Reaction Mechanisms

6. A stepwise mechanism has been suggested for the thermal conversion of cis-bicyclo[4.2.0]oct-7- ene into Z,Z-1,3-cyclooctadiene. What does molecular mechanics indicate about the feasibility of this? What about the analogous transformation of the [3.2.0] system? How well does molecular mechanics (a non-orbital calculation) mimic the orbital symmetry calculation?


11. Exo-fused norbornyl derivatives are know to undergo transannular hydride transfers in the carbocations. How close are the hydrogens in the hydrocarbons shown? What are the relative strain energies vs. the non-fused analogs?


35. Use molecular mechanics to calculate the energy, geometry, strain, etc. of the bicyclic alkene (shown to the right) and of its conjugate acid after protonation; do the calculations for n = 4, 5, and 6. Determine the distance from the "inside" H to the double bond and to the cationic center to see if there is a possibility of having a hydrido-bridged structure; see the cited article for the meaning of the preceding phrase.

[Sorensen, T. S.; Whitworth, S. M. J. Am. Chem. Soc. 1990, 112, 8135.]


43. The electrocyclic opening (with heat or with light) of cis- or trans- bicyclo[5.2.0]non-8-ene can produce cis,cis and/or cis,trans-1,3- cyclononadiene. Calculate the ground- state geometries and energies of both stereoisomers of the bicyclic reactant. Then, calculate the energies and geometries of both the cis,cis and cis,trans monocyclic dienes, not only in their lowest energy form but also in the conformation in which the four carbons of the diene are coplanar. See the cited article (Scheme II and p. 1578, left column) for details on this.

[Leigh, W. J.; Zheng, K.; Clark, K. B. J. Org. Chem. 1991, 56, 1574.]


86A. Upon heating (E)-1,3,5-hexatriene cyclizes to 1,3- cyclohexadiene, presumably by first undergoing electrocyclic ring closure to 3-vinylcyclobutene which then opens to (Z)-1,3,5-hexatriene, the immediate precursor to the six-membered ring. (Note: neither acyclic triene is shown in the conformation needed for ring closure to occur.) Calculate the heats of formation of all four compounds and compare your results with those shown in Figure 1 and Table 3 of the reference.

86B. (E,E)-1,3,5-heptatriene cyclizes to a six- membered cyclic diene. Unlike the case above, this initial diene can undergo a set of [1,5] sigmatropic shifts of H to give two isomeric cyclic dienes. Calculate the heats of formation of the four structures, and compare your results with those in Tables 2 and 3 of the reference.

[Doering, W. von E.; Roth, W. R.; Bauer, F.; Boenke, M.; Breuckmann, R.; Ruhkamp, J.; Wortmann, O. Chem. Ber. 1991, 124, 1461.]


88. The ene reaction can occur inter- (Eqn (l)) or intramolecularly (Eqn (2)). Calculate deltaH for Eqn (1) and for the intramolecular cases (Eqn (2)) in which n = 1, 2, or 3. Discuss the factors which lead to the variation observed for deltaH. Compare your answers with the calculate and experimental results in the cited article.



[Berson, J. A. Acc. Chem. Res. 1991, 24, 215.]


94. The ability of a series of ene-diynes to undergo thermal closure to a fused aromatic product (in a stepwise process via a diradical which abstracts hydrogens from solvent) depends critically on the distance between the termini of the two triple bonds. Use MM to calculate the bond distances, bond angles, dihedral angles, etc. of the hydrocarbons with X = CH2 and n = 0 or 1 or 2; of the hydrocarbon with X absent and n = 0; and of the heterocycle with X = S and n = 1. Compare your results with the calculated and experimental (X-Ray crystal structure) results in the cited article.

[Sakai, Y.; Nishiwaki, E.; Shishido, K.; Shibuya, M.; Kido, M. Tetrahedron Lett. 1991, 32, 4363; see also Sakai, Y.; Bando, Y.; Shishido, K.; Shibuya, M. Ibid. 1992, 33, 957; Nicolaou, K. C.; Zuccarello, G.; Riemer, C.; Estevez, V. A.; Dai, W.-M. J. Am. Chem. Soc. 1992, 114, 7360.]


