Expeditious synthesis of helicenes using an improved protocol of photocyclodehydrogenation of stilbenes

An improved procedure has been developed for photodehydrocyclization of stilbenes for the synthesis of phenanthrenes and helicenes. This procedure involves the use of THF as a scavenger of hydriodic acid produced during iodine mediated photodehydrocyclization. The use of THF is advantageous due to its higher boiling point, lower cost and easy availability as compared to propylene oxide. The method is applied to synthesize a number of phenanthrenes and helicenes.


Introduction
Helicenes 1 constitute a fascinating class of chiral helical molecules comprising ortho-fused aromatic rings having many intriguing features such as extended aromaticity, chirality, a capability to organize into columnar solid state architecture and an ability to behave as organic conductors.Potential applications of helicenes can be found in the fields of non-linear optics 2 and circularly polarized luminescence. 3The unique structure of functionalized helicenes make them very stable towards acids, bases as well as being stable at high temperature. 4These type of molecules are considered potentially useful new materials such as discotic liquid crystals 5 or conjugated polymers. 6Study of helical compounds is an active field of research in supramolecular chemistry due to their self-assembly and physiochemical properties. 7Also their rigid helical framework, high optical stability and unique chiral array can provide functionalized helicenes such as alcohols, 8 nitriles, 9 amines 10 and phosphines 11 for use as chiral catalysts, 12 ligands 13 and auxiliaries in asymmetric synthesis.Moreover helicenes possessing inherent chirality have attracted attention owing to their extraordinary electronic and optical properties. 14 A common method for the synthesis of phenanthrene and its derivatives involves the construction of a central ring by photodehydrocyclization of stilbene.This method involves exposure of cis/trans stilbene 1 to UV light, which causes its isomerization to the cis form.This form undergoes electrocyclic ring closure to produce dihydrophenanthrene 2, which on dehydrogenation generates a phenanthrene 3 (Scheme 1).This classical synthesis of ortho-fused benzene rings has been optimized and widely applied for the syntheses of a number of helical moieties. 15The required stilbene precursors are obtained either by the Wittig reaction or by the Mizoroki-Heck reaction.In recent years, preparation of heterohelicenes has been extensively studied in order to exploit the unique properties of these compounds. 16

