3,3‘-Diphosphoryl-1,1‘-bi-2-naphthol−Zn(II) Complexes as Conjugate Acid−Base Catalysts for Enantioselective Dialkylzinc Addition to Aldehydes

Abstract

A highly enantioselective dialkylzinc (R(2)(2)Zn) 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(=O)(NR(2))(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 R(2)(2)Zn(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 31P 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.

Lewis Base Catalysis in Organic Synthesis

“…A similar concept has been applied in the design of a binol-based ligand for the addition of diethylzinc to aldehydes by Ishihara and co-workers (Scheme 110). [368] The phenolic oxygen atom serves a similar role to that of the alcohol in 326 while the nearby phosphine oxide mimics the role of the dimethylamino group in 326. The high selectivity observed in the reactions discussed in this section is likely due to the constrained conformation of the complex and bound substrates.…”

Nonlinear Effects in Asymmetric Catalysis

“…[48] The presence of two P=O moieties at the 3,3'-positions in the binol skeleton was found to be necessary to achieve high catalytic activity. The authors noticed a linear correlation between ee prod and the ee value of 27,and concluded that the active catalyst had a monomeric form.…”

Investigation into the enantioselection mechanism of ruthenium–arene–diamine transfer hydrogenation catalysts using fluorinated substrates

“…4.5.11. (R)-1-(Naphthalen-1-yl)propan-1-ol (24) 50 . A reference compound was prepared as described for 20 starting with 1-(naphthalen-1-yl)propan-1-one (12) (230 mg, 1.25 mmol).…”