Study On The Development Of Highly Efficient Chalcogen-Bonding Catalysts,the Elucidation Of Their Weak Interaction Mechanism,and The Application Of These Catalysts In Catalytic Cyclization Reactions

Noncovalent S…O bonding interaction,is an evolutionary force that has been exploited by nature to regulate protein conformation and maintain specific enzyme activity.This weak interaction has been applied to the fields of crystal engineering,drug design,materials science.In addition,this type of weak interaction has been extensively investigated by theoretical scientists.However;such S…O interaction and analogous Se…0 interaction have not been applied to the field of organocatalysis so far.The reason is that such noncovalent force is comparatively weak.Therefore,in this thesis,we designed and synthesized a class of highly efficient chalcogen bonding catalysts and the weak interaction mode of these catalysts was elucidated.We developed the concept of "Chalcogen-Chalcogen Bonding Catalysis"(S…0 and Se…O)as well as the strategy of "Dual Chalcogen-Chalcogen Bonding Catalysis" to drive chemical reactions.Notably,the new strategy shows its advantage as it not only enables less reactive substrates working efficiently but tolerates inaccessible substrates using conventional methods.Part 1.The development of a class of highly efficient chalcogen bonding catalysts and their application of cyclization reactionThe S…O interaction has been observed in many crystal structures.This noncovalent force has been explained as the a-hole interaction by theoretical chemists.Considering the force between S…O or Se…O is very weak as demonstrated by theoretical and experimental results,we have significantly increased the depth of?-hole of divalent chalcogen by bonding a cation to the S atom or Se atom.As a result,we have developed a class of extraordinary catalysts featuring the structures of X+-Se-R and X+-S-R.The S…O,Se…O,Se…Cl and Se…Se interactions were observed from the single crystal structures of these catalysts.?-Ketoaldehyde derivatives can be activated by this type of chalcogen bonding catalyst by forming S…O or Se…O interaction.The reaction enables the assembly of discrete small molecules to construct N-heterocycles in a highly efficient manner.In addition,this type of catalyst can generate enols from non-activated ketones under neutral conditions.We discovered that Se…O activation of methyl ketone could generate enol which adds to the double bond to give bridged N-heterocycles in moderate yields.It is well-known that merely weak noncovalent forces are extremely difficult to generate enol from linear unactivated ketones.This finding undoubtedly expands the capacity of noncovalent forces.A series of control experiments demonstrate that Se…O bonding interaction is the driving force of these reactions.Part 2.The development of dual chalcogen-chalcogen bonding cooperative catalysis strategy and its application in catalytic cyclization reactionsIt remains an important goal how to realize traditional catalysis approaches through chalcogen bonding catalysis and in particular,to achieve challenging reactions that are unsuccessful by traditional methods.To this end,we have developed"dual chalcogen-chalcogen bonding cooperative catalysis" strategy that the distinct chalcogen atoms simultaneously interact with two chalcogen-based electron donors to give rise to the catalytic activity,thus facilitating chemical reactions.This catalytic mode enables shifting the intermolecular reantion to an 'intramolecular' manner,which opens up a new door for driving chemical reactions.To demonstrate the advantage and potential of this strategy,the Rauhut-Currier type reaction was investigated.Conventional approaches to the Rauhut-Currier-type reactions require the use of strongly nucleophilic Lewis bases as essential promoters.The implementation of this dual chalcogen-chalcogen bonding catalysis strategy allows the simultaneous Se…O bonding interaction between chalcogen-bonding donors and an enone and an alcohol,enabling the realization of the Rauhut-Currier-type reactions in a distinct way.The 13C,77Se and 31P NMR experiments confirmed that the interaction between the catalyst,the substrate and the alcohol is the Se…O bonding interaction.We implemented a series of insightful experiments to prove the mechanism of dual chalcogen bonding catalysis.For a dual chalcogen bonding catalysis approach,the reaction can only be preceded when a proper ratio of alcohol/enone was used.The further implementation of a consecutive dual Se…O bonding catalysis approach enables the achievement of an initial Rauhut-Currier-type reaction to give an enone product which further undergoes an alcohol addition induced cyclization reaction.This work demonstrates that the nearly linear chalcogen-bonding interaction can differentiate similar alkyl groups to give rise to regioselectivity.Moreover,this dual chalcogen bonding catalysis strategy can make less reactive substrates and specific substrates react smoothly,which otherwise are failed using the traditional Lewis base catalysis approach.This research highlights the potential of this strategy and we envision that this dual catalysis strategy would find more applications and provide a solution to other synthetic problems in the future.