4.3.4.ii DMQA + Cations - GENERAL INTRODUCTION

CHAPTER I GENERAL INTRODUCTION

I- 4.3.4.ii DMQA + Cations

For many years [n]helicenes have been intensively studied for their excellent ability to self-assemble,³⁷ their chiroptical, photochromic, nonlinear optical³⁸ and DNA-intercalating properties,³⁹ as well as for applications in asymmetric molecular recognition,⁴⁰ synthesis,⁴¹ sensors,⁴² polymer and material science fields.⁴³However, for many of these applications, the chiral (hetero)helicenes must be isolated in high enantiomeric purity.

Helicenes are ortho-condensed polycyclic aromatic compounds and due to the high steric demand of such arrangement, they adopt helical shaped chiral structures of M and P configuration (with left- and right-handed helicity respectively). Hence, they

37 Chen, L. X.; Shaw, G. B.; Tiede, D. M.; Zuo, X.; Zapol, P.; Redfern, P. C.; Curtiss, L. A.; Sooksimuang, T.; Mandal, B. K. J.

Phys. Chem. B 2005, 109, 16598-16609. Kitahara, Y.; Tanaka, K. Chem. Commun. 2002, 932-933. Choi, H. S.; Kim, K. S. J.

Phys. Chem. B 2000, 104, 11006-11009. Bender, T. P.; Wang, Z. Y. Macromolecules 2000, 33, 9477-9479. Fox, J. M.; Katz, T.

J.; Van Elshocht, S.; Verbiest, T.; Kauranen, M.; Persoons, A.; Thongpanchang, T.; Krauss, T.; Brus, L. J. Am. Chem. Soc.

1999, 121, 3453-3459.

38 Tani, Y.; Ubukata, T.; Yokoyama, Y.; Yokoyama, Y. J. Org. Chem. 2007, 72, 1639-1644. Okuyama, T.; Tani, Y.; Miyake, K.; Yokoyama, Y. J. Org. Chem. 2007, 72, 1634-1638. Wigglesworth, T. J.; Sud, D.; Norsten, T. B.; Lekhi, V. S.; Branda, N. R.

J. Am. Chem. Soc. 2005, 127, 7272-7273. Wachsmann, C.; Weber, E.; Czugler, M.; Seichter, W. Eur. J. Org. Chem. 2003, 2863-2876. Verbiest, T.; Sioncke, S.; Persoons, A.; Vyklicky, L.; Katz Thomas, J. Angew. Chem., Int. Ed. Engl. 2002, 41, 3882-3884. Norsten, T. B.; Peters, A.; McDonald, R.; Wang, M. T.; Branda, N. R. J. Am. Chem. Soc. 2001, 123, 7447-7448. Furche, F.; Ahlrichs, R.; Wachsmann, C.; Weber, E.; Sobanski, A.; Vögtle, F.; Grimme, S. J. Am. Chem. Soc. 2000, 122, 1717-1724.

Chen, C.-T.; Chou, Y. C. J. Am. Chem. Soc. 2000, 122, 7662-7672. Fukumi, T.; Sakaguchi, S.; Mya, M.; Oota, K.; Nakagawa, H.; Yamada, K.; Kawamo, H. Nonlinear optical material including three-dimensional sulfur-containing helicene. 05053161, 1993..

39 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.

40 Tamao, K.; Nakano, K.; Hidehira, H.; Takahashi, K.; Hiyama, T. Helical compounds useful for molecular recognition or for optical materials and their synthesis. 2006052200, 2006. Murguly, E.; McDonald, R.; Branda, N. R. Org. Lett. 2000, 2, 3169-3172. Owens, L.; Thilgen, C.; Diederich, F.; Knobler, C. B. Helv. Chim. Acta 1993, 76, 2757-2774.

41 Kawasaki, T.; Suzuki, K.; Licandro, E.; Bossi, A.; Maiorana, S.; Soai, K. Tetrahedron: Asymmetry 2006, 17, 2050-2053.

Soai, K.; Sato, I. Chirality 2002, 14, 548-554. Soai, K.; Sato, I.; Shibata, T. Chem. Rec. 2001, 1, 321-332. Sato, I.; Yamashima, R.; Kadowaki, K.; Yamamoto, J.; Shibata, T.; Soai, K. Angew. Chem., Int. Ed. Engl. 2001, 40, 1096-1098. Terfort, A.; Gorls, H.; Brunner, H. Synthesis 1997, 79-86. Reetz, M. T.; Beuttenmuller, E. W.; Goddard, R. Tetrahedron Lett. 1997, 38, 3211-3214.

