245672-30-4Relevant academic research and scientific papers
Catalytic Enantioselective Birch–Heck Sequence for the Synthesis of Phenanthridinone Derivatives with an All-Carbon Quaternary Stereocenter
Sexton, Mary,Malachowski, William P.,Yap, Glenn P. A.,Rachii, Diana,Feldman, Greg,Krasley, Andrew T.,Chen, Zhilin,Tran, My Anh,Wiley, Kalyn,Matei, Alexandra,Petersen, Samantha,Tien, Sabrina Tran
, p. 1154 - 1172 (2022/01/20)
Novel phenanthridinone analogues with an all-carbon quaternary stereocenter have been enantioselectively synthesized using the Birch–Heck sequence. Flat phenanthridinone structures have extensive bioactivity but consequently also suffer from poor therapeutic selectivity. The addition of a quaternary center to the phenanthridinone skeleton has the potential to generate more complex analogues with improved selectivity. Unfortunately, no general synthetic pathway to such derivatives exists. Herein we report a four-step process that transforms inexpensive benzoic acid into 22 different quaternary carbon-containing phenanthridinone analogues with a variety of substituents on all three rings: alkyl groups at the quaternary center; methyl, methoxymethyl, or para-methoxybenzyl on the amide nitrogen; and halogen and methyl substituents on the aryl ring. Good to very good enantioselectivity was demonstrated in the key intramolecular desymmetrizing Mizoroki–Heck reaction. Transformations of the Heck reaction products into molecules with potentially greater therapeutic relevance were also accomplished.
Homolytic dissociation of 1-substituted cyclohexa-2,5-diene-1-carboxylic acids: An EPR spectroscopic study of chain propagation
Jackson, Leon V.,Walton, John C.
, p. 1758 - 1764 (2007/10/03)
Hydrogen abstraction from 1-substituted cyclohexa-2,5-diene-1-carboxylic acids containing linear, branched and cyclic alkyl substituents, as well as allyl, propargyl (prop-2-ynyl), cyanomethyl and benzyl substituents, has been studied by EPR spectroscopy. For each carboxylic acid, EPR spectra of the corresponding cyclohexadienyl radicals were observed at lower temperatures, followed by spectra due to ejected carbon-centred radicals at higher temperatures. Rate constants, for release of the carbon-centred radicals from the cyclohexadienyl radicals, were determined from radical concentration measurements for the above range of substituents. The rate of cyclohexadienyl radical dissociation increased with branching in the 1-alkyl substituent and with electron delocalisation in the ejected carbon-centred radical; 3,5-and 2,6-dimethyl-substitution of the cyclohexadienyl ring led to reductions in the dissociation rate constants. Rate data for abstraction of bisallylic hydrogens from the cyclohexadienyl acids were also obtained for ethyl, n-propyl and isopropyl radicals. These results indicated a sharp drop in the rate of hydrogen abstraction as the degree of branching in the attacking radical increased. Small decreases in the hydrogen abstraction rate constants were observed for cyclohexadienes containing CO2R substituents.
Intramolecular conjugate addition reactions of amines and carbamates to 2,5-cyclohexadien-1-ones: Stereoselective synthesis of perhydroindoles
Bland, Douglas,Chambournier, Gilles,Dragan, Vladimir,Hart, David J.
, p. 8953 - 8966 (2007/10/03)
Intramolecular conjugate addition reactions of 4,4-disubstituted-2,5- cyclohexadien-1-ones are described within the context of possible approaches to manzamine A. Amine 4 provided tricycle 6, with improper relative stereochemistry for use in an approach to manzamine A. Carbamates 25 and 38 gave perhydroindoles 26 and 28 b under conditions of thermodynamic control, respectively, with the proper relative stereochemistry required for manzamine A. Carbamate 25 gave diastereomeric perhydroindole 27 under conditions of thermodynamic control.
