Just Musing…


Well, it has been rather quiet around here….the RajcaLab Weblog. We had four posts on Helicenes during the past month and a half period. I personally had fun writing these posts. I dunno if this was noticed… it wasn’t really all about Helicenes but rather about how the research projects were developed and how to figure out different ways to solve problems along the way. There were quite a bit of details in these posts, which could be boring to some but might be interesting and helpful to others. I hope at least those extra stuffs that were not written in the journal articles are interesting. Anyhow, I feel that these posts have signified the RajcaLab weblog, with some sort of identity….

It has been interesting two weeks since my last post. Having to resubmit our two NIH proposals in the past ten days, and then reading about the rich NIH investigators, I was in the mood to do something I never thought about before… drawing some cartoons….Here is my first strip.

cartoon_lotto1.gif

That’s it…my weekend musing….

Posted in Around the Lab, Uncategorized

Carbon-Sulfur [11]Helicenes: Syntheses, Structures and Properties


*This is the 4th post of the helicene series*

Yeah, asymmetric synthesis of carbon-sulfur [7]helicene was great! But with the iterative synthetic scheme, it seemed we could keep going and going…forever….ha ha ha,…on paper, of course. It was kinda fun… plugging away the connection/annelation sequences…go on and on in many different ways. Different routes were on the drawing board, but which ones to go after? A-ha, another fun game of pick and choose!

At a glance, it may seem easy to get to the [15]helicenes with the connection/annelation sequence of those [7]helicenes we just prepared. Yep, we have been trying to do just that, but….easy said than done…. Well, the retrosynthetic scheme for [11]helicene looked pretty good too. Have a look!

carbon-sulfur [11]helicene retrosynthetic scheme

Route A seemed straightforward…we already had in hands the annelated trithiophenes…. We could try di-connection—forming two β-β linkages between the annelated trithiophenes—by Suzuki and/or Negishi cross-couplings, followed by di-annelation, to give [11]helicene. But that didn’t work, even with the use of very active Pd-catalytic systems at mild conditions.

We moved on to consider Route B, which looked like a win-win strategy…. at least we should be able to get to [5]helicene! At this point, we also thought about how to introduce solubilizing groups…’cause…long carbon-sulfur annelated thiophene oligomers would likely to be very insoluble, as rock…. Having the alkyl chains at the terminal α-positions were the only possibility. We thought also that the β-β cross-couplings might be more favorable for the coupling between the relatively less hindered monothiophene and the annelated trithiophenes, as well as the coupling of those thiophenes functionalized with more robust alkyl chains, rather than with labile TMS-groups. Great! We went after Route B and started working on the synthesis of the [5]helicene.

carbon-sulfur [5]helicene synthesis

The connection step, the Negishi cross-coupling between functionalized monothiophene and annleated trithiophene, went rather smoothly. Once again, the annelation step gave us some headache!!!…the yields of [5]helicene were highly variable. What was going on? To understand this problem, we monitored the formation of the α,α’-dilithiated intermediate using 1H NMR spectroscopy with double solvent suppression, in which 2% of benzene-d6 was added to the reaction mixture in ether. This allowed us to optimize the formation of the dilithiated intermediate before the addition of (PhSO2)2S. With this procedure, we got ~40% isolated yields of the TMS-protected [5]helicene; deprotection of the TMS by treatment with trifluoroacetic acid (TFA), underwent in a nearly quantitative yield, to give [5]helicene.

The win-win strategy paid off, we got the new [5]helicene functionalized with the alkyl chains, the n-octyl groups, at the terminal α-positions. The synthesis was published in Synlett.

At this point, we thought….good chance to get to [11]helicene. So we went ahead and continued Route B, mono-annelation route; we tried Cu(II)-mediated oxidative homo-coupling of [5]helicenes. Unfortunately, the yields of the homocoupling product were not so good (35-40%); it might be that the β-thienyllithium intermediate of the Br/Li exchange on the [5]helicenes was highly unstable. We then tried different methodologies and found that Pd-catalyzed reductive CC-homocoupling was an efficient approach to the formation of sterically hindered β-β thiophenes linkage under mild conditions. It turned out that this approach to the connection step worked well for both Route B (mono-annelation) and Route C (tri-annelation) for the synthesis of [11]helicene. Here is the synthetic scheme.

carbon-sulfur [11]helicene synthesis

We were quite surprised with the results…. Route B synthesis, mono-annelation route, lead to (-)-[11]helicene, plus byproduct (-)-Dimer….. Route C synthesis, tri-annelation route, gave us the tri-annelations product (+)-[11]helicene and the di-annelations product dimer of [5]helicene. Interesting…..mono-annelation and tri-annelation lead to [11]helicene with opposite configurations!!!…..read the JACS communication for detail… But here is the beautiful structure….

