title: 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 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.
authors.affiliation: Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1 , 2 Avenue Leon Bernard, 35043 Rennes Cedex, France.
authors.forename: Van Ha
authors.initials: VH
authors.lastname: Vu
authors.forename: Fadila
authors.initials: F
authors.lastname: Louafi
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Ronan
authors.initials: R
authors.lastname: Marion
authors.forename: Thierry
authors.initials: T
authors.lastname: Roisnel
authors.forename: Vincent
authors.initials: V
authors.lastname: Dorcet
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hurvois
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D004563:Electrochemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry*; D011807:Quinolizines / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C000592672:8-(1-phenyl-ethyl)-1,4-dioxa-8-aza-spiro(4.5)decane-7-carbonitrile; D000470:Alkaloids; D009570:Nitriles; D011807:Quinolizines; D013141:Spiro Compounds; C519820:myrtine