||<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 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.
</p><p>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.</p>