carbon-sulfur [11]helicene

Just a brief note…. evidence of cross-conjugation nature of the π-systems in [7] and [11] helicenes was provided by the nearly identical electronic absorption onsets and near convergence of the first oxidation potentials. This result was confirmed by FT-Raman/IR studies on [7]helicene, [11]helicene, and annelated trithiophenes, a collaborative work with Professor J. T. Lopez Navarrete group at the University of Málaga and Professor Rainer Glaser at the University of Missouri-Columbia, who carried out the density functional theory (DFT) computations on these structures. This was published in J. Phys. Chem. C. On the basis of the absorption onsets at 355-356 nm, the optical band gap (Eg) of approximately 3.5 eV was estimated for the (C2S)n helix polymer.

Can you believe? These helicenes were mostly synthesized by one man, Dr. Makoto Miyasaka….talent, hardworking, dedicated postdoc. Ah, he basically put to rest the argument about the definition of “hardworking” habit in our lab….simply by his example…. Thanks, Mako, and we wish you the best in your new research frontier at Kanagawa U and in your future career.

OK, definitely there are more interesting helicenes but we will take a break from this subject….I’m a bit tired…of the same….


Read more about Carbon-Sulfur [11]Helicenes…

  • Makoto Miyasaka, Andrzej Rajca, Maren Pink, Suchada Rajca, “Cross-Conjugated Oligothiophenes Derived from The (C2S)n Helix: Asymmetric Synthesis and Structure of Carbon-Sulfur [11]Helicene“, J. Am. Chem. Soc., 2005, 127, 13806-13807 (Web Release Date: September 20, 2005), DOI:10.1021/ja55414c.
  • Makoto Miyasaka and Andrzej Rajca, “Synthesis of a Short Carbon-Sulfur Helicene: Pd-Catalyzed Cross-Coupling at the β-Positions of Thiophenes”, Synlett (Cluster Issue, invited) 2004.177-182. [Abstract]
  • Reyes Malavé Osuna, Rocío Ponce Ortiz, Víctor Hernández, Juan Teodomiro López Navarrete, Makoto Miyasaka, Suchada Rajca, Andrzej Rajca, Rainer Glaser, “Helically Annelated and Cross-Conjugated β-Oligothiophenes: An FT-Raman Spectroscopic and Quantum Chemical DFT Study“, J. Phys. Chem. C., 2007, 111, 4854 – 4860 (Web Release Date: January 18, 2007), DOI:10.1021/jp0677344. [animation]
Posted in Chiral, Helicene

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

Posted in Chiral, Helicene

Carbon-Sulfur [n]Helicenes: The Beginning.


*This is the second post of the Helicene series*

An unexpected discovery…that would be wonderful… But sometimes one research project could lead to another unexpectedly…. This was how we started the carbon-sulfur helicene project. So, when carrying out research projects, in addition to keeping our eyes wide open, we keep our mind open too.

Here is the story. In the mid 90s, one of the two major research projects in our lab was the synthesis and study of chiral conjugated π-systems with high configurational stability. Our focus was on derivatives of tetraphenylene.

tetraph_1.gifhorse.gifActually, tetraphenylene is an achiral, saddle-shape molecule derived from four phenylenes that are ortho-annelated to form an eight-membered ring in the center of the molecule. And, oh, I should mention that we gave it nickname as “horse”. You see, the symmetry of the tetraphenylene molecule may be broken by substitution or ring annelation to provide chiral π-conjugated systems with extraordinary high barriers for racemization. So, for a while tetraphenylene was a workhorse in our group… Visit this site for more information.

Anyway, we can’t keep doing the same things for a long, long, time, it’s boring, right?

So, in 1999 we started to explore conjugated π-systems of thiophenes. At that time, α-oligothiophenes were already quite popular in organic materials research field.

annelation.gifWe first looked into various modes of annelation of thiophenes using simple computational models. In α-oligothiophenes, the thiophene rings are connected at α-positions, forming a linearly extended, conjugated π-system. Ring annelations of such oligothiophenes would lead to a planar, rigid structure of quasi-linear oligomers (thienoacenes). We noticed that there were only a few reports of β-oligothiophenes and tetrathienylenes, which are thiophene-analogues of tetraphenylenes, aha…, our horses. Those structures in our consideration were achiral β-tetrathiophenes and its annelated analogue, an approximately planar cyclic β-octathiophene or [8]circulene. Then we moved on to consider analogous “defective” structures of [8]circulene missing one sulfur (seven annelated thiophene rings), surprise! surprise!, we got to see a on a computer screen a beautiful structure of helical β-heptathiophene. The space-fill was breathtaking! We were even more elated when we realized that such structure could be extended to all-thiophene, or carbon-sulfur, [n]helicenes, which could be viewed as fragments of a (C2S)n helical polymer. Take a look…(click the picture to see 3D model)

helix21.gif

It was exciting to come up with the unique conjugated π-systems of electroactive oligothiophenes helical structures. As we know, [n]helicenes possess some of the strongest intrinsic chiral properties. So, these electroactive carbon-sulfur [n]helicenes may provide both extraordinary chiral properties and optical transparency, which are desirable properties for organic optoelectronic materials and devices.

