Asymmetric Hydrolytic and Aminolytic Kinetic Resolution of Racemic Epoxides using Recyclable Macrocyclic Chiral Cobalt(III) Salen Complexes

Abstract

New chiral macrocyclic cobalt(III) salen complexes were synthesized and used as catalyst for the asymmetric kinetic resolution (AKR) of terminal epoxides and glycidyl ethers with aromatic/aliphatic amines and water as nucleophiles. This is the first occasion where a Co(III) salen complex demonstrated its ability to catalyze AKR as well as hydrolytic kinetic resolution (HKR) reactions. Excellent enantiomeric excesses of the epoxides, the corresponding amino alcohols and diols (upto 99%) with quantitative yields were achieved by using the chiral Co(III) salen complexes in dichloromethane at room temperature. This protocol was further extended for the synthesis of two important drug molecules, i.e., (S)‐propranolol and (R)‐naftopidil. The catalytic system was also explored for the synthesis of chirally pure diols and chiral cyclic carbonates using carbon dioxide as a greener renewable C1 source. The catalyst was recycled for upto 5 catalytic cycles with retention of enantioselectivity.magnified image

Chiral Cobalt‐Salen Complexes: Ubiquitous Species in Asymmetric Catalysis

“…Without being here exhaustive, convincing examples can be found for the preparation of β‐adrenergic antagonist drugs such as Timolol [36a] or other β‐blockers, [36b,c] as antihypertensive drugs. The protocol was efficiently extended to the aminolytic kinetic resolution of epoxides to allow the preparation of other important drugs [36d] . In this context, a 100% utilization of racemic naphthylglycidyl ether was reported via the preparation of ( R )‐Naftopidil (α 1 ‐adrenergic receptor antagonist) from the resolved epoxide and ( S )‐propanolol (β‐blocker) from the complementary opening product on a gram scale [36e] .…”

Chiral Salen Complexes for Asymmetric Heterogeneous Catalysis: Recent Examples for Recycling and Cooperativity

“…Finally, salen derivatives were incorporated as monometallic species in macrocycles formed via additional chiral linkers, delivering also active recyclable catalytic species. Thus, chiral macrocyclic Co‐salen complexes ( 29 , Scheme ) were prepared for both the AKR with a variety of amines and the HKR of terminal epoxides . These catalysts were highly regioselective towards the attack of the nitrogen nucleophile from the less hindered side of the epoxide, and led to the unreacted epoxides and the corresponding amino alcohols in good yields with excellent ee values.…”

“…Thus, chiral macrocyclic Co-salen complexes (29, Scheme 20) were prepared for both the AKR with a variety of amines and the HKR of terminal epoxides. [70] These catalysts were highly regioselective towards the attack of the nitrogen nucleophile from the less hindered side of the epoxide, and led to the unreacted epoxides and the corresponding amino alcohols in good yields with excellent ee values. Both chiral moieties of the catalysts were responsible for the high enantioselectivity, but the configuration of the targeted products only depended on the configuration of the chiral diamine.…”

Fabrication of Flexible Co‐salen Integrated Polymers for Hydration of Epoxides and Alkynes via Cooperative Activation

“…The heterogenization of Co-salen complexes has aroused great research attention due to their wide applications in a broad range of reactions, such as oxidation, [7][8] hydration, [9][10] hydrolytic kinetic resolution of epoxides, [11][12][13] and CO 2 cycloaddition. [14][15][16] The cooperative activation mode is usually involved in Co-salen catalyzed reactions, for example the asymmetric kinetic resolution of epoxides and the hydration of epoxide.…”