New Methods for the α-Functionalization of Thioesters and Activated Hydrazones and an Application Toward the Total Synthesis of Apratoxin D
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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.
The Morita-Baylis-Hillman (MBH) reaction is a particularly notable example of an anionic domino reaction which provides straightforward access to β'-hydroxy-α,β-unsaturated carbonyl compounds from aldehydes and α,β-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 β-substituted α,β-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 β-substituted α,β-unsaturated compounds.
Progress toward the asymmetric total synthesis of apratoxin D is described. The key step of the synthesis is the asymmetric α,α-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.
Tarsis, Emily Michelle (2010). New Methods for the α-Functionalization of Thioesters and Activated Hydrazones and an Application Toward the Total Synthesis of Apratoxin D. Dissertation, Duke University. Retrieved from https://hdl.handle.net/10161/3074.
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