ADDENDUM TO MOLECULAR MECHANICS PROBLEM SET Fall semester, 2005

A number of recent journal articles and review articles contain information that is relevant to a significant number of examples in the problem set. If you choose one of the following problems for your MMX project, you should be sure to consult the appropriate review article(s) (as well as the cited references where the problem is first presented).

There are three relevant review articles from the series "Advances in Strain in Organic Chemistry"; Halton, B., Ed.; JAI: London (available in the library):

for anti Bredt compounds and small-ring (Nos. 1, 13, others?): Szeimies, G.; 1992, Vol 2, p 1

for cyclophanes (Nos. 3, 27, 34, 52, 53, 56-58, 63, 119, 125, 181, 187, 189, 193, 197, 220, others?): Bickelhaupt, F.; de Wolf, W. H.; 1993, Vol 3, p 185

for fenestranes (Nos. 66-70, 161, others?): Luef, W.; Keese, R.; 1993, Vol 3, p 229

Dodziuk, H. Top. Stereochem. 1994, 21, 351: this is a review article on inverted or pyramidalized sp3- hybridized in strained compounds (Nos. 78, 149, 352, others?) A very recent paper from this same research group elaborates on several of the compounds calculated in 352 and suggests a new structure with only one inverted : Dodziuk, H.; Dolgones, G.; Leszcynski, J. Tetrahedron 2003, 59, 10013.

Kane, V. V.; De Wolf, W. H.; Bickelhaupt, F. Tetrahedron 1994, 50, 4575: this is another review article on the topic of cyclophanes (see earlier). An even more recent review article on the synthesis and reactivity of strained cyclophanes is by Bickelhaupt, F.; de Wolf, W. H. J. Phys. Org. Chem. 1998, 11, 362.

Beckhaus, H.-D.; Rüchardt, C.; Lagerwall, D. R.; Paquette, L. A.; Wahl, F.; Prinzbach, H. J. Am. Chem. Soc. 1994, 116, 11775 for experimental data on the heats of formation and strain energies of the C20H20 symmetrical compounds pagodane and (and their derivatives) for Problems 72, 77, 78, 83, 146, 147, 172, 186, and others. For additional work on unsaturated compounds and bridged compounds related to pagodane and dodecahedrane in Problems 113, 285, see Pinkos, R.; Weiler, A.; Voss, T.; Weber, K.; Wahl, F.; Melder, J.-P.; Fritz, H.; Hunkler, D.; Prinzbach, H. Liebigs Ann. Chem. 1997, 2069. For a recent summary of all of the MMX calculations on the pagodanes (and their various enes, , trienes, etc.) see Wollenweber, M.; Etzkorn, M.; Reinbold, J.; Wahl, F.; Voss, T.; Melder, J.-P.; Grund, C.; Pinkos, R.; Hunkler, D.; Keller, M.; Wörth, J.; Knothe, L.; Prinzbach, H. Eur. J. Org. Chem. 2000, 3855, especially Tables 7-10; Reinbold, J.; Bertau, M.; Voss, T.; Hunkler, D.; Knothe, L.; Prinzbach, H.; Neschchadin, D.; Gescheidt, G.; Mayer, B.; Martin, H.-D.; Heinze, J.; Prakash, G. K. S.; Olah, G. A. Helv. Chim. Acta 2001, 84, 1518.

Müller, P.; Mareda, J.; Milin, D. J. Phys. Org. Chem. 1995, 8, 507: this article gives many additional data points related to the solvolysis of bridgehead substrates, Problem 106B. An even more complete picture is obtained from calculations on gas-phase reactions in a very recent article: Abboud, J-L. M.; Herreros, M.; Notario, R.; Lomas, J. S.; Mareda, J.; Müller, P.; Rossier, J.-C. J. Org. Chem. 1999, 64, 6401.

Sygula, A.; Abdourazak, A. H.; Rabideau, P. W. J. Am. Chem. Soc. 1996, 118, 339: this article has calculations and experimental data related to corannulene and related compounds, Problem 231.

Marchand, A. P.; Xing, D.; Bott, S. G. Tetrahedron 1996, 52, 825 presents new information about the 2

crowded molecules (Z)- and (E)-1,2-di(1-adamantyl)ethene; cf Problem 198.