42 Wang, D. Z.; Katz, T. J. J. Org. Chem. 2005, 70, 8497-8502. Reetz, M. T.; Sostmann, S. Tetrahedron 2001, 57, 2515-2520.

Weix, D. J.; Dreher, S. D.; Katz, T. J. J. Am. Chem. Soc. 2000, 122, 10027-10032.

43 Miyasaka, M.; Rajca, A. Synlett 2004, 177-181. El Abed, R.; Ben Hassine, B.; Genêt, J.-P.; Gorsane, M.; Marinetti, A. Eur. J.

Org. Chem. 2004, 1517-1522. Donovan, P. M.; Scott, L. T. J. Am. Chem. Soc. 2004, 126, 3108-3112. Teplý, F.; Stará, I. G.;

Starý, I.; Kollárovic, A.; Saman, D.; Vyskocil, S.; Fiedler, P. J. Org. Chem. 2003, 68, 5193-5197. Sooksimuang, T.; Mandal, B.

K. J. Org. Chem. 2003, 68, 652-655. Paruch, K.; Vyklicky, L.; Wang, D. Z.; Katz, T. J.; Incarvito, C.; Zakharov, L.; Rheingold, A. L. J. Org. Chem. 2003, 68, 8539-8544. Carreño, M. C.; García-Cerrada, S.; Urbano, A. Chem. Eur. J. 2003, 9, 4118-4131.

Teplý, F.; Stará, I. G.; Starý, I.; Kollárovic, A.; Saman, D.; Rulisek, L.; Fiedler, P. J. Am. Chem. Soc. 2002, 124, 9175-9180.

Real, M. d. M.; Pérez Sestelo, J.; Sarandeses, L. A. Tetrahedron Lett. 2002, 43, 9111-9114. Harrowven, D. C.; Nunn, M. I. T.;

Fenwick, D. R. Tetrahedron Lett. 2002, 43, 7345-7347. Han, S. D.; Bond, A. D.; Disch, R. L.; Holmes, D.; Schulman, J. M.;

Teat, S. J.; Vollhardt, K. P. C.; Whitener, G. D. Angew. Chem., Int. Ed. Engl. 2002, 41, 3223-3227. Carreño, M. C.; García-Cerrada, S.; Urbano, A. Chem. Commun. 2002, 1412-1413. Dubois, F.; Gingras, M. Tetrahedron Lett. 1998, 39, 5039-5040.

Dai, Y.; Katz, T. J. J. Org. Chem. 1997, 62, 1274-1285. Dai, Y.; Katz, T. J.; Nichols, D. A. Angew. Chem., Int. Ed. Engl. 1996, 35, 2109-2111.

Chapter I. General Introduction

offer several interesting aspects such as unique structural, spectral, and optical features (closely associated to their inherent chirality).^37-43 A compelling example of such derivatives is the famous [6]helicene 22 which was first synthesized by M. S.

Newman and D. Lednicer in 1956 by means of a synthetic scheme that closed the two central rings by Friedel-Crafts cyclization of carboxylic acid compounds (see Figure I-11).⁴⁴

(P)-(+)-[6]helicene (M)-(-)-[6]helicene [6]helicene 22

Figure I-11. Representation of the two helical forms (P and M configurations) of the famous [6]helicene 22.

I-4.3.4.ii.b Cationic helicenes

Even though helicene chemistry has grown from the stage of a descriptive field of aesthetic and curious molecules to an important and immense field of research, to date only few examples concerning cationic helicenes have been reported. In the late 1990s cationic [6]heterohelicenes 23 designated as azonia[6]helicene have been synthesized by Arai by means of photocyclization reaction (see 23 in Figure I-12).⁴⁵ The range of functionality tolerated in such derivatives was further extended with the recent synthesis of derived azoniathiahelicenes.⁴⁶

In the same context, Hellwinkel showed that doubly closed triarylcarbenium cations of type 9, 24 and 25 which contain four ortho-condensed aromatic rings were

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

45 Arai, S.; Ishikura, M.; Yamagishi, T. J. Chem. Soc., Perkin Trans 1 1998, 1561-1567.

46 Sato, K.; Katayama, Y.; Yamagishi, T.; Arai, S. J. Heterocycl. Chem. 2006, 43, 177-181. Sato, K.; Okazaki, S.; Yamagishi, T.; Arai, S. J. Heterocycl. Chem. 2004, 41, 443-447.

