Helicene, synthesis

Laarhoven et al. 711 have studied the influence of chiral solvents on the optical yield of [6]helicene, synthesized by photodehydi ocyclization of various precursors. Most thoroughly investigated was the photochemical ring closure of 2-styrylbenzo[c]-phenanthrene in optically active fluids (Table 5). 

Nitrogen and oxygen heteroatoms can also be introduced into helicenes. 5,10-Dihydrocarbazolo[3,4-c]carbazole 119 was the first helicene synthesized (in 1927). Heterohelicenes containing several nitrogen atoms as well as hydrogenated hetero-helicenes have been synthesized by Teuber and Vogel These authors also studied the consequences of the presence of sp centers in helicenes... 

The first helicene synthesized, which was bridged by a ferrocene unit, is based on the pentahelicene skeleton At its terminal phenylene rings, cyclopentadienyl units were condensed. The di-lithium salt of this compound with iron(III)chloride yielded the helical ferrocene 142 with an uninterrupted conjugation between the two cyclopentadienyl rings (Fig. 55). The cyclopentadienyl moieties are clamped by the iron atom in an angle deviating 19.4° from parallelity. 

Further development of the efficient helicene syntheses, including [2 + 2 + 2] cycloaddition reactions, is expected for their application to functional materials and chiral reagents. 

Heck reaction, intramolecular, 60, 2 Helicenes, synthesis by photocyclization, 30, 1... 

D. Pena, A. Cobas, D. Perez, E. Guitian, L. Castedo, Dibenzo[ ,o]phenanfhro[3,4-sjpycene, a Configurationally Stable Double Helicene Synthesis and Determination of Its Conformation by NMR and GIAO Calculations, Org. Lett. 2003, 5, 1863-1866. 

The sequential intramolecular hydroarylation of alkynes has been applied to the catalytic helicene synthesis. The platinum-catalyzed sequential intramolecular hydroarylation of diynes proceeded to give substituted [6]hehcenes (Scheme 21.50) [56]. 

In 1999, Stara and Sttir s group [39] reported the application of a Ni(COD)2/PPhj (tilong with CpCo(CO)2/PPhj, see above) for helicene synthesis. The reactions took place with satisfactory yields. When the reaction was conducted with Ni(COD)2/(S)-(—)-MOP (40mol%) at —20°C, the product was obtained with an enantiopurity of 48% ee. 

Double intramolecular [2 + 2 + 2] cycloaddition enabled long helicene synthesis. A racemic anthra[ll]helicene was prepared via the cobalt-mediated double intramolecular [2 + 2 + 2] cycloaddition of a me.yo-hexayne followed by acetic acid elimination and dehydrogenation (Scheme 10.5) [8]. 

Complete intramolecular [2 + 2 + 2] cycloaddition of triynes is mediated by the cobalt(I), nickel(O), and rhodium(I) complexes. This method constructs three rings in one step, and double [2 + 2 + 2] cycloaddition of hexaynes enabled the long helicene synthesis through the formation of six rings. 

The Bucherer carbazole synthesis was pivotal in the preparation of the first hexahelicene 37a. Reaction of 2,7-dihydroxynaphthalene 35 with phenylhydrazine and sodium bisulfite afforded helicene 37a although in low yield. More recently, the synthesis was extended to the preparation of 37b using 2,5-dimethylphenylhydrazine 36b. ... 

Dihydrovinylphenanthrenes are more reactive than the corresponding vinyl phenanthrenes and undergo Diels-Alder reactions easily. They have been used in the synthesis of polycyclic aromatic compounds and helicenes. Examples of cycloaddition reactions of the 3,4-dihydro-1-vinylphenanthrene (70), [61] 3,4-dihydro-2-vinylphenanthrene (71) [68] and l,2-dihydro-4-vinylphenanthrene (72) [69] are reported in Equation 2.22 and Schemes 2.27 and 2.28. 

That chiral molecules can be produced in a CPL field, either from achiral precursors by photo-activated synthesis or by preferential chiral photodestruction of a racemic mixture, is now well demonstrated and has been reviewed. [46] In all cases currently known, however, such processes have proved very inefficient. For example, asymmetric photochemical ring-closures of achiral helicene precursors induced by CPL have produced only about 0.2% e.e. in the products. Likewise, the CPL-induced photolysis of racemic camphor produced about 20 % e.e., but only after 99% photodestruction, and photolysis of D.L-glutamic acid produced only 0.22 % e.e. after 52 % photodecomposition. [71]... 

