Intermolecular Noncovalent Hydroxy-Directed Enantioselective Heck Desymmetrization of Cyclopentenol: Computationally Driven Synthesis of Highly Functionalized cis-4-Arylcyclopentenol Scaffolds.
J Org Chem
; 81(5): 2010-8, 2016 Mar 04.
Article
em En
| MEDLINE
| ID: mdl-26836260
ABSTRACT
New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck-Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a-l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck-Matsuda desymmetrization of 3-cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4-arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons.
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Base de dados:
MEDLINE
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Brasil