I. Transition metal-catalyzed organosulfur chemistry. New synthetic methodologies. II. The use of porphine and tetra-t-butylpophyrin as important building blocks in organic synthesis

The sulfur-transition metal bond being extremely strong, these metals are often “poisoned” by sulfur in vitro, and yet Nature uses transition metal-catalysts (metalloenzymes) in the presence of organosulfur moieties. To understand how Nature has evolved such processes, we investigated transition metal-catalyzed cross-coupling reactions of organosulfur compounds. We wished to selectively transform carbon-sulfur bond to carbon-carbon bond. However, to develop a transition metal-catalyzed cross-coupling method, it is necessary to displace and scavenge the thiolate ligand in order to prevent the poisoning of the catalyst.; The use of an alkylative displacement was demonstrated for the synthesis of ketones from thioesters. The scope and limitations of a protocol, involving the use of a copper cofactor for the palladium-catalyzed coupling of organosulfur compounds was investigated for the synthesis of alkynes from thioalkynes and biaryls from arylthioethers. This chemistry was also extended to the coupling of aryl iodides. Finally, a new synthesis of aryl and alkenyl thioethers was also investigated.; During our exploration of the chemistry of porphyrins, porphine and tetra-t-butylporphyrin were prepared in good yields and large quantities following a procedure previously developed in our laboratory. We then wanted to evaluate the potential reactivities of porphine with the challenges of low solubility of porphine and selectivity in functionalizing the ring. Forming the porphyrin zinc complex was found to be crucial for solubilization of porphine. A selective nitration in the meso position was then demonstrated and the nitrated product could be further functionalized.; We also envisioned that with the four t-butyl groups, the solubility of tetra-t-butylporphyrin should be greatly improved, and selective functionalization of the ring should be controllable. It was indeed demonstrated that this porphyrin could be selectively functionalized in the β-position by a bromination reaction and further Suzuki cross-coupling reaction. Meso functionalization could also be accomplished by performing nitration reaction and subsequent reduction.