Q8(c). Birch-type reduction of α-cyperone: trans ring fusion

Introduction. Sodium in liquid ammonia reduces the conjugated C=C of an α,β-unsaturated ketone; the isolated isopropenyl group is not touched. In fused bicyclic enones the new C–H at the ring junction is formed so that the trans-decalone results.

Scheme: The angular methyl and H-5 end up trans; the C-4 methyl takes the equatorial position.

1. First electron: Na gives an electron to the enone LUMO; the radical anion has spin and charge spread over C-3 (O), C-4 and C-5.
2. Protonation at C-5 (β-carbon) by NH₃; a second electron converts the radical into a carbanion, i.e. the enolate (C3–C4).
3. Stereochemistry: the β-carbanion/radical centre takes up the proton (or electron pair) in the axial orientation that is perpendicular to the enolate π system (stereoelectronic control), and the ring junction formed is trans (H-5α, opposite to the 10β-methyl): the more stable trans-decalin.
4. Work-up: NH₄Cl protonates the enolate at C-4; the product isolated has the C-4 methyl equatorial (4α), the more stable epimer.
5. The isopropenyl C=C is isolated (no conjugation) and survives; the C=O survives as the enolate.

Conclusion. Product: trans-fused 4α,10β-dimethyl-7β-isopropenyl-decalin-3-one (dihydro-α-cyperone, C₁₅H₂₄O): conjugate reduction by two electrons and two protons, H-5 trans to the angular methyl.

Application. Lithium/ammonia reduction of steroid and terpene enones (Stork) is the standard way to set trans A/B ring fusions, e.g. in making 5α-androstan-3-ones from testosterone.