Synthesis of a Bulky and Electron-Rich Derivative of SEGPhos and Its Application in Ru-Catalyzed Enantioselective Hydrogenation of β-Ketoesters

Abstract

The synthesis and resolution of a bulky and electron-rich derivative of SEGPhos and its application in Ru-catalyzed asymmetric hydrogenation reaction of beta-ketoesters are reported. Up to 99.5% ee was achieved. Under solvent-free reaction conditions, acetoacetates could be reduced with good enantioselectivity and high efficiency; a TON of 20 000 was obtained within 3.5 h. The results obtained were comparable to those when SEGPhos was applied.

Ir-catalyzed asymmetric hydrogenation of β-keto esters with chiral ferrocenyl P,N,N-ligands

“…Although the results are not super than the best ruthenium catalysts reported, it represents a new catalyst system. [3][4][5][6][7][8][9][10][11][12][13][14][15] It is noteworthy that the steric and electronic effects of the group on the phenyl ring had important inuence on the enantioselectivities.…”

“…Since this pioneering work, a large number of chiral ligands such as Synphos, 5 diuorphos, 6 Tunephos, 7 Segphos, 8 Solphos, 9 P-Phos, 10 PQ-Phos, 11 MeO-Naphephos, 12 Taniaphos,…”

Asymmetric synthesis of (S)-ethyl-4-chloro-3-hydroxybutanoate using Candida parapsilosis ATCC 7330

“…The preferred method for the synthesis of optically active ethyl-4-chloro-3-hydroxybutanoate is asymmetric reduction of prochiral ethyl-4-chloro-3-oxobutanoate (COBE) and is known to be carried out by chemical catalysts [3][4][5][6] and biocatalysts [7][8][9][10]. The intrinsic advantage of the asymmetric reduction is that its yield could be 100%, whereas the yield of resolution can not be more than 50%.…”

Palladium‐Catalyzed Intermolecular Asymmetric Hydroamination with 4,4′‐Disubstituted BINAP and SEGPHOS

“…[6] SEGPHOS (2; Figure 1), [7] which is believed to have the narrowest dihedral angle among these bisphosphines, indeed gives better ees than others in many Ru-, [7,8] Rh-, [9] Pd-, [10] and Cu-catalyzed [11] reactions. We hypothesize that more enantioselective catalysts for intermolecular hydroamination reactions can be designed by combining the potential positive effects of bulky substituents and narrow dihedral angles in biaryl-based bisphosphines.…”

“…About 10 % ee enhance- ment was observed for 4,4'-(Me 3 Si) 2 -BINAP (tms-BINAP, 1g) over BINAP (entry 7 vs. entry 1). In addition to the introduction of bulky substituents on the 4,4'-positions of BINAP, the dihedral angle of the biaryl moiety can also have a positive effect on the enantioselectivity of BINAP analogues [6][7][8][9][10][11] . We thus tested SEGPHOS [7] in the hydroamination of aniline to p-fluorostyrene, and it indeed shows~7 % ee enhancement over BINAP (entry 8 vs. entry 1).…”