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The Photochemical Approach to Helicenes

Jan Storch1, Jaroslav Zádný1, Vladimír Církva1, Martin Jakubec1, Jan Hrbác2, and Jan Vacek3

1Department of Advanced Materials and Organic Synthesis, Czech Academy of Sciences, Institute of Chemical Process Fundamentals, Prague, Czech Republic

2Department of Chemistry, Faculty of Science, Masaryk University, Brno, Czech Republic

3Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic

1.1 Introduction

In this chapter, the authors have decided to follow the nomenclature recommendations of IUPAC [1] for class names of organic compounds, which classifies helicenes as "ortho-fused polycyclic aromatic or heteroaromatic compounds in which all rings (minimum five) are angularly arranged so as to give helically shaped molecules, which are thus chiral." Therefore, the following text includes [n]helicenes where n?=?5 and the photoreaction is the very last step of their preparation, unless stated otherwise.

Two basic photo-approaches (oxidative photocyclodehydrogenation and photoinduced elimination; for details, see Section 1.2) were used for the preparation of all helicenes listed in this chapter. The photochemically created bonds are highlighted in red in all figures. Non-oxidative photochemical approaches are discussed in specific cases.

At the beginning of the chapter, some general features are mentioned, including the mechanism of the photocyclization, reaction conditions, attempts at asymmetric photosynthesis, and the synthetic approach to starting materials. The appropriate helical structures and their preparations are described in sections on carbo-, aza-, thia-, and phosphahelicenes and other helicenes. Helicene-like molecules, including dihydrohelicenes, are discussed separately, as well as photochemical transformations of helicenes.

1.2 General Features

Historically, the photocyclization of stilbenes [2, 3] was discovered during the investigation of their cis/trans photoisomerization [4], but the reaction was not used synthetically until Mallory found that iodine catalyzed this reaction in 1964 [5, 6].

Figure 1.1 Photochemical reaction pathways for stilbene derivatives.

From the mechanistic point of view, the cis/trans photoisomerization of stilbenes is very fast with a high quantum yield, allowing stilbenes to be used as an isomeric mixture (Figure 1.1), although only the cis-isomer is capable of cyclization. The symmetry-allowed photoreaction typically takes place from the singlet S1 state by a conrotatory process according to the Woodward-Hoffmann rules. Thus triplet sensitizers do not sensitize the photocyclization, and triplet quenchers (such as oxygen) do not quench it. The unstable 4a,4b-dihydrophenanthrene (DHP) intermediate possesses trans-configuration [7] and can, unless trapped, relax back to the stilbene. In the presence of an oxidant, DHP forms a phenanthrene derivative. This type of photocyclization is called the Mallory reaction [8]. If the stilbene contains suitable leaving groups (R = OMe, Cl, Br, etc.) in ortho-position, the elimination reaction producing cyclization product can take place (in the absence of an oxidant) [9-11]. Photocyclizations are typically carried out at concentrations of 10-3 M and lower to avoid the competing photodimerization [12]. The proposed photocyclization mechanism is also applicable to aza-, thia-, and other stilbene derivatives.

Originally, air was used as an oxidant until Mallory discovered that oxidative trapping occurs much faster when iodine (5?mol%) is used together with air [5]. It was proposed that iodine is photochemically cleaved into radicals reacting with hydrogen to form hydrogen iodide, which is then reoxidized to iodine by oxygen [13]. Other oxidants (e.g. selenium radicals, TCNE, TCNQ, chloranil, etc.) were investigated by Laarhoven without any practical significance for photocyclizandation of helicenes [14].

Higher amounts of hydrogen iodide may contribute to side reactions including double bond saturation of stilbenes [13]. In 1986, Katz developed new photocyclization conditions using propylene oxide as a hydrogen iodide scavenger under inert conditions [15, 16]. As a consequence, the iodide could not be reoxidized by air, and its stoichiometric amount is needed. Accordingly, it allows for a higher concentration of starting material in the reaction mixture without the undesired formation of dimers. When speaking about photocyclodehydrogenation leading to [n]helicenes, these conditions are sometimes familiarly referred to as Katz's conditions. Other cyclic ethers (such as THF) are often used as HI scavengers too.

The previously mentioned conditions provide [n]helicenes in strictly racemic mixtures (1?:?1 ratio of (P)- and (M)-enantiomer). Although attempts to lead photocyclizations asymmetrically using circularly polarized light sources [17-23], chiral solvents [24-26], or cholesteric liquid crystals [27, 28] were made, the obtained results (% ee) were more or less at the level of experimental error and did not have any practical importance. Thus, the photochemical approach has to be followed by an optical resolution to obtain helicenes in their optically pure forms. The nonracemic helicenes are often photochemically accessible as corresponding diastereomers with (photo-stable) chiral auxiliaries (providing up to >99% de), which can be synthetically cleaved or transformed after cyclization [29-31]. Eventually, such diastereomers might be separated using standard chromatographic methods. When an enantiomerically pure [6]helicene moiety was a part of the precursor, nonracemic [n]helicenes (n = 8-11, 13) were obtained [32]. Other asymmetric photosyntheses to enantioenriched metallocene helicenes were developed by Katz [33-35]. Some studies suggested that only one chiral auxiliary is not sufficient, and a better result might be obtained with the chiral substitution at the most sterically hindered position [36]. The same phenomenon was observed by Carbery and Pearson [37]. For an overview see Ref. [26] and the references therein.

Conventional (Figure 1.2a) and transition metal-catalyzed (Figure 1.2b) methods of preparation of stilbene-like molecules as a common starting material for the photochemical synthesis of helicenes are described in the literature [38, 39], including several other synthetic procedures. In practice, the Wittig reaction (and its variations) and Pd-catalyzed cross-coupling reactions belong to commonly used methods.

Figure 1.2 Commonly used preparations of stilbene-like molecules by conventional (a) and metal-catalyzed (b) procedures.

The most widely used sources of UV-vis light for continuous irradiation in laboratory experiments are commercially available mercury lamps (low, medium, and high pressure) [40]. Their spectral irradiance is strongly dependent on the mercury vapor pressure. The lamp also produces a considerable amount of infrared radiation and heat. Therefore, cooling-water circulation must be utilized to protect the reaction solution from heating. Recently, new energy-efficient light sources like light-emitting diodes (LEDs) [41-43] (Figure 1.3d) became available, thus avoiding the use of optical filters and reducing consumption costs.

Figure 1.3 Common photoreactor types: (a) immersion well, (b) external chamber, (c) continuous-flow, (d) LED-type, and (e) electrodeless discharge lamps.

Photoreactors with an immersion well (Figure 1.3a) and external chamber (merry-go-round, Figure 1.3b) are the most common types of photochemical equipment on a preparative laboratory scale. Both reactor types are well established and in widespread utilization. The use of quartz allows light of all wavelengths above about 200?nm to enter the reaction mixture. For some photoreactions, higher yields can be obtained by employing Pyrex glass. This excludes from the reaction mixture light of wavelengths below about 300?nm and thereby protects the forming products from further photochemical degradation.

Following the experiments by Mallory [6], Scholz [44], and Martin [45], the batch setup of photocyclization of stilbene derivatives under UV-vis irradiation has become one of the most popular methods for the synthesis of helicenes [13]. This is mainly due to the synthetic accessibility of the stilbene precursors and functional group tolerance under the reaction conditions (pH, temperature, etc.). However, the development of this setup is limited by the necessary dilution of the reaction mixture (~10-3?mol·l-1) to prevent the undesired [2?+?2] cycloaddition,...