An interesting approach for the synthesis of enantiopure thiophene-based[7]helicene has been described which utilizes an intramolecular McMurry coupling using low-valent titanium as the key step <2004CEJ6531>. It was found that yields of the product varied widely due to the formation of varying quantities of the intermediate diol and desilylated starting material. 

The photochemical synthesis of helicenes by irradiation of 1,2-diarylethylenes in adilute solution and in the presence of an oxidizing agent is based on the well known photocyclodehydrogenation of stilbene into phenanthrene. There is an overwhelming amount of literature on this type of photoreaction. Details about scope and limitation can be found in previous reviews 7,8). Therefore, only a short survey will be given of the mechanism of the reaction. 

Table 2. Synthesis of Benzo- and Double Helicenes from Aryl Olefinic Precursors...

The P- and M-cis-syn-conformers give photoreactions, whose rates are proportional to el when left-handed CPL is used. Therefore, a high optical yield requires a high g-factor 69 After the excitation cyclization occurs leading to a DHP, which is readily oxidized to helicene. The precursor remains racemic as racemization in the ground state, is easy. Racemization in the excited state, however, may be slow, compared to cyclization. According to Kagan 69) this mechanism explains the asymmetric synthesis well. 

Macroscopical helical structures formed by cholesteric liquid crystals have been used as chiral helical media for the asymmetric synthesis of helicenes. 

The absolute configurations of helicenes have been firmly established by calculations 95 98), by X-ray analysis 99) and by synthesis l00).6 The dextrorotatory enantiomers of hexahelicene and a thiahexahelicene have been shown to possess the right-handed (P) helicity. From the correspondence of the ORD- and CD-curves of these hexahelicenes and higher helicenes positive rotations correspond in all cases with P-helicenes. 

Some aspects of the chemistry of helicenes require still more attention. Since the interpretation of the mass spectrum of hexahelicene by Dougherty 159) no further systematic work has been done on the mass spectroscopy of helicenes, to verify the concept of an intramolecular Diels-Alder reaction in the molecular ion. Though the optical rotation of a number of helicenes is known and the regular increase of the optical rotation with increasing number of benzene rings has been shown, the dependence of the rotation on the helicity is still unknown. The asymmetric induction in the synthesis of helicenes by chiral solvents, or in liquid crystals, though small, deserves still more attention because application to other organic compounds will be promoted when the explanation of observed effects is more improved. 

Finally, no report has still appeared about the synthesis of triple helicenes which can be seen as orthoannelated triphenyl derivatives. The first member in the series tribenzo[a,c,e]triphenylene has already been synthesized several years ago m). The racemizations and isomerizations of these compounds may reveal interesting new data. 

This chapter addresses synthetic aspects of molecules with highly annelated chiral JT-conjugated systems, with the focus on helicene-type oligomers [20], In addition to synthesis, configurational stability (barriers for racemization) and selected chiroptical properties of such molecules will be discussed. 

The first [nfhelicenes, [6]pyrrolohelicene (2) and [5]helicene (3), were reported in 1927 and 1933, respectively [22-24]. The synthesis of a non-racemic [n]heli-cene, [6]helicene (1), was first described by Newman and Lednicer in 1956 [25], Photochemical syntheses developed during the 1960s and 1970s provided the longest [nfhelicenes to date, that is, [n]helicenes [with up to n = 14 benzene rings (4)] and [n]thiahelicenes [with up to n = 15 alternating benzene and thiophene rings (5)] [26-30]. 

The extraordinarily strong chiral properties of [nfhelicenes provide an impetus for the development of synthetic approaches to nonracemic [nfhelicenes for applications as organic materials. From this point of view, asymmetric syntheses of functionalized long [n]helicenes (n > 7), and also [n]helicene-like molecules and polymers with novel electronic structures and material properties, are important. The properties of helicenes related to materials are relatively unexplored, compared with the more synthetically accessible n-conjugated molecules and polymers. Notably, redox states of helicenes are practically unknown [33, 34]. Assembly of helicenes on surfaces, their uses as liquid crystals, chiral sensors, ligands or additives for asymmetric synthesis and helicene-biomolecule interactions are in the exploratory stages [35-43],... 

In general, the synthesis of [n]helicenes involves two key synthetic steps, i.e. connection and annelation. The most efficient approaches to [njhelicenes use multiple annelations, forming two or more rings in one synthetic step however, relatively few annelation reactions have been implemented effectively. 

