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: 3782.

Adviser: John F. Hartwig.

New palladium complexes, based on the wide bite-angle bisphosphine Xantphos (9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene), have been developed as highly active catalysts for additions of arylamines to vinylarenes and 1,3-dienes. Reactions catalyzed by these complexes were shown to add selectively the amine N-H bond of arylamines to olefins in the presence of the types of functionality commonly found in natural products and pharmaceutically active materials. Measurements of the rate of addition to 113-benzyl complexes and unsymmetrical eta 3-allyl complexes, model intermediates for the hydroamination of vinylarenes and 1,3-dienes, respectively, have revealed a correlation between bite angle and rate of nucleophilic addition. Furthermore, a separate study conducted on the effect of electronic and steric properties of organometallic electrophiles on stoichiometric C(sp3)--N bond formation, has revealed that additions to eta3-benzyl complexes occur faster than additions to the corresponding eta3-allyl complexes.

Utilizing these highly active catalysts, we have conducted measurements of the thermodynamic parameters for the addition of arylamines to vinylarenes. Additions were found to be exothermic, but nearly thermoneutral in free energy. Consideration that the reaction yield is controlled in large part by thermodynamics allowed us to conduct the addition of aniline to indene under conditions resulting in high yields.

Work to expand the scope of nucleophile has resulted in palladium-catalyzed additions of N--X (X = N, O) compounds to allylic carbonates and 1,3-dienes generating monoallylated products with high branched regioselectivity. Rates of addition were related to the nature of the palladium catalyst while regioselectivity was largely unaffected. The origin of the regioselectivity has been traced to a difference in the rate of isomerization for the products of N--X addition versus the products from amine addition. Branched arylamine products isomerize in the catalytic system to the thermodynamically more stable linear products while branched N--X products undergo slow isomerization, allowing the kinetic, branched isomer to be the sole product from additions of N--X nucleophiles. Experimental and theoretical mechanistic studies conducted on bisphosphine ligated cationic eta3-allylpalladium complexes show that nucleophilic addition is endothermic and that proton transfer from the eta2-allylic ammonium complex is rate determining.