analogues to the family of [4]helicenes with same type of twisted helical chirality and associated properties (see [4]helcenium molecules (Figure I-12).⁴⁷

O O

Z Y X

1 13

(X, Y = O, S, NC₂H₅, CO, CS; Z = C, N) 24

25 N

R = CH, N 23

1 13

Figure I-12. Cationic helicene-like molecules

However, due to a lack of steric repulsion between the terminal atoms (e.g., 1 and 13), these compounds displayed a rapid interconversion between their two helical forms (a racemization barrier of 15.5 kcal.mol^-1 was determined for 24).⁴⁷ Only a few [4]helicene-like molecules were proven to be configurationally stable thanks to substituents appropriately introduced to ensure a sufficient configurational stability to the helicene core. The first report on such derivative dates back to the 1,12-dimethyl-[4]helicene 26 resolved in 1956 by Newman (a few months before the [6]helicene itself).⁴⁸ The only three other examples are represented in Figure I-13 (see compounds 27, 28, 29 described by Yamaguchi,⁴⁹ Carreño,⁵⁰ and Venkataraman respectively).⁵¹

47Hellwinkel, D.; Aulmich, G.; Warth, W. Chem. Ber. 1980, 113, 3275-3293. Hellwinkel, D.; Aulmich, G. Chem. Ber. 1979, 112, 2602-2608. Hellwinkel, D.; Aulmich, G.; Melan, M. Chem. Ber. 1976, 109, 2770-2784. Neugebauer, F. A.; Hellwinkel, D.;

Aulmich, G. Tetrahedron Lett. 1978, 4871-4874.

48 Newman, M. S.; Wise, R. M. J. Am. Chem. Soc. 1956, 78, 450-454.

49 Saiki, Y.; Sugiura, H.; Nakamura, K.; Yamaguchi, M.; Hoshi, T.; Anzai, J. J. Am. Chem. Soc. 2003, 125, 9268-9269. Saiki, Y.; Nakamura, K.; Nigorikawa, Y.; Yamaguchi, M. Angew. Chem., Int. Ed. Engl. 2003, 42, 5190-5192.

50 Carreno, M. C.; Garcia-Cerrada, S.; Sanz-Cuesta, M. J.; Urbano, A. J. Org. Chem. 2003, 68, 4315-4321.

51 Field, J. E.; Hill, T. J.; Venkataraman, D. J. Org. Chem. 2003, 68, 6071-6078.

Chapter I. General Introduction

As already mentioned, dimethoxyquinacridinium moieties (18, Figure I-8) can be isolated in good yields by the reactions of primary amines with the readily available salts of cation 11; the synthesis occurring through sequential aromatic substitution (S_NAr) of four MeO substituents by nitrogen containing residues. The molecular framework of cations 18 contains four ortho-condensed aromatic rings. As such, they display a huge structural analogy with [4]helicene derivatives with the additional advantages to exhibit substituents at the terminal positions and heteroatoms in the skeleton to enhance configurational and chemical stabilities respectively

tBu

Me Me

X Y

26 (X = H; Y = CH₂CO₂H) 28

29 (R* = camphanate) N

*RO

O O

N N

R R

tBu

18 27 (X = Y = CO₂H)

Figure I-13: Configurationally stable [4]helicenes (26 to 29) and R-DMQA⁺ (P enantiomers arbitrarily depicted).

The chemical structure of (P)-18 is depicted in Figure I-13 as to show the similitude with the family of [4]helicenes.⁵² The existence of a twisted helical conformation typical of helicene derivatives was further confirmed by the X-ray diffraction analysis of the tetraphenyl borate salt of 5,9-di-n-propyl-1,13-dimethoxyquinacridinium cation (or ⁿPr-DMQA⁺). It appeared to us that strong steric repulsions should occur between the methoxy substituents in positions 1 and 13, thus preventing the systems from being planar, to racemize and allowing potentially the resolution of compounds of type 18 into separated enantiomers.

52 This was confirmed by X-ray diffraction analysis of the tetrafluoroborate salt (Ph4B), which crystallized as a racemate with both enantiomers. See also ref 32, Laursen, B. W. Ph. D. Thesis, Univ. Copenhagen 2001, RisØ-R-1275 (EN).

