Asymmetric Inter‐ and Intramolecular Cyclopropanation Reactions Catalyzed by a Reusable Macroporous‐Polymer‐Supported Chiral Ruthenium(II)/Phenyloxazoline Complex

Abstract

The use of polymer-supported chiral catalysts (PSCCs) in asymmetric synthesis has been extensively investigated over the past three decades, as PSCCs have several advantages over homogeneous catalysts. [1,2] PSCCs are easy to handle and can be readily separated from the reaction mixture and recycled. Further, when using PSCCs, there is little or no contamination of the reaction product by the metal traces. It is well known that PSCCs can be used as powerful catalysts in various asymmetric reactions.[1] Among these reactions, cyclopropanation has been studied in detail by several research groups [2, 3] because cyclopropyl moieties are promising structural units that can be easily converted into useful compounds that have medical, pharmaceutical, and insecticidal properties.[4] In addition, cyclopropanes fused to five-or six-membered lactone rings are widely found in natural products.[5] Despite the tremendous efforts devoted to intermolecular cyclopropanations using polymer-supported chiral bis(oxazoline)s [6] or chiral pyridine-bis(oxazoline)s, [7] relatively low to moderate yields have so far been achieved. After an extensive literature survey, we concluded that all of the previously reported PSCCs depended on the polymerization of a monomeric chiral ligand or the grafting of a chiral ligand onto a polymeric support and subsequent complexation with a metal. [1][2][3] Unfortunately, in the PSCCs synthesized by these methods, there was a lack of certainty in the engagement between all the ligands sites in the polymer network and the metal centers, as shown by the low yields of the products. Furthermore, we found that most of the crosslinking polymers synthesized previously using the abovementioned strategies were macroreticular, and that the active sites were mainly present on the surface, because of which the yields obtained in the presence of these catalysts were low. The sterically hindered structure of box, pybox, and their derivatives was possibly one of the factors responsible for the low yields of the products obtained in the cyclopropanation reactions. Such factors are perhaps indicated by the leachability of the metal and the decline in reusability. Hence, the reactivity and enantioselectivity of the previously reported PSCCs were unsatisfactory.Herein, we report a novel strategy for synthesizing a macroporous polymer-supported chiral ruthenium(II)/phenyloxazoline (Ru II /pheox) complex (4 a; Scheme 1). 4 a afforded high reactivity, enantioselectivity, and reusability, even after storage of the used catalyst, without any loss of its catalytic activity or selectivity in inter-or intramolecular cyclopropanation reactions. First, the novel chiral ruthenium(II)/pheox complex 1 a was successfully prepared in a very good yield (80 %).[8] Interestingly, 1 a was an efficient and Scheme 1. A novel strategy for the synthesis of polymer-supported chiral catalysts. DCC = dicyclohexylcarbodiimide, DMAP = 4-(dimethylamino)pyridine.

Computational chemical analysis of Ru(II)‐Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions

“…Ru(II)‐Pheox–catalyzed intramolecular cyclopropanations of allyl diazoacetate derivatives (Table , entries 2‐5): These results were published in our previous report …”

“…In 2010, we developed a novel chiral complex, Ru(II)‐phenyloxazoline (Ru(II)‐Pheox) complex, which has a unique C 1 ‐symmetric structure (Figure ). Ru(II)‐Pheox can be easily synthesized from a commercially available benzoic acid derivative, an amino alcohol and a Ru source, and effectively promotes enantioselective intermolecular and intramolecular cyclopropanations with electron‐rich olefins, as well as electron‐deficient olefins, under mild reaction conditions.…”

Chiral catalysts immobilized on achiral polymers: effect of the polymer support on the performance of the catalyst

“…18), prepared by copolymerization of the corresponding monomeric complex with styrene and 1,4-divinyl benzene (DVB) in water : CH 2 Cl 2 (7 : 2). 165 The resulting catalyst displayed, in the cyclopropanation of styrene (50) with EDA (51), a higher activity than the homogeneous catalyst 93 (TOF of 3.034 h À1 , cis : trans: 88 : 12, 94% ee vs. TOF of 2.694 h À1 cis : trans: 90 : 10, 98% ee). Interestingly, the polymer 92, obtained under the same conditions as 90, but by initial polymerisation of the phenyloxazoline ligand followed by complexation with the metal, suffered from a significant drop in catalytic efficiency in terms of both activity and enantioselectivity (TOF of 1.102 h À1 , cis : trans: 83 : 17, 74% ee).…”

An Artificial Heme Enzyme for Cyclopropanation Reactions

“…With W96' pointing towards the hydrophobic core,the heme-carbene is directed towards the solvent, where it will be accessible for the styrene co-substrate (Figure 3c). Rotation of W96' to the [37] outside of the pore causes the heme-carbene (6)toremain at the dimer interface (Figure 3d,S8). Finally,t he effect of the second substrate (styrene) was studied.…”