Nucleophilic molecular orbitals

As with carbene complexes, metal carbynes display a range of reactivity with electrophiles and nucleophiles. Molecular orbital calculations show that even cationic Fischer carbyne complexes are polarized as M, +=C A neutral Fischer- and Schrock carbyne complexes have an even greater negative charge on Ccarbyne.93 If all reactions between carbyne complexes and other species were charge-controlled, we would predict that nucleophiles would always attack at the metal and electrophiles at Ccarbyne. As we should expect by now, the picture is more complicated in practice. 

One of the resonance structures exhibits a positive charge on the carbon atom, indicating that the carbon atom is deficient in electron density (5+). Inductive effects also render the carbon atom deficient in electron density. As a result, this carbon atom is particularly electrophilic and is susceptible to attack by a nucleophile. Molecular orbital calculations suggest that nucleophilic attack occurs at an angle of approximately 107° to the plane of the carbonyl group, and in the process, the hybridization state of the carbon atom changes (Figure 20.1). 

Thermodynamic properties such as heats of reaction and heats of formation can be computed mote rehably by ab initio theory than by semiempirical MO methods (55). However, the Hterature of the method appropriate to the study should be carefully checked before a technique is selected. Finally, the role of computer graphics in evaluating quantum mechanical properties should not be overlooked. As seen in Figures 2—6, significant information can be conveyed with stick models or various surfaces with charge properties mapped onto them. Additionally, information about orbitals, such as the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO), which ate important sites of reactivity in electrophilic and nucleophilic reactions, can be plotted readily. Figure 7 shows representations of the HOMO and LUMO, respectively, for the antiulcer dmg Zantac. 

Chemical Properties. The chemistry of ketenes is dominated by the strongly electrophilic j/)-hybridi2ed carbon atom and alow energy lowest unoccupied molecular orbital (LUMO). Therefore, ketenes are especially prone to nucleophilic attack at Cl and to [2 + 2] cycloadditions. Less frequent reactions are the so-called ketene iasertion, a special case of addition to substances with strongly polarized or polarizable single bonds (37), and the addition of electrophiles at C2. For a review of addition reactions of ketenes see Reference 8. 

Information on nucleophilic addition chemistry of quinones and various mechanistic rationali2ations have been discussed, and molecular orbital calculations have been proposed as more definitive approaches for explanation and prediction (63). 

The TT-electron density refers to the electron density at a given carbon atom obtained by summing the contributions from all the filled molecular orbitals. Electrophilic attack occurs where this density is highest, and nucleophilic attack where it is lowest tt-electron densities are not dominant in determining the orientation of homolytic substitution. 

Electron densities, bond densities, and spin densities, as well as particular molecular orbitals may be displayed as graphical surfaces. In addition, the value of the electrostatic potential or the absolute value of a particular molecular orbital may be mapped onto an electron density surface. These maps provide information about the environment around the accessible surface of a molecule. Electrostatic potential maps show overall charge distribution, while orbital maps reveal likely sites for electrophilic and/or nucleophilic attack. Surface displays may be combined with any type of model display. 

Frontier Orbitals and Chemical Reactivity. Chemical reactions typically involve movement of electrons from an electron donor (base, nucleophile, reducing agent) to an electron acceptor (acid, electrophile, oxidizing agent). This electron movement between molecules can also be thought of as electron movement between molecular orbitals, and the properties of these electron donor and electron acceptor orbitals provide considerable insight into chemical reactivity. 

Examine the highest-occupied molecular orbital (HOMO of cyanide anion. Is the larger lobe on carbon or nitrogen Would you expect cyanide to act as a carbon or nitrogei nucleophile Does this lead to the lower energy transitioi state (compare the energy of cyanide-l-methyl iodide ( attack and cyanide+methyl iodide N attack) ... 