OK, that was great! We began to focus our attention on the carbon-sulfur [n]helicenes.

But could we synthesize such molecules?

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


Note:

  • The longest oligothienoacenes, octathienoacene (eight fused thiphene rings), was reported by the research group at Nagoya U. in 2007. Chem Euro J., 2007, 13, 548. 10.1002/chem.200601064.
  • The carbon-sulfur [8]circulene was claimed by the research group at Moscow State U. in 2006. The title of the article was “Sulflower”: A New Form of Carbon Sulfide, and it was highlighted as the Angewandte Chemie journal cover. (Angewandte Chemie International Edition, 2006, 45, 7367; doi:10.1002/anie.200602190).We would love to congratulate the authors for their work but there was a concern. First, the reported red color was a surprise; the cross-conjugated π-systems, [8]circulene, should be colorless. Second x-ray powder diffraction was reported, not single crystal x-ray structure…. Interestingly, a few days after this article appeared, an e-mail, the subject “wilted sulflower?, arrived, so we were not alone!

My personal note (that is, come after me, not the RajcaLab):

  • Wanna publish in Angewandte? Hype up with some fancy figures and catch words, ah the Angewandte’s songbook…And hey, a doll was published there, which seemed to catch Excimer off guard!

Posted in Chiral, Helicene

Ah, Those Aesthetically Pleasing Structures …. [n]Helicenes


Helicene was recently posted by Molecule of the Day as example of chirality. The post included the link to the Wikipedia page that badly needed updated information. So, when you get to Wikipedia, keep in this in mind…you may miss tons of important stuffs…

Since helicene is one of the two major research projects in our group, we will take on to fill in some information.

Actually, the first racemic [n]helicence, [6]pyrrolohelicene was reported in 1927, followed by the racemic [5]helicence in 1933.

helicene1.gif[n]Helicenes structures possess n angularly (ortho) annelated (fused) aromatic rings, in which the steric repulsion of terminal rings force distortion from planarity, leading to helical π-conjugated structures. These molecules possess some of the strongest intrinsic chiral properties. Syntheses of structures with such high degree of ring annelation, and with significant strain are challenging. So, it took a long period of 23 years later before the first successful synthesis of non-racemic [6]helicene was reported by Newman and Lednicer in 1953.

14helicene_1.gif15thiahelicene_1.gifDuring the 60s and 70s, photochemical syntheses were developed, such method provided numerous [n]helicenes, with [14]helicene as the longest structure consisting of benzene rings. Various [n]helicenes consist of alternating benzene and thiophene rings were also synthesized by the photochemical methods, with the [15]helicene as the longest structure. The photochemical syntheses provided helicenes in low/moderate yield and with limited functionalities.

Katz group at Columbia have developed very efficient non-photochemical, gram-scale syntheses of functionalized enantiopure [n]helicenes (n = 5, 6, 7).

katz_helicene1.gif

Recently, two novel classes of helicenes were reported: [n]heliphenes by the Vollhard group at UC-Berkeley and carbon-sulfur [n]helicenes by our group.

helipcene_2.gifcs_helicene_2.gif

More posts will follow…perhaps a series of posts on each class of helicene structures.


  • Visit this site to see more cool carbon-sulfur helicene structures.
  • Recent review articles to read…
    • Andrzej Rajca, Suchada Rajca, Maren Pink, Makoto Miyasaka “Annelated, Chiral π-Conjugated Systems: Tetraphenylenes and Helical -Oligothiophenes”, SynLett, 2007,1799 – 1822 (account, invited) [Abstract].
    • Tomás Torroba, María García-Valverde, “Rigid Annulated Carbon-Sulfur Structures”, Angew. Chem. Int. Ed., 2006, 45, 8092-8096. [Abstract]
    • Shawn K. Collins, Martin P. Vachon, “Unlocking the potential of thiaheterohelicenes: chemical synthesis as the key”, Org. Biomol. Chem, 2006, 4, 2518-2524. [Abstract]
    Posted in Chiral, Helicene

    One Month Old, I am Just a Baby Blogger


    Exactly one month ago today, I started this weblog. One month old, I am just a baby blogger, still learning and developing. Maybe it is too early to say how productive this weblog will be. But, like we usually do when carrying out a research project, it is good to take a look at how we are doing along the way. OK, let’s take a look at the stats so far.

