1.Preamble

This manuscript will deal with positively charged helical scaffolds, and as such, this chapter will involve a brief description of helicenes, their aza analogues, to finally lead to a special class of cationic [4]helicenes known as the quinacridinium salts. All the molecules in this chapter shall be indicated to with a designating number preceded by a letter B to indicate that they belong to this bibliographic chapter.

Helicenes are a specific class of helical molecules comprised of ortho-condensed aromatic rings that form unique twisted nonplanar π-electron systems.¹ The combination of translation and rotation movements in such molecules gives the helical shape. Helix formation minimizes steric strain; as a consequence, helices are usually formed as a way of the molecule to relieve itself of the steric hindrance.

Figure I-1 Representation of a helice and its inherent chirality compared to human hands (Left) and of the double-strand helical shape of DNA (Right)

      

1 Martin, R. H. Angew. Chem., 1974; Vol. 86, pp 727-738. Meurer, K. P.; Vögtle, F. Top. Curr. Chem. 1985, 127, 1-76. Laarhoven, W. H.; Prinsen, W. J. C. Top. Curr. Chem. 1984, 125, 63-130. Rowan, A. E.; Nolte, J. M. Angew.

Chem., Int. Ed. 1998, 37, 63−68; Katz, T. J. Angew. Chem., Int. Ed. 2000, 39, 1921−1923. Urbano, A. Angew.

Chem. Int. Ed. 2003, 42, 3986-3989.

2 | P a g e  I-2.Concept of helical chirality

As can be seen from figures I-1 and I-2, helicity is an important type of chirality. Due to their nonplanar structure, helicenes are inherently chiral, even in the absence of any stereogenic center.¹ They exist in two possible enantiomeric forms and are generally compared to a screw and its rotating motion around an imaginary central axis. They are defined as having a right-handed or P-configuration (for Plus (+)/Δ) if clockwise oriented, or having a left-right-handed or M-configuration (for Minus (−)/Λ) if counterclockwise oriented.^2,3 (Figure I-2).

Figure I-2: Example of a helical molecule, the [6]helicene B1 in both of its enantiomeric forms

I-3.Nomenclature of helicenes:

It was Newman,⁴ who introduced the name “helicenes” to refer to ortho-condensed aromatic hydrocarbons in which all benzene rings are angularly annelated, such as to give helically shaped molecules.⁵ Wynberg later brought up the term heterohelicenes⁵ to differentiate fully carbonated helicenes from the ones containing heteroatoms such as nitrogen, oxygen, sulfur, etc.

Helicenes are generally considered as structural analogues of phenanthrene B2, from the smallest described 1,10-phenanthroline-N,N’-dioxide B3,⁶ to the higher analogs (Figure I-3).

In the following chapters of this manuscript, the molecules we shall deal with belong to this subclass of helicenes, the heterohelicenes. Aza and thiaheterohelicenes are among the most described in the literature since the thorough interest given to them by Wynberg.⁷

      

2 For a description of M and P nomenclature and how it is used to describe the stereochemistry of helicenes, see:

Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, 1994; Chapter 14, pp 1121, 1163-1166.

3 R. S. Cahn; C. K. Ingold; V. Prelog Angew. Chem., Int. Ed. Eng. 1966, 5, 385.

4 Newman, M.S. and D. Lednicer J. Am. Chem. Soc. 1956, 78(18), 4765-4770.

5 Wynberg, H., M.B. Groen, and H. Schadenberg, J. Org. Chem. 1971, 36(19), 2797-2809.

6 Rozen, S. and Dayan, S Angew. Chem. Int. Ed. 1999, 38, 3471-3473.

7 Wynberg, H.; Groen, M. B.; Schadenberg, H. J. Org. Chem. 1971, 36, 2797-2809. Tribout, J.; Martin, R. H.;

Doyle, M.; Wynberg, H. Tetrahedron Lett. 1972, 13, 2839-2842.

Figure I-3: Structural analogues of phenanthrene B2: 1,10-phenanthroline N,N’ dioxide B3 and [6]helicene B1

Usually, the number of ortho-fused rings involved in the overall helicity is indicated between brackets before the designating term “helicene”. As such, penta, hexa and heptahelicenes are simply: [5], [6] and [7]helicene respectively.

