Electrochemical Access to 8‑(1-Phenyl-ethyl)-1,4-dioxa-8-aza-spiro[4.5]decane-7-carbonitrile. Application to the Asymmetric Syntheses of (+)-Myrtine and Alkaloid (+)-241D

Abstract

The total syntheses of both enantiomers of <i>trans</i>-quinolizidine (+)-myrtine and <i>cis</i>-2,4,6-trisubstituted piperidine alkaloid (+)-241D are reported here. Our approach was based on the <i>N</i>-Boc-directed metalation of enantiopure 4-piperidone (−)-<b>11</b>, which was prepared in four steps from α-amino nitrile <b>6</b> through a stereoselective alkylation–reduction decyanation process. α-Amino nitrile <b>6</b> was prepared at the anode through electrochemical oxidation of 4-piperidone (+)-<b>5</b>. In our study, α-phenylethylamine (α-PEA) allowed an efficient 1–3 stereoinduction, and an orthogonal cleavage of the <i>N</i>-Boc protecting group in piperidone derivatives was carried out by stirring them in a suspension of SnCl₄·(Et₂O)₂ complex in diethyl ether. When appropriate, the er’s were determined by proton and carbon NMR spectroscopy utilizing (+)-<i>tert</i>-butylphenylphosphinothioic acid and (+)-DBTA as chiral solvating agents