Synthesis of carbohydrate-based chiral crown ethers as ligands in asymmetric hydrogenation

Starting from phenyl 2,3-di-O-allyl-4,6-O-benzylidene-beta -D-glucopyranoside (1) the chiral crown ethers 6 and 7, containing a 1,4-bridged alpha -D-glucopyranoside moiety, were synthesized in four steps via phenyl 2,3-O-allyl-6-O-benzyl-beta -D-glucopyranoside (2). To build up the corresponding polyethylene glycol side chain at 4-position, compound 2 was subsequently alkoxylated with bis(2-chloroethyl)ether and diethylene glycol or triethylene glycol yielding via 3 the polyethylene glycol derivatives 4 and 5, respectively. On a similar way phenyl 2,3-di-O-allyl-6-O-benzyl-4-O-{2-[omega -hydroxypenta(oxyethylene)ethyl]}-beta -D-galactopyranoside (15) was prepared from phenyl 4,6-O-benzylidene-beta -D-galactopyranoside (10) via the intermediates 11, 12 and 13. The chiral crowns 6, 7, and 16 were obtained in yields of 26-38% by intramolecular transglycosylation of 4, 5, and 15, respectively. Whereas a high alpha -stereoselectivity was found for the cyclization of the 1,4-bridged D-glucose crowns 6 and 7, galactose derivative 15 gave the beta -glycosidic linked crown 16. In order to obtain the rhodium chelates 18 and 20 as precatalysts for asymmetric hydrogenations, the gluco-crown ethers 6 and 7 were deallylated to 8 and 9 and phosphorylated under anaerobic conditions giving the bis(phosphinic esters) 17 and 19. The latter were used as ligands for 18 and 20. Finally, asymmetric hydrogenations of amino acid precursors 21a-d were investigated in the presence of the rhodium chelates 18 and 20. Under hydrogen, they show as catalysts in different solvents a diminished range of enantioselectivity in comparison with an analogous complex without such a crown ether ring. This can be explained by a stiffening effect of the anellated ring on the chelate ring conformation which is confirmed by the unusually uniform CD-spectra of 20 in solvents of different polarity.