Insight into substrate binding in Shibasaki's Li3(THF)n(BINOLate)3Ln complexes and implications in catalysis

Heterobimetallic Lewis acids M-3(THF)(n)(BINOLate)(3)Ln [M = Li, Na, K; Ln = lanthanide(III)] are exceptionally useful asymmetric catalysts that exhibit high levels of enantioselectivity across a wide range of reactions. Despite their prominence, important questions remain regarding the nature of the catalyst-substrate interactions and, therefore, the mechanism of catalyst operation. Reported herein are the isolation and structural characterization of 7- and 8-coordinate heterobimetallic complexes Li-3(THF)(4)(BINOLate)(3)Ln(THF) [Ln = La, Pr, and Eu], Li-3(py)(5)(BINOLate)(3)Ln(py) [Ln = Eu and Yb], and Li-3(PY)(5)(BINOLate)(3)La(py)(2) [py = pyridine]. Solution binding studies of cyclohexenone, DMF, and pyridine with Li-3(THF)(n)(BINOLate)(3)Ln [Ln = Eu, Pr, and Yb] and Li-3(DMEDA)(3)(BINOLate)(3)Ln [Ln = La and Eu; DMEDA = N, N'-dimethylethylene diamine] demonstrate binding of these Lewis basic substrate analogues to the lanthanide center. The paramagnetic europium, ytterbium, and praseodymium complexes Li-3(THF)(n)(BINOLate)(3)Ln induce relatively large lanthanide-induced shifts on substrate analogues that ranged from 0.5 to 4.3 ppm in the H-1 NMR spectrum. X-ray structure analysis and NMR studies of Li-3(DMEDA)(3)(BINOLate)(3)Ln [Ln = Lu, Eu, La, and the transition metal analogue Y] reveal selective binding of DMEDA to the lithium centers. Upon coordination of DMEDA, six new stereogenic nitrogen centers are formed with perfect diastereoselectivity in the solid state, and only a single diastereomer is observed in solution. The lithium-bound DMEDA ligands are not displaced by cyclohexenone, DMF, or THF on the NMR time scale. Use of the DMEDA adduct Li-3(DMEDA)(3)(BINOLate)(3)La in three catalytic asymmetric reactions led to enantioselectivities similar to those obtained with Shibasaki's Li-3(THF)(n)(BINOLate)(3)La complex. Also reported is a unique dimeric [Li-6(en)(7)(BINOLate)(6)Eu-2][mu-eta(1), eta(1)-en] structure [en = ethylene-diamine]. On the basis of these studies, it is hypothesized that the lanthanide in Shibasaki's Li-3(THF)(n)(BINOLate)(3)Ln complexes cannot bind bidentate substrates in a chelating fashion. A hypothesis is also presented to explain why the lanthanide catalyst, Li-3(THF)(n)(BlNOLate)(3)La, is often the most enantioselective of the Li-3(THF)(n)(BINOLate)(3)Ln derivatives.