Ethyl Ketone, Aryl Ester Synthesis Of New Methods And Its Asymmetric Transformation Research

Ethyl arylglyoxylates is a type of compound with the carbonyl and carboxyl, because the multi-positions of these compounds for reaction show special chemical properties, it has been playing an important role in organic synthesis and biological metabolism and has been widely applied to the pharmaceutical industry and metabolic balance, functional skin cosmetics, functional material composition and so on. In recent years, the a-keto acids having bioactivity have attracted considerable attention due to their applications in many areas, such as pharmaceutical synthesis and functional synthesis of heterocyclic compounds, etc. Meanwhile, the carbonyl carbon of the ethyl arylglyoxylates is prochiral carbon, so these compounds have been widely used in asymmetric synthesis.A number of important chiral compounds have been synthesized by the ethyl arylglyoxylates. For example, the asymmetric amination reduction of the ethyl arylglyoxylates can provide chiral a-amino acids,its asymmetric reduction can give chiral a-hydroxy acids, the asymmetric aldol reaction can supply precursors of muscarinic receptor antagonists, the chiral tertiary a-hydroxy acid esters can be synthesized using ethyl arylglyoxylates by the asymmetric addition with metal organic compounds, the P-nitro alcohols with multiple functional groups can be obtained by the asymmetric Henry reaction of nitro compounds and ethyl arylglyoxylates, etc. This paper presents the new synthetic method of ethyl arylglyoxylates and their asymmetric transformation as follows:1.A series of ethyl arylglyoxylates have been synthesized using aromatic compounds and the commercially available ethyl oxalyl chloride as the starting materials and AICl3 as catalyst by the Friedel-Crafts acylation reaction in organic solvents. The synthesis conditions were optimized, and the selectivity of reaction was investigated. This synthetic method exhibits several advantages such as mild reacting-conditions, simple workup procedures and high yields, etc.,which is a good way of synthesis of ethyl arylglyoxylates. The structures of synthesized compounds were confirmed by IR and 1HNMR.2.Due to ethyl oxalyl chloride and AlC13 are sense to moist, the synthesis of ethyl arylglyoxylates by Friedel-Crafts acylation reaction in the solvent must be in anhydrous condition.In the solvent-free conditions, ethyl arylglyoxylates can be also synthesized from aromatic compounds and ethyl oxalyl chloride in presence of AlCl3t by grinding at room temperature. A series of ethyl arylglyoxylates have been synthesized by grinding in solvent-Free condition, the synthesis conditions were optimized and the selectivity of reaction was also investigated. This method provided several advantages such as environmentally benign, high yield, good selectivity, simple workup procedure and lower costs, which is a facile method for synthesis of ethyl arylglyoxylates.3.(S)-Ethyl 2-hydroxy-2-(2-cyclopentanonyl) arylacetate was synthesized through the asymmetric aldol reaction of ethyl arylglyoxylate and cyclopentanone by catalysis of L-proline. The tertiary stereogenic center was constructed with good stereoselectivity, the asymmetric condensation conditions were optimized, and the study of the stereoselectivity is carried out. This asymmetry condensation reaction possesses of several advantages such as simple procedure, good stereoselectivity and high yield. The carbonyl of the condensation product was reduced using a modified Clemmensen reaction, which provided (S)-ethyl 2-cyclopentyl-2-hydroxy-2-arylacetate, a key intermediate for the synthesis of the muscarinic receptor. Their structures were characterized by IR,1H NMR,13C NMR spectroscopy. The enantioselectivity was analyzed by HPLC with chiral column.4.In presence of titanium(IV)ethoxide, the chiral menthyl arylglyoxylates were prepared from the transesterification of ethyl arylglyoxylate and the natural abundant menthol. In the auxiliaries of asymmetric factor, the new menthyl (2R)-2-hydroxy-2-aryl-3-nitropropionates were synthesized by the Henry reaction of menthyl arylglyoxylate and nitromethane. The conditions of the synthesis were optimized. The enantioselectivity was analyzed by HPLC with chiral column, the enantiomeric excess (e.e) of the condensation reactions are from 46.5% to 64.2%, which means the chiral induce of menthyl group has a great effect on controlling configuration of reaction product. Their structures were characterized by IR,]H NMR,13C NMR spectroscopy and elemental analysis.5.a-Hydroxy acid with the tertiary stereogenic center is an important pharmaceutical synthesis intermediate, which can be obtained by the asymmetric addition of a-keto esters and organometallic compounds.A series of novel compounds, (R)-menthyl-2-aryl-2-hydroxy butanoates, were synthesized by the addition of menthyl aryl glyoxylates and Et2Zn in presence of zinc chloride. The addition reactions exhibited good yields and high stereoselectivity (diastereoselectivities excess≥80%) analyzed by HPLC using a chiral column. The structures of the products were characterized by IR,1H NMR,13C NMR, MS and elemental analysis. The important pharmaceutical intermediates, (R)-2-aryl-2-hydroxy butyric acids, were obtained with high optical purities by the hydrolysis of (R)-menthyl-2-aryl-2-hydroxy butanoates.