Studies On C-H Activation-based Synthesis Of Allenioc Acids And 2,3-allenol-involved Oxidative Cross-Coupling Reactions

Allenes are compounds containing 1,2-propadiene fragments with two sets of ? bonds perpendicular to each other.The unique structure gives allene unique reactivities.Allene units are not only widely present in bioactive molecules and natural products,but also used as very useful building blocks in organic synthesis.Our group has been focusing on the synthesis and transformation of allenes for a long time.Based on this,my Ph.D.study is divided into two parts: C-H activation-based synthesis of allenoic acids and the Rh-catalyzed cross-coupling involving 2,3-allenols.Part ?:The synthesis of allenes,especially the synthesis of allenoic acids,has always been a very important topic of allene chemistry.In this part of the work,we have developed a method to synthesize allenoic acids based on C-H activation applying benzoic acid compounds and propargyl alcohol derivatives as starting materials with yields of 50%~75%.This method uses [Ru(p-cymene)Cl2]2 as the catalyst,and the reaction conditions are mild and can be easily executed on a gram scale.When optically active propargyl acetate was used,high efficiency of chirality transfer can be achieved smoothly to obtain highly optically active axial chiral allenoic acids.We also clarified the reaction mechanism through deuteration experiments and kinetic studies.Part ?:1.It was discovered that under the co-catalysis of rhodium/copper,the oxidative cross-coupling reaction between two molecules of allenols resulted in a series of dihydrofuran derivatives.It is compatible with both alkyl and aryl substituted 2,3-allenols.Through continuous optimization of the reaction,we have further improved the catalytic efficiency on the copper catalyst.Under the newly developed catalytic system,allenol compounds derived from bio-active molecules can also be successfully transformed.The reaction may easily be performed on gram scales.We explored the reaction mechanism through a series of control and deuteration experiments,and DFT calculations,and rationalized the exclusive E-selectivity observed.2.Based on the bimolecular allenol oxidative cross-coupling reaction,the cross-coupling reaction of terminal alkynes and 2,3-allenol was designed and developed.A series of 3-alkynyl enone compounds could be obtained.When unsubstituted 2,3-allenol is used as the substrate,3-alkynyl enal compounds can be obtained.This method also afforded the product with all exclusive E-selectivity.Mechanistic studies have shown that the reaction also includes the process of 1,4-H delivery.