I-4.3.4.ii.c Resolution of DMQA⁺ cations by Ion Pairing Association

The most obvious approach to resolve these cationic moieties would be to form diastereomeric salts by pairing the racemic cations with an enantiopure anion and then attempt to separate the diastereomers on solubility differences. Recently, the synthesis of chiral hexacoordinated phosphate BINPHAT anion 30 (∆^orΛ enantiomers) was reported by the group.^53,54 This anion can be prepared in a three-steps one-pot protocol using enantiopure BINOL, tetrachlorocatechol, o-chloranil and P(NMe2)3. With (S)-BINOL, only one of the four possible diastereomers (∆δ) is usually isolated (85%).

This anion is an efficient NMR chiral shift and asymmetry-inducing agent for cationic substances and organic derivatives in particular.⁵⁵

Figure I-14. Chemical structure of (∆)-BINPHAT 30 and (∆)-TRISPHAT 37.

In view to determine the chemical stability of cations 18 a fruitful collaboration between Prof. Laursen and the group was thus developed.⁵⁶ It resulted in the efficient resolution of ⁿPr-DMQA⁺ 18a (ee > 96.4%) through (i) an ion pairing association with 30, (ii) a selective precipitation of one diastereomeric salt (benzene/THF) and (iii) an ion metathesis with KPF6. The configurational assignment of the cationic moieties was realized thanks to vibrational circular dichroism (VCD) spectroscopy by comparison between experimental and calculated spectra of the helical cations.

53 BINPHAT = ((bis(tetrachlorobenzenediolato)mono([1,1′]binaphthalenyl-2,2′-diolato)phosphate(V)).

54 Lacour, J.; Linder, D. Chem. Rec. 2007, 7, 275-285. Lacour, J.; Hebbe-Viton, V. Chem. Soc. Rev. 2003, 32, 373-382. Lacour, J. Chimia 2002, 56, 672-675. Lacour, J.; Constant, S.; Hebbe, V. Eur. J. Org. Chem. 2002, 3580-3588.

55 Constant, S.; Lacour, J. Top. Curr. Chem. 2005, 250, 1-41. Pasquato, L.; Herse, C.; Lacour, J. Tetrahedron Lett. 2002, 43, 5517-5520. Pasquini, C.; Desvergnes-Breuil, V.; Jodry, J. J.; Dalla Cort, A.; Lacour, J. Tetrahedron Lett. 2002, 43, 423-426.

Vial, L.; Lacour, J. Org. Lett. 2002, 4, 3939-3942.

56 Herse, C. Ph. D. Thesis, Univ. Geneva 2003, 3416 (FR). Herse, C.; Bas, D.; Krebs, F. C.; Buergi, T.; Weber, J.; Wesolowski, T.; Laursen, B. W.; Lacour, J. Angew. Chem., Int. Ed. Engl. 2003, 42, 3162-3166.

Chapter I. General Introduction

Precise determination of the racemization barrier of the [4]heterohelicene was also performed using a CSP-HPLC assay. Thus, this compound was shown to be much more stable than the famous [6]-helicene (∆G^≠= 41.3 kcal.mol^-1 vs. 36.9 kcal.mol^-1; t_½

= 182.7 h at 200 °C vs. t½ = 13.4 min at 196 °C).

However, moderate yields at the precipitation stage (30%), low diastereomeric purity in the mother-liquor (d.e. 41%) and non-applicability of the process (selective precipitation of diastereomeric ion pairs) to lipophilic cations 18 (R = ⁿOct) prompted us to look for a more effective procedure.⁵⁷

I-4.3.4.ii.d Resolution of DMQA⁺ cations by Covalent Bond Formation

In this respect, in 2005, a novel and general resolution route was reported. This is the work of Benoît Laleu, Pierre Mobian and Christelle Herse.⁵⁸ The resulting protocol can be performed on multigram quantities (scaled-up to 10 mmol of cation 18a, 5.0 g, vide infra Scheme I-5).^59,60 It involves an alkylation of the racemic carbenium ions 18 (R = n-Pr, i-Pr, n-Oct, c-Hex) with the carbanion of (+)-(R)-Methyl-p-tolylsulfoxide (+)-(R)-31,⁶¹ a facile chromatographic separation of the resulting diastereomers (R,M)-32 (d.r. > 99:1) and (R,P)-32 (d.r. > 55:1) (∆Rf = 0.28-0.39) and the generation of the enantiopure cations (ee > 98%) under acidic conditions; i.e., with aq. HPF₆ in acetone for the generation of salts (M) and (P)-[18][PF6] respectively. In fact, this latest step was of particular interest as it shed light on an atypical and new mechanistic approach of the Pummerer reaction.

