A New Approach to the Total Synthesis of Rosuvastatin

A new multi‐step synthesis of the lipid‐lowering agent rosuvastatin, involving two homogeneously catalyzed reaction steps, is described. The key building block, N‐[4‐(4‐fluorophenyl)‐5‐formyl‐6‐isopropylpyrimidin‐2‐yl]‐N‐methylmethanesulfonamide (2), was prepared by Pd‐catalyzed formylation with CO/H2 (1:1, 50 bar, phosphane ligand/substrate ratio of 1:10). Several alternative pathways for the preparation of 2 were also tested, but were found to be inferior. Rosuvastatin precursor 1 was assembled by Wittig coupling of aldehyde 2 and ylide (R)‐3, derived from a Ru‐catalyzed asymmetric hydrogenation. The second stereogenic center was finally created by stereoselective reduction with Et2BOMe and NaBH4 to afford rosuvastatin ethyl ester. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)