UC Santa Barbara

Quaternary stereogenic centers are important structural motifs in natural products and biologically active compounds, and present some of the most challenging constructs in organic synthesis. The first part of this thesis reports our development of a highly enantioselective alkylation of both α-alkynyl carboxylic acids and α-allenoic acids forming all-carbon quaternary centers. Chiral lithium amides are used as noncovalent stereodirecting auxiliaries. Accompanying crystallographic studies provide mechanistic insight into the structure of well-defined chiral aggregates, highlighting cation-π interactions between lithium and alkyne groups. The synthetic utility of this method is further demonstrated in the enantioselective total synthesis of (+)-goniomitine.The second part will outline our efforts towards two heterodimeric bisindole alkaloids, bousigonine A and bisleuconothine A. The synthesis features a divergent-convergent retrosynthetic design that allows for efficient, practical synthesis with shorter longest linear sequence and fewer total steps. All the quaternary centers are formed using the asymmetric alkylation methods developed in our group. Three monoindole fragments in the target molecules, eburnamonine, quebrachamine and aspidospermidine are obtained and the final assemble of the monoindole fragments is under investigation.