Unsymmetrical Ferrocenylethylamine-Derived Monophosphoramidites:  Highly Efficient Chiral Ligands for Rh-Catalyzed Enantioselective Hydrogenation of Enamides and α-Dehydroamino Acid Derivatives

Abstract

[reaction: see text] A new family of unsymmetrical ferrocenylethylamine-derived monophosphoramidites were synthesized and successfully applied in the Rh-catalyzed enantioselective hydrogenation of a range of enamides and alpha-dehydroamino acid esters, and ee values of up to 99.5% were obtained for both types of substrate. These results suggest that unsymmetrical amine-derived monophosphoramidites can also exhibit excellent enantioselectivity for a broad range of substrates, comparable to or higher than those of the most efficient symmetrical amine-derived monophosphoramidites reported thus far.

Synthesis of Chiral, Monodentate Aminophosphane and Phosphoramidite Ligands Derived from Amino Acid Esters: Application in Rh‐Catalysed Asymmetric Olefin Hydrogenation Reactions

“…A literature survey revealed that, among this class of compounds, only Zheng's phosphoramidite 7, which is derived from an expensive ferrocenyl-amine, gave better ee's in the hydrogenation of cinammic acid esters than A. [36] Significantly lower enantioselectivities than those obtained for 3b were obtained with proline derivative 8 [25] as well as with phosphoramidite 9, [35] which contains two stereogenic centres in the amino group. Overall, these findings show that an improvement in the performances of A by using variants obtained from cheap, chiral amines remains a difficult task.…”

“…[19][20][21][22][23][24][25][26][27] In their seminal works, they independently demonstrated that these readily accessible monodentate li-ronment of the coordination sites occupied in this complex by the chlorine atoms is sterically more crowded than in 5.…”

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

“…We then initiated a study on the synthesis of a series of monodentate phosphoramidites (abbreviate as FAPhos, 22, Fig. 5) derived from unsymmetrical 1-ferrocenylethylamine and the investigation of their efficiency in the Rh-catalyzed asymmetric hydrogenation [21]. As expected, these newly developed monophosphoramidite ligands 22 showed excellent enantioselectivities for a broad range of substrates, including a-dehydroamino acids esters and aromatic enamides, providing comparable or higher efficiency than that obtained with the most efficient monophosphoramidites reported so far, with the hydrogenation performing under much milder conditions.…”

Combinatorial Transition‐Metal Catalysis: Mixing Monodentate Ligands to Control Enantio‐, Diastereo‐, and Regioselectivity

“…We have prepared more than 60 derivatives of phosphites 20 and about 10 phosphonites 21, and others have contributed as well. [66,71] It is also possible to prepare further analogues by using derivatives of binol, for example, 23, [72a] 24, [73] or 25 [74] although this entails additional synthetic effort. A fair number of phosphoramidites have also been prepared, 22 a-f being the most often used ligands in hydrogenation and in other transition-metal-catalyzed reactions.…”