Posted by: SR | February 23, 2008

Carbon-Sulfur [7]Helicenes: Syntheses, Structures and Properties

*This is the third post of the Helicene series*

Alright, we had the beautiful all-thiophene, or carbon-sulfur, [n]helicene structures drawn out. The question was…how to make them?

Organic synthesis can be very arduous and challenging, especially for molecules with complex structures and those with such high degree of ring annelation, as well as with significant strain. But that’s what we do…synthesize new cool structures with specific functionalities and investigate their properties…

We first analyzed the retrosynthetic scheme for carbon-sulfur [7]helicene and came up with an efficient synthetic scheme, an iterative synthesis based on two key steps: (1) connection, by carbon-carbon homocoupling between the β-positions of the thiophenes, and (2) annelation, by formation of two carbon-sulfur bonds between the α-positions of the thiophenes. And we could easily recognize that sequences of these iterations (connections and annelations) can provide the carbon-sulfur helicenes.

Carbon-Sulfur [7]Helicene retrosynthetic scheme

The mono-annelation pathway looked promising, so we gave it a try. It turned out that everything worked and we accomplished the racemic synthesis of the carbon-sulfur [7]helicene in a short period of time. That would have been hard to believe…without having the beautiful X-ray structure to prove it! The manuscript with title “Annelated Heptathiophene: a Fragment of a Carbon-Sulfur Helix” was published in Angew. Chem. in 2000.

Carbon-Sulfur [7]Helicenes SynthesisCarbon-Sulfur [7]Helicenes X-ray Structure

The synthesis was interesting. The connection steps went smoothly. Then, we were a bit surprise that the dibromo dithiophene (product of the first connection step) could be selectively di-protected with TMS-groups at the α-positions that were proximate to bromines without problem. The annelation steps were a bit tricky…you know… we were lucky at the beginning to get the isolated yields of about 65% for the first annelation step. But then when we went back to try to optimize the reaction conditions, especially on larger scales, the yields were lower, the average yield was about 40%. A few students and postdocs did several dozens of attempts to repeat the reaction. We tried many different things….. changing stirring speeds, controlling temperatures, etc. We knew from 1H NMR spectra (with double solvent suppression of non-deuterated solvent) of the reaction mixtures and the deuterium quenching experiments that the problem was not with generation of α,α’-dilithiated intermediate. Then we thought there might be problem with the addition of solid bis(phenylsulfonyl)sulfide ((PhSO2)2S). So, we again tried many things…..adding very slowly, grinding the solid to very fine powder, suspending the solid in solution and sonicating it before adding…Carbon-Sulfur [7]Helicenes Synthesis: Dimers, Trimers X-ray structures…and so on….. Ah, these drove us nuts!!!!! To think about it, in the annelation steps, two competing reaction pathways were possible: cyclization vs oligomerization. Although we did the annelations in relatively dilute solutions (0.01 M), dimers, a trimer, and polymers (about 30% yields) were still isolated from the reactions; we even got X-ray structures of dimer 1 and 2 and trimer.

It’s the rule — experiments must be reproducible — otherwise the results are not acceptable. Well, in this case, we had to compromise on the lower yield and move on… Oh, well, we had a much more challenging task ahead… asymmetric synthesis…

For the asymmetric synthesis, we relied on our experience with the asymmetric synthesis of tetraphenylenes, based upon (-)-sparteine and copper dibromide mediated homocoupling of 2,2′-dilithiobiaryls. So, we decided to see first if using (-)-sparteine in the final annelation step would work.

Carbon-Sulfur [7]Helicenes Asymmetric Synthesis

Yep, we got the excess of (-)-enantiomer, (-)TMS-[7]helicene. However, the overall yield calculated for the enantiomerically pure product was relatively low and we also found that higher yields were associated with lower ee’s and vice versa. Although extensive use of 1H NMR spectroscopy to follow directly the progress of the reaction gave us clues the mechanism of asymmetric induction, more complete understanding of the mechanism was attained in Makoto Miyasaka’s synthesis of higher helicenes…as it will be described in the fourth post of the Helicene series….

The CD spectra for the (-)TMS-[7]helicene showed characteristics of left-handed (M)-helicenes. This result was confirmed by vibrational circular dichroism studies, which were carried out in collaboration with Prof. L.A. Nafie and T.B. Friedman at Syracuse U. We also determined that the (M)-(-)TMS-[7]helicene was configurationally stable at room temperature and it racemized at 199 °C with a half-life of about 11 h.

Because the asymmetric synthesis provided only (-)TMS-[7]helicene in low yield, we then tried to isolated the enantiomers by resolution with menthol-based siloxanes. This method worked quite well, the diastereomers (-)- and (+)-[7]helicene, with two (-)-menthol moieties, were readily separable by preparative TLC, normal phase silica.

Carbon-Sulfur [7]Helicenes Resolution

Although the [7]helicene enantiomers were crystalline, attempts to obtain their X-ray crystal structures were not successful, even with the use of synchrotron radiation. For X-ray structure of the racemic [7]helicene, the molecules pack in “p-stacked” columns extending along the crystallographic a-axis and there were multiple short intermolecular S…S contacts, which may suggest an effective intermolecular electronic coupling in two-dimensions.

The fourth post of the Helicene series, Carbon-Sulfur [11]Helicenes: Syntheses, Structures and Properties, will follow….

Read more about Carbon-Sulfur [7]Helicenes…

  • A. Rajca, H. Wang, M. Pink, S. Rajca, “Annelated Heptathiophene: a Fragment of a Carbon-Sulfur Helix”, Angew. Chem. Int. Ed., 2000, 39, 4481. [Abstract]
  • A. Rajca, M. Miyasaka, M. Pink, H. Wang and S. Rajca, “Helically Annelated and Cross-Conjugated Oligothiophenes: Asymmetric Synthesis, Resolution, and Characterization of a Carbon-Sulfur [7]Helicene”, J. Am. Chem. Soc., 2004, 126, 15211-15222 (Web Release Date: November 2, 2004) DOI:10.1021/ja0462530

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