Electrochemical synthesis and chemistry of chiral 1-cyanotetrahydroisoquinolines. An approach to the asymmetric syntheses of the alkaloid (-)-crispine a and its natural (+)-antipode.
The stereoselective convergent total syntheses of both enantiomers of the tetrahydroisoquinoline (THIQ) alkaloid crispine A are described. The THIQ precursors (-)-6 (90:10 dr) and (-)-11 (85:15 dr) were prepared from the alkylation-reduction sequence of a common α-amino nitrile (+)-4 derivative that has been conveniently prepared by anodic cyanation. Elaboration of the pyrrolidine ring of the title compound was cleanly achieved by two efficient ring closures methods involving (a) the displacement of a halogen atom and (b) the formation of a cyclic iminium cation to afford (-)-crispine A in 90% and 85% yields, respectively. A crystallization of enantioenriched (-)-crispine A (90:10 er) with 1 equiv of (-)-DBTA afforded the tartrate salt (-)-14 (≥98:2 dr) in 81% yield. The absolute S configuration of (-)-crispine A was simply deduced from examination of the X-ray data of tartrate salt (-)-14. Likewise, the natural (+)-crispine A was prepared in seven workup steps in an overall 30% yield, and reciprocal crystallization with (+)-DBTA afforded the enantiomeric tartrate salt (+)-14 in a ≥98:2 dr. Both enantiomers of crispine A were liberated from their respective DBTA salts in ≥98:2 er's which were determined by proton and carbon NMR spectroscopy, utilizing (R)-(+)-tert-butylphenylphosphinothioic acid (+)-15 as chiral solvating agent.
Sciences Chimiques de Rennes, UMR 6226, CNRS-Université de Rennes 1, 2 Avenue Léon Bernard, 35043 Rennes Cedex, France.
Fadila
F
Louafi
Julie
J
Moreau
Saurabh
S
Shahane
Stéphane
S
Golhen
Thierry
T
Roisnel
Sourisak
S
Sinbandhit
Jean-Pierre
JP
Hurvois
D004563:Electrochemistry; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D007546:Isoquinolines; C523713:crispine A