Alright, Fall semester is upon us once again, starting on Monday! Wow, so many happy smiling faces around here.  Starting graduate school is surely exciting. It’s a new beginning…forget about the past record, it is all about the new ride.….The road toward the finish line could be long and bumpy or could be fun and rewarding. One of the critical steps is choosing the right vehicle for a fun ride….be sure to join the right research group! Thanks to the internet, plenty of good advices and tips on how to succeed in graduate school are just a few clicks away. Check these out…

• What makes a good PhD student?, G. Chenevix-Trench,  Nature 441, 252 (May 2006),  doi:10.1038/nj7090-252b.
• Ten Simple Rules for Graduate Students, J. Gu, P. E. Bourne, PLoS Computational Biology, e229 (November 2007) doi:10.1371/journal.pcbi.0030229.  (this was also posted by Amanda and Mitch)
• Following the law, I. P. Herman, Nature 445, 228 (January 2007) doi:10.1038/nj7124-228.

Share yours…..

Yes, big smile….and I was in the mood to draw some cartoons….

Huh, I am right back into blogging?

Hello, if you are considering graduate program in Chemistry, perhaps you should take a look at Nebraska. Hey, just look at the map….

Do you see…… the Nebraska Advantage?

No, I am not making this up! “Look at a map of the United States and you’ll immediately notice one of Nebraska’s biggest advantages — location!”, you can find this statement here.

And the slogan…NEBRASKA…the good life….

Yeah, life is pretty good around here, especially for grad students. The current annual stipend for a TA is approximately $21,000. Applicants with outstanding records are eligible for additional fellowships such as Othmer ($7,500/year) and Chancellor’s ($3,000/year). The Nebraska Advantage….relatively low cost of living in Lincoln, a friendly college town and the capital city of Nebraska…. take a virtual tour.

Yeah money is not everything. But hey, you may laugh at this (I did too), the University of Nebraska-Lincoln (UNL) rates 6^th in U.S. News ‘Most Popular College’ list, and it is the top most popular public university (News). There must be good things about the Big Red!

Seriously, we can do great Chemistry research here at UNL. Take a look at the Chemistry building, huge, Hamilton Hall. Take a tour. We have pretty good Research Instrumentation Facility, and I am sure the organickers would really love this: plenty of NMR time slots! And of course in the RajcaLab, there are many exciting cool research projects to work on. We have many sophisticated instruments in our lab—SQUID, EPR, CD… There are 7 vacuum lines and 3 gloveboxes for organic synthesis. Wanna see our lab, take a tour.

Remember, the purpose of going to graduate school is to learn, especially to develop the experimental skills and techniques, as well as to hone your problem solving abilities. In our group, you will learn many things…from multi-step organic syntheses (in particular those 1-2-milligram scale in which small equivalent amount of reagents are added…..by counting drops!), handlings of air and moisture sensitive materials, magnetic characterizations and so on…. Another big advantage… you will learn how to do things correctly from close interactions in small research group, like….learning directly from a master. Life is easier if you don’t have to learn from your own mistake, especially for inexperience undergrads.

So, are you ready? APPLY NOW. And you may be invited to visit us…

Still have questions…..post them here…. or contact me directly at srajca1 at unl dot edu.

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.

That’s it…my weekend musing….

*This is the 4^th 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!

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.

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.

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….

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 (E_g) 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….

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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]

*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.

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.

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……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.

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.

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….

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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

*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.

Actually, 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.

We 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)

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….

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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!

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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!