Utilization of industrial waste materials, 7: Synthesis of new, chiral β-sec-amino alcohols - regio- and diastereoselective α-hydroxyalkylation of (1R,5R)-2-azabicyclo[3.3.0]octane

Article abstract of DOI:10.1002/jlac.199719970318

New, chiral β-sec-amino alcohols 3a-d, 4a-e, and 5a-h have been synthesized from the enantiomerically pure amine (all-R)-2a. For the diastereo- and regioselective α-hydroxyaklyation of the chiral (all-R)-N-nitroso-2-azabicyclo[3.3.0]octane (all-R)-2d, Seebach's "one pot" method was chosen. The versatile nucleophilic intermediate reacts regio-and stereoselectively with a variety of electrophiles to afford 3-substituted pyrrolidine derivatives, e.g. (erythro)-(αR,βS)-amino alcohol frameworks with four sterically crowded stereogenic centers, and (βS)-configured tricyclic structures with a cycloalkynol building block (see formulae 3a-d, 4a-e, and 5a-h). Alkylation products are obtained in fair yields with a high degree of stereoselectivity (diastereomeric ratios dr up to 93:7). A mechanistic interpretation of the stereochemical course of this reaction is presented. - This is a further example of the synthesis of interesting new chiral ligands from the industrial waste material (all-R)-2-azabicyclo[3.3.0]octane-3-carboxylic acid benzyl ester (all-R)-1a. The catalytic ability of selected (erythro)- and new, related stereoisomeric amino alcohol structures were tested in the enantioselective borane reduction using the prochiral acetophenone as model substrate (enantiomeric excesses ee up to 86%). VCH Verlagsgesellschaft mbH, 1997.