Bicyclo[2.2.2]octane-derived chiral ligands—synthesis and application of BODOLs in the asymmetric reduction of acetophenone with catecholborane

Abstract

An improved synthetic route to the bicyclo[2.2.2]octane-2,6-diol ligands (2,6-BODOLs) allowed an increased structural variation of the ligand side-arm. The addition of aromatic or vinylic Grignard reagents to hydroxyketone 1 was highly selective and ligands 3f– 3l were isolated in 84–97% yield. The addition of alkyl Grignard reagents containing β-hydrogens resulted in lower yields (13–71%) due to competing ketone reduction. A number of 2,5-BODOLs were synthesized using a similar methodology. The ligands, together with Ti(O iPr) 4, were tested in the asymmetric reduction of acetophenone with catecholborane (up to 98% ee). 1-Naphthyl-BODOL 3i was employed as an allylboration reagent to benzaldehyde together with Sc(OTf) 3, resulting in (1 S)-1-phenyl-3-buten-1-ol in 80% ee.