Chelation-Controlled Reduction:  Stereoselective Formation of syn-1,3-Diols and Synthesis of Compactin and Mevinolin Lactone

Chelation-controlled reduction of chiral beta-alkoxy ketones containing a competing beta'-oxygen functionality has been investigated. Various syn-1,3-diols were prepared conveniently by reduction of beta-alkoxy ketones with LiI/LiAlH(4) (syn:anti selectivity up to >99:1). The corresponding beta-alkoxy ketones were derived from nitro-aldol reactions of chiral alkoxy aldehydes with a series of nitro compounds. This methodology is utilized in a short and efficient synthesis of the delta-lactone moiety of the HMG-CoA reductase inhibitors compactin and mevinolin.