Enantioselective polysiloxanes

Synthesis of enantioselective polysiloxanes comprises three main steps (a) synthesis of appropriately functionalized dichlorosilane monomers, (b) preparation of a fluid copolymer with a specified number of functional groups per weight unit and (c) covalent attachment of a suitable chiral enantio-selective moiety. 

Ultrapurification of 50 mmolL DNB-D,L-Leucine in a Cascade of Five Stages with Two Modules and Two Enantiomeric Carrier (Quinine and Quinidine Derivative with 5 vol% Polysiloxane-supported Carrier) Transmembrane Material Stream J, Enantioselectivity a, Enantiomer Excess ee, Purity, and Yield of DNB-D-Leucine... 

Asymmetric Diels-Alder reactions have also been achieved in the presence of poly(ethylene glycol)-supported chiral imidazohdin-4-one [113] and copper-loaded silica-grafted bis(oxazolines) [114]. Polymer-bound, camphor-based polysiloxane-fixed metal 1,3-diketonates (chirasil-metals) (37) have proven to catalyze the hetero Diels-Alder reaction of benzaldehyde and Danishefsky s diene. Best catalysts were obtained when oxovanadium(lV) and europium(III) where employed as coordinating metals. Despite excellent chemical yields the resulting pyran-4-ones were reported to be formed with only moderate stereoselectivity (Scheme 4.22). The polymeric catalysts are soluble in hexane and could be precipitated by addition of methanol. Interestingly, the polymeric oxovanadium(III)-catalysts invoke opposite enantioselectivities compared with their monomeric counterparts [115]. 

From our own experience, it should be emphasised that the enantioselectivity of modified cyclodextrin phases is considerably influenced by the polarity of the (non-chiral) polysiloxane solvents used. 

Programmed temperature (120 -200°C) chiral separation on a 0.25-mm x 25-m open tubular column with a 0.25-nm-thick stationary phase containing 10 wt% fully methylated p-cyclodextrin chemically bonded to dimethyl polysiloxane. [From W. Vetter and W. Jun, Elucidation of a Polychlorinated Bipyrrole Structure Using Enantioselective GC," Anal. Chem. 3002, 74,4287.]... 

This initial observation by Inoue et al. triggered intensive research in this area. Most of the efforts were dedicated to structural variation of the catalyst and to elucidation of the catalytic mechanism. With regard to the former, the many structural variations produced mainly confirmed 1 as the optimum catalyst. Variation of the aromatic amino acids involved [25, 26], side-chain methylation and/or modification [27], N-methylation [28], etc., all afforded catalysts of lower selectivity. In contrast, incorporation of a-Me-Phe led to diketopiperazines of activity and selectivity comparable with those derived from non-methylated Phe (for example 1) [29]. Similarly, attachment to Merrifield-resin or polysiloxane polymers proved detrimental to the enantioselectivity of the Inoue-catalyst 1 [30, 31]. Upon incorporation into a silicon based sol-gel glass matrix, however, the excellent enantioselectivity of the cyclic peptide 1 is preserved, and separation of the spent catalyst can easily be achieved by, e.g., filtration, centrifugation or simply decantation [32], Unfortunately, further catalytic cycles afforded much lower ee (ca. 30-35% max.) [32],... 

Ruderisch, A., Pfeiffer, J., and Schurig, V. (2003) Mixed Chiral Stationary Phase Containing Modified Resorcinarene and Beta-Cyclodextrin Selectors Bonded to a Polysiloxane for Enantioselective Gas Chromatography,/. Chromatogr. 994, 127-135. 

Enantioselective SMB-GC has been realized adapting the results previously obtained in the batch processes described above. Preliminary studies involved racemic enflurane with a separation factor of a 2 (Juza et al., 1998a Juza et al., 1998b Biressi et al., 2000) and isoflurane (Biressi et al., 2002a) which were separated on unpurified octakis(3-0-butanoyl-2,6-di-0-n-pentyl)-7-cyclodextrin, Lipodex E, in polysiloxane SE-54 and coated on Chromosorb P (AW, DMCS, 80-100 mesh). 

