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To synthesize palhinine alkaloids, a quaternary reductive aldol reaction was used to generate rapid stereochemical complexity from simple building blocks. This approach, which can also be used for diterpene synthesis, couples an asymmetric Diels Alder adduct with a N-containing aldehyde fragment while also generating an alcohol stereocenter. In subsequent steps, this intermediate is hydrogenated and isomerized into a cage-like structure through protecting group manipulation. This core has the prospective to be elaborated into the natural product isopalhinine A. In particular, the reductive aldol reaction was examined with a variety of substrates and catalysts, experimentally and computationally. The electron-rich tris(4- methoxyphenyl)phosphine oxide was used as a Lewis base catalyst capable of promoting both reduction and aldol. This catalyst was effective for a variety of substrates including lactones, lactams, and morpholine amides, which were coupled with aldehydes to generate quaternary aldol fragments. For several examples, a mixture of diastereomers is generated, and this stereochemistry was verified by X-ray crystallography. To model this reaction, DFT, Zstruct, and GSM were used to study the mechanisms of reduction, catalyst placement, and aldol for a variety of substrates and catalysts. Interestingly, it was found that reduction results in a trigonal bipyramidal Si complex with both catalyst and substrate equatorial, approximately 120° apart. According to DFT, axial catalyst and equatorial substrate placement, separated by approximately 90°, is the most stable conformation. However, for the aldol step, both ligands are axial, separated by approximately 180° to accommodate the incoming aldehyde partner. These isomers could interconvert through a Berry mechanism or by a stepwise dissociation and re-coordination. These DFT and TS structures set the stage for the goal of developing stronger and more selective Lewis base catalysts.

A new, efficient route was used in the synthesis of [2.2]-paracyclophane-2-carboxylic acid. The acid as then resolved and the Birch reduction performed yielding one enantiomer of tetrahydro-[2.2]-paracyclophane-2-carboxylic acid. The ultraviolet spectrum of tetrahydro-[2.2]-paracyclophane- 2-carboxylic acid in isopenthane shows one absorption at 206 nm (Emax = 5,271). There are three bands observed in the circular dichroism spectrum in isopentane at 236 nm ([] = 1.8 X 104), 201 nm ([0] = -16 X 104) and a positive band indicated below 180 nm but not observed. The bands were assigned and possible reasons for the occurrence of a mr'r* transition at unexpectedly long wavelengths are discussed.

The use of alkali and alkaline earth metals as reducing agents in liquid ammonia solvent for aromatic and conjugated systems has been investigated by chemists at least since the early 1900's, e.g., Lebau and Picon (1). By subsequent additions of a proton source, the system yielded the first successful partial reduction of a monobenzenoid system, as reported by Wooster and Godfrey (2), in 1937. As a result of that success a patent was issued to Wooster for the process (3). Little additional work was reported until Birch and his co-workers picked up the investigation in the early 1940's. It was through his vigorous study and development of this reduction system that Birch's name came to be associated with reductions of organic compounds by alkali metals in liquid ammonia, hence, the Birch reduction.In this thesis the Birch reduction of cinnamic acid is investigated.

It has been previously shown that benzenesulfonamide gives thiophenol and diphenyldisulfide upon Birch reduction. The sulfonamide group is easily reduced. Probably the electron deficient sulfur atom in sulfonamide can accommodate an electron easily.The present study involved the Birch reduction of benzenesulfonamide, N,N-dimethylbenzenesulfonamide, N,N-diisobutylbenzenesulfonamide and 2-mesitylenesulfonamide.