Results and Discussion
As a part of our ongoing research project, we require a simple an expeditious synthesis of functionalized benzo[c]phenanthrene.In the preliminary communication 17 we have reported an improved method for photocyclodehydrogenation of stilbenes to construct phenanthrenes, helicenes etc.In the classical iodine mediated photocyclodehydrogenation, propylene oxide is used as a scavenger to neutralize the co-product hydrogen iodide.This reagent is slightly expensive and has a low boiling point.In a typical photo reaction even under careful cooling, the reaction mixture warms up which causes the loss of propylene oxide.In our improved procedure we have replaced this scavenger by readily available and cheap tetrahydrofuran which has a higher boiling point and in this paper we present further applications of this modified procedure for the synthesis of a number of helical compounds.
The progress of the neutralization of hydrogen iodide with tetrahydrofuran and propylene oxide is studied by pH measurement of its solution.In this study tetrahydrofuran and propylene oxide neutralizes the HI due to the opening of both cyclic ethers.As a result of the neutralization of HI there is a gradual rise in the pH.We found that the propylene oxide reacts faster than the tetrahydrofuran, Figure 1.This is expected since the propylene oxide has a higher strain compared to tetrahydrofuran, nevertheless this study indicates clearly that even though less efficiently, the later can be used as a scavenger of HI.The ability of tetrahydrofuran to react with HI is also reported in the literature. 18  In this paper we report several photodehydrocyclization reactions using tetrahydrofuran as scavenger in stead of propylene oxide and hope to establish the generality of this method.With this aim several suitable stilbenes were prepared by various methods and subjected to photodehydocyclization using the present conditions by which a number of mono-and disubstituted phenanthrenes were prepared in excellent yields 17 (Scheme 2).The photodehydrocyclization of nitrostilbenes is known to offer some difficulty when a catalytic quantity of iodine is used. 19In order to test the present method on the nitro containing substrates, stilbenes 1a and 1b were synthesized and subjected to photolysis with I2-THF.The corresponding nitro phenanthrenes 2a and 2b were isolated in reasonable yields (Scheme 3).Furthermore, the nitro derivative of styrylnaphthalene (2-[2-(4-nitrophenyl)ethenyl]naphthalene) 20 3 was also successfully cyclized to 2-nitrobenzo[c]phenanthrene 4 indicating that the present method also tolerates nitro groups.Scheme 3. Preparation of nitro-substituted angularly fused arene.
The present method was screened for cyclization of 1,2-bis(2-naphthyl)ethylene 5 with the aim to prepare [5]helicene.However, the initially formed [5]helicene 6 was not isolated but underwent further 4+2 cyclization to form benzo[ghi]perylene 7 in good yield (Scheme 4). 21Since the photochemical ring closure had proven to be one of the simplest ways to obtain fused aromatics, we decided to study the reaction of different derivatives of ethylene, namely the compounds carrying a fused two-or three-ring aryl on one terminus and a monocyclic aryl on the other terminus of the double bond.The synthesis of these derivatives easily gave the desired helicenes and eventually opened the facile route for the formation of [6]helicenes or larger helicenes.
Encouraged by the previous results, several [6]helicene derivatives have been synthesized as shown in scheme 5. Alternatively 14 can be also synthesized by double photodehydrocyclization of 2,7-bisstyrylnaphthalene 18.This new route is presented in scheme 6, where initially 2,7dihydroxynaphthalene 16 is converted into the corresponding 2,7-dibromonaphthalene 17, which was reacted with styrene under Heck conditions with Pd-dppp to afford 2,7-bis-styrylnaphthalene 18.This was then subjected to the photodehydrocyclization to afford [6]helicene 14 in a single step (Scheme 6).
The method is further studied for the syntheses of [7]helicene.Scheme 7 illustrates an attempt for its synthesis.The readily available 2-methylnaphthalene 19 was converted to its Wittig salt 20 via benzylic bromination with NBS, and its reaction with triphenylphosphine.The salt Scheme 7. Towards [7]helicene.
The presence of the bulky naphthalene ring may prevent cyclization of 24 at the required angular location.In a modified route the double photocyclization/dehydrogenation was attempted starting from 30 where the bulky naphthyl group (as present in 24) had been replaced by the less bulky phenyl ring (Scheme 8).Accordingly, the required 3,6-(bis-styryl)phenanthrene 30 was synthesized by combination of Witting reaction, photodehydrocyclization and Heck reaction starting from 4-bromobenzaldehyde 27.Photodehydrocyclization of 30 under our improved conditions gave the desired [7]helicene 26 although in moderate yield.

Experimental Section
Reagents were purchased from Sigma-Aldrich Chemicals Limited, SD Fine, Sisco, Qualigens Limited etc. Tetrahydrofuran was refluxed and distilled on sodium benzophenone-ketyl.Toluene was distilled and stored 24 h over molecule sieves 4 Å prior to use.Thin Layer Chromatography was performed on Merck 60 F254 Aluminium coated plates.The spots were visualized under UV light or with iodine vapour.Photo reactions were performed in immersion well photo reactor with water jacket for cooling with 125 W or 250 W high pressure mercury vapor lamp made by General Electric (CEMA Electric Lighting Products India Pvt.Ltd).All the compounds were purified by column chromatography using SRL silica gel (60-120 mesh). 1 H NMR spectra were recorded on Bruker Avance 400 Spectrometer and were run in CDCl3 unless otherwise stated.Mass spectra were recorded on Thermo-Fischer DSQ II GCMS instrument.IR spectra were recorded on a Perkin-Elmer FTIR RXI spectrometer as KBr pallets.Melting points were recorded in Thiele's tube using paraffin oil and are uncorrected.Kinetic experiments were run on ELICO LI127 pH meter.

