The molecular electrostatic potential (MESP) V(r) data derived from a reliable quantum chemical method has been widely used for the interpretation and prediction of various aspects of chemical reactivity. A rigorous mapping of the MESP topology is achieved by computing both rV(r) data and the elements of the Hessian matrix at the critical points where rV(r) = 0. In the MESP topology, intra-and inter-molecular bonded regions show the characteristic (3, À1) bond critical points (BCPs) while the electron-rich regions such as lone pair and π-bonds show (3, +3) minimum (V min ) CPs. The V min analysis provides a simple and powerful technique to characterize the electron-rich region in a molecular system as it corresponds to the condensed information of the wave function at this point due to the nuclei and electronic distribution through the Coulomb's law. The V min analysis has been successfully applied to explain the phenomena related to chemical reactivity such as π-conjugation, aromaticity, substituent effect, ligand electronic effects, trans-influence, redox potential, activation energy, cooperativity, noncovalent interactions, and so on. The MESP parameters ΔV min and ΔV n , derived for arene systems have been used as powerful measures of substituent effects while V min at the lone pair region of ligands has been used as a reliable electronic parameter to assess their σ-donating ability to metal centers. Furthermore, strong predictions on the intermolecular interactive behavior of molecular systems can be made from MESP topology studies. This review summarizes the chemical reactivity applications offered by MESP topology analysis for a large variety of organic, organometallic, and inorganic molecular systems.
Alcohols and nitrile functionalities have widespread applications in biochemical and chemical synthesis. Catalytic transformations involving C−C bond formation relying on unsaturated coupling partners create important pathways for processes in synthetic, material, and medicinal chemistry. The discovery of a simple and selective coupling of nitriles with allylic alcohols catalyzed by a ruthenium pincer complex is described, which tolerates reactive functional groups such as carbamate, sulfonate, olefin, cyano, and trifluoromethyl-substituted benzyl nitriles. Homo allylic alcohols also provided 1,4-addition products following the isomerization of double bonds. Mechanistic studies supported that the allylic alcohols initially undergo selective oxidation by the catalyst to α,β-unsaturated carbonyl compounds followed by 1,4-conjugate addition of benzyl nitriles catalyzed by a base and subsequent catalytic reduction of carbonyl functionality, leading to the formation of δ-hydroxynitrile products. The catalytic cycle of this tandem process is established by density functional theory studies. Remarkably, anipamil drug is successfully synthesized using this catalytic protocol. The utility of the δ-hydroxynitrile products in the synthesis of biologically active molecules and their further functionalization are also demonstrated.
An efficient regioselective dearomatization of N-heteroarenes using a ruthenium precatalyst [Ru-(p-cymene)(PCy 3 )Cl 2 ] 1 is achieved. Reactions were performed under mild and neat conditions. A wide variety of N-heteroarenes undergo the addition of silanes in the presence of precatalyst 1, leading to exclusive N-silyl-1,2-dihydroheteroarene products. This catalytic method displays a broad substrate scope; quinolines, isoquinolines, benzimidazoles, quinoxalines, pyrazines, pyrimidines, and pyridines undergo highly selective 1,2-dearomatization. Both electron-donating and electronwithdrawing substituents on N-heteroaromatics are well tolerated in this protocol. Mechanistic studies indicate the presence of [Ru-(p-cymene) (PCy 3 )HCl] 4 in the reaction mixture, which may be the resting state of the catalyst. The complete catalytic cycle as revealed from density functional theory (DFT) studies show that the product formation is governed by N → Si tetrel bonding. Initially, PCy 3 dissociates from 1, and further reaction of [(p-cymene)RuCl 2 ] 20 with silane generates the catalytically active intermediate [(p-cymene)RuHCl] 7. Heteroarene coordinates with 7, and subsequent dearomative 1,3-hydride transfer to the C2 position of the heteroaryl ligand generates an amide-ligated intermediate in which the reaction of silane occurs through a tetrel bonding and provides a selective pathway for 1,2-addition. DFT studies also revealed that ruthenium-catalyzed 1,4-hydroboration of pyridines is a facile process with a free energy barrier of 3.2 kcal/mol, whereas a pathway for the 1,2-hydroboration product is not observed due to the steric effects exerted by methyl groups on pinacolborane (HBpin) and p-cymene. Notably, enabled by the amine−amide inter-conversion of the coordinated heteroarene ligand, the +2 oxidation state of ruthenium intermediates remains unchanged throughout the catalytic cycle.
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