Synthesis of aromatic sphingosine analogues by diastereoselective amination of enantioenriched trans-γ,δ-unsaturated β-hydroxyesters.

An effective route to N-Boc-protected aromatic sphingosine analogues is accomplished. The strategy is based on the diastereoselective amination of enantioenriched trans-γ,δ-unsaturated β-hydroxyesters to establish anti,N-Boc-α-hydrazino-β-hydroxyesters. Nonreductive E1cB elimination is essential for the successful N-N bond cleavage of hydrazine while preserving the trans double bond. Either the (3R,2S) and (3S,2R) enantiomer of N-Boc-protected sphingosine analogues has been synthesized in five steps with excellent optical purity with ∼99% ee and >99% de.