I-4.Synthesis and properties of carbohelicenes

Although known at the beginning of the 20^th century, these structures remained scarcely described in the early stages, since their syntheses were highly dependent on the designated targets and necessitated very diverse methods. ⁸

[5] helicene B4 was the first “true”⁹ helicene to be described in 1918 by Weitzenböck but its isolation was not achieved until 1933 by Pschorr cyclization.¹⁰ However, the first report of such a screw-like molecule goes back to 1903, when Meisenheimer and Witte introduced the diaza[5]helicene B5, obtained via reductive cyclization of 2-nitronaphthalene.¹¹ In 1927, the [6]pyrrolohelicene B6 was synthesized by Niszel and Fuchs via a double Bucherer reaction.¹²       

8 Laarhoven, W. H.; Cuppen, Th. H. J. M.; ibid, 1973, 92, 553. Laarhoven, W. H.; Veldhuis, R. G. M. Tetrahedron Lett., 1972, 28, 1823. Katz, T. J.; Pesti, J. J. Amer. Chem. Soc. 1982, 104, 346-347. Schreiner, P. R.; Fokin, A. A.;

Reisenauer, H. P.; Tkachenko, B. A.; Vass, E.; Olmstead, M. M.; Blaser, D.; Boese, R.; Dahl, J. E. P.; Carlson, R.

M. K. J.Amer. Chem. Soc. 2009, 131, 11292-11293.

9 By true, we mean carbohelicene.

10Cook, J. W. J. Chem. Soc. 1933, 1592.

Pschorr Reaction allows the preparation of biaryl tricyclics by intramolecular substitution of one arene by an aryl radical. This radical is generated in situ from an aryl diazonium salt by copper catalysis. Alternative one-electron donors that are more soluble have recently been discovered. F. W. Wassmundt, W. F. Kiesman, J. Org. Chem., 1995, 60, 196-201

11Meisenheimer, J.; Witte, K. Chem. Ber. 1903, 36, 4153.

12Fuchs, W.; Niszel, J. Ber. Dtsch. Ges. 1927, 60, 209; Carbazol synthesis from Naphthalene or Naphthylamine and Phenylhydrazin by means of Hydrogenosulfite.

4 | P a g e  Figure I-4: [5]helicene B4, diaza[5]helicene B5, diaza[6]helicene B6 and 1,12-dimethyl-[4]helicene B7.

These very diverse methods have acted as a major drawback towards this chemistry and it was with the pioneering work of Newman¹³ regarding the synthesis of [6]helicene B1 that the interest in these structures reemerged. Another breakthrough was achieved with Mallory’s report on phenanthrenes in 1964¹⁴ and following that, Martin’s claim that all that was required was to expose diarylthylenes of type B8 to light and oxidant to form these attractive scaffolds in fair to excellent yields. This oxidative photochemical conversion of trans-stilbene motifs, being the oldest and most widely used methodology allowed access to various derivatives of this class of compounds, fully carbonated and with heteroatoms of different lengths from [6] to [14] ortho-fused rings.

SchemeI-1: Photodehydrocyclization of trans-stilbene B7 into phenantrene B2.

The photocyclisation is a disrotatory allowed process (4n+2 electrons involved) and is interesting because of its extreme simplicity. The required building blocks, 1,2-diarylethylenes or bis(arylvinyl)arenes, are usually easy to make in excellent yields, either by Wittig reaction or similarly simple methods. The stereochemistry of the starting alkene is unimportant, due to the well known cis-/trans photoequilibrium. Also, substituted helicenes can be prepared provided that the substituent is already present in the building motifs prior to cyclisation. Nevertheless,       

13 Newman, M. S.; Lutz, W. B.; Lednicer, D. J. Amer. Chem. Soc. 1955, 77, 3420-3421. Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765-4770.

14 Mallory, F. B.; Wood, C. S.; Gordon, J. T. J. Amer. Chem. Soc. 1964, 86, 3094-3102.

some functional groups are not tolerated (such as acetyl, dimethylamino and nitro groups).

