Mechanism And Origins Of CuH-Catalyzed Regio- And Enantioselective Hydrocarboxylation Of Allenes

In recent years,the transition metal-catalyzed functionalization of unsaturated compounds has made great progress,and its application in organic synthesis is more and more extensive.Among them,CuH catalyst performs well in the functionalization of unsaturated compounds,and the reactions involved in the synthesis usually have high stereoselectivity.Since the 20 th century,the research on CuH-catalyzed unsaturated substrates has gradually full-fledged,but the related research on CuH-catalyzed hydrocarboxylation of unsaturated substrate is still deficient.In 2019,Buchwald et al.reported a method of synthesizing(S)-carboxylic acid compounds by CuH-catalyzed enantioselective hydrocarboxylation of allenes and fluoroformate.Based on this reaction,this paper studied the reaction mechanism and the origin of regioselective and enantioselective,mainly including the following:(1)Based on the lack of research on reaction mechanism in CuH-catalyzed hydrocarboxylation of allenes,the reaction process was calculated and analyzed by DFT calculation.The calculated reactions include migratory insertion of alkenes on Cu-H complexes,enantioselective addition of fluoroformate,the β-fluoride elimination and σ-metathesis.According to the experimental results and previous theoretical calculations on such reactions,we assume that there are three reaction pathways.The calculation results show that the pathway through the terminal alkene migratory insertion and the enantioselective addition via the six-membered transition state is the most feasible pathway.We used the distortion/interaction model to analyze the six-membered transition state and the four-membered transition state in the enantioselective addition,and explained the reason of their energy barrier difference.In addition,we also discussed other possible transition states of migratory insertion.Considering the weak interaction,we added B3LYP-D3 dispersion correction and replaced the LANL2 DZ basis set with def2-SVP basis set,and repeated the above calculation and analysis steps,and the conclusions remains the same.(2)Based on the experimental results and previous theoretical calculations of such reactions,we calculated the pathway of the Markovnikov migratory insertion.The calculation results show that the anti-Markovnikov migratory insertion is the dominant reaction pathway.We analyzed the migratory insertion step using the NBO analysis,and explain the reason for the difference of their energy barriers.In addition,we also discussed other possible regioselective migration insertion.Similarly,we use the B3LYP-D3/def2-SVP method to repeat the above calculation and analysis steps,and the conclusion remains the same.(3)Based on the experimental results and previous theoretical calculations on such reactions,we calculated the pathway of(R)-enantioselective addition.The calculation results show that(S)-enantioselective addition is the dominant reaction pathway,which is consistent with the experimental results.According to previous studies,we assumed that the ligand is the cause of enantioselectivity.Therefore,we analyzed the steric effects of phosphine ligand and the substrates,explained the cause of the difference in the transition state energy barrier of enantioselectivity.In addition,we also discussed other possible enantioselective addition transition states.Similarly,we use the B3LYP-D3/def2-SVP method to repeat the above calculation and analysis steps,and the conclusion remains the same.