3,3′-diphosphoryl-1,1′-bi-2-naphthol-Zn(II) complexes as conjugate acid-base catalysts for enantioselective dialkylzinc addition to aldehydes

A highly enantioselective dialkylzinc ((R2Zn)-Zn-2) addition to a series of aromatic, aliphatic, and heteroaromatic aldehydes (5) was developed based on conjugate Lewis acid-Lewis base catalysis. Bifunctional BINOL ligands bearing phosphine oxides [P(=O)R-2] (7), phosphonates [P(=O)(OR)(2)] (8 and 9), or phosphoramides [P(dO)(NR2)(2)] (10) at the 3,3 '-positions were prepared by using a phospho-Fries rearrangement as a key step. The coordination of a NaphO-Zn(II)-R-2 center as a Lewis acid to a carbonyl group in a substrate and the activation of (R2Zn)-Zn-2(II) with a phosphoryl group (P=O) as a Lewis base in the 3,3 '-diphosphoryl-BINOL- Zn(II) catalyst could promote carbon-carbon bond formation with high enantioselectivities (up to > 99% ee). Mechanistic studies were performed by X-ray analyses of a free ligand (7) and a tetranuclear Zn(II) cluster (21), a P-31 NMR experiment on Zn(II) complexes, an absence of nonlinear effect between the ligand (7) and Et-adduct of benzaldehyde, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition-state assembly including monomeric active intermediates.