An optimized version of the enantioselective SMB-GC unit was subsequently presented for enflurane enantiomers (chemical structure cf. insert in Figure 24) (Biressi et al., 2002b). It consisted of eight 80 cm x 15 mm (i.d.) stainless steel columns assembled in a home-made SMB-GC unit operated at 35°C (Scheme, cf. Figure 24). Each column with an adsorption bed volume of 140 ml each contained 20 % unpurified Lipodex E in the polysiloxane SE-54 and coated (17 %, w/w) on Chromosorb A (NAW, 20-30 mesh) 0.6 mm). This set-up represented the first gas-chromatographic SMB-GC unit for the preparative-scale separation of enantiomers. 

In some applications, it is also desirable to graft various molecules bearing OH groups or amine groups to the polysiloxane backbone. An example for a successful introduction of such a molecule has been shown by the grafting of cinchonidine. This molecule is well known to afford enantioselective reduction on metallic surfaces. The aim was first to use such a polymer to stabilize metal nanoparticles in organic solvents as well as to study the catalytic activities of such system. 

A review appeared on the practice and theory of enantioselective CGC with optically active selectors, e.g. 3-(perfluorobutyryl)-(17 )-camphorate residues forming complexes on a functionalized polysiloxane stationary phase (e.g. Chirasil, 65) SEC operates at temperatures lower than those of CGC, thus allowing better resolution, especially of thermally unstable enantiomers (e.g. those based on restricted free rotation, as is the case of dimethyl l,l -binaphthyl-2,2 -dicarboxylate, 66 ). Various analytical problems were addressed, such as determination of enantiomeric excess, assignment of absolute configuration, the elusive separation of protio- and deuterio-substituted enantiomers and the semipreparative separation of enantiomers. The following chromatographic parameters are related to the chemical and thermodynamic properties enclosed in parentheses of the enantiomeric system (i) peak retention (chemoselectivity, —AG), (ii) peak separation... 

A CSP based on polysiloxane-anchored permethyl-fi-CD, which has been coated onto macroporous silica, was reported to succeed well in the enantioseparation of barbiturates and other chiral drugs, as well as for underivatized aryl alcohols [268], In addition, the permethylated fi-CD CSP exhibited enantioselectivity for chiral steroids. 

The polymeric oxazaborolidine prepared from the linear copolymer of 29 and styrene was used in membrane reactor and resulted in high total turnover number with high enantioselectivity [44]. Another polystyrene-based soluble polymeric oxazaborolidine 38 was used in the same system. Polysiloxanes are also useful polymeric supports of catalyst 39 for the same purpose [45]. 

A. Dietrich, B. Maas and A. Mosandl. Diluted modified cyclodextrins as chiral cGC phases, the influence of the polysiloxane solvents to the enantioselectivity and column efficiency. J. Microcol. Sep., 6, 33-42 (1994). 

Ruderisch, A, J Pfeiffer and V Schurig (2003). Mixed chiral stationary phase containing modified resorcinarene and yS-cyclodextrin selectors bonded to a polysiloxane for enantioselective gas chromatography. Journal of Chromatography A, 994(2), 127-135. 

A number of groups have shown how enantiomeric resolution of amino acids derivatized with non-chiral reagents is possible in SFC with chiral stationary phases. N-Acetylamino acid t-butyl ester racemates were rapidly resolved [17] on (N-formyl-L-valylamino)propyl silica with CO2 modified with methanol, acetonitrile and diethyl ether. A similar stationary phase allowed (18 rapid (< 5 min) separation of racemic N-4-nitrobenzoyl-amino acid isopropyl esto-s with methanol-modified CO2 the enantioselectivity in SFC was comparable with that in HPLC with isopropanol/n-hexane as mobile phase. Capillary column SFC on polysiloxane stationary phases containing chiral side chains has been employed... 

To extend ocRGC to the catalytic asymmetric Gosteli-Claisen rearrangement, the following experimental setup is described. Catalytically active separation columns were used as the micro-capillary reactor and are subsequently coupled with enantioselective separation columns to perform analysis of the reaction products. The inner surface of fused-silica capillaries (i.d. 250 pm) was coated with [Cu (R,R)-Ph-box ](SbFg)2 (R R)-5 dissolved in an inert polysiloxane matrix... 

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