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 <i>build/couple/pair</i> 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, α-hydroxy aldehydes, and boronic acids, which undergo Petasis 3-component reactions (couple) to afford densely functionalized <i>anti</i>-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