Although in principle, the photocyclisation process can give rise to many isomers, it is rarely the case and usually the only cyclised product observed is the helicene. But in the cases of exception, the formation of undesired compounds, such as perylene derivatives, can be prevented using the improved method of Katz, by the introduction of bromine auxiliaries which protect their own and ortho positions from substitution, affording the control of the regioselectivity.¹⁵

Katz also reported that an excess of iodine instead of the catalytic amount suggested previously, with propylene oxide as a scavenger for the in situ generated HI could give access to higher yields and purities of the products.¹⁶ This procedure allowed the formation of the parent [5]helicene B4 in 83% overall yield from stilbene precursors.

Nevertheless, the non-applicability of this methodology to every possible compound, the low amounts of materials obtained as well as its low tolerance for functional groups, have directed increasing efforts at finding other alternatives.

A number of recent efforts have been directed at finding new non-photochemical routes for helicene synthesis.¹⁷ Among them Friedel-Crafts acylation,¹⁸ intramolecular oxidative cyclization,¹⁹ Diels-Alder reactions of benzoquinones by Katz, cyclisation of ammonium or       

15Liu, L.; Katz, T. J. Tetrahedron Lett. 1991, 32, 6831-6834.

16Liu, L.; Yang, B.; Katz, T. J.; Poindexter, M. K. J. Org. Chem. 1991, 56, 3769-3775.

17 For recent nonphotochemical syntheses, see: Carreno, M. C.; Garcia-Cerrada, S.; Urbano, A. J. Am. Chem. Soc.

2001, 123, 7929. Carreno, M. C.; Garcia-Cerrada, S.; Sanz-Cuesta, M. J.; Urbano, A. Chem. Commun. 2001, 1452.

Okubo, H.; Nakano, D.; Anzai, S.; Yamaguchi, M. J. Org. Chem. 2001, 66, 557. Eskildsen, J.; Krebs, F. C.; Faldt, A.; Sommer-Larsen, P.; Bechgaard, K. J. Org. Chem. 2001, 66, 200. Murguly, E.; McDonald, R.; Branda, N. R.

Org. Lett. 2000, 2, 3169. Okubo, H.; Nakano, D.; Yamaguchi, M.; Kabuto, C. Chem. Lett. 2000, 1316.

Modlerspreitzer, A.; Fritsch, R.; Mannschreck, A. Collect. Czech Chem. Commun. 2000, 65, 555. Minuti, L.;

Taticchi, A.; Marrocchi, A.; Gacs-Baitz, E.; Galeazzi, R. Eur. J. Org. Chem. 1999, 3155. Carreno, M. C.;

Hernandez-Sa´nchez, R.; Mahugo, J.; Urbano, A. J. Org. Chem. 1999, 64, 1387. Stara´, I. G.; Stary´, I.;

Kolla´rovicˇ, A.; Teply´, F.; Vyskocˇil, Sÿ.; Saman, D. Tetrahedron Lett. 1999, 40, 1993. Gingras, M.; Dubois, F.

Tetrahedron Lett. 1999, 40, 1309. Dubois, F.; Gingras, M. Tetrahedron Lett. 1998, 39, 5039. Okubo, H.;

Yamaguchi, M.; Kabuto, C. J. Org. Chem. 1998, 63, 9500. Minuti, L.; Taticchi, A.; Marrocchi, A. Synth. Commun.

1998, 28, 2181. Tanaka, K.; Suzuki, H.; Osuga, H. J. Org. Chem. 1997, 62, 4465. Tanaka, K.; Suzuki, H.; Osuga, H.

Tetrahedron Lett. 1997, 38, 457. Minuti, L.; Taticchi, A.; Marrocchi, A.; Gacs-Baitz, E. Tetrahedron 1997, 53, 6873. Cossu, S.; De Lucchi, O.; Fabbri, D.; Valle, G.; Painter, G. F.; Smith, A. J. Tetrahedron 1997, 53, 6073.

Pischel, I.; Grimme, S.; Kotila, S.; Nieger, M.; Vo¨gtle, F. Tetrahedron: Asymmetry 1996, 7, 109. Larsen, J.;

Bechgaard, K. J. Org. Chem. 1996, 61, 1151. Yamaguchi, M.; Okubo, H.; Hirama, M. Chem. Commun. 1996, 1771.

Dore, A.; Fabbri, D.; Gladiali, S.; Valle, G. Tetrahedron: Asymmetry 1995, 6, 779. Stara´, I. G.; Stary´, I.; Tichy´, M.; Za´vada, J.; Hanusˇ, V. J. Am. Chem. Soc. 1994, 116, 5084.

18Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765-4770.

19Rau, H.; Schuster, O. Angew. Chem., Int. Ed. Engl. 1976, 15, 114. Pereira, D. E.; Neelima; Leonard, N. J.

Tetrahedron 1990, 46, 5895. Larsen J.; Bechgaard, K. J. Org. Chem. 1996, 61, 1151.

6 | P a g e  phosphonium salts,²⁰ metal-catalysed [2+2+2] cycloisomerisation,²¹ olefin metathesis,²² carbenoid couplings,²³ and tandem radical cyclisation. Two elegant strategies are depicted below.

A tin-mediated, non-reducing tandem radical cyclisation developed by Harrowven in 2002, gave a new short and effective route to the parent [5]helicene and some of its derivatives in modest to good yields (35-49%, 58% for [5]helicene) (Scheme I-2).²⁴

Scheme I-2: Tandem radical cyclization process developed by Harrowven, affording [5]helicene B4.

Another approach to a carbohelicene was reported in 1998, by Gingras and Dubois, using a McMurry coupling of a dialdehyde (as shown by Tanaka on heterohelicenes²⁵) or carbenoid-type coupling of bis(bromomethyl) moieties as the key step.²⁶ The method was useful for the formation of [5] and [7]carbohelicene B4 and B14 derivatives. (Scheme I-3).

      

20Bestman, H. J.; Both, W. Angew. Chem. 1972, 84, 293. Stara´, I. G.; Stary, I.; Tichy, M.; Za´vada, J.; Hanus, V. J.

Am. Chem. Soc. 1994, 116, 5084.

21 Teply, F.; Stara, I. G.; Stary, I.; Kollarovic, A.; Saman, D.; Rulisek, L.; Fiedler, P. J. Am. Chem. Soc. 2002, 124, 9175-9180. Stara, I. G.; Stary, I.; Kollarovic, A.; Teply, F.; Saman, D.; Fiedler, P. Collect. Czech. Chem. Commun.

2003, 68, 917-930. Teply, F.; Stara, I. G.; Stary, I.; Kollarovic, A.; Saman, D.; Vyskocil, S.; Fiedler, P. J. Org.

Chem. 2003, 68, 5193-5197. Alexandrova, Z.; Stara, I. G.; Sehnal, P.; Teply, F.; Stary, I.; Saman, D.; Fiedler, P.

Collect. Czech. Chem. Commun. 2004, 69, 2193-2211. Stara, I. G.; Alexandrova, Z.; Teply, F.; Sehnal, P.; Stary, I.;

Saman, D.; Budesinsky, M.; Cvacka, J. Org. Lett. 2005, 7, 2547-2550.

22 Collins, S. K.; Grandbois, A.; Vachon, M. P.; Côté, J. Angew. Chem. Inter. Ed. 2006, 45, 2923-2926.

23 Dubois, F.; Gingras, M. Tetrahedron Lett. 1998, 39, 5039-5040. Gingras, M.; Dubois, F. Tetrahedron Lett. 1999, 40, 1309-1312.

24 Harrowven, D. C.; Nunn, M. I. T.; Fenwick, D. R. Tetrahedron Lett. 2002; 43, 7345-7347.

25 Tanaka, K.; Suzuki, H.; Osuga, H. Tetrahedron Lett. 1997, 38, 457-460.

26Dubois, F.; Gingras, M. Tetrahedron Lett. 1998, 39, 5039-5040. Gingras, M.; Dubois, F. Tetrahedron Letters 1999, 40, 1309-1312.

Scheme I-3: Carbenoid and McMurry couplings as a new way to access carbohelicenes.

