Orbital stabilization, secondary

The exo addition mode is expected to be preferred because it suffers fewer steric repulsive interactions than the endo approach however, the endo adduct is usually the major product because of stabilizing secondary orbital interactions in the transition state (Scheme 1.10). The endo preference is known as Alder s rule. A typical example is the reaction of cyclopentadiene with maleic anhydride which, at room temperature, gives the endo adduct which is then converted at... 

Known as the endo rule, it was first formulated by Alder and Stein530,532 and explained as the maximum accumulation of double bonds. Now endo selectivity is considered to be the result of stabilizing secondary orbital interactions.533 The endo rule, however, strictly applies only for cyclic dienophiles. 

The additional stabilizing secondary electronic effect in the Z form might be larger than that (=1.4 kcal/mol) observed in acetals, because the carbonyl bond in esters is a more polarized bond than the C—OR bond in acetals and therefore, the antibonding orbital of the o C—0 bond should be of lower energy allowing increased overlap. It has been postulated on that basis (1-3) that the greater stability of the Z form (=3 kcal/mol) by comparison with the form in esters would be due mainly to this secondary electronic effect. 

The [3 + 2] reaction of an allylsilane with an enone was proposed to proceed via a regiospecific electrophilic substitution (cf 80) of the enone at C-3 of the allylsilane followed by a cationic 1,2-silyl migration (equation 57). At the yyw-clinal transition state (81), the carbonyl group of the unsaturated ketone was assumed to occupy an endo orientation in relation to the allylsilane142. The transition state was thought to be favorable due to minimization of the charge separation and to possible secondary orbital stabilization. 

The role of secondary orbital interactions in control of the cycloaddition to substrates (Table 4, entries 12-14) has been invoked. Hence, the attractive interaction between the it orbitals (LUMO) of the carbonyls in the reference ring and the n -antisymmetric combination of the nitrogen lone pair orbitals stabilize the syn transition state for dienophilic attack at the syn cyclohexadiene face18,22 23. This view is supported also by the finding that maleimidcs and benzoquinone, which do not have lone pairs on the pertinent carbon atoms, add to propellenes (Table 4, entries 12 and 13) by exclusive anti addition (below the plane of the molecule)24. 

How do these auxiliaries frilhl their role If we go back to the vaHne-derived auxiliary and draw the auxiliary-bearing dienophile coordinated with the Lewis acid you can clearly see that the isopropyl group shields the back face of the alkene from attack when the cyclopentadiene moves in, it must approach from the front face (and remember it will align itself to gain maximum secondary orbital stabilization and therefore give the endo product). 

This discussion allows an explanation of the ortho effect presented earlier, in connection with the Diels-Alder reaction. When a C=X or a CsX unit (where X is a heteroatom) reacts with a 1-substituted diene, the ortho product is generally preferred. Ortho selectivity is explained by the size of the orbital coefficients. When coefficient size is combined with secondary orbital interactions (sec. 11.4.C), 3 >84 indicated in the transition state shown in Figure 11.10, the carbonyl orbital is responsible for a secondary interaction that stabilizes the ortho transition state. If the meta transition state is involved, then orbital symmetry dictates an exo mode and there is no possibility of secondary orbital interactions. Secondary orbital interactions such as this are possible only in an endo transition state. It should be noted that the application of secondary orbital interactions to this problem has been questioned. 5... 

In Fig. 15.1 we have represented the FMO in the transition state for the reaction between dipole 1 and nitroalkene 4. The preferred endo approach indicated by 8 is due to the stabilizing secondary bonding interactions between the Pz orbitals of the central nitrogen (-0.31) and endocyclic oxygen (+0.36) in the dipole, with the NO2 group of the dipolarophile (N -0.40 O +0.33, respectively). Although these interactions do not lead directly to new bonds, they lower the energy of the endo-transition state relatively to that of the exo-transition state 9, where these inteac-tions are absent. Hence, the enrfo-adduets are preferentially obtained. 