Another way to assess nucleophilic reactivity is to examii the shape of the nucleophile s electron-donor orbital (th is the highest-occupied molecular orbital or HOMC Examine the shape of each anion s HOMO. At which ato would an electrophile, like methyl bromide, find the be orbital overlap (Note This would involve overlap of tl the HOMO of the nucleophile and the lowest-unoccupif molecular orbital or LUMO of CH3Br.) Draw all of tl products that might result from an Sn2 reaction wi CHaBr at these atoms. 

Backside attack may be favored in order to facilitate transfer of nonbonding electrons from the nucleophile into the electrophile s lowest-unoccupied molecular orbital (LUMO). Efficient electron transfer requires maximal overlap of the LUMO and the donor orbital (usually a nonbonded electron pair on the nucleophile). Examine the LUMO of methyl bromide. How would a nucleophile have to approach in order to obtain the best overlap Is your answer more consistent with preferential backside or frontside attack ... 

Is the location of positive charge in the more stable cation also where the lowest-unoccupied molecular orbital (LUMO) is most concentrated Rationalize what you observe. Does attack by a nucleophile (bromide) lead to the Markovnikov or anti Markovnikov product ... 

The molecule below has four stereoisomeric forms exoO exoCH2Br, exoO endoCH2Br, and so on. Examine electrostatic potential maps of the four ions and identify the most nucleophilic (electron-rich) atom in each. Examine the electron-acceptor orbital (the lowest-unoccuped molecular orbital or LUMO) in each and identify electrophilic sites that are in close proximity to the nucleophilic. Which isomers can undergo an intramolecular E2 reaction Draw the expected 8 2 and E2 products. Which isomers should not readily undergo intramolecular reactions Why are these inert ... 

The product of nucleophilic attack can be anticipated by examining the lowest-unoccupied molecular orbital (LUMO) on protonated cyclopentene oxide. From which direction (top or bottom) would a nucleophile be more likely to approach each epoxide carbon in order to transfer electrons into this orbital Explain. Does one carbon contribute more to the LUMO, or is the orbital evenly spread out over both epoxide carbons Assuming that LUMO shape dictates product stereochemistry, predict which stereoisomers will be obtained, and their approximate relative amounts. Is the anticipated kinetic product also the thermodynamic product (Compare energies of 1,2-cyclopentanediol stereoisomers to tell.)... 

With strong nucleophiles such as methoxide, ring opening follows an Sn2 mechanism. Examine the next to lowest-unoccupied molecular orbital (LUMO+1) for propylene oxide. On which carbon is it most heavily concentrated Is this also the least crowded carbon (Examine a spacefilling model for propylene oxide.) What should be the product of Sn2 addition ... 

Another useful way to think about carbon electrophilicity is to compare the properties of the carbonyls lowest-unoccupied molecular orbital (LUMO). This is the orbital into which the nucleophile s pair of electrons will go. Examine each compound s LUMO. Which is most localized on the carbonyl group Most delocalized Next, examine the LUMOs while displaying the compounds as space-filling models. This allows you to judge the extent to which the LUMO is actually accessible to an approaching nucleophile. Which LUMO is most available Least available ... 

Display the lowest-unoccupied molecular orbital (LUMO) for equatorial methylcyclohexanone. This is the orbital into which the nucleophile s pair of electrons will go. Is it larger on the axial or equatorial face A clearer picture follows from the LUMO map, which gives the value of the LUMO on the electron density surface, that is, the accessible surface of the molecule. Display the LUMO map for equatorial methylcyclohexanone. Which face of the carbonyl group is more likely to be attacked by a nucleophile Which alcohol will result ... 