Qiao, X.; Padula, M. A.; Ho, D. M.; Vogelaar, N. J.; Schutt, C. E.; Pascal, R. A., Jr. J. Am. Chem. Soc. 1996, 118, 741 has additional calculated and experimental data on the twisted aromatic compounds found in Problem 64. Then, for some spectacular examples of a twisted polycyclic see the following: Qiao, X.; Ho, D. M.; Pascal, R. A., Jr. Angew. Chem., Int. Ed. Engl. 1997, 36, 1531; Tong, L.; Lau, H.; Ho, D. M.; Pascal, R. A., Jr. J. Am. Chem. Soc. 1998, 120, 6000.]

Boese, R.; Haumann, T.; Jemmis, E. D.; Kiran, B.; Kozhushkov, S.; de Meijere, A. Liebigs Ann. Chem. 1996, 913 presents calculations and X-ray crystal structures for the triangulanes of Problem 248; some even more spectacular triangulanes have been synthesized by this same research group: Seebach, M. von; Kozhushkov, S. I.; Boese, R.; Benet-Bucholz, J.; Yufit, D. S.; Howard, J. A. K.; de Meijere, A. Angew. Chem., Int. Ed. Engl. 2000, 39, 2495.

Alder, R. W.; East, S. P. Chem. Rev. 1996, 96, 2097 presents an extensive review of the experimental and computational details on bicyclo [m.n.o] compounds in which the bridgehead substituents are either both outside the ring (the normal situation) or one inside/one outside or both inside. This will be relevant to Problems 14 and 35 (both of which are mentioned in this review) and to other problems that you might devise on your own. Especially interesting are the MM2 calculated data in Table 1.

Gwaltney, S. L.; Sakata, S. T.; Shea, K. J. J. Org. Chem. 1996, 61, 7438 is the full paper of the 1992 communication that was the basis for Problem 142.

Sakamoto, Y.; Miyoshi, N.; Hirakida, M.; Kusumoto, S.; Kawase, H.; Rudzinski, J. M.; Shinmyozy, T. J. Am. Chem. Soc. 1996, 118, 12267 is the full paper related to the communication that served as the basis for Problem 257; for work on the mechanism by which this ?pinwheel” molecule inverts, see Hori, K.; Sentou, W.; Shinmyozu, T. Tetrahedron Lett. 1997, 52, 8955. See, also, the recent calculations on these compounds, reported by Bettinger, H. F.; Schleyer, P. von R.; Schaefer, H. F., III J. Am. Chem. Soc. 1998, 120, 1074.

Li, W.; Fox, M. A. J. Am. Chem. Soc. 1996, 118, 11752 presents data on dimers, trimers, tetramers, etc. from substituted cyclobutadienes; these "ladder" compounds are related to those in Problem 164. (See, also, Hopf's 2003 article on "ladderanes" that is mentioned on p. 4 of this addendum.)

Göttlich, R.; Kahrs, B. C.; Krüger, J.; Hoffmann, R. W. J. Chem. Soc., Chem. Commun. 1997, 247 has additional examples and insights related to Problems 265, 275, 276 and 347. See, also, Stahl, M.; Schopfer, U.; Frenking, G,; Hoffmann, R. W. J. Org. Chem. 1997, 62, 3702; Stahl, M.; Schopfer, U. J. Chem. Soc., Perkin Trans. 2 1997, 905; Hoffmann, R. W.; Schopfer, U.; Stahl, M. Tetrahedron Lett. 1997, 38, 4055; Götlich, R.; Schopfer, U.; Stahl, M.; Hoffmann, R. W. Liebigs Ann. Chem. 1997, 1757;Schopfer, U.; Stahl, M.; Brandl, T.; Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 1997, 36, 1745; Hoffmann, R. W.; Göttlich, R. Liebigs Ann. Chem. 1997, 2103. For an outstanding review on these restricted conformation molecules (and interesting extensions of them), see Hoffmann, R. W.; Stahl, M.; Schopfer, U.; Frenking, G. Chem. Eur. J. 1998, 4, 559. For even more recent data on these "flexible molecules with defined shape" see Hoffmann, R. W.; Stenkamp, D.; Trieselmann, T.; Göttlich, R. Eur. J. Org. Chem. 1999, 2915; Stenkamp, D.; Hoffmann, R. W.; Göttlich, R. Eur. J. Org. Chem. 1999, 2929. Another comprehensive review is Hoffmann, R. W. Angew. Chem., Int. Ed. Engl. 2000, 39, 2055. An interesting recent extension of these ideas is found "neighboring dimethylpentane segments": Hoffmann, R. W.; Göttlich, R.; Schopfer, U. Eur. J. Org. Chem. 2001, 1865. And for the very latest word, see the article about the conformational analysis of meso-2,3,4,5-tetramethylhexane and meso-2,3,4,5,6,7-hexamethyloctane: Hoffmann, R. W.; Menzel, K. Eur. J. Org. Chem. 2001, 2749.

