Combining the Petasis 3-Component Reaction with Multiple Modes of Cyclization: A Build/Couple/Pair Strategy for the Synthesis of Densely Functionalized Small Molecules

A build/couple/pair strategy for the synthesis of complex and densely functionalized small molecules is presented. The strategy relies on synthetically tractable building blocks (build), that is, diversely substituted hydrazides, a-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (couple) to afford densely functionalized anti-hydrazido alcohols. The resulting scaffolds can subsequently be converted via chemoselective cyclization reactions (pair), including intramolecular Diels-Alder or Ru-alkylidene catalyzed ring-closing metathesis, into sets of structurally diverse heterocycles in good yields in only 3-4 steps.