Asymmetric conjugate reductions of coumarins. A new route to tolterodine and related coumarin derivatives

Org Lett. 2009 Dec 3;11(23):5374-7. doi: 10.1021/ol9020404.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Benzhydryl Compounds / chemical synthesis*
  • Benzhydryl Compounds / chemistry
  • Benzhydryl Compounds / pharmacology
  • Catalysis
  • Coumarins / chemical synthesis
  • Coumarins / chemistry*
  • Coumarins / pharmacology
  • Cresols / chemical synthesis*
  • Cresols / chemistry
  • Cresols / pharmacology
  • Cyclization
  • Oxidation-Reduction
  • Phenylpropanolamine / chemical synthesis*
  • Phenylpropanolamine / chemistry
  • Phenylpropanolamine / pharmacology
  • Receptors, G-Protein-Coupled / agonists
  • Stereoisomerism
  • Tolterodine Tartrate

Substances

  • Benzhydryl Compounds
  • Coumarins
  • Cresols
  • FFAR1 protein, human
  • Receptors, G-Protein-Coupled
  • Phenylpropanolamine
  • Tolterodine Tartrate