Polymer ephedrine

The polymer-bound catalysts A-C. (Table 31) are prepared by reaction of the corresponding amino alcohols with partially chloromethylated 1 -2% cross-linked polystyrene. In the case of A, the enantioselectivity of the addition of dialkylzincs to aldehydes is higher than with the corresponding monomeric ephedrine derivatives (vide supra). Interesting insights into the mechanism of the alkylation of aldehydes by dialkylzinc reagents can be obtained from the experi-... 

Stereoselective reduction of a,(i-unsaturated ketones using lithium aluminium hydride has only been reported in conjunction with the ephedrine bases either in a two-phase system (80-90% yield, ee >70%) or immobilized on a polymer [18, 19]. 

The first report of a polymer-supported approach to this reaction appeared in 1987 [48]. Enantiopure amino alcohols such as ephedrine, prolinol, and 3-exo-amino-isoborneol were attached to Merrifield polymer. The use of polymer-supported 3-exo-aminoisoborneol 40 resulted in quite high enantioselectivity ( 95 % ee) in the ethylation of aldehydes with diethylzinc (Eq. 15), a result comparable with those obtained from the corresponding low-molecular-weight catalyst system (Eq. 16). A similar system was also reported in 1989, this time using ephedrine derivatives (41,42) and prolinol derivative (43) [49]. A methylene spacer was introduced between the polymer and the amino alcohol to improve activity [50]. Despite this the selectivity was always somewhat lower than that obtained from the low-molecular-weight catalyst (44). These chiral polymers were all prepared by the chemical modification method using Merrifield polymer. 

The amino alcohol-dialkylzinc system can be applied to ehiral amine synthesis. Polymer-supported ephedrine was found to be an effective chiral ligand in the reaction of N-diphenylphosphinoylimines with diethylzinc (Eq. 19) [77-79]. The polymeric catalysts were, however, less efficient than monomeric model reactions. Several dendrimeric chiral ligands containing the ephedrine moiety (60, 61) have also been synthesized and used in the asymmetric alkylation of 7 -diphenylphosphinylimines by diethylzinc [80]. Both yield and enantioselectivity of the reaction were, however, lower when the dendrimeric ligands were used. 

The polyvinylferrocene-supported ephedrines 19a—e were applied as chiral catalysts to the asymmetric ethylation of benzaldehyde in a heterogeneous system (hexane, room temperature). A quantity of 5 mol% of total ephedrine unit per benzaldehyde was used and the effect of the content of ephedrine unit in the polymers on enantioselectivity was investigated (Table 3-3). All chiral polymers 19a —e afforded (S)-l-phenylpropanol. Chiral polymer 19c, containing 32.8 mol% ephedrine units. 

As early as 1904, Willstatter attempted to separate optical isomers on the optically active natural polymers wool and silk [10]. About 35 years later, the first partial chromatographic resolution of the enantiomers ofp-phenylene-bis-imino-cam-phor on lactose was achieved by Henderson and Rule [11], and a few years later by Lecoq for the enantiomers of ephedrine [12], and by Prelog and Wieland for the enantiomers ofTroeger s base [13]. 

Figure 4.32 Chiral ephedrine-bearing dendronized polymers.

J Sevcik, Z Stransky, BA Ingelse, K Lemr. Capillary electrophoretic enantiosepara-tion of selegiline, methamphetamine and ephedrine using a neutral beta-cyclodex-trin epichlorhydrin polymer. J Pharm Biomed Anal 14 1098-1094, 1996. 

Elemental lithium is a catalyst. Catalysts are substances that speed up chemical reactions without themselves being consumed during the reaction. In pharmaceutical syntheses, an example is the synthesis of methamphetamine from ephedrine. In the polymer industry, lithium... 

Polymer-bound ephedrine has interesting possibilities for heterogeneous catalysis. It has been used as a catalyst for enantioselective addition of zinc alkyls to carbonyl compounds (Section D. 1.3.1.4.) and for the enantioselective reduction of ketones to secondary alcohols16. 

A mixture of 10.0 g of chloromethylated polystyrene (Merrifield polymer) (2.36 mmol of Ci g) and 11.7 g (70.8 mmol) of (-)-(lR,2S)-ephedrinc in 80 mL of DMF is stirred at 85 C for 4 d. The polymer is then filtered and washed repeatedly with EtOH, H20, and THF/H20 1 1, until no chloride is found in the wash liquid. Washing is then continued with THF and EtOH. After drying at 40 JC, 13.01 g of polymer are obtained. Nitrogen analysis indicates a loading of ephedrine corresponding to 1.81 mmol/g, while no chlorine remains on the polymer. 

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