Oxidative photocyclization of stilbene to phenanthrene, which was discovered in 1960, was first applied to the synthesis of [7]helicene by Martin and coworkers in 1967 [26, 44, 45]. This approach was extended to the syntheses of long [njhelicenes (n < 14) and [n]thiahelicenes (n < 15), using both mono- and diannelations. Numerous [nfhelicenes (n < 13) and [n]thiahelicenes (n < 13) were obtained in non-racemic form via the following methods (1) seeded crystallization of conglomerate (e.g. [7]-, [8]- and [9]helicene) [46, 47], (2) resolution by chromatography (e.g. [13]thiahelicene) [48] and (3) photocyclization from a resolved precursor (e.g. [13]helicene from hexahelicene-2-carboxylic acid) [49]. The oxidative photocyclization of stilbenes is still the method of choice for the preparation of selected [n]helicenes and their heteroatom analogs [50-58]. 

Annelation of racemic intermediate leading to racemic [n]helicene Larsen and Bechgaard reported the nonphotochemical synthesis of racemic [5]-and [9]thiahelicenes, relying on monoannelations of stilbene precursors [62], Electrochemical or chemical (FeCl3) oxidation was used in place of usual photooxidation, to provide thiahelicenes in 20-65% yields. For example, racemic [9]thiahe-licene 9 was obtained in —60% yield from stilbene 8 by oxidation with FeCl3 in methylene chloride (Fig. 15.3) a similar result was obtained by classical photooxidation of stilbene 8 [51]. 

Fig. 15.5 Synthesis of (M)-[8]helicene 13 from enantiopure [6]helicene derivative.

Elaboration of enantiopure (M)-[6]helicenebisquinone 12 into (M)-[8]helicene 13 with complete transfer of ee was reported (Fig. 15.5) [63]. [8]Helicene 13 is the longest enantiopure helicene prepared via nonphotochemical synthesis. 

Annelations via Friedel-Crafts acylation were applied to racemic syntheses of [njhelicenes with n up to 6. The 12-step synthesis of [6]helicene (1) by Newman and Lednicer employed stepwise diannelation, followed by oxidative aromatiza-tion and then resolution with the complex of a chiral n-acceptor, a-2,4,5,7-tetrani-tro-9-fhiorohdeneaminooxypropionic acid (TAPA) and 1 [25]. The one-step diannelation was ubiquitously applied to syntheses of triarylamine [4]helicenes,... 

Another important approach to the synthesis of helicenes is the convergent route based on energy-rich cis.cis-dienetriynes and their Ni(0)-catalyzed [2+2+2]-cycloisomerization, which was reported by Stara and coworkers [82, 83]. The potential of this methodology was demonstrated by the synthesis of functionalized... 

Fig. 15.13 Nickel(O)-catalyzed asymmetric synthesis of tetrahydro[6]helicene 38.

Iterative racemic synthesis and asymmetric synthesis of the [7]helicene 40 and resolution of its TMS-free derivative 41 were reported [84, 85], The racemic synthesis was based on iterative alternation of two steps CC bond homocouplings between the 3-positions of thiophenes and annelation between the a-positions of thiophenes (Fig. 15.15). 

Fig. 15.15 Iterative synthesis and asymmetric synthesis of carbon-sulfur [7]helicene 40.

Fig. 15.16 Structures of trithiophene 42, [5]helicene 43, [7]heli-cene 44, [1 ljhelicene 45 and (-)-sparteine-mediated asymmetric synthesis of [1 ljhelicene 45. LDA (mono- and triannelation) and n-BuLi (diannelation) were used as bases.

Recently, series of carbon-sulfur [n]helicenes substituted with w-octyl groups at the a-positions of the terminal thiophene rings were prepared (Fig. 15.16) [64, 87]. The helical structures of [7]helicene 44 and [ll]helicene 45 were confirmed by X-ray crystallography. Multiple short S-S contacts were found, especially for racemic [ll]helicene 45. Asymmetric synthesis of [ll]helicene 45 provided enantiomeric excess of either the (-)- or the (+)-enantiomer for the monoannelation or, unprecedented, triannelation approach (Fig. 15.16). Also, selective diannelation of octathiophene 47, followed by monoannelation of decathiophene 46, provided an efficient synthetic route to (-)-[ll]helicene 45, avoiding protection/deprotection steps [64],... 

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