Asymmetric Syntheses of 3‑Deoxy-3-aminosphingoid Bases: Approaches Based on Parallel Kinetic Resolution and Double Asymmetric Induction

The
asymmetric syntheses of a range of N- and O-protected 3-deoxy-3-aminosphingoid bases have been achieved
using two complementary approaches. dl-Serine was converted
to a racemic N,N-dibenzyl-protected
γ-amino-α,β-unsaturated ester which was resolved
using a parallel kinetic resolution (PKR) strategy upon reaction with
a pseudoenantiomeric mixture of lithium (R)-N-benzyl-N-(α-methyl­benzyl)­amide
and lithium (S)-N-3,4-dimethoxybenzyl-N-(α-methyl­benzyl)­amide, giving the corresponding
enantio- and diastereoisomerically pure β,γ-diamino esters.
Alternatively, elaboration of l-serine gave the corresponding
enantiopure N,N-dibenzyl-protected
γ-amino-α,β-unsaturated ester, and doubly diastereoselective
conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)­amide was found to proceed under
the dominant stereocontrol of the lithium amide reagent in both cases,
thus augmenting the accessible range of β,γ-diamino esters.
Both of these protocols were expanded to include in situ oxidation
of the enolate formed upon conjugate addition, giving access to the
corresponding α-hydroxy-β,γ-diamino esters. Elaboration
of these β,γ-diamino and α-hydroxy-β,γ-diamino
esters gave the protected forms of the 3-deoxy-3-aminosphingoid base
targets.