Exo/endo product ratio

When cyclic 1,3-dienes were employed, the reactions were found to be exo selective [Eq. (28)]. In contrast, the Diels-Alder reactions of free thio-and selenoaldehydes with cyclopentadiene occur with a preference for the endo isomer.235 Thus, coordination of thio- and selenoaldehydes to a penta-carbonylmetal fragment resulted in a reversal of the endo selectivity. The exo/endo product ratio of [W(CO)5 E = C(Ph)H ] was 7.3 1 (E = S) and 2.6 1 (E = Se), whereas the kinetically controlled exo/endo ratio of the cycloadducts obtained by trapping of the free heterobenzaldehyde with cyclopentadiene was reported to be 1 7236 and 1 4235 237 (E = S) and 1 2.6238 and 1 4239 (E = Se), respectively. 

In 3,2 shifts the migrating group acts as an internal nucleophile. The controversial arguments concerning high exo endo product ratios (Section 7.6.2.2) also apply to the stereospecificity of 3,2 shifts. The invariance in exo preference as a function of cation stability casts some doubt on the explanation of this phenomenon in terms of a delocalization524). 

In most cases the high exo endo rate ratio is accompanied by a high exo endo product ratio this can be explained by an almost microscopic reversibility of the process. There are cases, however, when a high exo endo product ratio accompanies a low rate ratio Apparently the difference in the energies of the transition state of... 

Corey showed 1963 that 2-exo-103 and 2-endo-norbornylamines 104 are deaminat-ed in acetic acid to yield practically identical mixtures both in the exo endo product ratio and in the retention degree of optical activity. He postulated both reactions to the same intermediate classical 2-norbornyl cation since no optically active products were obtained from a symmetrical nonclassical 2-norbornyl ion 5. Somewhat later Berson studied the composition of reaction mixtures from the deamination of amines 103 and 104 (Table 8) more carefully three essential difference in the compositions of reaction mixtures were pointed out ... 

The difference in the optical purity of exo acetate 66 and that in the exo endo product ratio on deamination of endo 104 and exo amines 103 can be explained as follows. Since endo products and optically active ones can only be formed from the classical ion 6, their amount on deamination of exo amine 103 must be less because exo amine 103 partially converts directly into the nonclassical ion 5. Deviation from 100% optical purity of endo acetate 105 seems to te due to a partial equilibrium between the classical cation 6 and its enantiomer which is likely to be established via the non-classical cation 5. 

The cyclization of 8, s-unsaturated acyl radicals has been the research subject of several groups [27]. The propagation steps for the prototype reaction are illustrated in Scheme 7.4. The 5-exo 6-endo product ratio varies with the change of the silane concentration due to the competition of hydrogen abstraction from the silane with the ring expansion path. 

This interpretation has not been universally accepted, one reason being that the product ratios do not decline in like manner to the rate ratios. Another factor is that, even if the rate ratios are taken to indicate the existence of some participation of the electrons in the bond between C-l and C-6 in the solvolysis of exo-2-norbornyl tosyl-ate, this is far removed from proving the existence of the symmetrical and hence fully delocalized ion at the transition state or as an intermediate in the reaction. Hence, if one concludes that the exo- and endo-derivatives of the restricted systems are solvolysing to essentially unbridged or classical ions, the extent of bridging to be deduced from high exo/endo rate ratios found with less restricted systems is unclear. 

The exo/endo rate ratio in the unsaturated series compares closely to that observed with the saturated tosylates homoconjugative interaction is therefore not apparent. Also, the products were those expected for solvolysis without participation.373 The dihydrotriquinacenyl tosylates solvolyze more slowly due die inductive contributions of the double bonds. The geometry of the p7T orbitals in the exo isomer are seen to have a very poor alignment for neighboring group participation. 

Since the publication of Haywood-Farmer s comprehensive review which covered the literature in detail up through 1972 and in part into 1973, the solvolyses of a number of additional cyclopropane-containing systems have been studied in which trishomocyclopropenyl cations were implicated or discussed. Thus, Masamune and coworkers and Gassman and Creary " " studied the solvolyses of the exo- and endo-anti-tricyclo[3.1.1.0 ]heptan-6-yl p-nitrobenzoate and tosylate (111 and 112) (Scheme 16). For these two compounds, the exo.endo rate ratio after correcting for different leaving groups and solvents was 56 1. From looking at the products and from consideration of the relative rates of the non-cyclopropanated materials = 10 ) it was proposed... 

As shown in Scheme 2, the reaction of 1 with a-terpinene leads to the stereoisomeric E/Z [2+2] cycloadducts 3 in competition with the formation of the Diels-Alder products exo/endo-4 (ratio E/Z-3 exo/endo-4 = 39 41 8 12). This result conforms with investigations on the cycloadditon between 1 and 1,3-cyclohexadiene [7], An analogous rearrangement of the [2+2] isomer A to the more stable bicyclic 2-silaoctene B (Scheme 1) via a dipolar intermediate could not be observed for the homologous terpinene cycloadducts. 

