Secondary orbital overlap

If the vinylallene possesses a substituent at the vinylic terminal position, an endo adduct is preferentially obtained owing to the secondary orbital overlap. Only the E-isomer of propenylallene underwent the regio- and stereoselective cycloaddition with methyl vinyl ketone to afford the endo-isomer as the major product. The Z-iso-mer was unreactive because it preferred the transoid conformation [165]. 

Moreover, enone 132 reacts with (t-Bu)Me2SiOTf and I its N to give the Diels-Alder adduct 134 in 82% yield via intermediate 133 (equation 54)184. Lactam 134 with a cis fused ring is more stable than the corresponding trans isomer, in which the Me3Si group must rotate into an axial position. The secondary orbital overlap and the steric requirements of the MesSi group on the dienophile moiety in 133 also appear to be critical to the observed stereoselectivity. 

Preferential formation of a syn derivative could be explained by steric factors if the dienophile is bulky. However, anti isomers sometimes predominate (yields of up to 100% occur), which implies that the reaction can be directed by attractive interactions occurring between X and the dienophile. As with endo-exo preferences, it is natural to think in terms of secondary orbital overlaps. 

Symmetry considerations have also been advanced to explain predominant endo addition. " In the case of [4 + 2] addition of butadiene to itself, the approach can be exo or endo. It can be seen (Fig. 15.11) that whether the HOMO of the diene overlaps with the LUMO of the alkene or vice versa, the endo orientation is stabilized by additional secondary overlap of orbitals of like sign (dashed lines between heavy dots). Addition from the exo direction has no such stabilization. Evidence for secondary orbital overlap as the cause of predominant endo orientation, at least in some cases, is that [4 + 6]-cycloaddition is predicted by similar considerations to proceed with predominant exo orientation, and that is what is found. However, this explanation does not account for endo orientation in cases where the dienophile does not possess additional n orbitals, and a number of alternative explanations have been offered. ... 

Intramolecular Diels-Alder reactions can give endo or exo products. We should first discover which this is. Drawing the transition state for the endo product, we find that the endo product is indeed formed. So electronic factors dominate, perhaps because the dienophile has such a low-energy LUMO and has two carbonyl groups for secondary orbital overlap with the back of the diene. 

Dendrobium Alkaloids.—8-Epidendrobine (14) has been synthesized employing a route involving a diene isomerization in a Diels-Alder reaction (Scheme 3). To account for the unexpected stereochemical result of the latter addition [(12)->(13) and epimeride] it is proposed that ester (15) assumes a very hindered conformation in the transition state, involving no secondary orbital overlap between diene and ester groups. However isomerization of the trisubstituted double bond to give (16) leads... 

Exo addition The opposite of endo addition, in that the smaller side of the dieneophile is under the cyclic diene and hence there is no opportunity for secondary orbital overlap. This leads to the thermodynamic product being formed. 

As part of this study, the intramolecular cyclization of a y9-benzyloxy-substi-tuted aldehyde was also examined [75 b]. Similar results are obtained with the reaction of E- and Z-2-butenylstannanes with that acceptor. A rationale for the observed stereoselectivity was put forward based on secondary orbital overlap. 

These results do not provide suitable models or predictions for the intermolecular addition of 2-butenylstannanes to aldehydes. The -2-butenylstannanes generally provide higher levels of stereoselectivity than the corresponding Z-2-butenylstan-nanes in intermolecular reactions. However, the hypothesis of secondary orbital overlap influencing stereoselectivity could also be applied to the intermolecular reactions. 

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 his analysis of transition states (Z)-ll and ( )-ll, Keck pointed out that in (Z)-ll, the a-carbon of the (Z)-crotyltri-n-butylstannane is farther from the aldehyde oxygen in transition state (Z)-ll than is the a-carbon of the ( )-crotyltri- -butylstannane in transition state ( -11, and thus is less able to participate in secondary orbital overlap interactions. The decrease in stereoelectronic stabilization of transition state (Z)-ll, compared to ( )-ll, allows access to other competing transition states which can lead to the diastereomeric anti homoallylic alcohol 3 (e.g. transition. states 13 or 14, Fig. 11-3, see above) in the reactions of the (Z)-crotylstannane reagent. Also, the (Z)-crotyltri-n-butylstannane in transition state (Z)-ll probably experiences increased steric interactions with the aldehyde R group relative to ( l)-crotyltri-n-buty]stannane in transition state ( )-ll. 

In the BF3-OEt2-catalyzed reaction of (Z)-158, the formation of 160 as the major adduct is rationalized by preferential bond formation through the synclinal transition state 166 (Fig. 11-15). The minor adduct 161 arises through the other synclinal transition state, 167. The ( j-stannane 159, on the other hand, forms 161 preferentially through the synclinal transition state 168. In both of the preferred transition states, 166 from (Z)-158 and 168 from (F)-159, the tin-bearing carbon is in close proximity to the aldehyde oxygen. As noted previously. Keck proposed that this situation is preferable because of secondary orbital overlap be-... 

