Enhancing the helical distortion in pyrrolo[1,2-a ][1,10]phenanthrolines

Nine new helical compounds were synthesized using a one-pot reaction between phenanthrolinium N -ylides and quinones as cyclic olefinic dipolarophiles. 1,4-naphthoquinone, 1,4-benzoquinone and 1,2-naphthoquinone were used as dipolarophiles, resulting in excellent to moderate yields. The structure of the compounds was deduced using NMR spectroscopy and the helical distortion was ascertained using X-ray analysis.


Introduction
The interest in helical molecules, although initially only academic, steadily increased due to their attractive properties.As a result, numerous papers and reviews exist on carbohelicenes. 1 These properties can be altered and diversified by including one or more heteroatoms in the helical ring system. 2 A special class of heterohelicenes are aza and polyazahelicenes 3,4 which exhibit interesting optical properties and have many other applications.Normally, for helicity to occur, the presence of five or more ortho-condensed aromatic rings is required.In the past two decades however, the synthetic strategies for aza and polyazahelicenes increased in number, as more papers describe the preparation of helical molecules of four or three ortho condensed rings. 5In the latter case, helicity is conferred by inserting bulky substituents in key regions of the molecules.

Results and Discussion
As previously mentioned, the helical distortion in pyrrolo [1,2-a] [4,5]diazafluorenones and pyrrolo [1,2-b] [1,10]phenanthrolines was well documented in the solid state by X-ray analysis, as well as in solution by NMR spectroscopy.Both methods indicated that pyrrolo[1,2a][4,5]diazafluorenones 1 8 are less helically distorted than pyrrolo[1,2-b][1,10]phenanthrolines 2. 7 This can be explained by the presence of a less bulky cyclopentanone ring in 1 as opposed to a larger and more rigid benzene ring in the case of 2 (Scheme 1).This influences the steric repulsion between the pyridinic nitrogen atom and the aroyl group, which in turn causes the overall helical distortion of the molecule.

Scheme 1
In order to increase the steric repulsion, the use of bulkier pyrrole substituents was considered.To this end, 1,4-benzoquinone, 1,4-naphthoquinone and 1,2-naphthoquinone were used as dipolarophiles instead of the symmetrical acetylenic diesters.Although some literature data are available on the reaction between N-ylides and 1,4-benzoquinone and 1,4naphthoquinone, 9 to our knowledge no previous report on the use of 1,2-naphthoquinone as dipolarophile exists.However, 1,2-naphthoquinone was used successfully as dienophile in the synthesis of cholesterol. 10he key intermediates, phenanthrolinium salts 4a-c, were obtained in 70-80% yield according to literature methods and were used without further purification (Scheme 2).

Scheme 2
Compounds 5 and 6 were obtained in excellent yields by reacting the corresponding phenanthrolinium salt 4 with 1,4-benzoquinone and 1,4-naphthoquinone, respectively, using triethylamine and TPCD as oxidant in DMF in a one-pot procedure (Scheme 3).When applying the same synthetic protocol using 1,2-naphthoquinone as dipolarophile, the yields obtained for compounds 7 were good, but lower than those for compounds 5 or 6.The purification of cycloadducts 5-7 was performed using Soxhlet extraction with chloroform and their NMR spectra were recorded in CDCl3 + TFA (trifluoroacetic acid) mixture.For comparison purposes, the 1 H-NMR spectra of 6b and 7b were also recorded in CDCl3 at high dilution.In the 1 H-NMR spectra, proton H-8, having the chemical shift of δ = 8.66 ppm is more deshielded than H-7, δ = 8.13 ppm, due to the spatial proximity of the oxygen atom from the quinone moiety.Protons H-5 and H-6 appear as an A2 system at δ = 8.41 ppm.As the terminal pyridine ring is protonated by the presence of TFA, protons H-2, H-3 and H-4 are strongly deshielded and appear at δ = 9.64 ppm, 8.31 ppm and 9.21 ppm, respectively.A very distinct feature of cycloadducts 5 are protons H-10 and H-11 which appear at δ = 7.06 ppm and 6.87 ppm with J = 10.2Hz.
The most distinctive characteristics of the 13 C-NMR spectra are the signals for the two CO groups at δ ~ 183.0 ppm for the 1,4-benzoquinone derivatives and δ ~ 181.0 ppm for the 1,4naphthoquinone cycloadducts.
When a different experimental procedure was used, consisting of reacting at room temperature the phenanthrolinium salt and 1,4-naphthoquinone in the presence of triethylamine in methylene chloride, the formation of the tetrahydro derivative 8 was observed together with that of 6a, in a 1:2 molar ratio (Scheme 4).Compound 8 was isolated and characterized using 1 H-NMR spectroscopy.The tendency of 8 to undergo an in situ oxidative aromatization to 6a was observed.

