Frontier orbital-controlled reaction

Next, we consider the first order mixed derivatives of the energy with respect to electron and spin number on one hand and the external potentials v and V5 on the other hand. These derivatives are generalizations of the Fukui function, the reactivity index used to probe frontier orbital-controlled reactions. The generalized Fukui function /jvjv can be considered as the spin-resolved extension of the regular Fukui function given in eqn (26)... 

Another aspect of qualitative application of MO theory is the analysis of interactions of the orbitals in reacting molecules. As molecules approach one another and reaction proceeds, there is a mutual perturbation of the orbitals. This process continues until the reaction is complete and the new product (or intermediate in a multistep reaction) is formed. PMO theory incorporates the concept of frontier orbital control. This concept proposes that the most important interactions will be between a particular pair of orbitals. These orbitals are the highest filled oihital of one reactant (the HOMO, highest occupied molecular oihital) and the lowest unfilled (LUMO, lowest unoccupied molecular oihital) orbital of the other reactant. The basis for concentrating attention on these two orbitals is that they will be the closest in energy of the interacting orbitals. A basic postulate of PMO... 

The importance of both frontier orbital-controlled and electronic charge-controlled factors in determining chemical reactivity has been recognized (16). These concepts are the key to interpreting two types of reactivity expected for carbene complexes, i.e., reactions with nucleophilic... 

Self-consistent field molecular orbital calculations by Fenske and coworkers have confirmed that nucleophilic additions to Fischer and related complexes [e.g., (CO)sCr=CXY, (T)5-C5H5)(CO)2Mn=CXY], are frontier orbital-controlled rather than charge-controlled reactions (7-9). Interaction of the HOMO of the nucleophile with the carbene complex LUMO (localized on Ca) destroys the metal-carbon w-interaction and converts the bond to a single one. 

Dnring an electron transfer, the acceptor places its LUMO at the electron disposal and the donor releases an electron that is located on its HOMO. These orbitals are frontier orbitals. In the corresponding ion-radicals, the distribution of an unpaired electron proceeds, naturally, under frontier-orbital control. This definitely reflects in the ion-radical reactivity and not always by a self-obvions manner. Let ns concisely trace peculiarities of ion-radical fragmentation reactions that are very important in organic synthesis. 

The reaction mechanism proposed for the LiBr/NEta induced azomethine ylide cycloadditions to a,p-unsaturated carbonyl acceptors is illustrated in Scheme 11.10. The ( , )-ylides, reversibly generated from the imine esters, interact with acceptors under frontier orbital control, and the lithium atom of ylides coordinates with the carbonyl oxygen of the acceptors. Either through a direct cycloaddition (path a) or a sequence of Michael addition-intramolecular cyclization (path b), the cycloadducts are produced with endo- and regioselectivity. Path b is more likely, since in some cases Michael adducts are isolated. 

A DFT study of the reactivity of pyridine and the diazabenzenes towards electrophilic substitution, assuming frontier orbital control of the reactions, predicts their low reactivity as the HOMOs of these substrates are not n-orbitals.5 For pyridine-N-oxide, however, the HOMO is an aromatic orbital. DFT studies giving Fukui indices predict6 the preferred sites of electrophilic attack on pyrrole, furan, and thiophene and calculation of the local softness of the reactive sites rationalizes relative reactivities. 

A DFT study of the molecular orbitals of pyridine and a number of heteroaromatics unreactive to electrophilic substitution shows that the HOMOs of these compounds are not r-orbitals and so their low reactivity can be explained by assuming frontier orbital control of their substitution reactions.1 Consistent with this rationalization is the fact that in the case of pyridine-A-oxide and a number of other reactive substrates the HOMOs are n-orbitals. 4,6-Dinitrobenzofuroxan (1) is a superelectrophile and reacts with some supernucleophilic l,3,5-tris(A,A-dialkylamino)benzenes to form the first observed Meisenheimer-Wheland zwitterionic complexes [e.g. (2)].2... 

Experimentally, MeBr gives O-methylation in the gas-phase reactions25 but RBr favors C-alkylation in solution. In general, charge control dominates gas-phase reactions because strong Coulombic effects26 are not attenuated by counterions or solvents. Since solution reactions are usually under frontier orbital control, the reactivity... 

So the only remaining question is when thioamides combine with a-haloketones, which atom (N or S) attacks the ketone, and which atom (N or S) attacks the alkyl halide Carbonyl groups are hard electrophiles—their reactions are mainly under charge control and so they react best with basic nucleophiles (Chapter 12). Alkyl halides are soft electrophiles—their reactions are mainly under frontier orbital control and they react best with large uncharged nucleophiles from the lower rows of the periodic table. The ketone reacts with nitrogen and the alkyl halide with sulfur. 

The analysis in the chapter (p. 1200 reproduced below) shows that we need the thioamide of renzoic acid (thiobenzamide available from Aldrich) and an a-bromoketone. We need these rarticular starting materials because the soft sulfur atom will displace the bromide in a frontier-orbital-controlled Sn2 reaction whilst the hard amino group will attack the ketone in a charge-controlled nucleophilic attack on a carbonyl group. 

Site selectivity in a number of other concerted cycloadditions which are not [4 + 2] cycloadditions is also explained by frontier orbital control. Thus diphenylketene (332) reacts with isoprene (333) mostly at the more substituted double bond, and with cis-butadiene-l-nitrile (334) at the terminal double bond.263 Dichlorocarbene reacts at the terminal double bond of cycloheptatriene (335),264 and the Simmons-Smith reaction (336 + 337)265 also takes place at the site with the higher coefficients in the HOMO. 

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