If the carbonyl group responsible for the endo secondary orbital overlap is not there, as in 130, the exo product 131 is formed at lower temperatures. This was just as well as the reaction was used to make allokainic acid 132 having the stereochemistry of 131. 

The high endo selectivity of aromatic aldehydes is also a result of their capability to participate in secondary orbital interactions. The mixing of the LUMO of benzaldehyde with the HOMO of the diene can form secondary orbital overlap which lowers the energy of the endo transition state. The electron-withdrawing effect of the catalyst [e.g. Eu(fod)3] on the aldehyde further enhances secondary orbital overlap with aromatic aldehydes by an additional reduction of the LUMO energy (Figure 2). Similar arguments have been made to rationalize the increase in endo selectivity of homo Diels-Alder reactions when Lewis acids are used as catalysts.Secondary orbital interactions are, however, absent when the dienophile is an aliphatic aldehyde in such reactions the cis (endo) stereoselectivity is based solely on steric interactions. 

We initially postulated the existence of bonding secondary orbital overlap interactions between the carbonyl carbon of the ester, E, and the odd electron centers located on the diyl ring of 26. To test this notion, we synthesized an analog of diazene 19 bearing a Z-substituted diylophile. As illustrated, if secondary interactions dominate, then the cis-syn adduct 28, resulting from the folded pseudochair transition state conformation 27, should correspond to the major product. In practice, the cis-anti adduct 29 still predominated, a 75 25 ratio of 29 to 28 being obtained. 

The endo product is formed faster when the dienophile has a substituent with tt electrons. It has been suggested that this is due to stabilization of the transition state by the interaction of the p orbitals of the dienophile s substituent with the p orbitals of the new double bond s being formed in what was the diene. This interaction, called secondary orbital overlap, can occur only if the substituent with the p orbitals lies underneath (endo) rather than away from (exo) the six-membered ring. 

Wiberg reported the Diels-Alder reaction of butadiene and cyclopropene [53] and Baldwin estimated from the reaction between cyclopropene and 1-deuteriobutadiene at 0°C that 99.4% of the formed cycloadduct was the endo isomer [54], There are many suggestions which attempt to explain endo selectivity in Diels-Alder reactions (Alder s rule [55]), but none are firmly established. According to Woodward and Hoffmann [56], the preference is the result of favorable Secondary Orbital Interactions (SOI) or secondary orbital overlap [57-59] between the diene and dienophile in the corresponding transition state structure. One can also find an explanation for the reaction preference in the difference between primary overlap [60], volumes of activation [61], and the polarity of the transition states [62]. Secondary orbital overlap between the diene and the dienophile does not lead to bonds in the adduct, but primary orbital overlaps do. 

Regio- and stereoselectivities of the cycloaddition of l-(6-chloropyridazin-3-yl)pyridinium-3-olate and l,r-(pyridazine-3,6-diyl)di(pyridinium-3-olate) at the 2- and 6-positions with mono-and disubstituted alkenes were elucidated and rationalized in part on the basis of secondary orbital overlap <97JCR(S)138>. An analysis of the factors involved with N- and 0-alkylation of... 

The reactions of l-ethoxycarbonyl-l//-l,2-diazepine (39) with Ma-diphenylnitrone and nitroso-benzene have been compared with those of 1-ethoxycarbonylazepine <92H(34)497> however, the products from the diazepine gave more insightful mechanistic information. These studies revealed the preference in the former case for reaction at the C(4>=C(5) double bond, with one preferred regiochemistry, (58) versus (59), but little or no stereochemical control due to secondary orbital overlap (Scheme 5). In contrast, nitrosobenzene behaved as a dienophile and gave a [4 + 2] adduct (60) in 26% yield. 

Secondary orbital overlap in the endo transition structure for the Diels-Alder dimerization of 1,3-butadiene. 

Generally, the endo form of the product predominates (endo-rule which is a result of secondary orbital overlap between the diene and dienophile), but endo/exo ratios may vary, depending on several steric and electronic factors and with reaction conditions. 

The exo compounds formed from a substituted dienophUe are more stable for steric reasons The substituent points away from the more congested part of the molecule. Indeed, the transition state for exo product formation must also be less crowded than the transition state for endo product formation. But the transition state for the endo product benefits from other factors that overwhelm steric considerations. Chemists have performed high-level molecular orbital calculations and have found that in the endo transition state, but not in the exo transition state, there can be secondary orbital overlap. This fancy-soimding phrase simply means that there can be interaction between the back diene orbitals and orbitals on the substituent X only in the endo transition state, figure 12.67 shows this effect for the first example... 

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