The Synthesis Of PEG Supported Chiral Catalysts And Their Application In Asymmetric Catalytic Domino Michael-aldol Reactions

Chiral diamine and chiral amino alcohols are two kinds of small molecular organocatalysts. which are widely used in asymmetric catalytic Michael addition, aldol condensation, Diels-Alder, hydrogenation and domino reactions with good catalytic effects. Polyethylene glycol (PEG) is one of the most widely used soluble polymers currently, which has good mechanical stability and chemical stability. It is soluble in dichloromethane, chloroform, toluene, acetonitrile, N, N-dimethylformamide, methanol, ethanol and water, while insoluble in ether, tert-butylmethylether,n-hexane, isopropylalcohol and cold ethanol. PEG supported catalysts can be reacted in a homogeneous system, which could be collected by extraction, precipitation and filtration when adding ether and n-hexane to the reaction system. More specifically, as a kind of water-soluble polymer, PEG can be reacted in nontoxic, cheap, abundant and environmentally friendly water.In this paper, we use PEG3400as a soluble supporter to prepare PEG supported chiral diamine and chiral amino alcohol, and then use them to catalyze the asymmetric domino Michael-aldol reactions of benzyl benzoylacetate with α,β-unsaturated ketones.Firstly, PEG supported double (S)-2-(4’-benzyloxygen)-N-methylethyl-1,2-diamine la and PEG supported double (S)-2-(4’-benzyloxygen)-β-amino alcohol lb were synthesized using natural L-tyrosine as initiating material and PEG3400as a soluble supporter by a series reaction steps with57%and76%yields respectively. The intermediates and products were characterized by IR,1H NMR and13C NMR and the data obtained was consistent with the structure of the target compound. The isolation and purification of products was monitored by TLC.Secondly, seven different α,β-unsaturated ketones were synthesized by various aromatic aldehydes with acetone with71-89%.yields.Thirdly, in the green solvent of water, using benzyl benzoylacetate with (E)-4-phenyl-3-buten-2-one as a template reaction, the asymmetric domino Michael-aldol reactions of benzyl benzoylacetate with α,β-unsaturated ketones catalyzed by PEG-supported chiral diamine la and chiral amino alcohol1b were studied. The effects of different acids, reaction temperature, reaction time and amount of catalyst on the catalytic Michael-aldol reaction were discussed and the optimized reaction conditions were:glyoxylic acid as cocatalyst, catalyst and cocatalyst was20mol%, the reaction temperature was25℃, the reaction time was7days. Under the optimized reaction conditions, the substrate scope of the reaction was investigated. Various Aromatic, heterocyclic and polycyclic α, β-unsaturated ketones effectively underwent the domino Michael-aldol reaction with benzyl benzoylacetate catalyzed by the chiral catalysts1a (73-88%yield,99:1dr,84-97%ee) and1b (71-93%yield,99:1dr,88-97%ee). In the catalytic reaction, PEG as a soluble supporter allows the reaction to proceed efficiently in water and PEG supported group provides the huge steric hindrance leading to a high diastereoselectivity.Fourthly, PEG supported chiral diamine la and chiral amino alcohol lb could be recycled with over90%recovery rate by simple extraction, precipitated and washed with ice ether when the asymmetric catalytic reaciton was finished. The stereoselectivity of the recycled catalyst remained almost intact for at least four reaction cycles, while the chemical efficiency of the recycled catalyst slowly eroded upon its iterative reuse.In conclusion, we have developed PEG supported double (S)-2-(4’-benzyloxygen)-N-methylethyl-1,2-diamine1a and PEG supported double (S)-2-(4’-benzyloxygen)-β-amino alcohols1b for the asymmetric domino Michael-aldol reactions of benzyl benzoylacetate with α, β-unsaturated ketones in water, providing the optically pure chiral products in good yields with excellent diastereoselectivities and good to excellent enantioselectivities. The excellent catalytic performance in water with no pollution to the environment and the easy separation and reuse of the catalysts make it a useful alternative to other catalysts system, which is in accordance with the principle of Green Chemistry.