1.3 Closed capped structures

For all these purposes, the chemistry of "open" geodesic polyarenes that is to say subunits of fullerenes that lack one or more of the rings but remain curved have thus attracted increasing attention.²⁰

97 98 99

Figure V-6. Molecular architecture of corannulene 97, sumanene 98 and circumtrindene 99.

These moieties which can be map onto the surface of fullerenes are remarkable synthetic targets²⁷ that can be use for the construction of fullerenes, CNTs and other artificial bent structures and receptors.²⁸ Famous examples of such class of

26 Deschenaux, R.; Donnio, B.; Guillon, D. New J. Chem. 2007, 31, 1064-1073. Campidelli, S.; Eng, C.; Saez, I. M.; Goodby, J.

W.; Deschenaux, R. Chem. Commun. 2003, 1520-1521.

27 Mack, J.; Vogel, P.; Jones, D.; Kaval, N.; Sutton, A. Org. Biomol. Chem. 2007, 5, 2448-2452. Jackson, E. A.; Steinberg, B.

D.; Bancu, M.; Wakamiya, A.; Scott, L. T. J. Am. Chem. Soc. 2007, 129, 484-485. Kawase, T.; Kurata, H. Chem. Rev. 2006, 106, 5250-5273. Petrukhina, M. A.; Scott, L. T. Dalton Trans. 2005, 2969-2975. Aprahamian, I.; Eisenberg, D.; Hoffman, R.

E.; Sternfeld, T.; Matsuo, Y.; Jackson, E. A.; Nakamura, E.; Scott, L. T.; Sheradsky, T.; Rabinovitz, M. J. Am. Chem. Soc. 2005, 127, 9581-9587.

28 Sygula, A.; Fronczek, F. R.; Sygula, R.; Rabideau, P. W.; Olmstead, M. M. J. Am. Chem. Soc. 2007, 129, 3842-3843. Perez, E. M.; Sierra, M.; Sanchez, L.; Torres, M. R.; Viruela, R.; Viruela, P. M.; Orti, E.; Martin, N. Angew. Chem., Int. Ed. Engl.

2007, 46, 1847-1851. Hayama, T.; Wu, Y.-T.; Linden, A.; Baldridge, K. K.; Siegel, J. S. J. Am. Chem. Soc. 2007, 129, 12612-12613. Tsefrikas, V. M.; Scott, L. T. Chem. Rev. 2006, 106, 4868-4884. Scott, L. T. Angew. Chem., Int. Ed. Engl. 2004, 43, 4994-5007. Mehta, G.; Rao, H. S. P. Tetrahedron 1998, 54, 13325-13370. Mehta, G.; Panda, G. PINSA-A: Proc. Indian Natl.

Sci. Acad., Part A 1998, 64, 587-608. Mehta, G.; Rao, H. S. P. In Advances in Strain in Organic Chemistry; Halton, B ed.;

Halton, B., Ed.; JAI: London, U.K., 1997; Vol. 6, pp 139-187.

Chapter V. Synthesis, Resolution and VCD Analysis of the First Enantiopure Diazaoxatricornan Derivative

compounds include corannulene 97, sumanene 98, circumtrindene 99 and intrinsically chiral hemibuckminsterfullerene 100 (see Figure V-6 and Figure V-7).

To our knowledge, most of the reported structures are achiral. The few chiral fully-fused polycyclic derivatives have been characterized in racemic form only owing to their configurational lability or to a lack of resolution. ^29,30,31 (typical examples include compounds 100 to 103 in Figure V-7). In this context, the isolation of an enantiopure closed-capped bowl shaped molecule would be an important novelty; the synthesis, resolution and absolute configuration assignment of the non-racemic structure being possibly a challenging task.

Figure V-7. Chiral hemibuckminsterfullerene 100, Hexamethyltriphenylene 101, Heteroacepentalene 102 and corannulene 103.

