Premium
Pd‐Catalyzed Decarboxylative Asymmetric Protonation (DAP) Using Chiral PHOX Ligands vs. Chiral Ligand‐Free Conditions Employing (1 R ,2 S )(–)‐Ephedrine – A Comparison Study
Author(s) -
James Jinju,
Akula Ramulu,
Guiry Patrick J.
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900267
Subject(s) - chemistry , aryl , cyclopentanone , protonation , substituent , ketone , steric effects , catalysis , enantioselective synthesis , asymmetric induction , cyclohexanone , ephedrine , stereochemistry , organic chemistry , medicinal chemistry , neuroscience , biology , ion , alkyl
Pd‐catalyzed decarboxylative asymmetric protonation (DAP) using (1 R ,2 S )‐(–)ephedrine as the proton source, previously developed for sterically hindered α‐aryl, lactone and dihydrocoumarin substrates, was applied to a range of α‐aryl β‐keto allyl ester substrates that were already successful in DAP with chiral P,N ‐ligands. An optimization study using a cyclopentanone‐derived α‐aryl, β‐oxo‐allyl ester with 2,4,6‐trimethoxyphenyl as the aryl substituent afforded high levels of enantioselectivity (91 % ee ). This encouraged us to examine other α‐aryl, β‐keto‐allyl ester substrates. The results from this substrate scope study with α‐aryl, cyclohexanone‐, isoflavanone‐, indanone‐, and tetralone‐derived substrates using (1 R ,2 S )‐(–)ephedrine as the protonating agent under Pd catalysis, compared favorably with enantioselectivities obtained in DAP reactions induced by Pd complexes of chiral ligands.