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

Engl. 2003, 42, 3162-3166.

58 Herse, C. Ph. D. Thesis, Univ. Geneva 2003, 3416 (FR).

59 Laleu, B. Ph. D. Thesis, Univ. Geneva 2006, 3784 (FR). Laleu, B.; Mobian, P.; Herse, C.; Laursen, B. W.; Hopfgartner, G.;

Bernardinelli, G.; Lacour, J. Angew. Chem., Int. Ed. Engl. 2005, 44, 1879-1883.

60 This procedure can be further utilized for the resolution of dissymmetrical cations DMQA⁺. This will be detailed in Chapter IV.

61 Andersen, K. K. Tetrahedron Lett. 1962, 93-95. Solladié, G.; Hutt, J.; Girardin, A. Synthesis 1987, 173. Carreño, M. C.

Chem. Rev. 1995, 95, 1717-1760.

S Column chromatography (SiO2); iv) aq. HPF6, acetone. p-tol = para tolyl.

I-4.3.5 Reaction Discovery and Methodology Development

I-4.3.5.i Unprecedented Pummerer Fragmentations

Classically, the treatment of sulfoxides with electrophilic reagents (E-X) such as anhydrides or strong acids results in Pummerer rearrangements.⁶² The mechanism begins by esterification (or protonation) of the oxygen atom of the sulfoxide by E-X.

Subsequent cleavage of the S-O and C_α-H bonds leads to the formation of a sulfonium

62 Padwa, A. Pure Appl. Chem. 2004, 76, 1933-1952. Kita, Y. Phosphorus, Sulfur Silicon Relat. Elem. 1997, 120 & 121, 145-164.

Chapter I. General Introduction

moiety, which is trapped by the counterpart of the electrophilic reagent or by any other (better) nucleophiles present in the reaction medium to generate a variety of functional groups (Scheme I-6, route a).

Scheme I-6. Mechanistic rationalization for the Pummerer rearrangement (a) and fragmentation (b) pathways. (E-X: reactive electrophile)

The Pummerer fragmentation of compound 32 (C_α-C_β bond cleavage i.e., Scheme I-6, route b) was the first of its kind. Care was thus taken to characterize the process.

Benoît Laleu from the group demonstrated, that depending upon the nature of substituent (R) at the β position of the sulfoxide moiety, a Pummerer reaction could be oriented “at will” towards C_α-H (rearrangement) or C_α-C_β bond cleavage (fragmentation) pathways; the driving force of the process being the electrofugal character of readily generated carbocations R⁺ vs. H⁺ ions. Furthermore, it was determined that the "turning point" for a "fair" competition between the two elimination routes requires a carbocation of pK_R+ value of 14.5. In other words, it was shown that the exceptional stability of carbenium ions 18 and 19 – translated in quantitative terms by a highly positive pKR+ value (≥ 19) was at the origin of this mechanistic "switch".⁶³

63 Laleu, B.; Machado, M. S.; Lacour, J. Chem. Commun. 2006, 2786-2788.

I-4.3.5.ii Stereoselective synthesis of topological objects: inherently chiral pseudo-rotaxanes Concerning a possible use of enantiopure cationic helicenes 18 in highly relevant applications the stereoselective construction of interesting topological objects such as inherently chiral pseudorotaxanes was considered.⁶⁴

Figure I-15. Schematic representation of the two possible Enantiomers of inherently chiral (pseudo)rotaxanes.

