Asymmetric conjugate reductions of coumarins. A new route to tolterodine and related coumarin derivatives.
The combination of catalytic amounts of [(R)-DTBM-SEGPHOS]CuH in the presence of stoichiometric DEMS (diethoxymethylsilane) in toluene at room temperature leads to asymmetric reductions of 4-substituted coumarins. Several targets or their known precursors can be prepared in high yields and ee's, including the muscarine receptor antagonist (R)-tolterodine.
Gallagher
Brian D
BD
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA.
Taft
Benjamin R
BR
Lipshutz
Bruce H
BH
D001559:Benzhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003408:Cresols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D010084:Oxidation-Reduction; D010665:Phenylpropanolamine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists; D013237:Stereoisomerism; D000068737:Tolterodine Tartrate
D001559:Benzhydryl Compounds; D003374:Coumarins; D003408:Cresols; C473034:FFAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D010665:Phenylpropanolamine; D000068737:Tolterodine Tartrate