INTRODUCTION OF A NEW CLASS OF LIGANDS FOR THE METAL-CATALYZED ENANTIOSELECTIVE SYNTHESIS

Protected thiosugars were prepared as ligands for the metal-catalyzed enantioselective synthesis. The protecting groups in these ligands were varied to test a proposed new concept for the metal-catalyzed enantioselective synthesis. This new concept centres on the use of a stair-like ligand with a large substituent on one side and a small substituent on the other rather than the commonly employed ligands which have C2 symmetry (see Fig. 3). In such a ligand, both substituents should have a major influence on the coordination of a prochiral substrate. To test this proposal, 3-thio-alpha-D-glucofuranose derivatives with the following substituents were synthesized: 1,2-O-isopropylidene-5,6-0-methylidene (see 24), 1,2:5,6-di-0-isopropylidene (see 2), 5,6-0-cyclohexylidene-1,2-0-isopropylidene (see 23), 1,2-0-cyclohexylidene-5,6-0-isopropylidene(see 14), 1,2:5,6-di-O-cyclohexylidene(see 13),5,6-0-(adamantan-2-ylidene)-1,2-0-isopropylidene (see 21), and 1,2:5,6-di-O-(adamantan-2-ylidene) (see 25, Table 2). As a representative of the allofuranoses, 1,2:5,6-di-0-isopropylidene-3-thio-alpha-D-allofuranose (6) was chosen. The following derivatives of 1,2-0-isopropylidene-alpha-D-xylofuranose were also synthesized: 1,2-0-isopropylidene-5-deoxy-3-thio-alpha-D-Xylofuranose (29), 1,2-0-isopropylidene-3-thio-alpha-D-xylofuranose (28) and 5-0-[(tert-butyl)-diphenylsilyl]- 1,2-0 -isopropylidene-3-thio-alpha-D-Xylofuranose (15, see Table 2). The proposed concept was tested using the copper-catalyzed 1,4-addition of BuMgCl to cyclohex-2-en-1-one. The enantioselectivity was very dependent on the ligand used and was up to 58 %.