Utilization of Industrial Waste Materials, 10. – Synthesis of New Chiral Bicyclic 3‐hydroxypiperidines – Highly Diastereoselective Ring Expansion of the Azabicyclo[3.3.0]octane System to Chiral Piperidine Derivatives

Abstract

AbstractNew, chiral bicyclic 3‐hydroxypiperidines (4S)‐2a–e are synthesized from the β‐amino alcohols (3R)‐1a–e. In an one‐step reaction (4S)‐2a–e are obtained by a high diastereoselective ring expansion (dr ⩾ 95:5). As well, the amino alcohol (3S)‐1a leads to the corresponding rearranged epimer bicyclic piperidine derivative (4R)‐2a (dr ⩾ 95:5). Thus, it is possible to clarify the influence of the three stereogenic centers of the parent compound regarding the diastereoselectivity of the ring expansion. After oxidation of the tert‐amino sec‐alcohol (4S)‐2a to the corresponding α‐amino ketone 4, new 3‐hydroxypiperidines (4Ξ)‐5a, b12 and (4RS)‐6 are obtained by a diastereoselective Grignard addition. Furthermore, the achiral and the chiral reduction of 4 to the β‐amino alcohols (4S)‐2a and (4R)‐2a is described. These are further examples of the utilization of industrial waste material (all‐R)‐2‐azabicyclo[3.3.0]octane‐3‐carboxylic acid (all‐R)‐3.