Rotaxanes and pseudorotaxanes are host-guest sytems composed minimally of a threadlike molecule surrounded by a macrocycle. For many years, these supermolecules have been attracting considerable attention.⁶⁵ Not only for their structural features, but also because of the variety of properties and functions that can be engineered within them. (pseudo)-rotaxanes can be chiral if either thread or macrocycle (ring) are oriented (see above Figure I-15). However, whereas their enantiopure or enantioenriched isolation by resolution of the racemic starting materials has been widely and successfully carried out previously, there have been only few reports concerning their stereoselective synthesis.^66,67

In this respect, a secondary ammonium thread 33 containing as chiral stopper heterohelicene 18a was synthesized in racemic and enantiopure form (M and P). Its association with oriented macrocycle 34 led to the formation of two inherently chiral diastereomeric rotaxanes 35 and 36. Although ¹H and ¹⁹F-NMR analysis revealed only a low diastereomeric excess from the interaction between ring and thread (d.e. ≤ 8%),

64 Mobian, P.; Banerji, N.; Bernardinelli, G.; Lacour, J. Org. Biomol. Chem. 2006, 4, 224-231.

65 Kay, E. R.; Leigh, D. A. Pure Appl. Chem. 2008, 80, 17-29. Meyer, C. D.; Joiner, C. S.; Stoddart, J. F. Chem. Soc. Rev. 2007, 36, 1705-1723. Champin, B.; Mobian, P.; Sauvage, J.-P. Chem. Soc. Rev. 2007, 36, 358-366. Sauvage, J. P.; Dietrich-Buchecker, C. Molecular Catenanes, Rotaxanes and Knots: A Journey Through the World of Molecular Topology; Wiley-VCH: Weinheim, Germany, 1999; and references cited therein.

66 Takata, T. personal communication.

67 Oshikiri, T.; Takashima, Y.; Yamaguchi, H.; Harada, A. J. Am. Chem. Soc. 2005, 127, 12186-12187. Li, X. Q.; Jia, M.;

Wang, X. Z.; Jiang, X. K.; Li, Z. T.; Chen, G. J.; Yu, Y. H. Tetrahedron 2005, 61, 9600-9610. Sandanayaka, A. S. D.; Sasabe, H.; Araki, Y.; Furusho, Y.; Ito, O.; Takata, T. J. Phys. Chem. A. 2004, 108, 5145-5155. Smukste, I.; Smithrud, D. B. J. Org.

Chem. 2003, 68, 2547-2558. Tokunaga, Y.; Kakuchi, S.; Akasaka, K.; Nishikawa, N.; Shimomura, Y.; Isa, K.; Seo, T. Chem.

Lett. 2002, 810-811. Meillon, J. C.; Voyer, N.; Biron, E.; Sanschagrin, F.; Stoddart, J. F. Angew. Chem., Int. Ed. Engl. 2000, 39, 143-145.

Chapter I. General Introduction

an interesting ion pairing effect was noticed as lipophilic (rac)-TRISPHAT^54,68,69 37 counter ion (see Figure I-14) afforded a much better supramolecular association between the ammonium salt and the disymetrical crown ether than its PF6 analog.⁶⁴

O O

Figure I-16. The association of a helicene-based Chiral ammonium thread 33·and an oriented ring 34 affords two inherently chiral rotaxanes 35 and 36. The (P)-18a arbitrarily depicted.

I-5 Conclusion

This survey has for now mostly detailed the knowledge in the group and the synthetic state-of-the-art in the literature prior to the start of this Ph.D. To extend the scope of the family of TMPA⁺, DMQA⁺ and TATA⁺ cations it was thus decided to try to introduce other atoms that nitrogen and oxygen at the periphery of the interesting carbenium ions and sulfur in particular (see Chapter II). We decided also to look for synthetic applications of the known cationic derivatives of type DMQA⁺ and TATA⁺ and in photochemistry and organocatalysis in particular (Chapter III and IV). Finally, it was decided to use some of the derivatives prepared for the new projects in a rather different research area and generate a new type of chiral non-racemic bowl-shaped molecules (see Chapter V).

68 TRISPHAT = (tris-(tetrachlorobenzenediolato)phosphate(V)).

69 Favarger, F.; Goujon-Ginglinger, C.; Monchaud, D.; Lacour, J. J. Org. Chem. 2004, 69, 8521-8524.

II-1 Introduction

II-1.1 Preamble

The quest for innovative technologies and advancely designed materials with improved properties is never-ending. In this context, chemistry of functional organic dyes that absorb and emit in the red-visible or near-infrared¹ (NIR) region of the optical spectrum increased attention since the early/middle of the last century:² from advances in photography³ through attempts at optical data storage⁴ and lasing⁵ to novel low-noise detection techniques in various analytical methods such as electrophoresis⁶ and immunoassays.⁷ However, with advances in imaging instrumentation research this area has undergone an important surge in the last decades. Thus, nowadays NIR dyes play a prominent role in many fields of medicinal chemistry and biotechnology,⁸ ranging from tomography⁹ through endoscopic imaging¹⁰ and tumor diagnostics¹¹ to drug discovery¹² and nucleic acid detection.¹³

