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.

本文报道了反式喹嗪啶（trans-quinolizidine）两种对映异构体(+)-桃金娘碱（(+)-myrtine）与顺式2,4,6-三取代哌啶类生物碱(+)-241D的全合成。本研究采用的合成策略基于对映纯4-哌啶酮(−)-11的N-叔丁氧羰基（N-Boc）导向金属化反应；该对映纯4-哌啶酮(−)-11可由α-氨基腈6经四步反应，通过立体选择性烷基化-还原脱氰过程制备得到。α-氨基腈6可通过4-哌啶酮(+)-5在阳极的电化学氧化反应制备。本研究中，α-苯乙胺（α-phenylethylamine, α-PEA）可实现高效的1-3位立体诱导；而哌啶酮衍生物的N-叔丁氧羰基保护基的正交脱除，则可通过将其置于四氯化锡·二乙醚（SnCl4·(Et2O)2）络合物的二乙醚悬浮液中搅拌完成。必要时，本研究采用质子核磁共振（1H NMR）与碳核磁共振（13C NMR）光谱法，以(+)-叔丁基苯基硫代膦酸（(+)-tert-butylphenylphosphinothioic acid）与(+)-二苯甲酰酒石酸（(+)-DBTA）作为手性溶剂化试剂，测定产物的对映体比例（enantiomeric ratio, er）。