Synthesis of Enantioenriched β-Aryl-β-aryloxy Esters via Sequential Photoisomerization and Enantioselective
Elizabeth C Swift1, Shashank Shekhar1, Brian J Kotecki1
1AbbVie, Inc., Process Research and Development, 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
Abstract:
A general method to prepare valuable chiral synthon β-aryl-β-aryloxy esters from enantioselective hydrogenation of (E)-β-aryl-β-aryloxy-α,β-unsaturated esters is described. The E-isomer was prepared via isomerization of the mixture of E- and Z-isomers using photocatalyst [Ir(ppy)2(dtbbpy)]PF6. A laser as the light source facilitated isomerization with only 0.05 mol % catalyst. The enantioselective hydrogenation was conducted with (NBD)2Rh(BF4) and a commercially available Josiphos ligand to provide the synthons in up to 95% yield with 97% ee.
Related Concept Videos
02:17Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
01:07Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
01:14Alkylation of β-Diester Enolates: Malonic Ester Synthesis
01:12Stereochemical Effects of Enolization
02:36Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...