100. Bromine adds to alkenes in stereospecific anti fashion. Consider the bromination of steroids 2- cholestene (1) and cholesterol (2, X = OH), shown as partial structures to the right. Anti addition of Br2 to each can (in principle) produce either of two diastereomers; in fact, only one diastereomer is initially formed (for reasons which will be discussed later in lecture), but it can rearrange to the other. Your job is to determine which diastereomer predominates for the case of trans-2,3-dibromocholestane and for three cases of addition to 2: X = H, OH, or Br.


105C. Consider the stepwise hydrogenation of the triene shown to the right. Calculate the energy of the triene; of the three possible dienes; of the monoene; and of the saturated final product. Discuss differences and similarities in the energy changes as each double bond is hydrogenated; compare your answers with those in the article.

105D. Consider the stepwise hydrogenation of "birdcage" dienes A, B, and C. Calculate the energies of these molecules as well as of the resulting monoenes and saturated hydrocarbons. Discuss differences and similarities in the energy changes as each double bond is hydrogenated; compare your answers with those in the article.

[Roth, W. R.; Adamczak, O.; Brueckmann, R.; Lennartz, H.-W.; Boese, R.; Chem. Ber. 1991, 124, 2499; see, also, Turner, R. B.; Jarrett, A. D.; Goebel, P.; Mallon, B. J. J. Am. Chem. Soc. 1973, 95, 790.]


108. Cyclization by intramolecular nucleophilic substitution of the anion to the right can produce either fused (1,2) or bridged (1,4) products, each of which can be either cis or trans in stereochemistry. One MM project would be to calculate the energies and structures of all of the 1,2-products for n =2 through n = 5. Another project would be to do the same for the 1,4-products (n = 2 through 5). For either project, compare your results with those found in the cited article.

[Auchter-Krummel, P.; Krummel, G.; Lex, J.; Müllen, K. Chem. Ber. 1991, 124, 2819.]


109. By calculating the energies of the alkenes and alkanes shown to the right, determine the heat of hydrogenation for each case; compare your results with those in the cited reference. Do calculations on the systems where n = 0, 1, and 2 and, for reference purposes, on the "unstrained" parent system where there is no bridge (i.e., bicyclo[3.3.0]- 1(5)-octene). Discuss the strain energy as a function of pyramidalization of the alkene unit.

[Branan, B. M.; Paquette, L. A.; Hrovat, D. A.; Borden, W. T. J. Am. Chem. Soc. 1992, 114, 774.]


144. Cleavage of a C-C bond in the cubylcarbinyl radical begins a "cascade" sequence in which a second and then a third bond C-C are broken. Note that the third and fourth structures are allylic radicals (even though only one contributor is indicated). Calculate the energies and geometries of these four radicals and discuss the factors that are involved in each of the three exothermic steps.

[Choi, S.-Y.; Eaton, P. E.; Newcomb, M.; Yip, Y. C. J. Am. Chem. Soc. 1992, 114, 6326.]


146. One can imagine a set of steps leading from "pagodane" (1) (see, also, problem 83) to "dodecahedrane" (2) via either (a) [2+2] cleavage of the central ring followed by hydrogenation steps and then by dehydrogenation or (b) alternating hydrogenation and dehydrogenation steps. Some of these "steps" are chemically unreasonable, but one can imagine real examples corresponding to them. The authors contend (see Scheme I and Fig. 1 in the article) that one sequence is inherently preferred to the other; confirm or disprove this by calculating the energies of all of the species along the two pathway.

[Fessner, W.-D.; Murty, A. R. C.; Spurr, P. R.; Pinkos, R.; Melder, J.-P.; Fritz, H.; Prinzbach, H. Chem. Ber. 1992, 125, 1697.]


147. Consider the possibility of introducing two double bonds into the "pagodane" skeleton after cleavage of the central four-membered ring. Do MMX calculations on six dienes: double bonds at b and c; at a and c; at a and d; at a and e; at a and f; and at a and g. Compare your answers with those in Table 1. Discuss the factors which are responsible for the very different energies of these dienes.

[Murty, A. R. C.; Pinkos, R.; Spurr, P. R.; Fessner, W.-D.; Lutz, H.; Fritz, H.; Hunkler, D.; Prinzbach, H. Chem. Ber. 1992, 125, 1719.]


153. Friedel-Crafts acylation of cyclohexene by 1-cyclopentenylacetyl chloride produces a mixture of racemic diastereomers that can interconvert via keto-enol type equilibria. Calculate the structure and energies of the four possible diastereomers based on the structure shown; also, for the all cis-fused isomer, do calculations on both of the double- chair conformations. Compare your results with those cited in the article; comment on differences, if any.

