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 substitutent on the other rather than the commonly employed ligands which have C 2 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‐α‐ D ‐glucofuranose derivatives with the following substituents were synthesized: 1,2‐ O ‐isopropylidene‐5,6‐ O ‐methylidene (see 24 ), 1,2:5,6‐di‐ O ‐isopropylidene (see 2 ), 5,6‐ O ‐cyclohexylidene‐1,2‐ O ‐isopropylidene (see 23 ), 1,2‐ O ‐cyclohexylidene‐5,6‐ O ‐isopropylidene (see 14 ), 1,2:5,6‐di‐ O ‐cyclohexylidene (see 13 ), 5,6‐ O ‐(adamantan‐2‐ylidene)‐1,2‐ O ‐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‐ O ‐isopropylidene‐3‐thio‐α‐ D ‐allofuranose ( 6 ) was chosen. The following derivatives of 1,2‐ O ‐isopropylidene‐α‐ D ‐xylofuranose were also synthesized: 1,2‐ O ‐isopropylidene‐5‐deoxy‐3‐thio‐α‐ D ‐xylofuranose ( 29 ), 1,2‐ O ‐isopropylidene‐3‐thio‐α‐ D ‐xylofuranose ( 28 ) and 5‐ O ‐[( tert ‐butyl)‐diphenylsilyl]‐1,2‐ O ‐isopropylidene‐3‐thio‐α‐ 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%.