Kuck, D. Liebigs Ann. Chem. 1997, 1043 has an updated discussion on centrosymmetric compounds (Problem 255); Kuck, D.; Krause, R. A.; Gestmann, D.; Posteher, F.; Schuster, A. Tetrahedron 1998, 3

54, 5247.

For a recent survey of compounds containing planar (or nearly planar) tetravalent carbons (Problems 65- 70, 161, 273), see Röttger, D.; Erker,. G. Angew. Chem., Int. Ed. Engl. 1997, 36, 812.

For recent work on the conformations of 1,4,7-cyclononatriyne (Problem 9 and others?) see Yavari, I.; Taherpour, A.; Jabbari, A. J. Chem. Res. (S) 1997, 210.

For further experimental and theoretical work on the strained Diels-Alder adducts of Problem 271, see Sauer, J.; Breu, J.; Herges, R. Neumann, H.; Kammermeier, S. Liebigs Ann. Chem. 1997, 1473.; Kammermeier, S.; Jones, P. G.; Herges, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 1757.

For further experimental work on the partial and complete hydrogenation of [2,2]-p-cyclophane (related to Problems 280 and 295), see Hopf, H.; Savinsky, R.; Jones, P. G.; Dix, I.; Ahrens, B. Liebigs Ann. Chem. 1997, 1499.

The full paper (calculations and experimental results) on the 10-membered ring diaza diynes in Problem 245 is Ritter, J.; Gleiter, R.; Irngartinger, H.; Oeser, T. J. Am. Chem. Soc. 1997, 119, 10599.

For further work on bridgehead allylic cations that are incapable of resonance stabilization (see Problems 90 and 112), there is a recent paper by Tokunaga, K.; Ohtsu, T.; Ohga, Y.; Takeuchi, K. J. Org. Chem. 1998, 63, 2209.

For a delightful and amusing (!) mini-review on the ?molecular brake” of Problem 214 and the ?molecular ratchet” of Problem 307, see Davis, A. P. Angew. Chem., Int. Ed. Engl. 1998, 37, 909. For extensive new experimental work on these "molecular motors," see Kelly, T. R.; Silva, R. A.; De Silva, H.; Jasmin, S.; Zhao, Y. J. Am. Chem. Soc. 2000, 122, 6935. For an extensive review of both the "molecular brake" of Problem 214 and the "molecular ratchet" of Problem 307, as well as for more recent developments, see Kelly, T. R. Acc. Chem. Res. 2001, 34, 514.

Much work has been done on the Bergman cyclization of enediynes to six-membered ring aromatic diradicals (see Problem 94, for example), a reaction of interest not only for its mechanistic but also for its biological connotations. For an update and for recent calculations on the product (a p-benzyne), see Schreiner, P. R. J. Am. Chem. Soc. 1998, 120, 4184.

For further work (calculational and experimental) on the conformations of 1,3,5,7-tetraoxadecalin (Problem 226), see the following: Linden, A.; Beckhaus, H.-D.; Verevkin, S. P.; Rüchardt, C.; Ganguly, B.; Fuchs, B. J. Org. Chem. 1998, 63, 8205; Grabarnik, M.; Lemcoff, N. G.; Madar, R.; Abramson, S.; Weinman, S.; Fuchs, B. J. Org. Chem. 2000, 65, 1636.

