Synthesis Of Heterocyclic Compounds And Polysubstituted Benzenes From Isonitriles Or Acetylenic Ketones

The chemical diversity of isonitrile makes it enable its crucial applicaation in organic synthesis.Which have been widely used as starting materials in organic synthesisand medicinal chemistry.At the same time,isonitrile can provide a very useful source of C1 in the reaction system.This property makes it widely used in many reaction systems,especially in the multi-component reaction?MCR?.Similarly,acetylenic ketone has high reactivity due to its multiple active reaction sites,and it is also an important precursor for the construction of heterocyclic compounds,which is relatively easy due to the influence of the carbonyl group in the acetylene on the alkyne.Electrophilic substitution reactions and electrophilic addition reactions occur.Therefore,they are favored by many organic chemists,making it widely used in the field of organic synthesis.In this context,we report the synthesis of 4,5-diaminothiazole,imidazo[4,5-d]thiazole,sulfonylbenzene,and furanone compounds.?1?Two types of thiazole derivatives are synthesized through amultistep cascade sequence with Pd-metalated phosphorus-doped porousorganic polymers?POPs?as heterogeneous catalysts.The POPs could beused as both ligands and catalyst supports.No obvious aggregation and lossof any catalytic activity of the catalysts were observed after 10 runs of thereaction.More importantly,imidazo[4,5-d]thiazoles,which are a new classof thiazole derivatives,could be obtained through K₂CO₃-promotedintramolecular cyclization of the synthesized polysubstituted thiazoles.Furthermore,the in vitro anticancer activity of these new compounds weretested with MTT assay,and compound 4b exhibited good antitumor activity toward T-24 and A549 cells with IC₅₀ values of 10.3±0.8 and 11.8±0.5?M,respectively.In addition,the action mechanism of 4b on tumor cells was determined.?2?Among the sulfone derivatives,beta-ketosulfone is highly valued by many organic chemists because of its different functional groups?ketone and sulfone?.In the past few years,people have been working on the Michael reaction of?-ketosulfone with conjugated olefins.On the contrary,the addition of?-sulfone ketones with alkynes has hardly been explored.In this chapter,a new method for the synthesis of 2-?methylsulfonyl?benzene from transition metal catalyzed terminal acetylenic ketones and?-ketosulfone was studied.Under the basic conditions,the addition of metheneof?-ketosulfonewith two molecules of terminal alkynes occurs first to form diketene intermediate,subsequently,the diketene undergoes cyclization reaction to give the the final product.Using this economical and green synthetic means,series of sulfonyl benzene derivatives were synthesized,with alkali as the sole catalyst,no metal,only water as the byproduct,and no environment pollution.?3?Furan is an important class of fivememberoxygen-containing heterocyclic compounds.It is a hot topic in organic synthesis chemistry to synthesize furanone derivatives using readily available starting materials.This chapter investigates a new method for the synthesis of furanones without transition metalcatalystfrom dialkynes and?-ketosulfones.The first is the addition of metheneof?-ketosulfone to alkynes on one side of the diketene under alkaline conditions to obtain the enoneintermediate,and secondly the intermediate is cyclized to give the unstable four-member ring,which is rapidly openedunder basic conditions.Thirdly,an intramolecular cycloaddition reaction takes place to form the final product.Using this reaction,a series of furanone derivativeswere synthesized.No metal catalyst,high yields,low cost,no by-products and no pollution to the environment are the major merits of this method.