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

Pauline Chaumont-Olive (1) , Jérôme Baudoux (2) , Jacques Maddaluno (3, 1) , Jacques Rouden (2) , Anne Harrison-Marchand (1)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 LCMT - Laboratoire de chimie moléculaire et thioorganique
3 INC-CNRS - Institut de Chimie - CNRS Chimie

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.

Domaines: Chimie organique

Pauline Chaumont-Olive, Jérôme Baudoux, Jacques Maddaluno, Jacques Rouden, Anne Harrison-Marchand. Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct. Journal of Organic Chemistry, 2018, 83 (15), pp.8081-8091. ⟨10.1021/acs.joc.8b00901⟩. ⟨hal-02019133⟩