Enzyme‐Inspired Chiral Secondary‐Phosphine‐Oxide Ligand with Dual Noncovalent Interactions for Asymmetric Hydrogenation

Abstract

Inspired by the unique character of enzymes, we developed novel chiral SPO (secondary-phosphine-oxide) ligand (SPO-Wudaphos) which can enter into both ion pair and H-bond noncovalent interactions. The novel chiral SPO-Wudaphos exhibited excellent results in the asymmetric hydrogenation of α-methylene-γ-keto carboxylic acids, affording the chiral γ-keto acids with up to over 99 % ee. A series of control experiments and DFT calculations were conducted to illustrate the critical roles of both the ion pair and H-bond noncovalent interactions.

Secondary Phosphine Oxides: Bifunctional Ligands in Catalysis

“…[29] More recently, this design was exploited further in SPO-Wudaphos complex 19 for Rh hydrogenation of α-methylene-γ-keto carboxylic acids. [30] According to DFT calculations, the high enantioselectivities obtained (over 99 % ee) were attributed to substrate-ligand ion pair and Hbond interactions, mimicking the mode of action of enzymes (Scheme 7).…”

Coordination chemistry and catalysis with secondary phosphine oxides

“…These ligands had a stereogenic phosphorus atom and a chiral backbone and were obtained from the well-known of Ugi's amine. In another approach, Chung, Dong, Zhang and coworkers, 79,80 inspired by the properties of enzymes, designed a special type of SPOs (called SPO-Wudaphos), also starting from Ugi's amine (Scheme 19). These ligands were designed to engage ion pair and H-bond noncovalent interactions for highly enantioselective asymmetric hydrogenations of several substrates.…”

“…Recently, Dong, Zhang and coworkers 79,80,274 used their ferrocenyl-based ligands SPO-Wudaphos (Scheme 19) in the hydrogenation of -methylene--keto carboxylic acids, 80,275 and -substituted ethenylphosphonic acids 274 obtaining exceedingly high enantioselectivities and very good conversions towards the hydrogenated product, which in many cases had biological applications (Scheme 113). In this reaction the unconsumed dinitrile, the monocarboxamide and the biscarboxamide were formed in non-racemic form, especially for the latter, which could be obtained in very high enantioselectivity.…”

Cobalt-catalyzed highly enantioselective hydrogenation of α,β-unsaturated carboxylic acids

“…Transition-metal-catalyzed enantioselective hydrogenation of α, β-unsaturated acids is one of the most atom-economic and efficient approaches to access chiral carboxylic acids 19 . Various noble metal-based catalysts, such as Ru catalysts with chiral diphosphine ligands [20][21][22][23][24] , Rh catalysts with chiral phosphorus or nitrogencontaining ligands [25][26][27][28][29][30][31] , and Ir catalysts with chiral P,O- 32 and P, N-ligands [33][34][35][36][37][38][39][40] have been developed for the hydrogenation of different unsaturated carboxylic acids in high enantioselectivities ( Fig. 2a).…”