The reactivity, regioselectivity and stereoselectivity of [3+2] cycloadditions of oxazoline 7V-oxides and a,P-unsaturated esters or nitroalkenes can be rationalized in terms of the FMO theory. The reactions are HOMO-dipole controlled and the preferred ewi/o-selectivity in those cycloadditions can be rationalized by stabilizing secondary orbital interactions only present in the en[Pg.105]

In the 1,3-dipolar cycloaddition reactions of especially allyl anion type 1,3-dipoles with alkenes the formation of diastereomers has to be considered. In reactions of nitrones with a terminal alkene the nitrone can approach the alkene in an endo or an exo fashion giving rise to two different diastereomers. The nomenclature endo and exo is well known from the Diels-Alder reaction [3]. The endo isomer arises from the reaction in which the nitrogen atom of the dipole points in the same direction as the substituent of the alkene as outlined in Scheme 6.7. However, compared with the Diels-Alder reaction in which the endo transition state is stabilized by secondary 7t-orbital interactions, the actual interaction of the N-nitrone p -orbital with a vicinal p -orbital on the alkene, and thus the stabilization, is small [25]. The endojexo selectivity in the 1,3-dipolar cycloaddition reaction is therefore primarily controlled by the structure of the substrates or by a catalyst. 

The endo exo selectivity for the Lewis acid-catalyzed carbo-Diels-Alder reaction of butadiene and acrolein deserves a special attention. The relative stability of endo over exo in the transition state accounts for the selectivity in the Diels-Alder cycloadduct. The Lewis acid induces a strong polarization of the dienophile FMOs and change their energies (see Fig. 8.2) giving rise to better interactions with the diene, and for this reason, the role of the possible secondary-orbital interaction must be considered. Another possibility is the [4 + 3] interaction suggested by Singleton... 

The complexation with Lewis acids or the protonation influences both the energy and the coefficients of carbon atoms of the LUMO orbital of the dienophile. The coefficient of the carbonyl carbon orbital increases (Scheme 1.16) consequently, the stabilizing effect of the secondary orbital interaction is greatly increased and the endo addition is more favored. 

When the carbonyl groups are present, the transition state for syn attack is sta-bihzed by interactions between the in-phase combination of the NN lone pairs and the antisymmetric n orbital of the CO-X-CO bridge (100). Although the secondary effect (SOI) operates only during syn approach and contributes added stabilization to this transition state, the primary orbital interaction (see 103) between the HOMO of the cyclohexadiene moiety of 100 and the n orbital of the dienophile (NN, Fig. 16) is differentiated with respect to the direction of attack, i.e., syn or anti, of triazolinedione (NN, Fig. 16). 

Secondary orbital interaction had been proposed to explain predominant formation of endo attack prodncts in Diels Alder reaction of cyclopentadiene and dienophiles by Hoffmann and Woodward [22]. According to this rnle, the major stereoisomer in Diels-Alder reactions is that it is formed through a maximum accumulation of double bonds. In the Diels-Alder reactions, secondary orbital interaction consists of a stabilizing two-electron interaction between the atoms not involved in the formation or cleavage of o bonds (Scheme 19). 

There were proposed some applications of secondary orbital interaction to explain the tr-facial selectivity. Anh proposed that the selectivity in the reactions of 5-acetoxycyclopentadiene 1 was ascribed to the stabilization by the interaction between the LUMO of a dienophile and n-orbital of the alkoxy oxygen of the acetoxy moiety [25] (Scheme 20). 

Stabilize a neighboring, empty p-orbital, so too, alkyl groups can stabilize a neighboring, partially filled orbital. This preference for forming a tertiary radical (rather than a secondary radical) dictates that Br" will attack the less substituted carbon. This explains the observed anti-Markovnikov regiochemistry. 

This reflects the greater stability of a secondary rather than a primary carbocation shifts in the reverse direction can, however, take place where this makes available the greater delocalisation possibilities of the ir orbital system of a benzene ring (i.e. tertiary — secondary) ... 

This approach did not provide a complete explanation for the observed degree of stereoselectivity. On the whole, the endo approach of olefin to nitronate is stabilized by secondary orbital interactions but, at the same time, is destabilized due to steric hindrance. 

The authors (162) attempted to explain the stereochemical outcome of the reactions (Schemes 3.169 and 3.170) in the terms used earlier (337), that is, by steric factors, which destabilize the endo approach of a dipolarophile, and the electronic effect (secondary orbital interactions), which is most typical for electron-rich dipolarophiles and can slightly stabilize the endo approach of these olefins. 

Variations to the cis addition have been found in the transtition state in some cases and a mixture of products has been reported. Two possible stereochemical variations have been reported because of endo and exo addition. Thus in the dimerisation of butadiene Hoffmann and Woodward have shown that besides the primary orbital interactions between C, and C4 of the diene and Cj and C2 of the dienophile, there are also secondary interactions (shown by dotted lines and also called endo addition) between C-2 of the dieno and C-3 of the dienophile. Such orientations are only possible in endo orientation and this will stabilize the transition state. 

---