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

✍ Scribed by Wilken, Jörg ;Kossenjans, Michael ;Saak, Wolfgang ;Haase, Detlev ;Pohl, Siegfried ;Martens, Jürgen

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 725 KB
• Volume: 1997
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199719970319

✦ Synopsis

Abstract

New, chiral bicyclic 3‐hydroxypiperidines (4__S__)‐2a–e are synthesized from the β‐amino alcohols (3__R__)‐1a–e. In an one‐step reaction (4__S__)‐2a–e are obtained by a high diastereoselective ring expansion (dr ⩾ 95:5). As well, the amino alcohol (3__S__)‐1a leads to the corresponding rearranged epimer bicyclic piperidine derivative (4__R__)‐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 (4__S__)‐2a to the corresponding α‐amino ketone 4, new 3‐hydroxypiperidines (4__Ξ__)‐5a, b^12^ and (4__RS__)‐6 are obtained by a diastereoselective Grignard addition. Furthermore, the achiral and the chiral reduction of 4 to the β‐amino alcohols (4__S__)‐2a and (4__R__)‐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.