For ab initio calculations on the [n]-peristylanes and their oxo derivatives (see Problems 357, 300, 77, and 72), see Sharma, P. K.; Jemmis, E. D.; Vidya, R.; Mehta, G. J. Chem. Soc., Perkin Trans 2 1999, 257. For very recent work on the synthesis, structure, and properties of several "oxa bowls" including pentaoxa[5]- and hexaoxo[6]-peristylane, see Mehta, G.; Vidya, R. J. Org. Chem. 2001, 66, 6905, 6913.

Conformational analysis of the crowded 1-alkyl-2,2,6,6-tetramethylpiperidines was addressed in Problems 150 and 180. Now there are new calculations that shed some doubt on the earlier interpretations. See Belostotskii, A. M.; Gottlieb, H. E.; Aped, P.; Hassner, A. Chem. Eur. J. 1999, 5, 449.

For a follow-up on the conformations of tetraethylmethane (3,3-diethylpentane) from Problem 330, see Alder, R. W.; Allen, P. R.; Hnyk, D.; Rankin, D. W. H.; Robertson, H. E.; Smart, B. A.; Gillespie, R. J.; Bytheway, I. J. Org. Chem. 1999, 64, 4226. 4

A recent article describes the stereochemical relationship of the aromatic rings in the [n,n]metapara- cyclophanes (where n=2, 3, or 4); these are related to Problems 193 and 220; see Hong, B. H.; Lee, J. Y.; Cho, S. J.; Yun, S.; Kim, K. S. J. Org. Chem. 1999, 64, 5661.

For further work on compounds related to the annelated of Problem 274, see the review by Komatsu, K. Eur. J. Org. Chem. 1999, 1495.

For further calculations on the possibility of a planar tetracoordinate carbon (cf. Problems 174. 338), see Rasmussen, D. R.; Radom, L. Angew. Chem., Int. Ed. Engl. 1999, 38, 2876; Rass,ussen, D. R.; Radom, L. Chem. Eur. J. 2000, 6, 2470.

Problems 207 and 237 focused on the “twistatrienes” and their reactions. Now there are recent calculations on the twistatetraenes and related tricyclic C12H12 tetraenes: Bettinger, H. E.; Pak, C.; Xie, Y.; Schleyer, Paul v. R.; Schaefer, H. F. III J. Chem. Soc., Perkin Trans 2 1999, 2377. And for some very recent experimental and theoretical work on Cope rearrangement the twistadienes and trienes (Problem 237), see Lange, H.; Loeb, P.; Herb, T.; Gleiter, R. J. Chem. Soc., Perkin Trans 2 2000, 1155.

Three very complete accounts of the polyspiro ethers from Problems 258 and 345 are given by Paquette, L. A.; Tae, J.; Hickey, E. R.; Trego, W. E.; Rogers, R. D. J. Org. Chem. 2000, 65, 9160; Paquette, L. A.; Tae, J.; Branan, B. M.; Bolin, D. G.; Eisenberg, S. W. E. ibid. 2000, 65, 9173; Rablem, P. R.; Paquette, L. A.; Borden, W. T. ibid. 2000, 65, 9180.

A recently published book on chemistry has discussions of many of the types of compounds that are found throughout these problem sets: prismanes, Platonic solids, twisted , cyclic , bridgehead alkenes, cyclophanes, etc. If you are doing a project that involves some sort of unique or strained or implausible hydrocarbon, a brief "stroll" through this book should prove rewarding: Hopf, H. Classics in Hydrocarbon Chemistry; Wiley-VCH: Weinheim, 2000.

If you are working any of the exercises involving fenestranes (66-70, 161, 273), you might be interested in some recent MM3 and MMX calculations on a naturally occurring 5/5/5/7 fenestrane system: Weavers, R. T. J. Org. Chem. 2001, 66, 6453.

Problem 249 called for calculations on the major conformations of Et2N-CH(CH3)2. This molecule has been examined, again, this time using MM3 (instead of MM2) and very careful low temperature 13C- NMR analysis. Be sure to include the new energy data from Figure 1, if you choose to work on this problem: Sebag, A. B.; Forsyth, D. A.; Plante, M. A. J. Org. Chem. 2001, 66, 7967.

