Photochemical decarbonylation of ketones in the solid state and in solution. Progress towards the total synthesis of natural products

Photochemistry in combination with solid state chemistry can be used as a powerful new technique in organic synthesis. However as for any other methodology, its generality and usefulness needs to be established. The aim of this dissertation is to expand on photochemical reactivity patterns in the solid state. The goal is to arrive at structures with potential biological activity that are difficult to obtain by other methods. Previous results in our laboratories have shown the advantages of working in the solid state, which include high chemo- and enantio-selectivities as well as working in the absence of solvents. As a result of comparing solution versus solid state reactivity in a variety of chemical structures, new and interesting patterns and pathways were found in both media.;Chapter 1 offers a brief introduction on the general mechanistic concerns of the photodecarbonylation reaction. The main focus of this chapter is to introduce the reader to solid state photochemistry through examples found in literature by us and others. Its reactivity, advantages and limitations are described.;In Chapter 2, the relative efficiencies of the solid state photochemical decarbonylation of dicumyl ketones in the presence of mild electron donor and withdrawing groups through their corresponding dicumyl radicals are described. Reactions performed in the solid give only one product whereas reactions done in solution yield a range of undesired by-products. Mechanistic aspects are described therein followed by comparison to literature values found in solution.;In Chapter 3, nanocrystalline suspensions of 1,3-dithiophenyl propanone are used as a way to overcome filtering effects observed when the reaction was carried out on microcrystalline powders. In addition, the power of the solid state photodecarbonylation reaction in the presence of sulfur containing heterocyclic system is described.;Chapter 4 deals with the photochemically induced 2+2 cycloaddition of 2,4-dimethyl-2-S,S(thiophen-3-yl)oxide-4-(thiophen-3-yl)pentan-3-one in the solid state. The reaction pathway is described and studied with the help of x-ray crystallography. Also, transitions of reactants to products before, during and after reaction are examined. Additionally, the thermal 4+2 cycloaddition of the same system is explained.;Chapter 5 describes the diastereoselective synthesis of ketones containing phenylpyrrolidinone groups as substituents. The decarbonylation of these substituted ketones was studied in solution and the results obtained suggested a memory of chirality effect. Crystallography and sensitized photoreactions helped unravel some of the mechanistic aspects of this reaction.;Chapter 6 treats with similar ketones as those described in the previous chapter, however the synthesis of chiral structures to obtain enantiomerically pure ketones was achieved. In addition, the memory of chirality effect in solution previously observed was assessed and determined with the help of mass spectrometry, chiral shift reagents and x-ray crystallography. Different experiments were devised in order to change the outcome of the reaction and examine more of the mechanistic aspects of the photochemical transformation.;In Chapter 7, the range of compounds described in the two previous chapters was expanded by varying the protecting groups. Photochemical reactivities in the solid state as well as in solution of these substituted ketones are described. Limitations as well as advantages were found when varying the protecting groups. Results varied from extremely efficient to inefficient chemo- and diastereoselectivities in the solid.