Previously, Siegel et al have reported the synthesis of trioxatricornan derivatives that constitute an interesting class of polyaromatic molecular cavities useful for the construction of macrocyclic cages. The synthesis of these organic building blocks is straightforward, versatile, and can be achieved on a large scale through the simple addition of a hydride or an organometallic reagent to salts of trioxatriangulenium

29 In this study, we are only considering fully ring-closed polycyclic structures devoid of preexisting stereogenic centers or elements. For examples of such molecules see: Song, Q. L.; Ho, D. M.; Pascal, R. A. J. Org. Chem. 2007, 72, 4449-4453. Mori, T.; Grimme, S.; Inoue, Y. J. Org. Chem. 2007, 72, 6998-7010. Na, J. E.; Lee, K. Y.; Seo, J.; Kim, J. N. Tetrahedron Lett. 2005, 46, 4505-4508. Pascal, R. A., Jr.; Mathai, M. S.; Shen, X.; Ho, D. M. Angew. Chem., Int. Ed. Engl. 2001, 40, 4746-4748.

Steffens, R. J.; Baldridge, K. K.; Siegel, J. S. Helv. Chim. Acta 2000, 83, 2644-2654.

30 Hayama, T.; Baldridge, K. K.; Wu, Y. T.; Linden, A.; Siegel, J. S. J. Am. Chem. Soc. 2008, 130, 1583-1591. Mascal, M. J.

Org. Chem. 2007, 72, 4323-4327. Wang, Y.; Stretton, A. D.; McConnell, M. C.; Wood, P. A.; Parsons, S.; Henry, J. B.; Mount, A. R.; Galow, T. H. J. Am. Chem. Soc. 2007, 129, 13193-13200. Narahari Sastry, G. THEOCHEM 2006, 771, 141-147. Seiders, T. J.; Baldridge, K. K.; Grube, G. H.; Siegel, J. S. J. Am. Chem. Soc. 2001, 123, 517-525. Priyakumar, U. D.; Sastry, G. N. J.

Phys. Chem. A 2001, 105, 4488-4494. Priyakumar, U. D.; Sastry, G. N. J. Org. Chem. 2001, 66, 6523-6530. Biedermann, P. U.;

Pogodin, S.; Agranat, I. J. Org. Chem. 1999, 64, 3655-3662. Sygula, A.; Rabideau, P. W. J. Chem. Soc., Chem. Commun. 1994, 1497-1499.

31 Wu, Y.-T.; Hayama, T.; Baldridge, K. K.; Linden, A.; Siegel, J. S. J. Am. Chem. Soc. 2006, 128, 6870-6884. Lofthagen, M.;

Vernonclark, R.; Baldridge, K. K.; Siegel, J. S. J. Org. Chem. 1992, 57, 61-69.

cations of type 10. Typical examples are compounds 104 detailed in Figure V-8 (R=

H, t-Bu; R’= H, alkyl, allyl, vinyl, etc.).^31,32

Such trioxatricornans are achiral by virtue of the symmetrical distribution of the substituents at the periphery of the core structure. However, any unsymmetrical pattern for functional groups or side chains at the exterior of the molecule creates a dissymmetry and the occurrence of molecular chirality. Regioisomeric derivatives 105 and 106 (Figure V-8), prepared by electrophilic substitution reactions onto compounds of type 104 (R=H, R’=Me) are two typical examples of chiral analogues with C1- and C3-symmetry respectively. To the best of our knowledge, compounds of type 105 and 106 have only been reported in racemic form.

O O

O Me

X

X O O

O Me

X X

X

105 106

O O

O R' R

R

R

104 O

O O

R

R R

10

X

Figure V-8. Trioxatriangulenium cation 10 and trioxatricornan derivatives 104, 105 and 106.

R = H, ^tBu; R’ = Me, vinyl, allyl, CH2COCH3; X = NO2, Br, SiMe3.

