179237-91-3Relevant academic research and scientific papers
The palladium-catalyzed aerobic kinetic resolution of secondary alcohols: Reaction development, scope, and applications
Ebner, David C.,Bagdanoff, Jeffrey T.,Ferreira, Eric M.,McFadden, Ryan M.,Caspi, Daniel D.,Trend, Raissa M.,Stoltz, Brian M.
supporting information; experimental part, p. 12978 - 12992 (2010/06/19)
The first palladium-catalyzed enantioselective oxidation of secondary alcohols has been developed, utilizing the readily available diamine (-)-sparteine as a chiral ligand and molecular oxygen as the stoichiometric oxidant. Mechanistic insights regarding the role of the base and hydrogen-bond donors have resulted in several improvements to the original system. Namely, addition of cesium carbonate and tert-butyl alcohol greatly enhances reaction rates, promoting rapid resolutions. The use of chloroform as solvent allows the use of ambient air as the terminal oxidant at 23°C, resulting in enhanced catalyst selectivity. These improved reaction conditions have permitted the successful kinetic resolution of benzylic, allylic, and cyclopropyl secondary alcohols to high enantiomeric excess with good-toexcellent selectivity factors. This catalyst system has also been applied to the desymmetrization of meso-diols, providing high yields of enantioenriched hydroxyketones.
Asymmetric synthesis of antimicrotubule biaryl hybrids of allocolchicine and steganacin
Joncour, Agnes,Decor, Anne,Liu, Jian-Miao,Tran Huu Dau, Marie-Elise,Baudoin, Olivier
, p. 5450 - 5465 (2008/03/12)
The asymmetric synthesis of novel axially chiral hiaryl compounds 5 a-f containing a seven- or eight-memhered heterocyclic medium ring is described. These molecules can he considered to he structural hybrids of allocolchicine- and sleganacin-lype natural products. The synthesis featured an atropo-diastereoselective biaryl Suzuki coupling in which a benzylic stereocenter efficiently transferred its stereochemical information to the biaryl axis. The coupling conditions were optimized. and two biphenylphosphane ligands (DavePhos and S-Phos) were found to give Ihe highest yields and diastereoselectivities. A three-element stereochemical model was proposed to explain the observed diastereoselectivities. In a second key step, the medium ring of the target molecules was formed by a stercoselective SN1-type cyclodehydration that probably involved a configurationally stable carbocationic intermediate, as supported by calculations. Alternatively. S N2-type cyclizations were employed on the same Suzuki coupling products to give the target molecules in a stereodivergent or stereoconvergent manner. These cyclization methods furnished the target hybrid analogues 5 a-f with ee values above 94%. All analogues were evaluated as antimicrotubule agents and against a panel of cancer-cell lines using colchicine (1) and N-acetylcolchinol (3) as references. Promising activities were found for R,a R-configured compounds 5 a, b and 5 f; in particular, ethyl analogue 5 b showed a twofold antimicrotubule activity relative to colchicine.
Biaryl axis as a stereochemical relay for the enantioselective synthesis of antimicrotubule agents
Joncour, Agnes,Decor, Anne,Thoret, Sylviane,Chiaroni, Angele,Baudoin, Olivier
, p. 4149 - 4152 (2007/10/03)
(Chemical Equation Presented) Return to sender: A biaryl configuration that is controlled by a benzylic stereocenter in an atropo-selective Suzuki coupling in turn controls the stereocenter configuration in an SN1-type dehydrative cyclization performed at low temperature. Promising antimicrotubule biaryls of high optical purity are obtained in this manner. TFA = trifluoroacetic acid, pin = pinacolato.
