Asymmetric Synthesis of 2‐Amino‐1,3‐diols and D ‐erythro‐Sphinganine

The asymmetric synthesis of protected 2‐amino‐1,3‐diols (S,R)‐5 starting from 2,2‐dimethyl‐1,3‐dioxan‐5‐one is described. The stereogenic centres are generated by α‐alkylation using the SAMP/RAMP hydrazone methodology and diastereoselective reduction of the ketones (S)‐2 with L‐selectride. The resulting alcohols (S,S)‐3 are converted into the amines (S,R)‐4 by nucleophilic substitution with sodium azide and subsequent reduction with lithium aluminium hydride. The products are obtained in high diastereomeric and enantiomeric excesses (de ⩾ 96%, ee = 90−94%). By employing this methodology, the ammonium salt of D‐erythro‐sphinganine (R,S)‐11 was synthesised starting from RAMP‐hydrazone (R)‐1 in 47% overall yield and with excellent diastereomeric and enantiomeric excess (de, ee ⩾ 96%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)