Part one. Studies towards the total synthesis of azaspirocyclic containing alkaloids. Part two. tert-butylsulfonyl (Bus), a new protecting group for amines

Part one. Chapter one. A brief overview of azaspirocyclic-containing alkaloids is presented.; Chapter two. Approaches towards the synthesis of azaspiro core structure 42 of pinnaic acid (7) and halichlorine (9) are described. The initial strategy based on a novel intramolecular imino ene reaction to construct 42 was unsuccessful, presumably due to steric factors in the generation of a quaternary carbon at C9. Two other approaches, an intramolecular cyclization reaction involving bis-homoallylic N-acyliminium ion 72 and an intermolecular nucleophilic addition to N-acyliminium species 82, were more successful in generating the C9 center, but failed to establish the correct stereochemistry at C5 of 42. A new approach that would utilize an intramolecular Michael addition to establish the correct stereochemistry at C5 proceeded successfully, but the project was terminated when we learned that the same strategy as ours was utilized by Danishefsky in a total synthesis of (+)-halichlorine.; Chapter three. Studies towards the total synthesis of lepadiformine (20), which also contains an azaspiro moiety, are described. Initial approaches to the azaspiro core of lepadiformine which were based on a proposed intramolecular hetero Diels-Alder reaction gave positive results, but extensive effort failed to improve the yield of this transformation to an acceptable level. An intramolecular allyltrimethylsilane addition to N-acyliminium species 207 was then devised, which afforded azaspirocyclic structure 208 that contains the required stereochemistry for lepadiformine. Advanced intermediate 228 was then synthesized in 8 steps from 208.; Part two. The development of the tert-butylsulfonyl (Bus) group as a new amine protecting group is described. The Bus group is stable towards a variety of acidic and metallation conditions. The removal of this protecting group can be achieved by treatment of N-Bus protected amines with 0.1 N triflic acid in CH ₂Cl₂. In addition, tert-butylsulfonamides derived from secondary amines can also be deprotected when treated with neat TFA/anisole overnight at rt. Selective deprotection of a Bus-protected secondary amine in the presence of a primary amine was also achieved.