Introduction of a New Class of Ligands for the Metal‐Catalyzed Enantioselective Synthesis

Abstract

AbstractProtected 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 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‐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%.