Synthesis of Carbohydrate-based Chiral Crown Ethers as Ligands in Asymmetric Hydrogenation

Abstract

Starting from phenyl 2,3-di-O-allyl-4,6-O-benzylideneb-D-glucopyranoside (1) the chiral crown ethers 6 and 7, containing a 1,4-bridged a-D-glucopyranoside moiety, were synthesized in four steps via phenyl 2,3-O-allyl-6-O-benzyl-b-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, (15) was prepared from phenyl 4,6-O-benzylidene-b-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 a-stereoselectivity was found for the cyclization of the 1,4-bridged D-glucose crowns 6 and 7, galactose derivative 15 gave the b-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.Carbohydrate-based chiral crown ethers find increasing interest in asymmetric organic synthesis. 1-10 Therefore, these compounds should be useful tools for the separation of enantiomers, chiral recognition in enzymatic reactions, and for the control of asymmetric syntheses. However, only a few of them proved to be effective in enantioselective reactions. 2b,3b,4,5,7c Rhodium(I) chelates of D-hexopyranoside-2,3-O-bisphosphinites are extremely useful in the asymmetric hydrogenation of amino acid precursors 11 and have even found application in the industrial production of L-DOPA. 12 Our aim was to synthesize analogous catalysts containing an anellated crown ether-like ring in the 1,4-position of the carbohydrate. Since it is well known that solvent polarity and the formation of cryptate species with alkali ions strongly influence the conformation of crown ethers, 13 we wanted to investigate whether the tuning of these effects would increase the enantioselectivity of these new catalysts. More detailed background information on asymmetric hydrogenation can be found in the latest review by Brown. 14 Based on a strategy reported before, 8 the 17-membered and 20-membered macrocyclic compounds 6 and 7, were synthesized in four steps according to Scheme 1. At first, the benzylidene acetal of p...

Planar-Chiral Macrobicycles Comprising Cyclam Moiety

“…The best chemical yields of macrobicycle 11a (40-50 %) were achieved using ligands L1, L2, L4, L6, L7 (entries 3, 4, 6, 8, 9), while traditional BINAP provided 22-28 % yields (entries 1, 2). As for enantiomeric excess, only ligands L3, L4, L7 were to some extent efficient providing 9, 11 and 13 % ee, respectively (entries 5,6,9). For the synthesis of 11b, ligand L3 was better than BINAP considering its chemical yield (entries 11 and 12), however, the asymmetric induction was too small though the chain of the corresponding amine was shorter (4 atoms in 10b vs 5 atoms in 10a).…”

“…[5] Chiral carbohydrate-based crown ethers were employed as ligands in asymmetric hydrogenation. [6] The catalysts for C-C coupling reactions may contain the complexes of chiral macrocycles with the transition metals. [7] Macrocycles with planar chirality occupy a special position among other chiral macrocycles, and yet no general and convenient synthetic procedures has been developed for their synthesis.…”

One‐Step Synthesis of Chiral Azamacrocycles via Palladium‐Catalyzed Enantioselective Amination of 1,5‐Dichloroanthraquinone and 1,5‐Dichloroanthracene

“…[5] Chiral carbohydrate-based crown ethers were used as ligands in asymmetric hydrogenation. [6] Besides, complexes of chiral macrocycles with the transition metals may serve as catalysts for C À C coupling reactions. [7] Macrocycles with planar chirality occupy a special position among the other chiral macrocycles, and yet no general and convenient synthetic procedures have been developed for their synthesis.…”

A Synthetic Approach to Macrocyclic, Chiral Phosphane Derivatives with Crown‐Ether‐Like Structures

“…[10] In all the diphosphanes above, the phosphorus centre, usually a diphenylphosphanyl group, is connected to the crown ether moiety through carbon linkers. A conceivable alternate approach to crown-ether-like phosphanes would be to design macrocycles incorporating a phosphorus centre in a polyoxygenated chain.…”