Comparison of propylene oxide and tetrahydrofuran as scavenger of HI:
For the comparison of opening of propylene oxide and tetrahydrofuran as scavenger, the HI was synthesized by heating NaI (5.0 g, 0.033 mol) and H3PO4 (3.7 mL, 0.05 mol, 1.5 eq.) in a round bottom flask.18b It was condensed in a dry round bottom flask.From the distilled sample of HI (0.505 g) was taken and diluted with distilled water to 25 mL.For the comparison study two sets were prepared, one for propylene oxide and another for tetrahydrofuran.From this diluted solution (5 mL, 0.103 g of HI, 0.8 mmol) was taken for each set.In one set propylene oxide (0.0935 g, 0.11 mL, 1.6 mmol, 2 equiv) and distilled water was added to adjust the volume of the system to 15 mL.For the second set, tetrahydrofuran (0.1161 g, 0.13 mL, 1.6 mmol, 2 eq.) and distilled water was added to make the volume of the system to 15 mL.Both sets were stirred at the same speed continuously while the pH was measured using a glass electrode attached to a pH meter at the interval of 5 min.Readings for the comparison are presented below in Table 2 and a graph was plotted (pH vs time in min.)as shown in Figure 1.

4-Bromo-4′-nitrostilbene (1b) General procedure for Wittig Reaction (Method C)
A solution of Na metal (0.083 g, 3.63 mmol) in anhydrous methanol (5 mL) was added dropwise to a suspension of the (4-bromobenzyl)triphenylphosphonium bromide salt (1.685 g, 3.63 mmol) and p-nitrobenzaldehyde (0.500 g, 3.63 mmol) in anhydrous methanol (10 mL) under N2 at room temperature.The color of the solution changed to yellow.After completion of the addition, the resulting solution was stirred for 24 h at room temperature, till no starting material was seen on tlc.
The mixture was poured in cold water to separate the precipitate.The aqueous solution along with the precipitates was extracted with ethyl acetate and solvent layer was washed with water, brine and dried over sodium sulfate.The solvent was removed under reduced pressure and crude product was purified on silica gel column to afford mostly trans form of the title stilbene as yellow solid (0.915 g, 91%  (22), 149 (39), 114 (27), 113 (100), 112 (51), 111 (23), 97 (17).

Figure 1 .
Figure 1.Comparison of propylene oxide and tetrahydrofuran as scavenger of HI.

Table 2 .
Comparison of consumption of HI by propylene oxide and tetrahydrofuran Mizoroki-Heck Reaction (Method A): Preparation of Catalyst SolutionA solution of palladium acetate (0.011 g, 0.00495 mmol, 0.1 mol%) and 1-(α-1-piperidylbenzyl)-2naphthol (ligand A) (0.0018 g, 0.0059 mmol, 1.2 eq. of Pd(OAc)2) was prepared in N,Ndimethylacetamide (5 mL) under nitrogen atmosphere.The mixture was stirred at room temperature until a homogeneous solution was obtained.This catalyst solution was repeatedly purged by N2 prior to use.A two neck r.b. flask was charged with p-bromonitrobenzene (1.0 g, 4.95 mmol), dry potassium carbonate (1.71 g, 12.37 mmol, 2.5 eq.), TBAB (0.319 g, 0.99 mmol, 20 mol%) and N,Ndimethylacetamide (10-15 mL).The solution was repeatedly purged with N2.Styrene (0.773 g, 7.42 mmol, 1.5 eq.) was added at 60 o C and the mixture was heated up to 100 o C. When the temperature reached 100 o C, the previously prepared Pd catalyst solution was added dropwise and the mixture was heated to 140 o C for 48 h.After the completion of the reaction, the mixture was poured in 6N HCl and extracted with dichloromethane.The combined organic phase was washed with water, brine and dried over anhydrous sodium sulfate.The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel using petroleum ether as eluent to afford pale yellow solid (0.623, 77%), mp.156 o C (Lit.154-157 o C).26IR  (KBr) cm.-1 : 3077,1631, 1589, 1508, 1338, 1185, 1105, 969, 873, 833, 765, 693.