I-5. Configurational stability, thermal racemization and racemization barrier:

The first few helicenes reported were not very stable at 25 °C and they always racemized even at very low temperatures such as -20 °C.¹

Configurational stability can be increased with the number of ortho-fused rings as shown between [5] and [6]helicene. It is also possible to achieve an increase of steric hindrance by substitution of the carbohelicenes at terminal positions. The “relatively” low potential barriers for these racemizations can be best justified by the fact that all the molecular deformations regarding bond torsions and necessary bending, are spread over a large part of the bonds in the molecule. The helicenes are thus shown to be more flexible than originally thought. Thus, they racemize thermally but in this sense, are rather stable photochemically. The [5]helicene displays a half-life of racemisation t1/2 of 62 min at 57 °C, whereas [6]helicene is known to be much more stable (ΔG^≠ = 154.3 kJ/mol; t1/2 = 13.4 min at 196 °C).⁴

Several studies have been undertaken to understand the reaction pathways for thermal racemization of helicenes. In 1974, it was shown by Martin et al. that a conformational pathway

8 | P a g e  is in fact best adapted to explain the process.²⁷ Lindner calculated the energy differences between the ground state and some assumed transition states for a [6]carbohelicene and argued that the most plausible geometry for a transition state is one in which a slippage is involved which allows the racemisation of the compound.²⁸ (Scheme I-4)

Scheme I-4: Racemization mechanism of the 1-methyl[6]helicene B15.

I-6. Resolution methods:

There are a number of methods available for the isolation of enantiopure helicenes, although not equivalently effective.²⁹ For instance, the high improvement of HPLC techniques has been a life-saver in many cases where the separation of racemic mixtures was most strenuous.

Crystallization has also been thoroughly utilized especially in the early days when “hand-picking” crystals was a good way to optically pure material or for the isolation of charge-transfer complexes.

Other ways have included derivatisation of the racemic mixture of enantiomers to obtain chromatographically separable diastereoisomers through addition of chiral auxiliaries. These approaches will only be detailed on two historical and important classes of carbohelicenes.

      

27 Martin, R. H.; Marchant, M. J. Tetrahedron 1974, 30, 347-349.

28 Lindner, H. J. Tetrahedron 1975, 31, 281-284; Janke, R. H.; Haufe, G.; Würthwein, E.-U.; Borkent, J. H. J. Amer.

Chem. Soc. 1996, 118, 6031-6035; Johansson, M.; Patzschke, M. In; WILEY-VCH Verlag, 2009, 15, 13210-13218.

29 Newman, M. S.; Chen, C. H. J. Org. Chem. 1972, 37, 1312-1314. Newman, M. S.; Wise, R. M. J. Am. Chem. Soc.

1956, 78, 450-454.

The first resolution³⁰ of a purely aromatic hydrocarbon whose asymmetry comes from its intramolecular overcrowding, was reported for the [6]helicene B1 in 1956 by Newman and Lednicer. In the absence of a peripheral functional group in [6]helicene B1, this was achieved using the α-(2,4,5,7-Tetranitro-9-fluorenylideneaminoöxy)-propionic Acid, or TAPA B16, a new reagent for resolution by charge transfer complex formation, nowadays known as Newman’s reagent. The non-active racemic helicene was dissolved in a benzene solution with TAPA. The subsequent addition of ethanol to the benzene mixture afforded crystallization of the active helicene with the same sign of optical rotation as the TAPA³¹ derivative. It was therefore shown that TAPA can form complexes of different stability with each enantiomer of [6]helicene. This resolving agent is easily obtained by reacting (±)- α-(isopropylideneaminooxy)-propionic acid (B18) with 2,4,5,7-tetranitro-9-fluorenone (B17). The optically active TAPA is afforded by interchange of the active starting material (propionic acid) after its resolution with (−)-ephedrine.

Figure I-5: Synthesis of TAPA, Newman’s reagent

Another example by Katz et al.,³² utilized (1S)-camphanates as chiral resolving agent to afford optically pure helicene-quinone derivatives, after removal of the auxiliary.³³ Its presence was also useful in determining the absolute configuration of the isolated non-racemic helicenes. As a general rule, the M helicene attached to the (1S)-camphanates eluted faster than the one bearing the P helicity. Such a trend was also reported by Venkatamaran³⁴ and Dötz.³⁵ This elution order       

30 Newman, M. S.; Lednicer, D. J. Am. Chem. Soc. 1956, 78, 4765-4770.

31 Newman, M. S.; Lutz, W. B.; Lednicer, D. J. Amer. Chem. Soc. 1955, 77, 3420-3421.

32 Newman, M. S.; Chen, C. H. J. Org. Chem. 1972, 37, 1312-1314.

33 Thongpanchang, T.; Paruch, K.; Katz, T. J.; Rheingold, A. L.; Lam, K.-C.; Liable-Sands, L. J. Org. Chem. 2000, 65, 1850-1856.

