| Evolution of intramolecular aza-[3 + 3] annulation reaction from its discovery to applications in natural product synthesis is described.; Part 1 of this thesis concentrates on development of enantioselective version of the cycloaddition reaction promoted by chiral secondary amine salts. The dependence of enantioselectivity on the structural features of these catalysts has been thoroughly investigated. A very interesting reversal of the stereochemistry in the respective annulation products obtained using C1- and C2-symmetric amine salts was found. On the basis of these experimental results and semi-empirical calculations, a unified mechanistic model was proposed. Developed methodology was also successfully applied for total synthesis of enantioenriched R-(+)Deplancheine.; Part 2 describes application of the intramolecular aza-[3 + 3] annulation reaction to total synthesis of Coccinellidae defensive alkaloids. All five members of this family: precoccinelline, hippodamine, coccinelline, convergine, and myrrhine were successfully synthesized from the same common intermediate which was derived from a stereoselective aza-[3 + 3] annulation reaction. Stereoselectivity of the cycloaddition reaction was rationalized on basis of semi-empirical calculations. This work provided a de novo stereoselective approach toward 2-methyl-perhydro-9b-azaphenalene family of alkaloids.; Part 3 focuses on expanding the scope of intramolecular aza-[3 + 3] annulation to vinylogous amides tethered with alpha,beta-unsaturated ketones. Quest for suitable conditions for this transformation as well as current progress toward synthesis of propyleine alkaloid featuring discovered reaction are described in the third part of the thesis. |
