Asymmetric Synthesis of Pyrrolidinoindolines. Application for the Practical Total Synthesis of (−)-Phenserine
- 12 October 2004
- journal article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 126 (43) , 14043-14053
- https://doi.org/10.1021/ja046690e
Abstract
A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted pyrrolidinoindolines is described in which diastereoselective dialkylation of enantiopure ditriflate 10 with oxindole enolates is the central step. These reactions are rare examples of alkylations of prostereogenic enolates with chiral sp3 electrophiles that proceed with high facial selectivity (10−20:1). The scope of this method is explored, and a model to rationalize the sense of stereoselection is advanced. This dialkylation chemistry was used to synthesize (−)-phenserine on a multigram scale in six steps and 43% overall yield from 5-methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis of (−)-physostigmine (2).Keywords
This publication has 25 references indexed in Scilit:
- Catalytic Asymmetric Synthesis of Quaternary Carbons Bearing Two Aryl Substituents. Enantioselective Synthesis of 3-Alkyl-3-Aryl Oxindoles by Catalytic Asymmetric Intramolecular Heck ReactionsJournal of the American Chemical Society, 2003
- Total Synthesis of (−)-Horsfiline via Asymmetric NitroolefinationThe Journal of Organic Chemistry, 1999
- Kinetics of Human Erythrocyte Acetylcholinesterase Inhibition by a Novel Derivative of Physostigmine: PhenserineBiochemical and Biophysical Research Communications, 1998
- A Convenient Methodology for the N-Alkylation of Isatin CompoundsSynthetic Communications, 1998
- A New Efficient and Mild Synthesis of 2-Sxindoles by One-Pot Wolff-Kishner Like Reduction of Isatin DerivativesSynthetic Communications, 1994
- Selective Reduction of Diaryl or Aryl Alkyl Alcohols in the Presence of Primary Hydroxyl or Ester Groups by Etherated Boron Trifluoride-Triethylsilane SystemSynthetic Communications, 1988
- Aromatization of aliphatic compounds. VII. Benzofuranones, indoles and oxindolesJournal of Heterocyclic Chemistry, 1982
- Total synthesis of racemic sesbanineThe Journal of Organic Chemistry, 1980
- Generation of azasulfonium salts from halogen-sulfide complexes and anilines. Synthesis of indoles, oxindoles, and alkylated aromatic amines bearing cation stabilizing substituentsJournal of the American Chemical Society, 1974
- Ueber die Bohne von CalabarEuropean Journal of Organic Chemistry, 1864