Electronic Effects in Asymmetric Catalysis: Structural Studies of Precatalysts and Intermediates in Rh-Catalyzed Hydrogenation of Dimethyl Itaconate and Acetamidocinnamic Acid Derivatives Using C(2)-Symmetric Diarylphosphinite Ligands

• Published in: Journal of organic chemistry 1999-05, Vol.64 (10), p.3429-3447
• Main Authors: RajanBabu, T. V., Radetich, Branko, You, Kamfia K., Ayers, Timothy A., Casalnuovo, Albert L., Calabrese, Joseph C.
• Format: Article
• Language: English
• ISSN: 1520-6904

Enantioselectivity of Rh(I)-catalyzed asymmetric hydrogenation of dehydroamino acid derivatives and dimethyl itaconate can be enhanced by the appropriate choice of substituents on the aromatic rings of vicinal diarylphosphinites derived from carbohydrates as well as trans-cyclohexane-1,2-diol. For example, the use of phosphinites with electron-donating bis(3,5-dimethylphenyl) groups at phosphorus provide high ee's in these reactions whereas electron-withdrawing aryl substituents decrease the enantioselectivity. In this paper, an attempt is made to clarify the origin of these remarkable electronic effects at two levels. First, crystal structures of a number of precatalysts ([phosphinite](2)Rh(+)[diolefin]X(-)) were determined and their structures were studied in detail to examine the electronic effects, if any, on the ground-state conformations of these molecules. A study of six of these complexes reveals that the gross conformational features of these precatalysts are largely unaffected by electronic effects, which suggests that other explanations have to be sought for the electronic amplification of enantioselectivity. One possibility is a change in the diastereomeric equilibrium between the initially formed [substrate]Rh(+)[phosphinite] complexes as a function of electronic effect of the ligand. In the Rh-catalyzed hydrogenation of dimethyl itaconate, we have examined this equilibrium between the major and minor complexes by (31)P NMR. There is a clear difference in the ratio of these two diastereomers when 3,5-dimethylphenylphosphinite vis-à-vis the unsubstituted diphenylphosphinite is used. Electron-deficient ligands such as 1,2-bis-3,5-diflurophenylphosphinite and 1,2-bis-3,5-bis-trifluromethylphenylphosphinite appear to form these diastereomers more readily at room temperature, even though the exact ratio of the diastereomers could not be established with any certainty.