UCLA

Chapter 1

The synthesis of the tricyclic core of the diterpene guanacastepene A is described. Based on previous studies in the laboratory of professor Ohyun Kwon, the densely functionalized six-membered ring of the natural product was constructed utilizing an intermolecular Diels-Alder cycloaddition between maleic anhydride and a highly substituted alkoxydiene. The requisite diene was synthesized via a Stille cross coupling reaction for which an efficient synthesis of the necessary vinyl stannane was developed. An alternative synthesis of the diene based on copper mediated coupling of vinyl boronates with alcohols was also devised, which allowed for the preparation of gram quantities with minimal purification. The five-membered ring of guanacastepene A was appended through coupling with a highly functionalized zinc cuprate. While previous studies in the Kwon laboratory showed that a conjugate addition/Mukaiyama aldol strategy to install the C11 methyl group and forge the seven-membered ring was efficient in forming the two desired carbon-carbon bonds, poor diastereoselectivity of the initial conjugate addition was observed. The research described here uses the Nozaki-Hiyama-Kishi reaction to close the central seven-membered ring without prior installation of the C11 methyl group.

Chapter 2

The synthesis of 3-carbethoxy-2-substituted-3-pyrrolines via the phosphine-catalyzed intramolecular γ-umpolung addition of N-tosyl α-aminoalkylallenic esters is described. The current transformation provides a compliment to the known syntheses of similarly substituted pyrrolines via the phosphine-catalyzed [3 + 2] annulation between imines and allenoates. The flexibility in substitution at the 2-position, including alkyl groups, offers benefits over many of the previously reported syntheses of similarly substituted pyrrolines. The N-tosyl α-aminoalkylallenic esters were prepared via a novel decarboxylative rearrangement of allenylic carbamates.

Chapter 3

The enantioselective total synthesis of the monoterpene indole alkaloid (+)-ibophyllidine is described. The employed strategy was based on a key asymmetric phosphine-catalyzed [3 + 2] annulations between a γ-ethyl allenoate and the N-tosyl imine derived from indole-3-aldehyde using Kwon's L-4-hydroxyproline-derived chiral phosphine catalyst. This key transformation constructed the stereochemically dense D-ring with exceptional levels of diastereo- and enantioselectivity. A subsequent diastereoselective hydrogenation of the pyrroline double bond led to the fully functionalized, all syn pyrrolidine ring of the natural product. An intramolecular alkylation at the C3 position of indole formed the C-ring while an intramolecular aza Baylis-Hillman reaction was utilized to forge the E-ring leading to the pentacyclic skeleton of (+)-ibophyllidine.