Orbital overlap, stereoelectronic effect

The term stereoelectronic refers to the effect of orbital overlap requirements on the steric course of a reaction. Thus, because of stereoelectronic effects, the Sw2 substitution gives inversion (see Section 4.2) and E2 elimination proceeds most readily when the angle between the leaving groups is 0° or 180° (see Chapter 7, p. 369). Stereoelectronic effects also play an important role in pericyclic reactions, which are the subject of Chapters 11 and 12. 

The 1,6-addition to a,s, y, a-dienones is also subject to stereoelectronic effects. Addition on the bottom face of dienone 137 leads to a chair-like intermediate while that on the top face leads to a boat-like intermediate 140 in order to maintain maximum orbital overlap. Also, in 140 the R group encounters an eclipsed 1,2-R/H interaction and more importantly, a 1.4-CH3/R steric interaction which resembles the bowsprit flagpole arrangement of a twist-boat form of cyclohexane. This analysis of Marshall and Roebke (48) predicts that the trans product 139 should prevail over the cis product 141. 

Molecular orbital calculations have also provided theoretical justification for these stereoelectronic effects in tetracovalent and pentacovalent phosphorus species (2-7). As has been shown in molecular orbital calculations on the X -P-X2 (X = 0,N) structural fragments, the X.-P bond is strengthened (as indicated by an increase in the Mulliken overlap population) while the P-X3 bond is weakened when the X atom lone pair is app to the P-X3 bond. Thus, in the g,t conformation of dimethyl phosphate (Structure ll the overlap population for the trans P-0 bond is. 017 electron lower than the overlap population for the gauche P-0 bond. As shown for g,t dimethyl phosphate one lone pair (shaded in 1) on the gauche bond oxygen is app to the trans bond, while no lone pairs on the trans bond oxygen are app to the gauche bond. Thus, the weakest X.-P bond has one app lone pair and no lone pairs on X. app to the P=X2 bond. 1... 

This so-called stereoelectronic factor operates to maximize or minimize orbital overlap, as the case requires, to obtain the most favorable energy. This was evident from the three- and four-center systems we have discussed by the VB and HMO methods. It was also implicit in favored anti-1,2-additions, 1,3-cyclizations (Fig. 23), fragmentations (e.g. (174)), etc. Here we have selected several reaction types to illustrate the principle. In this and other sections, we show that the tendency for reaction centers to be collinear or coplanar stems largely from orbital symmetry (bonding), but may also derive from steric and electrostatic effects, as well as PLM. 

For the E(O) enolate, the stereoselection is best understood in terms of stereoelectronic effect. The most stable conformation of the 2,3-allylic bond of an acyclic enolate corresponds to the smallest substituent eclipsing the double bond whatever the geometry of the enolate (A1,3 strain)459. Then, in the transition state, the maximum overlap of the better ally lie a-donor and the n -orbital of the enolate directs the antiperiplanar attack of the electrophile (Scheme 95). 

In such conformation the scissible bond is collinear with the n orbitals of the aromatic system bearing the unpaired electron, and the best orbital overlap for intramolecular ET, required for bond cleavage, can be achieved. Interestingly, when competition between C-H and C-C bond cleavage is possible, stereoelectronic effects generally play a significant role, because the former process is depressed owing to its steric requirements, which are much smaller than those of a C-C bond. In such circumstances, therefore, the conformation with the latter bond collinear with the n system is the most favored (see later). 

Free-radical cyclization reactions (i.e., the intramolecular addition of an alkyl radical to a C=C ir bond) have emerged as one of the most interesting and widespread applications of free-radical chemistry to organic synthesis. Free-radical cyclizations are useful because they are so fast. The cyclization of the 5-hexenyl radical to the cyclopentylmethyl radical is very fast, occurring at a rate of about 1.0 X 105 s-1. In fact, the rate of formation of the cyclopentylmethyl radical is much faster than the rate of cyclization to the lower energy cyclohexyl radical. This stereoelectronic effect is derived from the fact that the overlap between the p orbital of the radical and the rr MO of the double bond is much better when Cl attacks C5 than when it attacks C6. The relative rates of 5-exo and 6-endo ring closures are strongly dependent on the nature of the substrate and especially on the amount of substitution on the ir bond. Cyclization of the 6-heptenyl radical in the 6-exo mode is also very favorable. 

Denmark argued that the synclinal transition state 19 may be favored due to stabilization by stereoelectronic effects such as secondary orbital overlap or minimization of charge separation. The allylstannane HOMO and the aldehyde LUMO could participate in. secondary orbital overlap in transition state 19, with specific-interactions between the allylstannane a-carbon and the aldehyde oxygen [50, 55]. Alternatively, the preference for the synclinal transition state 19 can also be attributed to minimization of charge separation in the transition state, compared to the situation in the antiperiplanar transition state 20 [50, 56],... 

In the backdrop of the orbital symmetry rules, a need was felt to evaluate the strength of the orbital overlap component of the stereoelectronic effect by designing experiments in which both the competing pathways are orbital symmetry allowed but one pathway is preferred to the other pathway for better orbital overlap. Berson has explored this avenue exhaustively by replacing one double bond of a simple model system by a cyclopropane ring because such a structural change was expected to cause one of the two orbital symmetry-allowed pathways to enjoy better orbital overlap than the other pathway (see below). 

To sum up the above discussion, we have witnessed that the orbital overlap component of the stereoelectronic effect is indeed a very powerful tool as it controls both the stereochemistry and the rates of a range of pericyclic reactions by allowing exclusively one of the two possible symmetry-allowed pathways for the very simple reason of better overlap of the breaking bonds. 

Two of the factors that determine the reactivity of tethered ir-nucleophiles in Mannich-type cycliza-tions have been emphasized stereoelectronic effects and reaction medium effects. The stereoelectronics of orbital overlaps between the ir-nucleophile and the iminium electrophile are best evaluated by considerations such as antiperiplanar addition trajectories and Baldwin s rules for ring formation. The critical importance of the reaction medium has received serious attention only recently. However, it already appears clear that Tr-nucleophiles that would lead, upon cyclization, to relatively unstable carbocations can have their reactivity markedly increased by carrying out the cyclization in the presence of a nucleophilic solvent or additive which, by nucleophilic participation, can obviate the formation of high energy cyclic carbenium ion intermediates. 

Although this is the only chapter in which stereoelectronics appears in the title, you will soon recognize the similarity between the ideas we cover here and concepts like the stereospecificity of E2 elimination reactions (Chapter 17) and the effect of orbital overlap on NMR coupling constants (Chapter 18). We will also use orbital alignment to explain the Karplus relationship (Chapter 32), the Felkin-Anh transition state (Chapter 33), and the conformational requirements for rearrangement and fragmentation reactions (Chapter 36). 

It is well-known that a-overlap of two p-orbitals or two s-orbitals does not take full advantage of the available orbital density. In order to maximize o-overlap, the interacting atoms change their orbital shapes in a non-symmetric way (rehybridize). Because hybridization is associated with changes in orbital overlap, it can be considered as one of the most basic stereoelectronic effects that can impose significant modulations on other stereoelectronic interactions. 

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