Bisoxazoline ligand

In chemistry, bisoxazoline ligands (BOX ligands for short) are chiral ligands based on a bis oxazoline skeleton and used in combination with a metal compound in asymmetric synthesis as a chiral catalyst ["Bisoxazoline (BOX) Ligand-Metal Complexes: An Emerging Chiral Catalyst" Ramkrishna Basak Synlett 2003, No. 8, 1223–1224 [http://www.thieme-connect.com/ejournals/pdf/synlett/doi/10.1055/s-2003-39914.pdf Article link] ] . Three frequently encountered such ligands are PyBOX, tBuBOX and PhBOX. BOX ligands exist as organic compounds with the organometallic complex formed in-situ or as pre-prepared metal complexes.

In 1984 Brunner ["Asymmetric syntheses. 20. Enantioselective hydrosilylation of ketones with [Rh(cod)Cl 2/thiazolidine catalysts" Henri Brunner, Richard Becker, and Georg Riepl Organometallics; 1984; 3(9) pp 1354 - 1359; DOI|10.1021/om00087a006] started the development of nitrogen containing ligands because phosphine ligands tended to fail in enantioselective hydrosilylations which was the focus of many research groups. One 1984 study describes a nitrogen-nitrogen bidentate ligand with a pyridine group fused to a thiazolidine group.

In 1989 Brunner replaced the thiazolidine (difficult to control stereochemistry) by an oxazoline group ["Asymmetric catalysis. 44. Enantioselective monophenylation of diols with cupric acetate/pyridinyloxazoline catalysts" Henri Brunner, Uwe Obermann, and Peter Wimmer Organometallics; 1989; 8(3) pp 821 - 826; DOI|10.1021/om00105a039] and demonstrated the new ligand in a monophenylation of a diol by the organobismuth compound triphenylbismuth diacetate.

As before, the ligands are obtained by reaction of an acid chloride with L-valinol (which is the reduced form of valine) followed by ring-closure to the acetal and an elimination reaction (facilitated by either thionyl chloride or tosyl chloride) to the oxazoline.

Both Masamune and Evans demonstrated their nearly identical BOX ligands in a cyclopropanation reaction via diazotation.

References