New Methods for the α-Functionalization of Thioesters and Activated Hydrazones and an Application Toward the Total Synthesis of Apratoxin D

<p>Cascade reactions, also referred to as domino reactions, have been widely used for the formation of carbon-carbon bonds. This type of reaction has the potential to circumvent protection and deprotection steps, shortening an overall synthetic process.</p><p>The Morita-Baylis-Hillman (MBH) reaction is a particularly notable example of an anionic domino reaction which provides straightforward access to &#946;'-hydroxy-&#945;,&#946;-unsaturated carbonyl compounds from aldehydes and &#945;,&#946;-unsaturated carbonyls. However, despite the importance of the Baylis-Hillman reaction, it is slow, reaction yields are quite low, and the process is not general, as it rarely works for &#946;-substituted &#945;,&#946;-unsaturated carbonyl species. Herein, we report an alternative approach to the preparation of MBH adducts employing an anti-selective direct aldol cascade reaction followed by oxidative elimination. This alternative process is rapid, efficient, and generally applicable, even to &#946;-substituted &#945;,&#946;-unsaturated compounds. </p><p>Progress toward the asymmetric total synthesis of apratoxin D is described. The key step of the synthesis is the asymmetric &#945;,&#945;-bisalkylation of chiral N-amino cyclic carbamate (ACC) hydrazones, a new methodology developed by our group. Herein we demonstrate the utility of this method for convergent total syntheses.</p>

Author dc:creator

• Tarsis, Emily Michelle

Advisor dc:contributor.advisor

• Coltart, Don M

• Organic Chemistry

Handle dc:identifier.uri

https://hdl.handle.net/10161/3074

OAI identifier oai:identifier

oai:dukespace.lib.duke.edu:10161/3074