Frontier-Orbital Control

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. 

One-electron rednction of triorganyl sulfoninm, selenoninm, and tellnroninm salts (R R R Chalc ) proceeds according to the following sequence (Beak and Snllivan 1982, Eriksson et al. 2005)  

Let ns scrutinize this reaction on the example of phenyl dialkyl snlfoninm salts. According to Saveant (2002), rednctive cleavage of these salts obeys the stepwise mechanism. In other words, 

The reaction of methoxy thioanisole with metallic sodium in hexaphosphotriamide initially results in the formation of the methoxy thioanisole anion-radical. SOMO in this anion-radical localizes much more at the thiomethyl group than at the methoxyl group. Scission of the thiomethyl group is the next step of the reaction. The obtained product is not reduced further. 

Strict selectivity of the reaction is explained by electroacceptor properties of sulfur d orbitals. These orbitals are not as high in energy as oxygen d orbitals are (Testaferi et al. 1982). 

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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. 

The model predicts that frontier orbital-controlled addition at position (1) should be favorable for octahedral or pseudooctahedral complexes of... 

The preferred orientation for electrophiles is out of the plane defined by the Y-S-Z bonds, and about 20° from the normal (n) to the plane [50], whereas nucleophiles tend to lie in the plane, and cluster close to the line defined by the extension of the Y-S (or Z-S) bond. Similar interactions have been observed for selenium (Ramasubbu and Parthasarathy, 1984). The conclusion, as before, is that these interactions are frontier-orbital controlled, with the HOMO being a sulphur lone pair, and the LUMO an antibonding o- C-y(Z) orbital. 

This reactivity pattern is certainly unexpected. Why should low-valent complexes react as electrophiles and highly oxidized complexes be nucleophilic Numerous calculations on model compounds have provided possible explanations for the observed chemical behavior of both Fischer-type [3-8] and Schrock-type [9-17] carbene complexes. In simplified terms, a rationalization of the reactivity of carbene complexes could be as follows. The reactivity of non-heteroatom-stabilized carbene complexes is mainly frontier-orbital-controlled. The energies of the HOMO and LUMO of carbene complexes, which are critical for the reactivity of a given complex, are determined by the amount of orbital overlap and by the energy-difference between the empty carbene 2p orbital and a d orbital (of suitable symmetry) of the group L M. 

In contrast to the alkynyl anion, coordination to a metal center results in Co, being electron-poor and subject to frontier-orbital controlled nucleophilic attack, while the... 

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. 

Based on this result as well as related investigations, the following have been unveiled (87) (a) Under equilibrating conditions (use of LiBr/NEt3), the cycloaddition and the Michael addition path compete each other via the common intermediate A (Scheme 11.16) (b) the intermediate B is stereoselectively formed through the chelation- and frontier orbital controlled transition state A (c) the... 

For pyrroles with electron acceptor substituents in the 1-position electrophilic substitution with soft electrophiles can be frontier orbital controlled and occur at the 2-position, whereas electrophilic substitution with hard electrophiles can be charge controlled and occur at the 3-position. 

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... 

Pentanone is fairly flexible, so an antiperiplanar attack can occur at either face. The o cc orbital lies lower in energy than o CH so frontier orbital control favors the anti transition state by 3.73 kcal mol-1. Therefore, the flattening rule may be generalized as follows antiperiplanar attack and frontier orbital control in general are only important for reasonably flexible ketones. 

The reduction mechanism was elucidated by calculating the electronic structures (ab initio STO 3G method) of the possible complexes and by comparing them to the a-enone structures. Thus it was demonstrated that these tropones are reduced under frontier orbital control and that carbonyl complexation by the alkali cations is essential. 

The question of the most relevant (delocalized) conjugation pathway in porphyrins (75M18) sometimes still causes confusion. Thus, meso reactivity of porphyrins toward electrophiles is frontier orbital controlled. This (75M15) has been taken as evidence for Fleischer s model of an internally delocalized n-system, as shown in structure XVIII (84T2359). 

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. 

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