title: Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared α-Amino Nitriles.
abstract: α-Amino nitrile 2a was conveniently prepared in two individual steps from chiral hexafluorophosphate salt isoquinolinium (-)-8b including anodic cyanation as an efficient means to activate the sp(3) C1-H bond of the THIQ nucleus. The lithiation of 2a was carried out in THF at -80 °C in the presence of LDA to produce a stable α-amino carbanion which was condensed on a large variety of alkyl halides. The resulting quaternary α-amino nitriles were subjected to a stereoselective reductive decyanation in ethanol in the presence of NaBH4 as the hydride donor to yield N-Boc-1-alkyl-THIQs (+)-10a-g in up to 97:3 er's after removal of the chiral auxiliary group. Examination of the ORTEP view of THIQ (+)-1f revealed that the newly created stereogenic center had an absolute S configuration. Likewise, (-)-xylopinine was synthesized in four workup steps in an overall 63% yield from α-amino nitrile (+)-2b. In this process, crystallization of an enantioenriched mixture (90:10) of (-)-norlaudanosine with 1 equiv of (-)-N-acetyl-l-leucine afforded the leucinate salt (+)-13 (99:1 dr). Similarly, (+)-salsolidine was displaced from its (-)-DBTA salt (-)-12 in 99:1 er, which was determined by proton and carbon NMR spectroscopy in the presence of thiophosphinic acid (+)-14 as the chiral solvating agent.
authors.affiliation: Laboratoire de Chimie des Matériaux, Faculté des Sciences Exactes, Université de Constantine 1 , route de Ain El Bey, 25000 Constantine, Algérie.
authors.forename: Lotfi
authors.initials: L
authors.lastname: Benmekhbi
authors.affiliation: Unité de Recherche CHEMS, Faculté des Sciences Exactes, Université de Constantine 1 , route de Ain El Bey, 25000 Constantine, Algérie.
authors.forename: Fadila
authors.initials: F
authors.lastname: Louafi
authors.affiliation: Centre de Diffractométrie X, Institut des Sciences Chimiques de Rennes, UMR CNRS 6226, CNRS-Université de Rennes 1 , Bat. 10 B, Campus de Beaulieu, Avenue du Général Leclerc, 35042 Rennes Cedex, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Roisnel
authors.affiliation: Institut des Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1 , 2 Avenue Léon Bernard, 35043, Rennes Cedex, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Hurvois
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D000478:Alkylation; D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D018360:Crystallography, X-Ray; D004566:Electrodes; D007546:Isoquinolines / Q000737:chemistry; D007930:Leucine / Q000031:analogs & derivatives / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009570:Nitriles / Q000737:chemistry*; D010084:Oxidation-Reduction; D012490:Salsoline Alkaloids; D012997:Solvents; D013237:Stereoisomerism; D044005:Tetrahydroisoquinolines / Q000737:chemistry*
chemical_list: D000470:Alkaloids; D007546:Isoquinolines; D009570:Nitriles; D012490:Salsoline Alkaloids; D012997:Solvents; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D002244:Carbon; D007930:Leucine; C088117:acetylleucine; C059665:salsolidine