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)