| This thesis describes the progress made towards the synthesis of the lysergine ring system 1. Approaches based on benzyne, oxindole, and indole intermediates were explored. Results of these three central strategies are discussed.; The benzyne route as outlined in Chapter 2 illustrated the potential to synthesize a key bicyclic intermediate, 3-but-3-enyl-4-iodo-1-methyl-1,3-dihydro-indol-2-one 33. This approach utilized our existing results in benzyne chemistry to construct the lysergine AB ring system. Formation of 33 via a benzyne reaction would be followed by an intramolecular Heck cyclization reaction, resulting in formation of intermediate 34. Due to low yields and difficulty in reproducing 33 in the benzyne reaction, this route was abandoned.*; The oxindole route (Chapter 3) was an extension of the ideas developed during the exploration of the benzyne reaction. This approach examined the potential for an intramolecular Friedel Crafts reaction using oxindole-3-propionic acid as the starting material, followed by a Wittig olefination to yield the desired tricyclic intermediate 34. Unfortunately, the Friedel Craft product 70 was highly unstable therefore, this route was also abandoned.*; The indole approach described in Chapter 4 combined the original ideas from both the benzyne and oxindole routes. Here, we demonstrated the ease of synthesis in obtaining 2,2-dimethyl-1-(5-methylene-4,5-dihydro-3H-benzo[c,d]indol-1-yl)-propan-1-one 77, the N-pivalyl protected version of intermediate 34. The success in forming 77 enabled us to proceed with the construction of Ring D using a selenium-dioxide allylic oxidation reaction to afford the α-alcohol 87. In addition, the α,β-enone isomer 88 was obtained via modified Mannich reaction conditions. The successes realized with the indole approach presented a unique and promising synthetic approach to lysergine 1.; *Please refer to dissertation for diagram. |
