| Chapter 1 discloses investigations into the asymmetric Heck reaction. The influence of the carbonyl group in the asymmetric Heck cyclizations of α,β-unsaturated anilides was probed in these studies. In all, the syntheses of thirteen new Heck substrates and their asymmetric Heck cyclizations are reported. The results of these asymmetric Heck cyclizations establish that enantioselection in the neutral pathway of the asymmetric Heck reaction is not favored by having a carbonyl group in the tether. However, disparate reactivity of the α,β-unsaturated anilides was observed in both the neutral pathway and cationic pathways. In addition, when there was no carbonyl in the tether, (i) enantioselection was greater if the β-substituent was in a cis-orientation relative to the tether and (ii) the enantiomeric preference was correlated to the geometry of this β-substituent.; Chapter 2 presents the first total synthesis of asperazine. The details of this synthesis are preceded by an introduction that (i) presents a summary entailing the variety of structural motifs found within the pyrroloindole class of alkaloids and (ii) describes some of the synthetic literature involving diketopiperazine-containing pyrroloindole alkaloids and 3a-aryl pyrroloindole ring systems. The total synthesis of asperazine employed readily available amino acid starting materials (D-serine, L-tryptophan, and D-phenylalanine) as the sole source of stereogenicity. A Stille coupling was utilized to fashion the key C3–C24 bond. The highlight of our approach was the application of an innovative Heck cyclization to construct the tryptophan-substituted quaternary center. This synthesis confirms the structure of asperazine. |
