Study On Highly Stereoselective Synthesis Of Multi-substituted Tetrahydrothiophene Heterocycles

Tetrahydrothiophenes are a class of fundamentally important heterocycles in organic chemistry widely found in numerous important natural products and medicines,and have been widely used in food,medicine,pesticide and chemical industry.For this reason,development of highly efficient method for the construction of tetrahydrothiophene compounds and their derivatives has been actively pursued by chemists for decades.Currently,the synthetic approches of tetrahydrothiophene compounds could be classified in multi-step and one-step cyclization syntheses.As for the the multi-step synthetic strategy,a large amount of the methods are availabe,but these approches typically require lenthy synthetic route and the overall yield is low.Moreover,this strategy is only suitable for the synthesis of single target peoduct with specific structure.Compared to the multi-step synthesis,the highly efficient one-step synthesis of tetrahydrothiophene compounds has attracted much more attention from the synthetic chemists.To date,such one-step strategy predominantly relies on the[3+2]cyclization reactions,However,as an alternative strategy,[4+1]cyclization approaches,have been far less developed.Finally,it has to be noted that most of the current methods are carried out in organic solvents.As we know,organic solvents are considered as not environmentally benign reaction medium.For this reason,development of novel one-step method to efficiently construct tetrahydrothiophene compounds in a greener manner remains highly desirable.In this thesis,we have designed and synthesized a series of bifunctional sulfur compounds,which function as electrophilic sulfur and carbon reagents,to engage in cascade C-S and C-C bond-forming reactions with one-carbon unit nucleophiles such as1,3-dicarbonyl compounds,thereby affording a distinct formal[4+1]cyclization reaction for the synthesis of functionalized 2,2,3-trisubstituted tetrahydrothiophene compounds,including those challenging structures bearing three consecutive chiral centers.The new reaction was operationally simple and afforded the products with high yields（>71%）and excellent stereoselectivities（dr>20:1）under the very mild conditions.More importantly,this tandem cyclization reaction could be carried out in H₂O,indicating signigicant advantages in green chemistry.Overall,we have developed a new method for the construction of functionalized tetrahydrothiophenes,which show the merits of environmental benifits,high yields,and high selectivities.