Total Synthesis of (±)-Azaspirene via Crystallization-induced Diastereomer Transformation

The total synthesis of racemic azaspirene was accomplished over 12 steps in a 17% overall yield via a convergent strategy featuring the coupling of isocyanate and 3(2H)-furanone and an intramolecular aldol reaction to construct the spiro core. Later, a complete conversion was achieved via the crystallizationinduced diastereomer transformation of the kinetically favored epimer® produced primarily via spirocyclic construction® to the thermodynamically stable and desirable epimer. Finally, a stereoselective hydration produced the target azaspirene.