Highly Enantioselective Hydrogenation of α-Arylmethylene Cycloalkanones Catalyzed by Iridium Complexes of Chiral Spiro Aminophosphine Ligands

摘要

Chiral allylic alcohols are important and versatile intermediates innorganic synthesis because they can be readily converted into a varietynof biologically active molecules, such as pharmaceuticals and naturalnproducts.1 The transition-metal-catalyzed asymmetric hydrogenationnof the carbonyl group of R,u0001-unsaturated ketones is a direct methodnto produce chiral allylic alcohols.2 The Ir-complexes of phosphinenligands were the first catalysts used for asymmetric hydrogenation ofnR,u0001-unsaturated ketones but yield the corresponding chiral allylicnalcohols with low ee values.3 High enantioselectivity (up to 98% ee)nin the hydrogenation of R,u0001-unsaturated ketones was obtained bynNoyori et al. using Ru-BINAP/diamine catalysts in 1995.4 Since then,nthe catalysts used in the asymmetric hydrogenation of R,u0001-unsaturatednketones to chiral allylic alcohols have been dominated by Rudiphosphinediamine complexes, and various acyclic and endo-cyclicnR,u0001-unsaturated ketones have been hydrogenated with good to excellentnenantioselectivities.5 However, the asymmetric hydrogenation of exocyclicnR,u0001-unsaturated ketones is still a challenge,6 despite the factnthat the corresponding hydrogenation products, exo-cyclic allylicnalcohols, serve as key intermediates for the synthesis of chiral drugsn(e.g., the trinem antibiotic sanfetrinem)6c and natural products (e.g.,nslaframine).6d Thus, the development of highly efficient methods fornthe asymmetric synthesis of exo-cyclic allylic alcohols is highlyndesirable.