2.4- Hexadien substituent effect

The 1,4-disubstituted cases are degenerate, so no averaging is needed. The chameleonic model suggests that the substituent effects should be additive, or a predicted value of A/ = 31.6 kcal mol for l,4-dicyauo-l,5-hexadiene and AH = 31.4 kcal mol for l,4-diphenyl-l,5-hexadiene. The computed barriers are actually lower thau these values. The barrier for the 1,3,4,6-tetrasubstituted... 

These results suggest a competitive interaction between the active and nodal substituents. The geometries of these transition states support this competition their values are quite similar to the distance found in the parent 1,5-hexadiene. Computational examinations of the substituent effects on the Cope rearrangement conclude that the centauric model does not apply. The chameleonic model makes a better accounting of the cooperative and competitive ways the substituents affect the Cope rearrangement. Borden has proposed a simple mathematical model that allows for the prediction of the stabilization of the transition state by substituents solely on the change in... 

Hrovat, D. A. Chen, J. Houk, K. N. Thatcher, B. W. Cooperative and competitive substituent effects on the Cope rearrangements of phenyl-substituted 1,5-hexadienes elucidated by Becke3LYP/6-31G calculations, 7. Am. Chem. Soc. 2000, 722, 7456-7460. 

The torquoselectivity on account of electronic effects is less pronounced in the disrotatory ring opening of 5,6-disubstituted 1,3-hexadienes. The effect is rather more steric in nature than electronic, and the larger substituents move outward [25, 26]. For instance, a hexatriene with both 1- and 6-substituents on trans-double bonds reacts faster than a hexatriene with one substituent on a trans-double bond and the other substituent on a s-double bond. The transformation 66 —> 67 has been estimated to proceed 20 times faster than the transformation 68 —> 69 under otherwise identical reaction conditions. 

Rate accelerations by acceptor substituents (c.g. COOCH3) and retardations by donor substituents (e.g., OCHj) are observed experimentally53,54. Substituent effects on the entropies of activation are often counterbalanced by opposing enthalpy effects, so that the effects on the rates of the [1.5] hydrogen migration in acyclic systems arc attenuated. For example, with substituents in the 3-position of the (Z)-l,3-hexadienes, only a rate factor of about 20 is observed53. 

The experimental values of A// in Table 30.1 show that phenyl groups at Cl, C3, C4, and C6, which stabilize structure C, also give rise to a strongly cooperative substituent effect. When a pair of phenyl groups is attached to Cl and C3 of 1,5-hexadiene, the barrier to the Cope rearrangement is decreased by 3.0 kcal/mol from that for the unsubstituted molecule. If the phenyl substituent effects on the Cope rearrangement were additive, augmentation of a pair of phenyl substituents at Cl and C3 by another pair at C4... 

In contrast to the cooperative substituent effects described above, placement of phenyl groups at Cl, C3, and C5 of 1,5-hexadiene results in a competitive substiment effect. By stabilizing structure A, a single phenyl group at C2/C5 lowers A// by 4.2 kcal/mol and, by stabilizing structure C, phenyl groups at Cl and C3 lower A// by 3.0 kcal/mol. However, the simultaneous presence of phenyl groups at Cl, C3, and C5 lowers A// by... 

Therefore, the competitive substituent effect, both predicted and found for the Cope rearrangement of l,3,5-triphenyl-l,5-hexadiene, is a consequence of the fact the value of R in the TS is a compromise between the value of R= 1.599 A, at which the phenyl group at C5 can provide optimal stabihzation for the contribution of structure A, and the value of R = 2.218 A, at which the phenyl groups at Cl and C3 provide optimal stabilization for the contribution of structure C. At the compromise value of/ = 2.110A the three phenyl groups in 1,3,5-triphenyl-1,5-hexadiene are calculated to provide 4.5 kcal/mol less TS stabilization than the total amount they furnish in the Cope rearrangements of 2-phenyl-1,5-hexadiene at R= 1.599 A and in l,3-diphenyl-l,5-hexadiene at / = 2.218 A. 

Thus, the case for a non-concerted 3,3-shift via a cyclohexane-1,4-diyl is weak. Nonetheless, substituent effects on the rate of the 3,3-shift were intially interpreted in terms of the diyl species. In particular, Dewar found the 2-phenyl and 2,5,-diphenyl-l,5-hexadiene rearrange 40 and 1600 times, respectively, more rapidly than that of the parent diene. Further, semi-empirical MINDO/3 calculations supported the proposition that even the parent species proceeded via the chair-like cyclohexane-1,4-diyl. These observations and calculations provided stimulus for a substantial effort in the subsequent years to address the question of transition state structure in and the energy surface for the 3,3-sigmatropic shift of 1,5-hexadiene. 

The Houk and Borden groups °° ° have collaborated on a couple of important studies to address the effect of multiple substituents on the Cope rearrangement. They examined the effects of cyano, phenyl, and vinyl substituents at various positions on 1,5 -hexadiene. All three substituents give similar results, but only the cyano and phenyl cases will be discussed here. The cyano case was also examined by Staroverov and Davidson, " coming to the same conclusions as presented here but with a slightly different analysis. 

In a finding of greater practical significance. Overman and coworicers showed that the reactions could be carried out with catalytic amounts of the palladium(II) complex, and that the catalytic effect was broadly applicable to acyclic 1,5-dienes as well7 In a typical example (equation 32), 2-methyl-3-phe-nyl-l,5-hexadiene rearranges in 1 h at room temperature in 87% yield in the presence of 0.06 equiv. of bis(benzonitrile)palladium dichloride, in contrast to the thermal rearrangement which has t n = 13 h at 177 °C. The cat yst thus provides an estimated rate acceleration of about 10 °. The product is a 93 7 mixture of ( )- and (Z)-isomers, corresponding to the equilibrium ratio. Palladium acetate and tetra-kis(triphenylphosphine) were ineffective as catalysts. One serious limitation is that the catalyzed reaction occurs only with those 1,5-dienes which possess an alkyl or aryl substituent at C-2 or C-5 (but not both). 

However, the cyclodimerization of 1,3-cyclohexadiene and also the addition of the cis,cis isomer of 2,4-hexadiene to 1,3-cyclohexadiene are only modestly stereoselective. The addition of cis,rra i-2,4-hexadiene to 1,3-cyclohexadiene is highly stereoselective for the addition to the lra s-propenyl group, but only modestly stereoselective for the addition to the cw-propenyl group. Further, the addition of a dienophile having a pendant, unsubstituted vinyl double bond to this diene is also highly endo stereoselective. The installation of a cis group at the terminus of the dienophilic moiety consistently appears to reduce the endo stereoselectivity to a more modest level. It has been proposed that the cis substituent attenuates the secondary interaction involving the endo double bond in the transition state for cycloaddition [47, 48]. The effect has been termed the cfs-propenyl effect . The addition of the ira j-anethole cation radical to both 1,3-cyclohexadiene and 1,3-cyclopentadiene is, however, only moderately diastereospecific (ca 3 1) [49]. 

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