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>Dissertatio

A Mismatch-Free Strategy for the Diastereoselective α,α-Bisalkylation of Chiral Nonracemic Methyl Ketones

A chiral auxiliary-based diastereoselective transformation that entirely avoids the stereochemically mismatched pairing, providing equally high levels of asymmetric induction in the formation of each diastereomer is described. In particular, we show that chiral nonracemic methyl ketones undergo α,α-bisalkylation using phenylalanine-derived <i>N</i>-amino cyclic carbamate (ACC) auxiliaries with essentially perfect diastereoselectivity, as well as excellent yield and regioselectivity. Significantly, with the use of a single enantiomer of the auxiliary, either diastereomeric product can be synthesized with an equally high level of asymmetric induction