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

The
total syntheses of both enantiomers of trans-quinolizidine
(+)-myrtine and cis-2,4,6-trisubstituted piperidine
alkaloid (+)-241D are reported here. Our approach was based on the N-Boc-directed metalation of enantiopure 4-piperidone (−)-11, which was prepared in four steps from α-amino nitrile 6 through a stereoselective alkylation–reduction decyanation
process. α-Amino nitrile 6 was prepared at the
anode through electrochemical oxidation of 4-piperidone (+)-5. In our study, α-phenylethylamine (α-PEA) allowed
an efficient 1–3 stereoinduction, and an orthogonal cleavage
of the N-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 (+)-tert-butylphenylphosphinothioic
acid and (+)-DBTA as chiral solvating agents.