Juliá-Colonna Asymmetric Epoxidation in a Continuously Operated Chemzyme Membrane Reactor

Abstract

Two novel soluble polymer-bound oligo-L-leucines 2 and 5, which can be retained by a membrane reactor system, have been prepared and used as catalysts for the continuously operated asymmetric epoxidation of chalcone. The optimized batch reaction conditions yield epoxychalcone in high enantioselectivities (up to 94%) and conversions (over 99%) after 15 minutes.Epoxides are widely used compounds in organic synthesis. 1 For this reason several approaches to effect enantioselective epoxidation have been made. 2 Among the welldeveloped methods, the Juliá-Colonna epoxidation, which utilizes chiral polyamino acids (in particular poly-L-leucine) as heterogeneous catalysts, has emerged as the first reliable method for the asymmetric epoxidation of electron-deficient olefins, exhibiting exceptionally high chiral induction for chalcone. 3Degussa and their partners from the University of Liverpool have worked intensively on the improvement of heterogeneous Juliá-Colonna oxidation. A noteworthy modification includes the introduction of percarbonate in dimethoxyethane as a cheap oxidant/solvent system for the use in some polyamino acid-catalysed epoxidations. 4The poly-L-leucine catalyst remained insoluble under all the reaction conditions applied. The first homogeneous version of the Juliá-Colonna epoxidation of trans-chalcone was reported recently. 5 However, the conversion observed was only 39% after 1 hour and 80% after 24 hours with an ee of 95-98%.Since the chiral information has to be transferred from the catalyst to the olefinic substrate, homogeneous asymmetric catalysis is a more attractive method for the synthesis of chiral epoxides. However, up to now, no process has made the step from an academically promising method to an application on larger scale.The interest of Degussa in developing methods for asymmetric synthesis in a chemzyme membrane reactor 6 promoted further investigation of the homogeneous enantioselective epoxidation of a,b-unsaturated ketones.We reasoned that the preparation of polymer enlarged oligo(L-leucine)s which were soluble in common organic solvents and large enough to be retained in a membrane reactor could allow us to develop a continuously operated asymmetric epoxidation of trans-chalcone.There are two major approaches to synthesize homogeneously soluble polymer-enlarged catalysts, that is using either linear polymers or dendrimers as carriers.We have focused our work on linear polymers, because they demand less synthetic effort. Thus, we prepared two types of soluble polymer enlarged oligo(L-leucine)s 2 and 5 (Scheme 1, Scheme 2). The approach to catalyst 2 involved the co-polycondensation of 1 equivalent of commercially available O,O-bis(2-aminoethyl)-polyethyleneglycol 20000 1 with 16 equivalents of L-leucine-N-carboxyanhydride in CHCl 3 . 7 Scheme 1 Synthesis of homogeneously soluble oligo(L-leucine) 2.We found that the resulting polyethyleneglycol-supported oligo(L-leucine) 2 can act as an efficient homogeneous chiral catalyst in the epoxidation of trans-chalcone 6 employing the urea ...

Immobilization of Organic Catalysts: When, Why, and How

“…(27)] carried out at the industrial level in 99 % yield and 94 % ee in a continuously operated membrane reactor where catalyst recycling was made possible by a nanofiltration membrane. [11,69] In subsequent work, Kelly and Roberts prepared a new soluble catalysts 22a by attaching a polyleucine chain to MeOPEG 5000 NH 2 ( Figure 8). [70] This catalyst, the peptide fragment of which was shown by CD measurements to exist mostly in the a-helical structure (86 %), was found to promote the epoxidation of chalcone with the urea/hydrogen peroxide complex in 95 % conversion and 97 % ee (DBU, THF, room temperature, 3 h).…”

“…This is the case, for instance, of continuous flow methods, [95] when the immobilized catalyst permanently resides in the reactor where it transforms the entering starting materials into the exiting products. [69,79,96] The retention of the catalyst inside the reaction vessel can be achieved by different techinques ranging from ultrafiltration through an M W -selective membrane to immobilization on a silica gel column. It is important to note that, under continuous flow conditions, product separation from the catalyst, catalyst recovery, and catalyst recycling are achieved in a single operation.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…As a further demonstration of chiral pool inspired catalysts, proline-derived aminoalcohols (e.g., 445) promote asymmetric epoxidation of enones through non-covalent catalysis [494,495]. Oligopeptides also show promise as chiral auxiliaries [496] illustrated by the novel poly(ethylene glycol)-supported oligo(L-leucine) catalyst 447 used to carry out the Juli a-Colonna epoxidation of chalcone through a continuously operated chemzyme membrane reactor with urea-hydrogen peroxide as the terminal oxidant [497]. The chiral ytterbium complex formed from Yb(i-PrO) 3 and 6,6 0 -diphenyl-BINOL (450) catalyzed the epoxidation in 91% yield and 97% ee using cumene hydroperoxide as the oxygen source [498].…”

Asymmetric Michael Reactions on Polymeric Support: Auxiliary Immobilization and Stereoselective Construction of Quaternary Stereocenters

“…[11] Also the application of soluble polymer catalysts for a continuously operated asymmetric reaction was reported. [12] After preparation of the PEG-immobilized chiral linker 1d (vide infra), enamine formation with cyclopentanone and cyclohexanone carboxylate 2d and 2a was carried out in the presence of catalytic amounts of TFA without removal of water (Scheme 4). The corresponding PEG-bound enamines 3d and 3e, which are formed almost quantitatively, were converted with methyl vinyl ketone (4) in asymmetric Michael reactions catalyzed by copper() acetate.…”