Diastereo- and Enantioselective Synthesis of Vicinal Amino Alcohols by Oxa Michael Addition ofN-Formylnorephedrine to Nitro Alkenes

Abstract

The first intermolecular asymmetric oxa Michael additions with removable chirality information within the hydroxide source are reported. As enantiopure oxygen nucleophile functioning as chiral hydroxide equivalent N-formylnorephedrine (7) was used and conjugate additions to aliphatic (E)-nitro alkenes 2a–j were carried out in good yields (35-87%) and excellent diastereomeric excesses (de = 94–≥98%). After reduction of the nitro group and protection of the amino function (11a–h, 73-87%, both steps), the cleavage of the auxiliary occurred without epimerisation (69-99%) using Na/NH3. The Boc-protected 2-amino alcohols 12a–h could be obtained in good overall yields (30-58 %, four steps) and excellent diastereomeric and enantiomeric excesses (de, ee = 94–≥98%). Transition states explaining the overall stereochemical outcome are presented based on the absolute configuration determined by X-ray structure analysis on 8b.