Crystallographic Evidence of [1,5]Prototropic Shifts Occurring upon Transannular Diels–Alder Reaction of a 14-Membered Macrocycle leading to a 5α-Steroid Skeleton

Reversible prototropic shifts from a stable 14-membered ring macrocycle (4Z,10E,12Z)-[1R^*,14S^*]-1,8,8-tris(methoxycarbonyl)-5-methyl-3,17- dioxobicyclo[12.3.0]heptadeca-4,10,12-triene, C₂₄H₃₀O₈, occurred when the compound was heated to form rac-(5Z,11Z,13Z)-1,8,8-tris(methoxycarbonyl)-5-methyl-3,17-dioxobicyclo[12.3.0]heptadeca-5,11,13-triene, C₂₄H₃₀O₈. The resulting compound crystallizes in a highly disordered fashion. After a transannular Diels-Alder reaction, the resulting adduct rac-3,3-bis­(methoxycarbonyl)-18- oxo-5α,9β-androst-6-en-11,17-dione, C₂₄H₃₀O₈, was then easily converted to a 5α-steroid core, rac-3,3-bis(methoxycarbonyl)-18-oxo-5α-androst-6-en-11,17-dione, C₂₄H₃₀O₈. The final adduct is an highly advanced intermediate for the total synthesis of naturally occurring aldosterone.

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