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Physostigmine is an alkaloid isolated from the calabar bean of West Africa, which has received considerable attention as a possible treatment for Alzheimer's Disease. But, physostigmine's utilization as a treatment for cholinergic dysfunction has been limited by the few practical enantiospecific syntheses of its pyrroloindole skeleton, and the limited efficacy due to its toxicity and short duration of action. Through the use of new methodology a series of ortho heteroatom substituted aryl cuprates were developed as key intermediates to address this problem. The nitrogen atom of several aniline derivatives were protected with either tert-butoxy dicarbonate or trifluoroacetic anhydride to form the corresponding N-BOC carbamates or anilides. Several phenol derivatives were also protected to form either an N,N-diethylcarbamate or the methoxy methyl phenyl ether. Directed ortho metallation reactions were effectively carried out, allowing for the subsequent transmetallation with CuBr-Me$\sb2$S, to form the corresponding aryl cuprates. The introduction of chiral alkynyl sulfoxides allowed for a smooth conjugate addition reaction, which lead directly to the ortho heteroatom substituted aryl vinyl sulfoxides. These sulfoxides were submitted to a 3,3-sigmatropic rearrangement to produce enantiomerically enriched $\gamma$-butyrolactones. The formation of an oxonium intermediate was realized through the initial halogenation of the aryl sulfide in the g-position of the lactone. Subsequent heterocyclization occurred very smoothly as the protected aromatic nitrogen was able to attack the reactive oxonium species, which lead to the formation of the tetrahydrofurano-(2,3-b) -indole system. Subsequent amination of the lactone, followed by acid catalyzed heterocyclization, gave the tetrahydropyrrolo-(2,3-b) -indole product. (-)-Esermethole, the penultimate precursor of (-)-Physostigmine was generated in one step through the reduction of both the lactam carbonyl and the methyl carbamate groups. The synthesis of the racemic compounds 6-N-methyl carbamoyl-1,3a,8-trimethyl pyrrolo-(2,3-b) -indole 150, and 5-methoxy-3a-methyl-2,3,3a,8,8a-tetrahyrofuro-(2,3-b) -benzofuran 169 were structural analogs of physostigmine completed using our methodology. Initial examination of analog 150's ability to inhibit human erythrocyte acetyl cholinesterase indicated poor activity, if any, in the mM range.