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Updated: Feb 8, 2026

Retropinacol/Cross-pinacol Coupling Reactions - A Catalytic Access to 1,2-Unsymmetrical Diols
Published on: April 4, 2014
Access to Anti or Syn 2-Amino-1,3-diol Scaffolds from a Common Decarboxylative Aldol Adduct
Pauline Chaumont1, Jérome Baudoux2, Jacques Maddaluno1
1Laboratoire COBRA (UMR 6014 & FR 3038) , Normandie Université, UNIROUEN, INSA Rouen, CNRS , 76000 Rouen , France.
Abstract:
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.
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The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.

