| Small organic molecule-triggered carbon-carbon bond formation reactions areextensively involved in synthetic organic chemistry. However, it should benoteworthy that most of them were discovered through trial and error or serendipity.Nowadays, quantum study has been employed as a versatile tool to rationally designdetailed reactions even more. In this work, two new reactions were established for thefacile construction of C-C bond under the supervision of computational studies.In the first section of this paper, a combined theoretical and experimental studyshowed that the phosphine-triggered self-cycloaddition reactions of allenoates involvehigh order1,5-,1,7-, and1,9-zwitterionic intermediates other than1,3-zwitterions.Computational studies based on DFT method were made from the perspective ofthermodynamics to evaluate the existence of these1,n-zwitterionic intermediates （n=5,7,9，…）. Then, self-cycloaddtion reactions of allenoates were developed referringto computational predict. In addition to cyclopentene derivative, two unprecedentedseven-and nine-membered ring compounds were obtained in moderate to good yields.Furthermore, some novel [5+3] and [5+2] annulations of1,5-zwitterionicintermediates with different electrophilic-coupling partners, including azomethineimines, nitroolefin, and fumarate, have been developed for the one-pot‘synthesis ofdiverse carbo-and heterocycles. These studies highlight the growing potential of thesehigh order zwitterions of allenoate-PR3.In the second section of this paper, by using DFT method （BHandHLYP/6-31G*）we investigated the detail mechanism about the arylation reactions of aromaticmonofluoromethyl, di-fluoromethyl, and trifluoromethylketones, as well asmethylketones with indoles. Calculated results confirm our previous hypothesis thatthe CF3group of the aromatic ketone plays a perfect double role in activating thesubstrate and stabilizing the Friedel-Crafts product of tertiary alcohol.Fluorine-substitution in methyl group of aromatic ketone affects the activation energyinvolving the dehydration process of the resulting alcohol, and determines whether thesubsequent re-arylation proceed or being suppressed. According to computationalresult, we employed an appropriate experimental condition, and furnished diarylationproducts in95-98%yield for aromatic CH2F-, CHF2-, CF3-ketones. Furthermore, theorigin of the high enantioselectivity of the chiral phosphoric acid-catalyzed arylation of trifluoromethyl ketone has been studied with the two-layer ONIOM method. It hasbeen found that the Re-facial attack TS could be more favored by the strongerhydrogen bonding interaction between catalyst and indole, and the weaker stericrepulsion of the3,3‘-bulky groups on the chiral phosphoric acid with the substrates.The experimentally observed enantiomeric excess can be successfully reproduced andrationalized.Aforementioned research cases indicate that computational chemistry could beemployed as potentially adjective tool in the rational design and further-developmentof new C-C bond-forming reactions. Thus, future efforts will focus on examining themechanistic details more extensively and expanding the application of theoreticalprediction-directed experiment design in organic synthesis. |