If you are working on any of the problems (310, 341, 362, 374) concerning polyalkylated aromatic compounds (like hexaethylbenzene) that come from the Biali and Gottlieb research groups, you should consult a very recent review article: Marks, V.; Gottlieb, H. E.; Biali, S. E. Eur. J. Org. Chem. 2003, 1825.

"Ladderanes" are the subject of three earlier problems (164, 213, and 244) and are mentioned briefly on p. 2 of this handout. One of the leading practitioners, Henning Hopf, has published a brief review on the preparation and characterization of these molecules, including a discussion of the ladderanes that are found in Nature. If you decide to do an MMX project in this area, you need to look at this recent review: Hopf, H. Angew. Chem., Int. Ed. Engl. 2003, 42, 2822. See, also, a very recent article on construction of ladderanes in the solid state: Gao, X.; Friscic, T.; MacGillivray, R. Angew. Chem., Int. Ed. Engl. 2004, 43, 232.

A number of problems (e.g., 2, 9, 10, 269, 302, and 368) have explored the use of alkynes as spacers in rings of moderate size. For the latest word on these and others not yet set as problems, be sure to consult Marsden, J. A.; Palmer, G. J.; Haley, M. M. Eur. J. Org. Chem. 2003, 2355. 5

Problem 339 was concerned with the structure and reactivity of polyspirocyclobutanes. A recent article by the same research group describes the synthesis and stereochemistry (racemic or meso) for several of these compounds: Fitjer, L.; Kanschik, A.; Gerke, R. Tetrahedron 2004, 60, 1205.

Problem 387 focused on a series of compounds with a central ring, fused to which were various bicyclic units. A related series of molecules has recently been synthesized; someone who chooses to do this problem should also consult the more recent work: Dastan, A.; Fabris, F.; De Lucchi, O.; Güney, M.; Balci, M. Helv. Chim. Acta 2003, 86, 3411.

A review article covering all sorts of strained has recently appeared. If you are doing calculations on propellanes (Problem 13), trans-fused bicyclo[n.1.0] (Problem 105), anti-Bredt bridgehead alkenes (Problems 1 and 117), etc., you should compare your MMX calculations with the experimental and ab initio results reported by Wiberg, K. B. In Reactive Intermediate Chemistry; Moss, R. A.; Platz, M. S.; Jones, Jr., M. Eds.; Wiley, 2004; Chapter 15.

For a recent research article and for a review article on the strained pyramidalized alkenes of Problems 279, 306, and 363, see: Camps, P.; Fernández, J. A.; Font-Bardia, M.; Solans, X.; Vázquez, S. Tetrahedron 2005, 61, 3593; Vázquez, S.; Camps, P. Tetrahedron 2005, 61, 5147. Another type of pyramidalization is found in strained polycyclic alkenes (e.g., Problems 26, 109, 113, 270, 383, 386, 400); many of these and many new ones are found in a recent article: Williams, R. V.; Margetic, D. J. Org. Chem. 2004, 69, 7135.

For calculations on the strain energy of poly-fused three- and four-membered rings (with planar or nearly planar carbons) (Problems 69, 70, 161, and 352), see: Takeuchi, K.; Horiguchi, A.; Inagaki, S. Tetrahedron 2005, 61, 2601.

For problems involving [2,2]cyclophanes, whether p,p or p,m or m,m (e.g., 23, 58, 183, 227, 2412, 248, 316, 355, 375, 395) see the most recent calculations in Caramori, G. F.; Galembeck, S, E,; Laali, K. K. J. Org. Chem. 2005, 70, 3242.

For some of the latest work on the "superphanes" (benzene rings held together by three, four, five, or six bridges of -CH2CH2- ) in Problems 197, 257, and 344, see Nogita, R.; Matohara, K.;; Yamaji, M.; Oda, T.; Sakamoto, Y.; Kumagai, T.; Lim, C.; Yasutake, M.; Shimo, T.; Jefford, C. W.; Sinmyozu, T. J. Am. Chem. Soc. 2004, 126, 13732.