Part A. Phenols in palladium catalyzed reactions. Enantioselective total syntheses of (-)-galanthamine, (-)-aflatoxin B(1) and (-)-calanolide A and B. Part B. Ruthenium catalyzed carbon-carbon bond forming reactions

In part A, several new palladium catalyzed transformation of phenols were developed. First, a catalyst system derived from a palladium(+2) or palladium(0) complex and formic acid was developed for the synthesis of coumarins from the coupling of phenols and alkynoates. Second, a novel approach to the regio- and enantioselective O- and C-alkylation of phenols was developed. This approach employs palladium catalyzed asymmetric allylic alkylation (AAA) of phenols to produce the O-alkylated phenols in 85–95% ee. A highly regioselective europium catalyzed aromatic Claisen rearrangement was employed to produce the C-alkylated phenols with 95–100% chirality transfer. The palladium catalyzed AAA of phenols was applied to the first asymmetric synthesis of the selective acetylcholine esterase inhibitor (−)galanthamine. This synthesis employed the AAA in combination with an intramolecular Heck reaction to produce (−)-galanthamine it 14 steps and 1.5% overall yield. Third, the palladium catalyzed dynamic kinetic asymmetrif transformation (DYKAT) of 5-acyloxy-2-(5H)-furanones was developed. A combination of the palladium catalyzed DYKAT of butenolides and reductive Heck cyclization was utilized in the first asymmetric synthesis of (−)-aflatoxin B₁ (8 steps 1.6% overall yield). Fourth, a working model for the regio- and enantioselective addition of phenols unsymmetrical π-allylpalladium intermediates was developed. This reaction was applies an asymmetric total synthesis of the HIV-1 reverse transcriptase inhibitors (−)-calanolid, and B (8 steps, 5% overall yield).; In part B, a series of tris(acetonitrile) cyclopentadienylruthenium(+2) hexafluorophosphate catalyzed reactions were developed. This complex catalyzed the inter- and intramolecular ene-type reaction of alkenes and alkynes. A mechanism involving an intermediate ruthenacyclopentene is proposed. Cycloheptenes are available frog ruthenium catalyzed reaction of 1,8-enynoates by a process involving allylic C-H activation. The complex also catalyzed the intramolecular [5+2]-cycloaddition of alkynes and vinylcyclopropanes and the intramolecular [4+2]-cycloaddition of alkynes and enones.