Facile and Highly Diastereoselective Synthesis of syn- and cis-1,2-Diol Derivatives from Protected -Hydroxy Ketones

An efficient method for the synthesis of monoprotected syn- or cis-1,2-diol derivatives by reduction of easily accessible -(2,2,6,6-tetramethylpiperidinyloxy) ketones is reported. The -(tetramethylpiperidinyloxy) group as the stereodirecting group induces in unhindered acyclic or cyclic ketones complete syn- or cis-diastereoselectivity, respectively, with L-Selectride. For more hindered derivatives, where L-Selectride becomes unreactive, LiAlH4 proved effective, essentially showing the same high selectivity. The diastereoselectivity of the reduction can be rationalized for acyclic ketones by the Felkin-Anh model, whereas for cyclic substrates, attack from the face opposite to the tetramethylpiperidinyloxy group predictably prevails with high selectivity regardless of the substitution pattern. The liberation of free diols was achieved by reductive N-O bond cleavage of the alkoxyamine unit.