34 Field, J. E.; Muller, G.; Riehl, J. P.; Venkataraman, D. J. Am. Chem. Soc. 2003, 125, 11808-11809.

35 Schneider, J. F.; Nieger, M.; Naettinen, K.; Lewall, B.; Niecke, E.; Dötz, K. H. Eur. J. Org. Chem. 2005, 1541-1560.

10 | P a g e  was rationalized as due to a preferred antiperiplanar conformation in the case of the M derivative vs a synperiplanar conformation for its antipode.³⁶

B22

Figure I-6: Selected examples of helicene-like compounds resolved by introducing (1S)-camphanate moiety as chiral auxiliary.

I-7. Properties of helicenes:

Martin wrote at the end of his review in 1974:³⁷ “it is our intimate conviction that further work on these unique molecules... should be highly rewarding in many fields of chemistry.”

Indeed, because of their non-planar dissymmetric backbone, helicenes present an intriguing variety of properties and applications from areas of chiroptical³⁸ and photochromic materials.³⁹ excellent self-assembly,⁴⁰ in domains such as asymmetric catalysis,⁴¹ supramolecular chemistry⁴²       

36 Thongpanchang, T.; Paruch, K.; Katz, T. J.; Rheingold, A. L.; Lam, K.-C.; Liable-Sands, L. J. Org. Chem. 2000, 65, 1850-1856.

37 Martin, R.H., The helicenes, in Angew. Chem. 1974. p. 727-38.

38 Graule, S.; Rudolph, M.; Vanthuyne, N.; Autschbach, J.; Roussel, C.; Crassous, J.; Réau, R. J. Amer. Chem. Soc.

2009, 131, 3183-3185.

39 Furche, F.; Ahlrichs, R.; Wachsmann, C.; Weber, E.; Sobanski, A.; Vögtle, F.; Grimme, S. J. Am. Chem. Soc.

2000, 122, 1717-1724; Norsten, T. B.; Peters, A.; McDonald, R.; Wang, M. T.; Branda, N. R. J. Am. Chem. Soc.

2001, 123, 7447-7448; Verbiest, T.; Sioncke, S.; Persoons, A.; Vyklicky, L.; Katz, T. J. Angew. Chem. Int. Ed.

2002, 41, 3882-3884; Field, J. E.; Muller, G.; Riehl, J. P.; Venkataraman, D. J. Am. Chem. Soc. 2003, 125, 11808-11809; Wachsmann, C.; Weber, E.; Czugler, M.; Seichter, W. Eur. J. Org. Chem. 2003, 2863-2876; Champagne, B.;

Andre, J.-M.; Botek, E.; Licandro, E.; Maiorana, S.; Bossi, A.; Clays, K.; Persoons, A. ChemPhysChem. 2004, 5, 1438-1442; Lebon, F.; Longhi, G.; Gangemi, F.; Abbate, S.; Priess, J.; Juza, M.; Bazzini, C.; Caronna, T.; Mele, A.

J. Phys. Chem. A 2004, 108, 11752-11761.

40 Nuckolls, C.; Katz, T. J.; Castellanos, L. J. Amer. Chem. Soc. 1996, 118, 3767-3768. Dai, Y.; Katz, T. J. J. Org.

Chem. 1997, 62, 1274-1285. Nuckolls, C.; Katz, T. J. J. Amer. Chem. Soc. 1998, 120, 9541-9544.

molecular machines⁴³ and material sciences⁴⁴ have been reported and thoroughly studied by Katz and coworkers.⁴⁵

Introduction of peripheral functional groups onto helicene skeletons have also been the focus of many other research groups⁴⁶ since the functionalisation could account for many changes in their properties. The introduction of polar hydroxy groups and amines, carboxylates or diphosphines have given access to applications in catalysis,⁴¹ molecular recognition⁴⁷ and DNA interaction.⁴⁸ This last property will be detailed in chapter III. Katz and coworkers have mostly developed helicenebisquinones and these moieties have shown fascinating self-assembling properties. As a matter of fact, all these mentioned derivatives are neutral.

Nevertheless, most carbohelicenes have properties rather far from the compounds of study (vide infra, chapters II-V) and as such, details will not be further given. Emphasis will, on the other hand, be made on azahelicenes and quinacridinium derivatives in particular.