We know that nitrogen-analogues of the trioxaangulenium cation 10 can also be readily prepared and, for the interest of this study, diazaoxatriangulenium cations 21 in particular (Figure V-9, R¹ = R² = n-Pr, n-Hex, n-Oct).^33,34 This novel family of carbenium ions, featuring both aza- and oxa-bridge(s), have been studied for their

32 Lofthagen, M.; Siegel, J. S.; Hackett, M. Tetrahedron 1995, 51, 6195-6208. Lofthagen, M.; Siegel, J. S. J. Org. Chem. 1995, 60, 2885-2890. Lofthagen, M.; Chadha, R.; Siegel, J. S. J. Am. Chem. Soc. 1991, 113, 8785-8790.

33 Laursen, B. W.; Krebs, F. C. Chem. Eur. J. 2001, 7, 1773-1783.

34 Laursen, B. W.; Reynisson, J.; Mikkelsen, K. V.; Bechgaard, K.; Harrit, N. Photochem. Photobiol. Sci. 2005, 4, 568-576.

Herse, C.; Bas, D.; Krebs, F. C.; Burgi, T.; Weber, J.; Wesolowski, T.; Laursen, B. W.; Lacour, J. Angew. Chem., Int. Ed. Engl.

2003, 42, 3162-3166. Laursen, B. W.; Krebs, F. C. Angew. Chem., Int. Ed. Engl. 2000, 39, 3432-3434. Laursen, B. W.; Krebs, F. C.; Nielsen, M. F.; Bechgaard, K.; Christensen, J. B.; Harrit, N. J. Am. Chem. Soc. 1998, 120, 12255-12263.

Chapter V. Synthesis, Resolution and VCD Analysis of the First Enantiopure Diazaoxatricornan Derivative

photochemical and photophysical properties. Their global chemical reactivity is however undocumented.^34,35

In terms of chirality, it occurred to us that these planar achiral derivatives could actually constitute an interesting platform for the formation of novel closed-capped chiral bowl molecules. In fact, any addition of a nucleophile to the central sp² carbon of an unsymmetrical diazaoxatriangulenium cation (21, R¹ ≠ R²) would generate a curved diazaoxatricornan derivative that would be chiral due to the symmetry-breaking presence of the different nitrogen substituents.

107 O

N N

21

R¹ R² N N

O R'

R¹ R² N N

O Me

Ph Pr

107a

Figure V-9. Diazaoxatriangulenium cations 21 (R¹ = R² = n-Pr, n-Hex, n-Oct) and chiral diazaoxatricornan derivatives 107 (R’, R¹≠ R²).

However, close examination of the known properties of these carbenium ions 21 was raising several issues about the feasibility of the project. First of all, it was debatable whether these highly stable carbenium ions (pKR+ 19.4 for 21 vs. 9.1 for 10) would be electrophilic enough to react with hydride or organometallic reagents and afford products of type 107, diazaoxatricornan derivatives. Then, if possible, it was unclear whether these compounds 107 would actually be stable under air (oxidative) and moisture conditions; the very electron-rich nature of the core favoring possible electron-transfer and/or ionic decomposition pathways.³⁶ Herein, we report that chiral compounds of type 107 can indeed be made as we detail the synthesis, resolution and vibrational circular dichroism (VCD) analysis of an enantiopure diazaoxatricornan derivative (107a, Figure V-9, R’ = Me, R¹ = Ph, R² = n-Pr); compound 107a being furthermore the first non-racemic closed-capped chiral bowl molecule for which the chirality is due to the intrinsic dissymmetry of the central core only.

35 Dileesh, S.; Gopidas, K. R. J. Photochem. Photobiol., A 2004, 162, 115-120.

36 Cations 21 (pKR+ ~ 19) are, most probably, strong electrofugal groups (e.g., Pummerer fragmentation): Laleu, B.; Machado, M. S.; Lacour, J. Chem. Commun. 2006, 2786-2788. Laleu, B.; Mobian, P.; Herse, C.; Laursen Bo, W.; Hopfgartner, G.;

Bernardinelli, G.; Lacour, J. Angew. Chem., Int. Ed. Engl. 2005, 44, 1879-1883. See also Chapter I, § 4.3.5.i.

V-2 Results and Discussion