Selective Synthesis Of Cis-Stilbenes Using Ruthenium (Ⅱ) Porphyrins As Catalysts

Stilbenes distribute widely in nature. They have multiple biological activity, such as anti-oxidization. subdue lipo in blood, anti-thrombo. anti-tumour. There are several drugs sold at market, whose skeleton are 1,2-stilbenes, such as Diethylstilbestrol, Nitromifene. Tamoxifen, Raloxifen. Resveratrol , whose skeleton is trans 1,2-stilbenes, can suppress the initiate, development and proliferation of tumour cells. Extracted from plants, combrestatins with simple construction but great suppression to tumour cells, have cis- 1,2-stilbenes skeleton.Combrestatins are thought to be new medicinal sorce for anti-cancer,To selectivly synthesis stilbenes is becoming a focus in medicinal chemistry. The synthetic procedures ever reported, such as Wittig-type reaction,condensations of aldehyde tosylhydrazones with stabilized carbanions, reductive coupling of carbonyl compounds. self-coupling of α-lithiated benzylic sulfones, are lower selectivity, or main products are trans-isomers. It draws our attention to selectivly synthesis cis- stilbenes.Ruthenium(II) porphyrin-catalyzed carbenoid C-H insertion reaction is high local- and stereoselectivity. So we decide to synthesis cis-stilbenes usingcis-isomers(69%~87%); some even got pure cis products(99%). In a word, tosylhydrazons from halogen-substitued arylaldehyde react with good yields and selectivity; tosylhydrazons from arylaldehydes containing hetercyclic atom give no products; tosylhydrazons from some ketones process reaction only when adding benzacid into the reaction mixture.We introduce different substituent groups into the porphrin, and use other metals complex containing copper, ruthenium, rhodium and manganese, to enlarge reaction stereoselectivity.Expreiments results showed that when a ortho-chloro-phenyl is the substituent of porphrin , the ratio of cis- stilbenes of products improve obviously(~95 % ); when 3,4,5-methoxy-phenyl is the substituent group, there is still cis-selectivity of products(~86%); however when a para-fluo-phenyl substituent catalyst is used, the reaction is stangely trans-selectivity(the ratio of cis:trans is 19:81). However the results of reactions catalyzed by other metals complex depended on substrates.When added optical regeant into the reaction mixture, we found that L-(+)-tartaric acid can improve the cis-selectivity(90%); whereas D- (-)-tartaric acid lower the cis-selectivity (69%).To be concluded, Ruthenium(Ⅱ) porphyrin -catalyzed self-coupling of tosylhydrazones salts from arylaldehyde or ketones yield cis- stilbenes as main products, which is different from the ever reported routes. It may be a new and useful method. We intend to establish reaction conditions to selectively synthesis such compounds based on more experiments. Finally we hope such high stereoselective reaction can be efficiently used in medicine and natural products synthesis.