%0 Journal Article %T Synthesis of Tetrahydroisoquinoline Alkaloids and Related Compounds through the Alkylation of Anodically Prepared α-Amino Nitriles %+ Institut des Sciences Chimiques de Rennes (ISCR) %A Benmekhbi, L. %A Louafi, F. %A Roisnel, T. %A Hurvois, J.-P. %< avec comité de lecture %@ 0022-3263 %J Journal of Organic Chemistry %I American Chemical Society %V 81 %N 15 %P 6721--6739 %8 2016 %D 2016 %R 10.1021/acs.joc.6b01419 %M 27410716 %K Chiral solvating agents %K Chiral auxiliaries %K Anodic cyanation %K Stereo-selective %K Hexafluorophosphate salt %K Related compounds %K Amino acids %K Carbon %K Nuclear magnetic resonance spectroscopy %K Stereogenic centers %K Tetrahydroisoquinolines %K Cyanides %Z Chemical SciencesJournal articles %X 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 sp3 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. %G English %L hal-01367242 %U https://univ-rennes.hal.science/hal-01367242 %~ UNIV-RENNES1 %~ CNRS %~ INSA-RENNES %~ ENSC-RENNES %~ ISCR %~ SCR-CD %~ SCR-PNSCM %~ STATS-UR1 %~ UR1-SPM %~ ISCR-PRATS %~ INC-CNRS %~ UR1-UFR-SPM %~ UR1-HAL %~ ISCR-CORINT %~ UR1-SDLM %~ TEST-UNIV-RENNES %~ TEST-UR-CSS %~ UNIV-RENNES %~ INSA-GROUPE %~ UR1-MMS %~ ISCR-CORINT3 %~ TEST2-HALCNRS