 

      

41 Reetz, M. T.; Beuttenmuller, E. W.; Goddard, R. Tetrahedron Lett. 1997, 38, 3211-3214. Terfort, A.; Gorls, H.;

Brunner, H. Synthesis 1997, 79-86. Reetz, M. T.; Sostmann, S. J. Organomet. Chem. 2000, 603, 105-109. Reetz, M.

T.; Sostmann, S. Tetrahedron 2001, 57, 2515-2520.

42 Murguly, E., R. McDonald, and N.R. Branda, Org. Lett. 2000, 2, 3169-3172; Kitahara, Y. and K. Tanaka, Chem.

Commun 2002, 932-933; Tanaka, K., H. Osuga, and Y. Kitahara, J. Org. Chem. 2002, 67, 1795-1801.

43 Kelly, T. R.; Cai, X.; Damkaci, F.; Panicker, S. B.; Tu, B.; Bushell, S. M.; Cornella, I.; Piggott, M. J.; Salives, R.;

Cavero, M.; Zhao, Y.; Jasmin, S. J. Amer. Chem. Soc. 2006, 129, 376-386.

44 Dai, Y. J.; Katz, T. J. J. Org. Chem. 1997, 62, 1274-1285; Fox, J. M.; Lin, D.; Itakagi, Y.; Fujita, T. J. Org. Chem.

1998, 63, 2031-2038; Stone, M. T.; Fox, J. M.; Moore, J. S. In Org. Lett., 2004; Vol. 6, pp 3317-3320; Miyasaka, M.; Rajca, A.; Pink, M.; Rajca, S. Chem. Eur. J. 2004, 10, 6531-6539; Miyasaka, M.; Rajca, A.; Pink, M.; Rajca, S.

J. Am. Chem. Soc. 2005, 127, 13806-13807.

45 Katz, T.J. Angew. Chem. Int. Ed. 2000, 39, 1921-1923.

46 Dreher, S. D.; Paruch, K.; Katz, T. J. J. Org. Chem. 2000, 65, 806-814. Paruch, K.; Vyklicky, L.; Wang, D. Z.;

Katz, T. J.; Incarvito, C.; Zakharov, L.; Rheingold, A. L. J. Org. Chem. 2003, 68, 8539-8544. Fox, J. M.; Goldberg, N. R.; Katz, T. J. J. Org. Chem. 1998, 63, 7456-7462.

47 Owens, L.; Thilgen, C.; Diederich, F.; Knobler, C. B. Helv. Chim. Acta 1993, 76, 2757-2774. Wang, D. Z.; Katz, T. J. J. Org. Chem. 2005, 70, 8497-8502. Murguly, E.; McDonald, R.; Branda, N. R. Org. Lett. 2000, 2, 3169-3172.

Reetz, M. T.; Sostmann, S. Tetrahedron 2001, 57, 2515-2520.

48 Xu, Y.; Zhang, Y. X.; Sugiyama, H.; Umano, T.; Osuga, H.; Tanaka, K. J. Am. Chem. Soc. 2004, 126, 6566-6567.

Honzawa, S.; Okubo, H.; Anzai, S.; Yamaguchi, M.; Tsumoto, K.; Kumagai, I. Bioorg. Med. Chem. 2002, 10, 3213-3218.

12 | P a g e  I-8. Synthesis and properties of azahelicenes

Azahelicenes,⁴⁹ a subgroup of helicenes containing at least one sp²-hybridized nitrogen atom within the helicene framework, have more recently caught the attention of the scientific community.⁵⁰ Their use in asymmetric catalysis,⁵¹ in metal complexation (for instance with Ag+)⁵⁵, proton affinities, self-assembly is extremely interesting.

They have been mainly synthesized by the photochemical route⁵² as shown by Caronna⁵³ who managed to obtain through this route very diverse monoaza and diaza helicenes B26 (Scheme I-5). The position of the nitrogen was varied in the end target by modifying the precursors.

