Efficient, Stereodivergent Access to 3‑Piperidinols by Traceless P(OEt)<sub>3</sub> Cyclodehydration

2016-02-18T15:03:17Z (GMT) by Peter H. Huy Ari M. P. Koskinen
A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5–6 steps), and scalable synthesis (up to 14 g) of <i>cis</i>- and <i>trans</i>-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a “traceless” (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)<sub>3</sub> as a substitute for PPh<sub>3</sub> is developed.