Date of Award
Doctor of Philosophy
Levi M. Stanley
This dissertation presents the development of new catalysts for enantioselective, rhodium-catalyzed alkene hydroacylation to form polycyclic heterocyclic ketones, the first examples of nickel-catalyzed alkene carboacylation via amide C−N bond activation, and the first examples of enantioselective, intermolecular palladium-catalyzed alkene carboacylation via ester C−O bond activation.
Chapter II describes the enantioselective synthesis of polycyclic nitrogen, oxygen, and sulfur heterocycles by rhodium-catalyzed intramolecular alkene hydroacylation. The intramolecular hydroacylation reactions generate 1,4-dihydrocyclopenta[b]indol-3(2H)- ones and 3,4-dihydrocyclopenta[b]indol-1(2H)-one in moderate-to-high yields (65-99%) with good-to-excellent enantioselectivities (84-99% ee). The catalyst system also promotes alkene hydroacylation of 3-vinylfuran-, 3-vinylbenzothiophene-, and 3-vinylthiophene-2- carboxaldehydes to generate the corresponding ketone products in moderate-to-high yields (71-91% yield) with excellent enantioselectivities (97-99% ee).
Chapter III discusses nickel-catalyzed formal carboacylation of ortho- allylbenzamides with arylboronic acid pinacol esters. The reaction is triggered by oxidative addition of an activated amide C−N bond to a Ni(0) catalyst and proceeds via alkene insertion into a Ni(II)-acyl bond. The exo-selective carboacylation reaction generates 2- benzyl-2,3-dihydro-1H-inden-1-ones in moderate to high yields (46−99%) from a variety of arylboronic acid pinacol esters and substituted ortho-allylbenzamides. These results show that amides are practical substrates for alkene carboacylation via amide C−N bond activation, and this approach bypasses challenges associated with alkene carboacylation triggered by C−C bond activation.
Chapter IV describes palladium-catalyzed formal intermolecular carboacylation of aryl benzoate esters with sodium tetraarylborates and norbornene. The reaction is triggered by oxidative addition of an activated amide C−O bond to a Pd(0) catalyst and proceeds via alkene insertion into a Pd(II)-acyl bond. The three-component intermolecular carboacylation reaction generates phenyl(3-phenylbicyclo[2.2.1]heptan-2-yl)methanones in up to 99% yield with 1:1 diastereomeric ratio and in moderate to high enantiomeric excess from a variety of aryl benzoate esters and sodium tetraarylborates. These results show that esters are practical substrates for enantioselective, intermolecular alkene carboacylation via ester C−O bond activation. This approach bypasses challenges associated with alkene carboacylation triggered by C−C bond activation and expands alkene carboacylation via carbon-heteroatom bond activation beyond twisted amides.
Kevin Leon Vickerman
Vickerman, Kevin Leon, "Transition metal-catalyzed alkene hydroacylation and carboacylation" (2018). Graduate Theses and Dissertations. 17343.