Enantioselective Mannich-Type Reactions Using a Novel Chiral Zirconium Catalyst for the Synthesis of Optically Active β-Amino Acid Derivatives

Abstract

Catalytic enantioselective Mannich-type reactions of silyl enol ethers with aldimines have been successfully performed using a novel chiral zirconium catalyst prepared from zirconium(IV) tert-butoxide (Zr(O t Bu)4), 2 equiv of (R)-6,6‘-dibromo-1,1‘-bi-2-naphthol ((R)-6,6‘-Br2BINOL), and N-methylimidazole. The use of aldimines having N-substituted hydroxyphenyl moieties is essential for obtaining high selectivities, and the N-substituted groups were converted to free amines using oxidative cleavage. Aldimines derived from aromatic aldehydes as well as heterocyclic and aliphatic aldehydes reacted with silyl enol ethers smoothly to afford the corresponding β-amino acid derivatives in high yields and high enantioselectivities. Several NMR experiments have been conducted to clarify the structure of the chiral Zr catalyst and also the catalytic cycle of this asymmetric reaction. Finally, a new BINOL derivative, (R)-6,6‘-bis(trifluoromethyl)-1,1‘-bi-2-naphthol ((R)-6,6‘-(CF3)2BINOL), has been prepared. It was shown that the turnover of the catalyst using this novel ligand was improved, and high levels of yields and selectivities were obtained in the presence of a small amount of the zirconium catalyst.

Self‐Supported Heterogeneous Titanium Catalysts for Enantioselective Carbonyl–Ene and Sulfoxidation Reactions

“…The mixture was stirred for 15 min before CMHP (80 % in cumene, 180 mL, 1 mmol) was added dropwise at 0 8C, and the heterogeneous mixture was stirred at room temperature for 72 h. After the isolation of the solids by filtration, the insoluble catalyst was recharged with CCl 4 (3 mL), substrates (0.5 mmol), and oxidant (1 mmol) for the next run. The filtrate was concentrated and the residue was submitted to column chromatography on silica gel using hexane/ethyl acetate + , 126 (54), 97 (15), 78 (100), 51 (32).…”

Air-stable, storable, and highly efficient chiral zirconium catalysts for enantioselective Mannich-type, aza Diels–Alder, aldol, and hetero Diels–Alder reactions

“…Compared with asymmetric Mannich-type reactions using stoichiometric amounts of chiral sources (13)(14)(15)(16), little is known concerning catalytic asymmetric versions. In 1997, we reported an example of truly catalytic enantioselective Mannich-type reactions of imines with silicon enolates by using a zirconium catalyst prepared from zirconium (9).…”

Crystal structure of dichloro-N,N-bis(pyridine-2-ylmethyl)cyclohexamino copper(II), C18H23Cl2CuN3

“…The ligands of 2,2-dipyridylamine and derivatives thereof have an affinity for various transition metals such as platinum [4],iron [5], palladium [6] and avariety of others [7][8]. The interest in these ligands and complexes thereof, is due to their potential applications as anti-cancer agents [9][10] and catalysts [11][12][13].T he dichloro-N,N-bis(pyridine-2-ylmethyl)cyclohexamino copper(II) (Figure 1) complex crystallized in the monoclinic space group P2 1 /c ,with four molecules per unit cell. Thus the asymmetric unit consists of aCu(II) atom coordinated to one tridentate N,N-bis(pyridine-2-ylmethyl)cyclohexamino ligand and two chlorine atomstoform adistorted trigonal bipyramid.…”