Iterative Methodology for the Stereocontrolled Synthesis of Polyol Chains Employing 2-Acetylthiazole as Lactaldehyde Equivalent

The anti-diastereoselective addition (ds 90-92%) of the lithium enolate of 2-acetylthiazole to chiral (poly)alkoxy aldehydes and the stereocontrolled ketone reduction of the resultant aldols using diisobutylaluminum hydride/tetramethylammonium triacetoxyborohydride followed by the aldehyde unmasking from the thiazolering, afford three-carbon higher homologue aldehydes bearing a syn-or anti-1,3-diol unit. The iterative repetition of the sequence provides a route to polyhydroxylated chains having 1,3- and 1,2-diol units. In this methodology 2-acetylthiazole serves as the surrogate of lactaldehyde and its lithium enolate as the equivalent of the α-hydroxypropanal β-anion synthon.