Highly Modular POP Ligands for Asymmetric Hydrogenation: Synthesis, Catalytic Activity, and Mechanism

Abstract

A library of enantiomerically pure P-OP ligands (phosphine-phosphite), straightforwardly available in two synthetic steps from enantiopure Sharpless epoxy ethers is reported. Both the alkyloxy and phosphite groups can be optimized for maximum enantioselectivity and catalytic activity. Their excellent performance in the Rh-catalyzed asymmetric hydrogenation of a wide variety of functionalized alkenes (26 examples) and modular design makes them attractive for future applications. The lead catalyst incorporates an (S)-BINOL-derived (BINOL = 1,1'-bi-2-naphthol) phosphite group with computational studies revealing that this moiety has a dual effect on the behavior of our P-OP ligands. On one hand, the electronic properties of phosphite hinder the binding and reaction of the substrate in two out of the four possible manifolds. On the other hand, the steric effects of the BINOL allow for discrimination between the two remaining manifolds, thereby elucidating the high efficiency of these catalysts.

Synthesis of Elusive Chloropnictenium Ions

“…To establish the positive effects of the supramolecular recognition between alkali cations and the metallacrown ether catalysts on both hydrogenation activity and enantioselectivity, a series of α‐arylenamides were hydrogenated by employing the Rh/( 3a +K) complex as the catalyst under the optimized conditions. As shown in Table 3, the hydrogenation of α‐ para ‐substituted phenylenamides 6a – 6f proceeded smoothly with full conversions and excellent enantioselectivities (93–99 % ee ), which are comparable to or even better than the best results obtained for phosphine–phosphite ligands with a chiral backbone 5a,5b. For meta ‐chlorophenylenamide 6g , fairly good enantioselectivity was observed (Table 3, Entry 7).…”

“…Having realized the effective formation of chiral rhodium metallacrown ether catalysts, we then evaluated their catalytic properties in the asymmetric hydrogenation of α‐arylenamide derivatives. In general, rather few phosphine–phosphite/metal catalysts have been found to be highly enantioselective in the asymmetric hydrogenation of enamide substrates,5a,5b although such phosphorus ligands offer the advantages of easy preparation and derivatization as well as high air‐stability. Gratifyingly, 100 % conversions were achieved within 12 h for all of the reactions screened.…”

“…High efficiency and enantioselectivity have usually been achieved by utilizing such phosphine–phosphite ligands with more than one chiral element 4a. However, for enamide substrates, rather few phosphine–phosphite/metal catalysts have been found to be highly enantioselective in the asymmetric hydrogenation 5a,5b,5g,6c. Considering the widespread application of phosphine–phosphite ligands4a and as a continuation of our ongoing endeavor to develop effective chiral supramolecular catalysts based on crown ethers,2g,6h,6i herein, we report the preparation of a new class of metallacrown ether catalysts.…”

Rhodium Phosphine–Phosphite Catalysts in the Hydrogenation of Challenging N-(3,4-dihydronaphthalen-2-yl) Amide Derivatives

“…Moreover, the configurations of 7 and 6d indicate the same sense for addition of hydrogen to 3 and 1d, respectively (Figure 3). 27 If an analogous pathway is followed in the present system, dissociation of the arene ring from the 18-electron [Rh (4) nicely demonstrated the detrimental effect that the formation of stable η 6 -arene complexes produce on hydrogenation rate, due to the reduced available amount of rhodium complex for catalysis. 23c Following this reasoning, the coordination mode exhibited by 1d would agree with the relatively low rates exhibited by substrates 1.…”

Silyl Imine Electrophiles in Enantioselective Catalysis: A Rosetta Stone for Peptide Homologation, Enabling Diverse N-Protected Aryl Glycines from Aldehydes in Three Steps

“…In some cases, such as Fmoc-protected 10e , the product can be prepared by either pathway via B or C (Figure 1) with similarly high enantioselection. 24 However, the low yield observed in the former case further emphasizes the practical value of the pathway through C . In other comparisons, such as the acyl-protected 10a , the increased reactivity of the acyl imine intermediate leads to poor enantioselection and yield.…”