Access to Anti or Syn 2‑Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct

A straightforward
synthetic pathway allowing the access to anti
or syn 2-amino-1,3-diol scaffolds is presented. The strategy relies
on a diastereoselective organocatalyzed decarboxylative aldol reaction
of a N-Boc-hemimalonate that is easily formed from
commercial N-Boc-diethyl malonate. Although this
method has been optimized previously with the N-Bz-hemimalonate
analogue, this key step was reinvestigated with the N-Boc derivative to improve the required reaction time, the yield,
and the diastereoselectivity. The new conditions enhance this transformation,
and quantitative yields and anti/syn ratios up to 96:4 can be obtained.
The anti aldol product was easily isolated in pure form and then taken
forward as the key precursor in the preparation of both a set of ten
N-/O-alkylated anti 2-amino-1,3-diol derivatives and the syn congeners.