Hemisynthesis of 2,3,4-13C3-1,4-Androstadien-3,17-dione: A Key Precursor for the Synthesis of 13C3-Androstanes and 13C3-Estranes.

In this contribution, we describe two simple and efficient routes for the preparation of keto-aldehyde 1, a key intermediate for the synthesis of 13C3-androstanes and 13C3-estranes. In the first route, the targeted aldehyde 1 was obtained in 40% overall yield from 1,4-androstadien-3,17-dione (3 mmol scale) via a two-step sequence involving a one-pot, abnormal ozonolysis/sulfur oxidation/retro-Michael/ozonolysis process. Alternatively, a second route from 4-androsten-3,17-dione, using a six-step sequence, was optimized to produce 40 mmol batches of the key intermediate 1 in 42% overall yield. At the final stage, the A-ring was reconstructed through a Wittig reaction with the 1-triphenylphosphoranylidene-13C3-2-propanone 2, followed by an intramolecular condensation assisted by thioacetic acid via a Michael addition/retro-Michael reaction sequence to provide 2,3,4-13C3-1,4-androstadien-3,17-dione.