Relatively few other routes have been used for this class of molecules.⁵⁴

Scheme I-5: Photochemical approach to diverse mono and diaza derivatives B26

The interesting approach pioneered by Starý, Stará et al. to afford helicenes via metal catalyzed [2+2+2] cycloisomerisation reactions was successfully employed in the formation of 1,14-diaza[5]helicene B28 and 1- and 2-aza[6]helicene B29 from triyne key precursors B27 (Scheme       

49 Recent review: Dumitrascu, F.;Dumitrescu, D. G.; Aron I. ARKIVOC 2010, 1-32.

50 Sato, K.; Arai, S. Heterohelicenes Containing Nitrogen Aromatics: Azahelicenes and Azoniahelicenes In Cyclophane Chemistry for the 21st Century Takemura, H., Ed., Research Signpost: Kerena, India, 2002, 173 – 197.

51 Takenaka, N.; Chen, J.; Captain, B.; Sarangthem, R. S.; Chandrakumar, A. J. Amer. Chem. Soc. 2010, 132, 4536-4537. Samal, M.; Mísek, J.; Stará, I. G.; Starý, I. Collect. Czech. Chem. Commun. 2009, 74, 1151.

52 Sato, K.; Okazaki, S.; Yamagishi, T.; Arai, S. J. Heterocyclic Chem 2004; 41, 443-447. Bazzini, C.; Brovelli, S.;

Caronna, T.; Gambarotti, C.; Giannone, M.; Macchi, P.; Meinardi, F.; Mele, A.; Panzeri, W.; Recupero, F.; Sironi, A.; Tubino, R. Eur. J. Org. Chem. 2005, 2005, 1247-1257.

53 Bazzini, C.; Brovelli, S; Caronna, T.; Gambarotti, C.; Giannone, M.; Macchi, P.; Meinardi, F.; Mele, A.; Panzeri, W.; Recupero, F.; Sironi, A.; Tubino, R. Eur. J. Org. Chem. 2005, 1247-1257. Caronna, T.; Fontana, F.; Longhi, G.;

Mele, A.; Sora, I. N.; Panzeri, W.; Viganò, L. Arkivoc, 2009, 145. Abbate, S.; Bazzini, C.; Caronna, T.; Fontana, F.;

Gambarotii, C.; Gangemi, F.; Longhi, G.; Mele, A.; Sora, I. N.; Panzeri, W. Tetrahedron 2006, 62, 139.

54 El Abed, R.; Ben Hassine, B.; Genet, J.-P.; Gorsane, M.; Marinetti, A. Eur. J. Org. Chem., 2004; 1517-1522.

I-6).⁵⁵ The resolution of the monoaza derivatives was successful using chiral HPLC and their absolute configuration determined by comparing the CD spectra with the one known of hexahelicene.⁵⁵ These compounds were shown to be useful for metal complexation.⁵⁵

Scheme I-6: [2+2+2] cycloisomerisation to form 1- and 2-aza[6]helicene B29

Takenaka reported very recently the use of a Stille-Kelly reaction of dihalogenated cis-stilbene-type precursors to form azahelicene derivatives that were active as hydrogen bond donor catalysts (Scheme I-7).⁵⁶ Another method was also recently published using a mixed catalyst of PtCl4 and InCl3 and a double C-H activation process which gave the desired molecule in 80 % yield (Equation I-1).⁵⁷

      

55 Mísek, J.; Teplý, F.; Stará, I. G.; Tichý, M.; Saman, D.; Císarová, I.; Vojtísek, P.; Starý, I. Angew. Chem. Inter.

Ed. 2008, 47, 3188-3191.

56 Takenaka, N.; Chen, J.; Captain, B.; Sarangthem, R. S.; Chandrakumar, J. Amer. Chem. Soc. 2010, 132, 4536-4537.

57 Storch, J.; Cermák, J.; Karban, J.; Císarová, I.; Sýkora, J. J. Org. Chem. 2010, 75, 3137-3140.

14 | P a g e  Scheme I-7: Radical-mediated cyclisation to afford azahelicene B31.

Equation I-1: Metal-catalyzed process for the synthesis of 2-aza[6]helicene B33.

A completely different type of azahelicene was recently reported by the group of Venkatamaran.

These derivatives of triphenylamine were constructed in the aim of developing well-ordered compounds for further use in material sciences,⁵⁸ using a strategy initially demonstrated by

These derivatives of triphenylamine were constructed in the aim of developing well-ordered compounds for further use in material sciences,⁵⁸ using a strategy initially demonstrated by

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