One way to investigate the electrophilic properties of these molecules is to examine the orbital that each uses to accept electrons from a nucleophile. This orbital is the lowest-unoccupied molecular orbital (LUMO). Examine the LUMO for methyl acetate (Z=OCH3), acetaldehyde (Z=H), N,N-dimethylacetamide (Z=N(CH3)2) and acetyl chloride (Z=C1) (acetaldehyde is not a carboxylic acid derivative, but is included here for comparison). What is the shape of the LUMO in the region of the carbonyl group Is it a o or 7U orbital Is it bonding or antibonding What other atoms contribute to the LUMO Which bonds, if any, would be weakened when a nucleophile transfers its electrons into the LUMO ... 

Compare atomic charges for the enolate anion and the lithium salt. Are there major differences, in particular, for the oxygen and the a carbon Also compare the highest-occupied molecular orbital (HOMO) in the two molecules. This identifies the most nucleophilic sites, that is, the most likely sites for attack by electrophiles. Are the two orbitals similar or do they differ substantially Elaborate. 

Some electrophile-nucleophile reactions are guided more by orbital interactions than by electrostatics. The key interaction involves the donor orbital on the nucleophile, i.e., the highest-occupied molecular orbital (HOMO). Examine the HOMO of enamine, silyl enol ether, lithium enolate and enol. Which atom is most nucleophilic, i.e., which site would produce the best orbital overlap with an electrophile ... 

Hydration of methylbenzyne is believed to require nucleophilie attack by hydroxide. Examine the lowest-unoccupied molecular orbital (LUMO) of methylbenzyne. How many sites are there for nucleophilic attack Does hydroxide attaek in the plane of the ring, or perpendicular to the ring plane Explain. 

Next, consider the reactivity of phenyl diazonium ion. Are either of the reactions shown above consistent with nucleophilic attack at the ion s most electron-poor site Examine the lowest-unoccupied molecular orbital (LUMO) of phenyl diazonium ion. What electrophilic sites are identified by the LUMO Are either of the reactions shown above consistent with an orbital-controlled addition ... 

Examine the highest-occupied molecular orbital (HOMO) of singlet methylene. Where is the pair of electrons, inplane or perpendicular to the plane Next, examine the electrostatic potential map. Where is the molecule most electron rich, in the o or the 7t system Where is the most electron poor Next, display the corresponding map for triplet methylene. Which molecule would you expect to be the better nucleophile The better electrophile Explain. Experimentally, one state of methylene shows both electrophilic and nucleophilic chemistry, while the other state exhibits chemistry typical of radicals. Which state does which Elaborate. 

Next, examine the highest-occupied and lowest-unoccupied molecular orbitals (HOMO and LUMO) of dichlorocarbene. Were the reaction a nucleophilic addition , how would you expect CCI2 to approach propene Were the reaction an electrophilic addition , how would you expect CCI2 to approach propene Which inteqDretation is more consistent with the geometry of the transition state ... 

Abbreviations Aik, alkyl AN, acetonitrile Ar, aryl Bu, butyl cod, 1,5-cyclooctadiene Cp, cy-clopentadienyl Cp , pentamethylcyclopentadienyl Cy, cyclohexyl dppm, diphenylphosphinome-thane dpme, Ph2PC2H4PMe2 Et, ethyl fod, 6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octane-dionate HOMO, highest occupied molecular orbital LUMO, lowest unoccupied molecular orbital Me, methyl MO, molecular orbital nbd, norbornadiene Nuc, nucleophile OTf, triflate Ph, phenyl Pr, propyl py, pyridine THE, tetrahydrofuran TMEDA V,V,M,M-tetramethylethylenediamine. 

Ab initio molecular orbital calculations are being used to study the reactions of anionic nucleophiles with carbonyl compounds in the gas phase. A rich variety of energy surfaces is found as shown here for reactions of hydroxide ion with methyl formate and formaldehyde, chloride ion with formyl and acetyl chloride, and fluoride ion with formyl fluoride. Extension of these investigations to determine the influence of solvation on the energy profiles is also underway the statistical mechanics approach is outlined and illustrated by results from Monte Carlo simulations for the addition of hydroxide ion to formaldehyde in water. 

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