Mechanistic Basis for High Reactivity of (salen)Co–OTs in the Hydrolytic Kinetic Resolution of Terminal Epoxides

Abstract

The (salen)Co(III)-catalyzed hydrolytic kinetic resolution (HKR) of terminal epoxides is a bimetallic process with a rate controlled by partitioning between a nucleophilic (salen)Co–OH catalyst and a Lewis acidic (salen)Co–X catalyst. The commonly used (salen)Co–OAc and (salen)Co–Cl precatalysts undergo complete and irreversible counterion addition to epoxide during the course of the epoxide hydrolysis reaction, resulting in quantitative formation of weakly Lewis acidic (salen)Co–OH, and severely diminished reaction rates in the late stages of HKR reactions. In contrast, (salen)Co–OTs maintains high reactivity over the entire course of HKR reactions. We describe here an investigation of catalyst partitioning with different (salen)Co–X precatalysts, and demonstrate that counterion addition to epoxide is reversible in the case of the (salen)Co–OTs. This reversible counterion addition results in stable partitioning between nucleophilic and Lewis acidic catalyst species, allowing highly efficient catalysis throughout the course of the HKR reaction.

Evaluation of enantiopure and non-enantiopure Co(III)-salen catalysts and their counter-ion effects in the hydrolytic kinetic resolution (HKR) of racemic epichlorohydrin

“…Thus, the similar reactivity seen in Table 1, entires 4 and 5 demonstrates that rapid counter-ion exchange occurs between the Co(III)-salen species during catalysis and, therefore, mixed chiral-racemic ligand systems cannot be used to reduce the cost of HKR reactions. It should further be noted that the counter-ion scrambing is consistent with the mechanism of Nielsen et al [24].…”

“…With an accumulation of Co(III)-salen-OH occurring in the HKR, the catalytic activity decreases because Co(III)-salen-OH is a poorer Lewis acid than Co(III)-salen-X (X / = OH) [16]. If X = − OTs, HKR catalysis is highly efficient, as counter-ion addition is reversible, because Co(III)-salen-OTs is not suggested to completely convert to Co(III)-salen-OH [24]. If X is non-nucleophilic, such as SbF 6 − , there should be no nucleophilic attack of the counter-ion on the epoxide, thus no generation of Co(III)-salen-OH [16].…”

A broadly applicable and practical oligomeric (salen)Co catalyst for enantioselective epoxide ring-opening reactions

“…Ring opening of phenolic substrates (entries 7–9) generated enantioenriched dihyrobenzofurans; however, higher catalyst loadings were required to attain high levels of enantioselectivity. Consistent with the cooperative bimetallic mechanism established for epoxide openings, 13 use of oligomeric complex 4a lowered the required catalyst loading by 10–500-fold compared to (salen)Co monomer 1 (X=OTf) in all cases studied. Enantioselectivities were comparable with monomeric and oligomeric catalyst in oxetane ring-opening reactions, with the exception of the tetrahydropyran-forming reaction (entry 10) wherein the oligomeric catalyst 4a afforded much higher product ee.…”

“…The recognition that the HKR 13 and related 14 epoxide ring-opening reactions proceed via cooperative bimetallic mechanisms, wherein both the epoxide electrophile and nucleophile are activated by separate (salen) Co complexes in the rate-limiting ring-opening event (Figure 1), 15 has motivated the preparation and study of a wide variety of linked multi- (salen) metal complexes. The goal of these efforts has been to achieve higher catalytic activity by reducing the entropic cost of a second-order bimetallic pathway.…”

Variety of Crystal Structures of Chiral Schiff Base Lu(III)-Ni(II)/ Cu(II)/Zn(II) and the Related Complexes

“…Chiral Schiff bases transition metal complexes, so-called salen-type ligands, are one of the most studied chiral catalysts in asymmetric synthesis because of their ability to act as chiral catalysts or as co-catalysts [1][2][3][4][5][6][7]. Moreover, their binuclear complexes containing transition metals and rare earth metals have gained importance from the viewpoint of special interest in photophysical and magnetic properties arising from interactions between metal ions as well as sole metal ions having suitable electronic states or unpaired electrons [8][9][10][11][12][13][14][15][16][17][18][19].…”