1 The near-infrared (NIR) region covers wavelengths from 700 to 2000 nm.

2 Fabian, J.; Nakazumi, H.; Matsuoka, M. Chem. Rev. 1992, 92, 1197-1226.

3 Rogers, D. The Chemistry of Photography: From Classical to Digital Technologies; Royal Society of Chemistry: Cambridge, UK, 2007. Fujita, S. Organic Chemistry of Photography; Springer-Verlag: Berlin, Germany, 2004. Dahne, S. J. Imaging Sci.

Technol. 1994, 38, 101-117.

4 Matsuoka, M. Mol. Cryst. Liq. Cryst. Sci. 1993, 224, 85-94.

5 Fabian, J. J. Prakt. Chem. 1991, 333, 197-222.

6 McWhorter, S.; Soper, S. A. Electrophoresis 2000, 21, 1267-1280.

7 Swamy, A. R.; Danesvar, M. I.; Evans, L.; Strekowski, L.; Narayanan, N.; Szurdoki, F.; Wengatz, I.; Hammock, B. D.;

Patonay, G. ACS Symp. Ser 1997, 657, 146-161.

8 Daehne, S.; Resch-Genger, U.; Wolfbeis, O. S.; Editors Near-Infrared Dyes for High Technology Applications; Daehne, Siegfried; Resch-Genger, Ute; Wolfbeis, Otto S ed.; Kluwer, Dordrecht, 1998;.

9 Gurfinkel, M.; Ke, S.; Wen, X. X.; Li, C.; Sevick-Muraca, E. M. Dis. Markers 2003, 19, 107-121.

10 Dekker, E.; Fockens, P. Eur. J. Gastroenterol. Hepatol. 2005, 17, 803-808.

11 Ballou, B.; Ernst, L. A.; Waggoner, A. S. Curr. Med. Chem. 2005, 12, 795-805.

12 Licha, K.; Olbrich, C. Adv. Drug Delivery Rev. 2005, 57, 1087-1108.

13 Wang, Y. B.; Yang, J. H.; Wu, X.; Li, L.; Sun, S.; Su, B. Y.; Zhao, Z. S. Anal. Lett. 2003, 36, 2063-2094.

Chapter II

SULFUR-BRIDGED TRIANGULENIUM DERIVATIVES: TOWARDS NEAR-INFRARED

ABSORBING DYES

Chapter II. Sulfur-bridged triangulenium derivatives: towards near-infrared absorbing dyes

These dyes require low optical band gaps in other words, a small difference in energy between the HOMO¹⁴ and LUMO orbitals.

N N

Figure II-1. Examples of rylenes- (38), boronorondipyrromethene- (39), squaraines- (40), croconic acid- (41), dithiolenes- (42), cyanines- (43), and triarylmethyl- (44) based dyes absorbing in the near infrared region.

To date this situation was attained using strong donor–acceptor interactions in the molecule (e.g., the so-called push-pull effect),¹⁵ rigidifying the core structure of the dye,¹⁶ extending the π-system,¹⁷ or sometimes with the additional incorporation of heavy elements¹⁸ such as nickel,¹⁹ selenium²⁰ and tellurium.²¹

14 Highest occupied molecular orbital.

15 Villalonga-Barber, C.; Steele, B. R.; Kovac, V.; Micha-Screttas, M.; Screttas, C. G. J. Organomet. Chem. 2006, 691, 2785-2792. Kachkovskii, A. D. Theor. Exp. Chem. 2005, 41, 139-164. Tian, M.; Tatsuura, S.; Furuki, M.; Sato, Y.; Iwasa, I.; Pu, L.

S. J. Am. Chem. Soc. 2003, 125, 348-349. Kohl, C.; Becker, S.; Mullen, K. Chem. Commun. 2002, 2778-2779.

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Derecskei-Kovacs, A.; Burgess, K. Chem. Commun. 1999, 2501-2502.

17 Avlasevich, Y.; Mullen, K. Chem. Commun. 2007, 4440-4442. Pschirer Neil, G.; Kohl, C.; Nolde, F.; Qu, J.; Mullen, K.

Angew. Chem., Int. Ed. Engl. 2007, 45, 1401-1404. Makarov, S.; Litwinski, C.; Ermilov, E. A.; Suvorova, O.; Roder, B.;

Wohrle, D. Chem. Eur. J. 2006, 12, 1468-1474. Tsuda, A.; Osuka, A. Science 2001, 293, 79-82. Adachi, M.; Nagao, Y. Chem.

