Stereoselective construction of a steroid 5α,7α-oxymethylene derivative and its use in the synthesis of eplerenone

A new and practical method for a stereoselective construction of a steroid 5α,7α-oxymethylene derivative has been developed and successfully applied to the stereoselective synthesis of eplerenone (8). Starting with available 11α-hydroxyl canrenone (1), eplerenone (8) was synthesised in seven steps with a 48% overall yield.

Research highlights▶ A new and practical method for a stereoselective construction of a steroid 5α,7α-oxymethylene derivative is described. ▶ 1,6-Michael addition of 9(11)-canrenone (3) with i-PrOMe2SiCH2MgCl/CuI·2LiCl or i-PrOMe2SiCH2MgCl/CuBr·Me2S catalyzed by BF3·OEt2 provides the desired 7α addition product. ▶ This method is successfully applied to the stereoselective synthesis of Eplerenone (8).