Investigation On Hydrocarboxylation Of Olefins And Aminoboration Of Alkynes

(1)Carboxylic acids are a class of organic compounds of great importance in pharmaceuticals and fine chemicals.Regioselective hydrocarboxylation of olefins provides a straightforward approach to carboxylic acids.Traditionally,this process involves the use of toxic and flammable CO under high pressure and/or high temperature,which may limit its application in laboratories.Thus,it would be highly desirable to develop effective,mild,and operationally simple hydrocarboxylation processes with nongaseous CO surrogates.However,prior to our studies,only limited examples of such reaction were reported primarily with formic acid or esters as a CO source and Ir or Rh as a catalyst at high temperature(>100 ?).Based on this,we have developed an efficient Pd-catalyzed regioselective hydrocarboxylation of aryl olefins under mild reaction conditions.With HCOOH as the sole CO surrogate and Pd(OAc)2 as catalyst,a variety of 2-and 3-arylpropanoic acids have been obtained in good yields with generally high regioselectivities by the judicious choice of ligand.Nonsteroidal anti-inflammatory agents,ibuprofen and naproxen,can be readily obtained with high yields and regioselectivities.The reaction process requires no handling of toxic CO gas and is operationally simple.Finally,deuterium studies were carried out to probe the reaction mechanism and a reasonable catalytic circle was proposed.(2)The inconformity that lies between the experimental results and DFT calculations of the intramolecular arminoboration of unfunctionalized olefins,reported by the Li group in 2015,brought us to a careful reinvestigation on this reaction.We proposed that the aminoboration of alkenes is activated by the interaction between C=C double bond and BCl3.The new mechanism gives an overall free energy barrier of about 20 kcal mol-1,in good agreement with the fact that reactions occur at room temperature.We also studied the reactivity of an unfunctionalized alkyne both computationally and experimentally.The computational results indicate that the protodeboronation is feasible due to the unique enamine structure of intermediate,and the generation of hydroamination product is more favored both thermodynamically and kinetically at the post-aminoborylation stage.Thus,we learned that it is unlikely to realize the single selectivity for the BCl3 mediated aminoboration of unfunctionalized alkynes,but hydroamination with single product is feasible.To confirm the generality of the conclusion,we synthesized a series of alkynes and realized the first BCl3 promoted metal-free hydroamination of alkynes.(3)Recently,Yan group discovered a metal-free oxidative B-N coupling of carborane with pyridine and its derivatives.To gain a whole picture of the reaction pathway,we conducted DFT calculations to simulate the reaction.A successive single electron transfer(SET),hydrogen atom transfer(HAT)and nucleophilic attack pathway is proposed.With intermolecular B-N coupling conditions,the overall activation barrier was found to be 26.7 kcal mol-1,which is comparable with the experimental conditions(at 80 ?).Furthermore,based on the mechanism of the intermolecular reaction,DFT calculations predicted that the reaction temperature could be lowered to room temperature with additional pyridine,which is verified by experiments later.In addition,the computed activation free energy for the intramolecular B-N coupling is as low as 20.8 kcal mol-1,which accounts for the mild reaction conditions at ambient temperature.Finally,we extended our calculation to the unsymmetric substrate.To our delight,the predicted regioselectivity is comparable with the experimental ratio.