The Application Of3-Oxo-2,3-diarylpropionaldehydes In Preparation Of Several Organic Compounds

The formation of3-oxo-2,3-diarylpropionaldehydes by the Lewis acid-catalyzed Meinwald rearrangement reactions of chalcone epoxides has been known for a century. Though it is a powerful method for the construction of β-ketoaldehydes that has demonstrated excellent substrate scope, the synthetic potential of these aldehydes have not been extensively explored. This dissertation focuses on extending the application scope of these versatile molecules, there are mainly three parts as the following.1. The application of3-oxo-2,3-diaryl-propionaldehydes in the construction of unsymmetric benzils.Benzil derivatives have found wide application in many fields of science. However, efficient synthesis of unsymmetrically substituted benzils is one of the difficult and hot spots. In the first part, we attempted to develop an efficient and practical method for the synthesis of substituented and unsymmetric benzils by utilizing3-oxo-2,3-diaryl-propionaldehydes as starting material.1)3-oxo-2,3-diaryl-propionaldehydes react with aqueous sodium hypochlorite afford the the key intermediate α,α-dichloroketones, aqueous sodium hypochlorite applied as efficient chlorination and oxidation reagent. Subsequent, a,a-dichloroketones treated with AcOH/H2O solutions gave the corresponding benzils. This method advantages include:readily available and non-hazardous materials, short reaction time, easy work-up and high yields.2) Under the optimized reaction conditions, a large variety of substrates with different functionality have been explored. By means of this method, various unsymmetric1,2-diaryldiketones bearing functional groups have been obtained in84%to94%yields regardless of the steric and electronic properties. Importantly, unsymmetrical heteroaromatic1,2-diketones were also obtained in excellent yields.3) A possible reaction mechanism was proposed. On the basis of synthesis, separation, identify the intermediates isolated from the reaction mixture, a plausible reaction mechanism is proposed:NaClO oxidation of3-oxo-2,3-diarylpropionaldehydes to the corresponding3-oxo-2,3-diphenylpropanoic acids, spontaneous decarboxylation of3-oxo-2,3-diphenylpropanoic acids in the reaction condition to provide the deoxybenzoins. Then, chlorination of deoxybenzoins by molecular chlorine which generated from the equilibrium composition of aqueous sodium hypochlorite produce the dichloroketone. At last, hydrolysis of dichloroketone in acetic acid solutions leading to the desired benzyl.2. The application of3-oxo-2,3-diaryl-propionaldehydes in the construction of2-arylbenzo[b]furans derivatives2-Arylbenzo[b]furans represent an important class of heterocyclic nucleus which have been found in many bioactive molecules and natural products. In the second part, we have developed an efficient and practical method for construction of2-arylbenzo[b]furans and2-aryl-3-substituented benzo[b]furans from3-oxo-2,3-diarylpropionaldehydes, which can be prepared from chalcone epoxides.1) Through the Meerwein rearrangement of2-methoxychalcone epoxides catalyzed by2mol%of BF3Et2O and the successive deformylation in one-pot,2-methoxydeoxybenzoins was prepared successfully. Afterwards,2-arylbenzo[b]furans were obtained in high yield (87-100%) by intramolecular cyclodehydration of2-methoxydeoxybenzoins with48%HBr.2) Under the optimized reaction conditions the reaction worked well to give a series of2-arylbenzo[b]furans derivatives in moderate yields (60%-72%). In addition,2-methoxydeoxybenzoins can be deprotonated to form highly reactive ketone enolates, which can attack electrophiles directly to offer functionalized aryl ketones. When functionalized aryl ketones reacted with demethylation reagents,2-aryl-3-substituented benzo[b]furans analogues were obtained in excellent yields.3) Moreover, the effectiveness of the protocol was demonstrated by the synthesis of Stemofuran A and the key intermediate of Eupomatenoid6,4-(5-bromo-3-methylbenzofuran2-yl)-phenol.3. The application of3-oxo-2,3-diaryl-propionaldehydes in the construction of3-formyl-2-arylbenzo furan derivatives.The3-formyl-2-arylbenzo[b]furan scaffold widely presented in natural products and bioactive molecules, however, their preparation is limited. In the third part, we have developed an efficient method for preparation of3-formyl-2-arylbenzofuran derivatives from2-(2-methoxyphenyl)-3-oxo-3-phenyl propanal.1)2-(2-Methoxyphenyl)-3-oxo-3-phenylpropanals were used as synthetic precursors for the synthesis of3-chloro-2-(2-methoxyaryl)-l-aryl-prop-2-en-1-one upon treatment with (COC1)2. Followed by an intramolecular ring closure under boron tribromide catalysis to afford the3-(dibromomethyl)-2-phenylbenzofuran derivatives as key intermediate. At last,3-(dibromomethyl)-2-phenylbenzofuran derivatives were reacted with DMSO leading to the corresponding3-formyl-2-arylbenzofurans in excellent yields. By utilization of this approach, various3-formyl-2-arylbenzofuran derivatives bearing functional groups have been obtained in78%-85%yield.2) The inhibitory activities of these newly3-formyl-2-arylbenzofuran derivatives were investigated in gastric cancer cell line MGC-803, and the preliminary results showed that compound4-7d,4-4d and4-5d possess modest MGC-803cell inhibitory activity(IC50=3.8μM,5.0μM,5.4μM,). The results provided useful information for the further study.