109640-30-4Relevant academic research and scientific papers
Asymmetric Hydrogenation of Unfunctionalized Tetrasubstituted Acyclic Olefins
Bachmann, Stephan,Bigler, Raphael,Denmark, Scott E.,Gosselin, Francis,Han, Chong,Hildbrand, Stefan,Mack, Kyle A.,Pfaltz, Andreas,Scalone, Michelangelo,Shen, Jeff,Tosatti, Paolo,Zhang, Haiming
supporting information, p. 2844 - 2849 (2020/02/05)
Asymmetric hydrogenation has evolved as one of the most powerful tools to construct stereocenters. However, the asymmetric hydrogenation of unfunctionalized tetrasubstituted acyclic olefins remains the pinnacle of asymmetric synthesis and an unsolved challenge. We report herein the discovery of an iridium catalyst for the first, generally applicable, highly enantio- and diastereoselective hydrogenation of such olefins and the mechanistic insights of the reaction. The power of this chemistry is demonstrated by the successful hydrogenation of a wide variety of electronically and sterically diverse olefins in excellent yield and high enantio- and diastereoselectivity.
Synthesis, Conformational Considerations, and Estrogen Receptor Binding of Diastereoisomers and Enantiomers of 1-phenyl>-1,2-diphenylbutane (Dihydrotamoxifen)
McCague, Raymond,Leclercq, Guy
, p. 1761 - 1767 (2007/10/02)
As part of a study into nonisomerizable antiestrogens, the diastereoisomeric dihydrotamoxifens 7 and 8 were prepared by catalytic transfer hydrogenation of (Z)- and (E)-tamoxifen and were shown by NMR spectrometry to exist in preferred conformations with hydrogen atoms in an antiperiplanar relationship.The corresponding 4-hydroxy derivatives 9 and 10 were prepared from hydrogenated precursors of (Z)- and (E)-4-hydroxytamoxifen.The relative binding affinities (RBA) of the compounds to estrogen receptors are consistent with the assigned conformations and parallel reported data on derivatives of the nonsteroidal estrogen hexestrol.The growth-inhibitory activity against the MCF-7 human breast cancer cell line in vitro was for 10 comparable to that of 4-hydroxytamoxifen, although increasing the concentration from 10-8 to 10-6 M did not significantly improve the growth inhibition.The derivative 9 analogous to (E)-4-hydroxytamoxifen antagonized the growth-stimulating effect of added estradiol and is therefore also an antiestrogen but at low concentration (10-8 M) in the absence of estradiol, MCF-7 cell growth was stimulated, indicating an estrogenic influence.The enantiomers of the dihydrotamoxifen 8 were individually prepared from the resolved enantiomers of 2-phenylbutanoic acid, the key reaction step being a lithium-ammonia reduction of the 1-(4-methoxyphenyl)-1,2-diphenyl-1-butanol to generate the triphenylbutane.The enantiomers of 8 gave identical RBA values in cytosol.
