Stereoselective Synthesis of Functionalized trans-2,5-Disubstituted Tetrahydrofurans

The addition of the titanium enolates of N-acetyl, N-propionyl, and N-bromoacetyl (R)-oxazolidin-2-ones to γ-lactol 2, derived from (S)-glutamic acid, afforded trans- and cis-2,5-disubstituted tetrahydrofurans (trans/cis ratio:  R = H, 2:1; R = Me, 8:1; R = Br, 10:1) after desilylation with aqueous HF/CH3CN. Chromatographic separation and LiBH4 reduction allowed the efficient preparation of the corresponding trans-2,5-disubstituted tetrahydrofuran diols and the recovery of the chiral auxiliary.