The use of the Petasis three-component reaction to yield densely functionalized anti-�-amino alcohols, followed by intramolecular cyclization reactions, has previously been shown to be a very efficient approach for the generation of structurally diverse small molecules in few synthetic steps. In the present study, we wish to report how alkene-containing a-hydroxy aldehydes, boronic acids and amines systematically undergo Petasis-three component reactions in satisfying yields (35-90%). The resulting compounds strategically display pair-wise reactive combinations of alkene moieties which can be utilized in ring-closing metathesis and intramolecular Diels-Alder reactions, thus yielding skeletally diverse and constrained small molecules in good yields (29-95%). By carefully tuning the reaction parameters, the ring-closing metathesis step could be coupled in situ to a novel Ru-catalyzed double bond isomerization-cyclization cascade process that yields bicyclic azepine-type ring systems in high yields.

Rapid and systematic synthesis of compound collections using Petasis three-component and ring-closing metathesis reactions

239th National Meeting (2010)

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