Yield is based on conversion to the a-methylene lactone. Yield is based on conversion to the methiodide. ° A 1 4 ratio of exo endo products was determined independently by Mosher et al but using the iminium salt (30) instead of (32). The starting materials are shown to the right. 

The exo endo rate ratio can be correctly predicted without due regard for anchimeric assistance this points to its absence. Hence the initial product to ionize these systems is the classical tertiary 2-norbornyl cation. This conclusion, however, does not preclude the possibility of the subsequent rearrangement of the classical cation into a nonclassical one, nor does it give any evident of the relative stability of classical and nonclassical tertiary 2-horbomyl cations. 

Cg—C, bonds diminishes. On the other hand, the break away of the endo-X does not decrease the torsional strain since the C—X bond was not ecUpsed in the ground state but there is an increase in the long-range steric interaction between X and the endo-H-6. Besides, there appears an eclipsed interaction between the C —R and C —H bonds. These effects are quite sufficient to arate ratio of solvolysis with tertiary norbomyl derivatives and, in conformity with the microscopic reversibiUty, for the high exo endo ratio of the products, e.g., on addition of a hydride-ion... 

The configuration of chlorine affects little the acetolysis rate the acetolysis rate ratios of 75, 77 and 124,125 are only 2. However the exo endo rate ratio for the two anti-epimers 77 and 125 and for the two syn-epimers 75 and 124 are 80 and 246, respectively these values are quite comparable with the exo endo rate ratio for unsubstituted 2-norbomyl tosylates. The absolute values of rates for the four epimers are tially lower (about 300 times) than those for the respective unsubstituted 2-norbomyl tosylates as expected from the inductive effect of the chlorine at C . All four epimeric tosylates yield qualitatively the same mixtures of products, identical by GLC from anti-chloro tosylates 77 and 125, quantitatively rather different from syn-isomers 76 and 124. 

Gassman s results on the solvolysis of compounds 77 and 125 are of great interest the high exo endo rate ratio, the formation of the same products, and the absence of endo products show that the norboraanes in which a cationic centre on C is suppressed by electronic effects behave like unsubstituted 2-norbomyl tosylates. 

Let us now return to the question of solvolysis and how it relates to the structure under stable ion conditions. To relate the structural data to the solvolysis conditions, the primary issues which must be considered are the extent of solvent participation in the transition state and the nature of solvation of the cationic intermediate. The extent of solvent participation has been probed by comparison of solvolysis characteristics in trifluoroacetic acid with the solvolysis in acetic acid. The exo-endo reactivity ratio is 1120 in trifluoroacetic acid as compared to 280 in acetic acid. In both cases the product is the exo ester. While the endo isomer shows solvent sensitivity typical of normal secondary tosylates, the exo isomer reveals a reduced sensitivity. This indicates that the transition state for solvolysis of the exo isomer possesses a greater charge dispersal, which would be consistent with bridging. This fact, along with the rate enhancement, indicates that the cr participation commences prior to the transition state so that it can be concluded that bridging is a characteristic of the solvolysis intermediate, as well as of the stable ion structure. 

The importance of steric effects in solvolysis of norbornenyl derivatives is further emphasized by Peters and Brown. Rates were measured for (492)— (499) and the relative rates are shown. The introduction of a double bond leads to a rate reduction relative to the saturated compound and hence double-bond participation is minimal and the ratio reflects the inductive effect of the double bond. This view is substantiated by the absence of tricyclic products. The high exo endo rate ratios in the absence of significant a- or 7r-stabilization are explained on steric grounds solvolysis of the endo-derivatives are retarded by steric hindrance to ionization. 

The Diels-Alder reaction provides us with a tool to probe its local reaction environment in the form of its endo-exo product ratio. Actually, even a solvent polarity parameter has been based on endo-exo ratios of Diels-Alder reactions of methyl acrylate with cyclopentadiene (see also section 1.2.3). Analogously we have determined the endo-exo ratio of the reaction between 5.1c and 5.2 in surfactant solution and in a mimber of different organic and acpieous media. These ratios are obtained from the H-NMR of the product mixtures, as has been described in Chapter 2. The results are summarised in Table 5.3, and clearly point towards a water-like environment for the Diels-Alder reaction in the presence of micelles, which is in line with literature observations. 

Table 5.3. Endo-exo product ratios of the Diels-Alder reaction of 5.1c with 5.2 in surfactant solution compared to water and organic solvents.

In the alkylative cyclization of the 1,6-enyne 372 with vinyl bromide, formation of both the five-membered ring 373 by exn mode carbopalladation and isomerization of the double bonds and the six-membered ring 374 by endo mode carbopalladation are observed[269]. Their ratio depends on the catalytic species. Also, the cyclization of the 1,6-enyne 375 with /i-bromostyrene (376) affords the endo product 377. The exo mode cyclization is commonly observed in many cases, and there are two possible mechanistic explanations for that observed in these examples. One is direct endo mode carbopalladation. The other is the exo mode carbopalladation to give 378 followed by cyclopropana-tion to form 379, and the subsequent cyclopropylcarbinyl-homoallyl rearrangement affords the six-membered ring 380. Careful determination of the E or Z structure of the double bond in the cyclized product 380 is crucial for the mechanistic discussion. 

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