[Faure, R.; Pommier, A.; Pons, J.-M.; Rajzmann, M.; Santelli, M. Tetrahedron 1992 48, 8419.]


156. This problem has to do with the application of the Winstein-Holness-Eliel equation to a particular elimination reaction. Calculate the energies of all three staggered conformations (about the central C-C bond) of both the erythro and threo stereoisomers of 1,2-diphenyl-1-bromopropane [Ph-CH(CH3)-CH(Br)-Ph], and use this to estimate which stereoisomer eliminates more rapidly.


165. Dimerization of 1,3-diphenylallene occurs exclusively in [2+2] head-to-head fashion to give three (of six possible) stereoisomers. To simplify the problem, consider the dimerization of 1,3-dimethylallene - the six stereoisomers (not counting enantiomers) correspond to the various arrangements at the two double bonds and at the two stereogenic centers in the ring. Compare the relative energies with those reported for the diphenyl series.

[Brattesani, A. J.; Maverick, E.; Muscio, O. L., Jr.; Jacobs, T. L. J. Org. Chem. 1992, 57, 7346.]


172. This problem is reminscent of Nos. 83 and 146. The series of dienes (to the right) can, in principle, undergo intramolecular [2+2] cycloaddtion to the caged adduct. Compute the heats of formation and strain energies for both structures for the series n = 0, 1, 2, and 3. Compare your calculated energies and geometrical parameters with those in the article. Comment on the likely success or failure of this reaction.

[Wollenweber, M.; Hunkler, D.; Keller, M.; Knothe, L.; Prinzbach, H. Bull. Soc. Chim. Fr. 1993, 130, 32.]


185. Birch reduction of trans-fused aromatic compound 1 followed by methylation gives a mixture of diastereomers. Similar reaction of cis-fused 2 gives another pair of diastereomers. Do MMX calculations on the four diastereomers; note that those derived from 2 can, because of the cis fusion, exist in either of two conformations. Discuss the factors that lead to differences in energy of these various stereoisomers and conformations.

[Vila. A. J.; Cravero, R. M.; González-Sierra, M. Tetrahedron 1993, 49, 4511.]


186. The diene (to the right) can conceivably undergo [2+2] cycloaddition as shown, even though the ring strain should increase. Compute the change in enthalpy and in strain energy for this reaction and for the series of reactions in which the C=C's are replaced, singly or in pairs, by benzo and naphtho groups. For these aromatic compounds, the increase in strain will be accompanied by a loss in resonance energy. Also compute the distance between the reacting pi systems in the reactants. Compare your results with those in the Table of the cited reference.

[Thiergardt, R.; Keller, M.; Wollenweber, M.; Prinzbach, H. Tetrahedron Lett. 1993, 34, 3397.]


191. Thermal [2+2] dimerization of the all s- trans linear triene can lead to cyclobutane- containing dimers in which the decalin-like units have either a syn or anti relationship. When optically pure reactant (say R configuration) reacts, three dimers are possible (see Scheme IV in the reference). When racemic material reacts, the R + S combination leads to three other possible dimers (Scheme V). Calculate the MMX energies of these six structures and compare your results with the MM2 values in the reference (Table I).

[Doering, W. von E.; Belfield, K. D.; He, J. J. Am. Chem. Soc. 1993, 115, 5414.]


205. The [2+2] syn dimer of acenaphthalene is hydrogenated under vigorous conditions to its H16 derivative; further hydrogenation to the H18 and H20 derivatives proved impossible. Do calculations on all four compounds and discuss why complete hydrogenation does not occur. Compare your structural parameters with those in the cited article.

[Boldt, P.; Döring, D.; Jones, P. G.; Köpper, H.; Trog, R.-S. Chem. Ber. 1994, 127, 219.]


209. In a problem reminiscent of No. 144, generation of the 9- basketyl radical, C10H11·, leads via a cascade to new radicals by the cleavage of one, two, and then three of the C- C bonds to the "upper" cyclobutane. Calculate the energies of all of these species and comment on the feasibility of this proposed sequence of steps. Speculate on why the last radical does not undergo cleavage of the one remaining C-C bond.

[Binmore, G. T.; Della, E. W.; Elsey, G. M.; Head, N. J.; Walton, J. C. J. Am. Chem. Soc. 1994, 116, 2759.]


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