    Blog Stats: Total Views: 231; Best Day Ever: 23 — Sunday, January 13, 2008
    Totals: Posts: 6; Comments: 12; Categories: 7
    Spam: Akismet has protected your site from 1 spam comments

    Glad that we have 231 hits, not a big number, not that we expect the big number anyway, just hope the visits were worthwhile for those who stopped by. Hey, we even had the visits by blogger gurus, Jean-Claude Bradley, Mitch, and Ψ*Ψ, and hey, thanks for taking time to leave the comments. As expected, the most visits were referred from our group homepage.

    I still hope to have other lab members to join the fun with this weblog. I have approached a couple guys but so far no one jumped in yet. Heck, I don’t even know if they read my posts! I think blog, if utilized properly, is one of the great platforms for developing important skills such as writing, presentation, communication, and more importantly, for developing ideas and presenting them. I admire those, especially undergrad and grad students, who choose to write blog posts rather than doing other things, like playing video games, watching TV, etc. For me, this blog is more or less a way to relieve boredom…from the good life in the Corn Nation… Learning and developing should be good medicine for that! At the same times, I thought documenting some activities in and around the lab would be a good idea, especially I hope to write about some interesting experiences and technical details of some experiments that usually are not included in papers. I think these are good materials for blog posts and they might be of interest and helpful to some. All in all, this blog is like one bullet for two birds!

    Over all evaluation–with a few hits and only 6 posts, plus my failure to convince anyone in the lab to join in–I would give myself a D grade. What grade would you give me?

    Posted in Uncategorized

    A Long, Tough Road Toward an Organic Magnet


    Yes, preparation of practical organic magnet remains a very difficult, challenging problem. Many may believe it is impossible, some may have doubt, some may say–waste of time! It is not easy to go against the nature…those electrons are happy to be paired, coupled their spins in opposite direction (antiferromagnetic coupling), forming chemical bonds, so why bother… Like most of us, loneliness is hard, so most going with the mainstream. Look at the history, Mose Gomberg got scoffed at for his report on the triarylmethyl radical in 1900 and he had to fight for over the period of 15 years to defense the free radical concept. And we all know the impact of his discovery, but no, Gomberg is not on the list of Nobel Laureates in Chemistry1. One thing I wonder though, why Gomberg ended his paper with this interesting statement.

    gomberg_1.gif

    (M. Gomberg, “An Instance of Trivalent Carbon: Triphenylmethyl’’, J. Am. Chem. Soc, 1900, 22, 757-771 doi:10.1021/ja02049a006)

    Beside that strange statement, Gomberg’s courage gives us motivation to forge forward, toward the ultimate goal of organic magnet. It has been a long and tough road but we have made good progress.

    At the current stage, we know more or less how to rational design structures with a large number of strongly interacting unpaired electrons that give rise to net ferromagnetic couplings (Magnetic Ordering in an Organic Polymer, Science, 2001, 294, 1503-1505, doi:10.1126/science.1065477). It took us 13 years to get this far, 101 years since Gomberg reported the first organic radical. Here is the timeline of the development2

    apoc_rad1.gif

    The triarylmethyl polyradicals are unstable; they have to be handled at below 170 K in absence of oxygen. The magnetic ordering temperature of the triarylmethyl-based polymer at 10K is too low for any application. To make a practical material, we must implement the structure design with organic radicals (spin units) that are stable at normal working condition (on air at room temperature), while maintaining strong ferromagnetic couplings to reach ordering temperature above room temperature. These are two critical benchmarks we are striving to obtain.

    stable_rad.gifThere are only a few known highly stable organic radicals. Currently, we are working on the nitroxides and aminyls, following the bottom-up approach to prepare and study high-spin polyradicals that are stable on air at room temperature. Once again, we will learn, step by step, laying a solid foundation. We hope to find a way to reach our ultimate goal of an organic magnet that we will stick on our refrigerator doors…. Along the way, we will take advantage of what we have learned to prepare various nitroxides and aminyls that process good solubilities in aqueous solutions and investigate them for magnetic resonance imaging (MRI and EPRI) applications. For more information, visit this site.

    1Interesting discussion about this subject: Lennart Eberson, “Gomberg and the Nobel Prize”, Advances in Physical Organic Chemistry, 2001, 36, 59-84.

    2Learn more about this development here and here (the site is old and should be updated soon) and from the following review articles: A. Rajca, “The Physical Organic Chemistry of Very High-Spin Polyradicals”, Adv. Phys. Org. Chem., 2005, 40, 153-199; N M Shishlov, “From the Gomberg radical to organic magnets“, Russ Chem Rev, 2006, 75, 863-884 doi:10.1070/RC2006v075n10ABEH003621.

    Posted in organic radical
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