Synthesis of ( E )-1,4-diaryl-2-butene-1,4-diones

We report a facile route for the preparation of symmetric and unsymmetric ( E )-1,4-diaryl-2-butene-1,4-diones 3 by a two-step route, including (1) nucleophilic substitution of 1 with sulfinic acid sodium salts, and (2) K 2 CO 3 mediated alkylation of β-ketosulfones 4 with 1 followed by sequential desulfonylation of the resulting 1,4-diketones 5 in acetone. These products were obtained in high yields.

Although this one-pot route is mild, simple and convenient, the probability for two incomplete conversions should increase, especially for the formation of an unsymmetric skeleton of ene-1,4dione, including (1) a nucleophilic substitution of α-bromoacetophenone (1a) with TolSO2Na (2a, 0.5 equiv) in the presence of K2CO3 (1.5 equiv) affording β-ketosulfone and followed by (2) a desulfonylative elimination of the resulting β-ketosulfone with α-bromo 4-methylacetophenone (1b, 1.0 equiv) producing ene-1,4-dione 3a.Under a highly concentrated reaction mixture (1.5 M, based on all substrates/DMF), we assumed that a different solubility of substrates should perform a competitive reaction easily during the overall process.However, this domino route often had other drawbacks, such as the use of a high boiling point solvent, and moderate isolated yields.Inspired by this route and with our interest in exploring practical applications of β-ketosulfones, herein we report the synthesis of symmetric and unsymmetric (E)-1,4-Diaryl-2-butene-1,4-diones by the conventional step-by-step route (Scheme 2 and eq 2).Initially, the nucleophilic substitution of 1a with 1.0 equivalent of 2a provided 4a in a quantitative yield after the recrystallization process.
4] On the basis of these significant characteristics, many protocols have been developed for the synthesis of quinoxalines.According to reported literature, the most popular procedures are derived from the condensation of 1,2diaminobenzenes with a number of polar ortho-carbon units, such as aldehydes, ketones, 1,2diketones, epoxides, vicinal diols, diazoketone, alkenes, and alkyne. 45Among these starting substrates, only one example on the skeleton of 1,4-enediketone has been reported for the formation of quinoxaline. 46Furthermore, condensation of 3b with 1,2-diaminobenzenes 6a-d in dioxane for 4 h at reflux provided quinoxalines 7a-d (78%-86%) and acetophenone (8) via a tandem process of the condensation of 3b and 6, the intramolecular Michael addition of intermediate I, and the retro-aldol reaction of intermediate II.

Conclusions
We have developed a mild and facile synthesis of substituted symmetric and unsymmetric ene-1,4diketones 3 in good yields by a two-step route, including (1) nucleophilic substitution of αbromoacetophenones 1 with sulfinic acid sodium salts 2 in a co-solvent of dioxane and water at rt for 1 h, and (2) K2CO3 mediated alkylation of β-ketosulfones 4 with substituted αbromoacetophenones 1 followed by sequential desulfonylation of the resulting α-sulfonyl 1,4diketones 5 in acetone at reflux for 4 h.Morever, quinoxalines 7 have been synthesized from a condensation of ene-1,4-diketone 3b with 1,2-diaminobenzenes 6.Further investigation regarding the synthetic applications of β-ketosulfones will be conducted and published in due course.

Experimental Section
General.All other reagents and solvents were obtained from commercial sources and used without further purification.Reactions were routinely carried out under an atmosphere of dry nitrogen with magnetic stirring.Products in organic solvents were dried with anhydrous MgSO4 before concentration in vacuo.Melting points were determined with a SMP3 melting apparatus.A representative procedure for compounds 3a-r is as follows.A solution of sodium arenesulfinic acid salts 2 (0.25 mmol) in H2O (2 mL) was added to a solution of substituted αbromoacetophenones 1 (0.25 mmol) in dioxane (8 mL) at rt.The reaction mixture was stirred at rt for 1 h and the solvent was concentrated.The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL).The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product 4a-f in nearly quantitative yields.Without further purification, K2CO3 (52 mg, 0.377 mmol) was added to a solution of the resulting 4 (~0.25 mmol) in acetone (8 mL) at rt.The reaction mixture was stirred at rt for 5 min.α-Bromoacetophenones 1a-i (0.25 mmol) in acetone (2 mL) was added to the resulting reaction mixture at rt.The reaction mixture was refluxed for 4 h, cooled to rt, and the solvent was concentrated.The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL).The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product.Purification on silica gel (hexanes/EtOAc 10/1~3/1) afforded compounds 3a-r.A representative procedure of compounds 7a-d is as follows: 1,2-Diaminobenzenes 6a-d (0.25 mmol) were added to a solution of 3b (60 mg, 0.25 mmol) in dioxane (5 mL) at rt.The reaction mixture was stirred at reflux for 4 h, cooled to rt, and the solvent was concentrated.The residue was diluted with water (10 mL) and the mixture was extracted with CH2Cl2 (3 x 20 mL).The combined organic layers were washed with brine, dried, filtered and evaporated to afford crude product.Purification on silica gel (hexanes/EtOAc 10/1~3/1) afforded skeleton 7a-d.

Table 1 .
Optimal conditions a