However, the majority of such substances are difficult to synthesize and many of them are labile or possess low thermal- and photo-stabilities. Recent efforts have thus been focused to fulfil all the requirements for an ideal NIR moiety: complex structures have been developed by the combination of several rylene units with quite a number of donor - acceptor groups.¹⁷ Conformational restricted aza-dipyrromethene boron difluoride derivatives (aza-BODIPY) were synthesized.²² Squaraine²³ and croconic²⁴ based structures were also considered as another interesting approach. Nevertheless a concept for attaining bathochromic (long wavelength) absorption with simple dyes is still rare. Typical examples of such NIR absorbing dyes are reported in Figure II-1 (e.g., 38 to 44).

II-1.2 Rationale

It is useful to recall that for each electronic transition (i.e., between the fundamental and excited transition state) one can define an electric and a magnetic transition dipole. They are allied to the electron cloud redistribution taking place during the transition: if the initial and final states are labelled i and j respectively, a linear charge displacement brings about a non-vanishing electric transition dipole

≠0

µij whereas a rotation of electrons leads to a magnetic transition dipole m^ij ≠0.

Both situations can lead to the absorption of radiation: the intensity (or better the integral) of an absorption band is directly related to the oscillator strength where the two vectors are expressed in suitable units.²⁵

Mater. 2001, 13, 662-669. Geerts, Y.; Quante, H.; Platz, H.; Mahrt, R.; Hopmeier, M.; Bohm, A.; Mullen, K. J. Mater. Chem.

1998, 8, 2357-2369.

18 Namba, K. Metal complex dyes; Plenum: New York, N. Y., 1990. Yang, J.; Dass, A.; Sotiriou-Leventis, C.; Tyson, D. S.;

Leventis, N. Inorg. Chim. Acta 2005, 358, 389-395.

19 Marshall, K. L.; Painter, G.; Lotito, K.; Noto, A. G.; Chang, P. Mol. Cryst. Liq. Cryst. 2006, 454, 449-481.

20 Saito, Y.; Ookago, Y.; Murayama, T. Organic metal complex, infrared-absorbing dye and infrared absorption filter containing the same, and filter for plasma display panel. 2001005894, 2001. McGowan, D. A.; Garcia, P. P.; Lee, J. W.; Spencer, T. K.;

Telfer, S. J.; Zuraw, M. J. Asymmetric pentamethine squarate dyes, squarylium intermediates with one heterocyclic nucleus, and the preparation of both. 2067959, 1992.

21 Detty, M. R.; Fleming, J. C. Adv. Mater. 1994, 6, 48-51.

22 Zhao, W. L.; Carreira, E. M. Chem. Eur. J. 2006, 12, 7254-7263.

23 Basheer, M. C.; Santhosh, U.; Alex, S.; Thomas, K. G.; Suresh, C. H.; Das, S. Tetrahedron 2007, 63, 1617-1623.

Ajayaghosh, A. Acc. Chem. Res. 2005, 38, 449-459.

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Sitha, S.; Bhanuprakash, K.; Rao, V. J. J. Phys. Chem. A 2005, 109, 8604-8616. Tatsuura, S.; Matsubara, T.; Tian, M.; Mitsu, H.; Iwasa, I.; Sato, Y.; Furuki, M. Appl. Phys. Lett. 2004, 85, 540-542. Langhals, H. Angew. Chem., Int. Ed. Engl. 2003, 42, 4286-4288.

25 Berova, N.; Di Bari, L.; Pescitelli, G. Chem. Soc. Rev. 2007, 36, 914-931.

Chapter II. Sulfur-bridged triangulenium derivatives: towards near-infrared absorbing dyes

Thus, in the case of the electron rich azatriangulenium derivatives, which are more or less devoid of any rotational issues, one can assume that the electric dipole term is very much larger than the magnetic one (µij〉mij). Hence, by replacing one nitrogen or oxygen bridge by a strong electron withdrawing moiety, we can expect to create a significant electronic dipole into the molecules and that the optical absorption properties of these derivatives might be pushed towards the long wavelength region.

At the same time, absorption intensity should increase. For this purpose, a sulfur atom

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