Diastereo‐ and Enantioselective Synthesis of 1,2‐Amino Alcohols from Glycol Aldehyde Hydrazones; Asymmetric Synthesis of (<i>R,R</i>)‐Statin

Abstract

Electrophilic α-alkylation and nucleophilic 1,2-addition to glycol aldehyde 1 (P = protecting group) affords syn-1,2-amino alcohols 2 in good yields and with high selectivities (89 to <99% de, 94 to ≥99% ee). This method, in which 1 is first converted into a chiral hydrazone, provides a flexible, direct route to γ-amino-β-hydroxycarboxylic acids such as statin 3, an essential component in natural peptidic enzyme inhibitors (R1 = CH2 = CHCH2, R2 = iBu).