| In the past few decades,the functionalization of olefins at remote specific sites has gradually become one of the research hotspots in the organic field.Compared with the traditional reaction that reacting center is at the original double bond position,the remote inert carbon-hydrogen bond and carbon-carbon bond functionalization of olefins via the metal promoted "chain walking" strategy has attracted widespread attention.However,despite numerous related works have been reported,the remote functionalization at different carbon centers of the olefins via the "chain walking" process,especially the controllable “chain walking” process is still the major challenge in synthetic chemistry.As for zirconium chemistry,it has been discovered for nearly half a century(1974)that organozirconocenes can walk on the alkyl chain(“chain walking”)and activate the remote chemical bond.However,to date,how to control the selectivity and direction of the remote migration of alkylzirconocenes is still an unsolved scientific problem.This thesis mainly studied the terminal Bpin group directed “chain walking” process of terminal and internal alkylzirconocenes,generating the gem-borazirconocene reagent with excellent yield and regioselectivity.The reagent can further react with aryl halides under the visible-light-induced nickel-catalyzed cross-coupling reaction conditions to afford the high value-added benzyl borate products.This mild method displayed excellent functional group tolerance and broad substrate scope,and can be used for the late-stage modification of natural compounds,like the sugar and steroid derivatives.At the same time,the benzyl borate products generated from the nickel catalyzed cross-coupling reaction condition can be further transformed into the furan,thiophene,alcohol,olefin,and ketone derivatives via the diverse conversion of the carbon-boron bond.Based on the experimental data and the QM computation,the detailed mechanism of the Bpin group directed “chain walking” process of alkylzirconocenes was investigated.Compared with the process to generate the terminal Bpin substituted primary alkylzirconcene reagents,our data indicated that the process to generate the gem-borazirconocene reagent via the “chain walking” strategy is more favorable in terms of thermodynamics and kinetics.According to the Boltzmann distribution,the distribution ratio of the primary alkylzirconcene reagent and the alkyl gem-borazirconocene reagent is about 1:80,which is closed to the experimental data 1:40.The computation data also supported that there is a ?-p hyperconjugation effect between the carbon-zirconium bond and the unoccupied p orbital of the boron atom,which might be able to interpret the higher reactivity of the alkyl gem-borazirconocene reagent.Besides attracted wide attention from the researchers in drug discovery,the chiral boron ester structure was also sought after by synthetic chemists for its utility in quickly and diversely synthesizing other types of chiral compounds via the stereospecific conversion of the chiral carbon-boron bond.The rapid introduction of the chiral carbon-boron bond into the substrates has been recognized as an efficient synthetic strategy in the organic synthesis field.Based on the success of cross-coupling reaction between gem-borazircocene reagent and aryl halides,we further developed the asymmetric version of this cross-coupling reaction,forging a series of benzylic boronic acid ester compound with high yield and excellent enantioselectivity.The chiral benzylic boronic acid ester product can be transformed into the corresponding chiral thiophene,furan,alcohol,and olefin derivatives via the stereospecific conversion of the carbon-boron bond.The key steps of the chirality control and the catalytic cycle of the reaction were studied in detail.The computation data supported that the oxidative addition of alkyl radical to the chiral bivalent nickel complex is the enantioselctivity-determing step. |
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