Scheme 4
In order to measure the helical distortion in the series 5-7, X-ray single crystal analysis was performed on the representative compound 6a.Crystals were grown by slow evaporation from chloroform.
Figure 1 shows the molecular structure of 6a 11 with the seven rings labeled for reference.The compound was isolated in the form of its 1:1 solvate with chloroform.Several abnormally short intramolecular contacts in the molecule of 6a contribute to the ring system A-F adopting helical chirality, namely N1C18 2.437 Å, N1C15 2.808 Å, N1C20 2.875 Å, C20O30 2.968 Å (all e.s.d.s 0.003 Å).As a result of these steric influences, rings A-F present an undulating, helical surface (Figure 2) with the following angles of intersection between their successive mean planes: A^B 0.5, B^C 3.9, C^D 6.1, D^E 11.5, E^F 7.3 (all e.s.d.s 0.1).The cumulative effect of these progressive ring twists is that the acute angle between terminal rings A and F is 27.0(1).Accompanying this distortion, ring D adopts a slightly twisted conformation, with the endocyclic torsion angles ranging from 0.2(3) (C9-C10-C11-N12) to -13.5(3) (C8-C13-N12-C11), such that atoms C9 and C10 lie above the plane of ring C. Proceeding from ring D to E to F there is progressive bending of the ring system downward.In addition, the severe steric constraints result in atom C18 lying 0.366(2) Å above the plane of ring C and they direct the carbonyl bond C18-O19 and the plane of the phenyl ring G roughly perpendicular to ring C (Figure 1

Conclusions
Three new heterocyclic ring systems were obtained using a one-pot reaction between phenanthrolinium N-ylides and quinones as dipolarophiles.The use of 1,4-benzoquinone and 1,4-naphthoquinone resulted in high yields, while the novel use of 1,2-naphthoquinone as dipolarophile gave moderate yields.
Structural assignment was established on the basis of elemental analysis and NMR spectroscopy.The helical nature of the new compounds was determined using X-ray analysis.As compared to similar cycloadducts, the new compounds possess a higher degree of helical distortion, warranting a possible enantiomeric separation either by using a chiral complexing agent or by using chromatographic methods.

Experimental Section
General.Melting points were determined on a Boëtius hot plate.The NMR spectra were recorded on a Varian Gemini 300 BB instrument, operating at 300 MHz for 1 H and 75 MHz for 13 C. Supplementary evidence was given by HETCOR and COSY experiments.

General procedure for compounds 5, 6 and 7
To a solution of the corresponding salt (5 mmol) and quinone (5 mmol) in 35 ml DMF, a solution of triethylamine (0.7 mL, 5 mmol) dissolved in 5 mL of DMF was added dropwise.After 20 minutes of stirring at room temperature, 5 mmol TPCD (tetrakis pyridino cobalt(II) dichromate) were added and the reaction mixture was stirred at 80-90 ºC for 6 h on a water bath.After cooling to room temperature, 50 ml of a 5% aqueous HCl solution was added.The resulting precipitate was filtered and washed with ethanol.The crude product was purified by Soxhlet extraction with chloroform.

Figure 1 .
Figure 1.ORTEP diagram of the asymmetric unit in the crystal of 6aCHCl3.Non-H atoms are drawn at the 50% probability level.

Figure 2 .
Figure 2. Perspective view of the non-hydrogen atoms of rings A-F viewed parallel to the plane of ring C. Key atoms are labeled.