musings on music and life

September 8, 2016

Latest publication

Filed under: Chemistry — Tags: — sankirnam @ 11:06 am

I just saw yesterday that another paper has been published based on work I did in my PhD. I was aware of this because the student wrapping this project up was in touch with me, writing up the paper from one of my thesis chapters and requesting copies of the characterization data (NMR, GC-MS, and HRMS) for all the compounds I had synthesized. This paper is the continuation of the Organic Letters paper that was published several months ago, and I’m relieved that I finally have a first-author paper, even if it is only in Journal of Fluorine Chemistry (which has an impact factor of 2.2), and coming a bit too late (over a year and a half after getting my PhD!) to be useful. But hey – it’s another line under the “publications” section in my CV, and at this point, anything helps.

EDIT (4/13/2017): Personal link to paper, valid until June 1, 2017.

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April 6, 2016

Classics in Organic Chemistry, Part I

Filed under: Classics in Organic Chemistry — Tags: — sankirnam @ 1:07 pm

I’ve decided to start a new series of posts where I discuss classic old papers from the organic chemistry literature. Of course, my focus will be on Physical Organic Chemistry, but anything that I deem important will be discussed.

I’ve decided to start this series with a paper by Prof. J. C. Martin from 1979. I gave a brief overview of his work earlier; I remember coming across it when I was studying for my qualifying exams and got instantly hooked. The nature of his work is fascinating and unorthodox, and led to developments in “elemento-organic” chemistry; that is, organo-iodine, organo-sulfur, organo-selenium, organo-tellurium, organo-bromine, organo-bismuth, and many other new types of chemistry. These were all developed around a growing understanding of the nature of “hypervalent” bonding. Previously, VSEPR theory invoked the use of s,p, and d orbitals in order to generate trigonal bipyramid and octahedral geometries. However, this was slowly coming under attack, and the “hypervalent” bond, which is the apical-apical bond in trigonal bipyramid and octahedral complexes, came to best be described as a “3-center 4 electron” system stabilized by electronegative ligands. Our knowledge of this type of bonding is still being refined by theoreticians today.

The significance of this manuscript is that it describes the characterization of the first 5-coordinate compound of carbon! This is distinct from the “onium” ions such as CH5+, that are best described as “5-center 8-electron systems”. In this case, you’re actually trying to cram extra electron density onto the central carbon so that it has 5 formal bonds (although one should recall that in the perfect SN2 transition state, the total number of bonds is still 4, as the bond-forming and bond-breaking events are synchronous).

fig1

The synthesis of this compound is a few steps from the starting 1,8-dichloroanthraquinone, which is commercially available. Previous studies with similar model compounds had shown they underwent a “bell-clapper” rearrangement; the result being that the central carbon underwent reversible binding with the apical atoms, and the resulting compounds had a fluxional structure with a moderate activation enthalpy (10 kcal/mol) for rearrangement. In this case, the asymmetric structures and the p-quiniodal dicationic structures are ruled out on the basis of 1H-NMR shift assignments.

However, more concrete evidence in favor of this structure is lacking. As Prof. Martin mentions in the communication, they were unable to grow X-ray crystals in order to provide conclusive proof of structure. This is consistent with my experience; growing X-ray crystals of charged substances is incredibly difficult, as these tend to be more sensitive to handle. 13C NMR evidence was also lacking, and was only published much later; the follow-up articles to this communication were only published in 1993! The 13C NMR peak of the central carbon is δ 109.3, which is in the range for an sp2 carbon, but at the same time not shifted quite as dramatically as one would expect for an extremely electron-rich carbon (remember, it now has 10 electrons instead of 8)! Theoretical studies would serve as a very useful complement to this extremely nice experimental work. For instance, it would give a useful handle on the activation energy to desymmetrization, as well as what orbitals are actually involved in bonding. J. C. Martin also published some follow-up electrochemical studies on this compound as further proof of the hypervalent nature of the central carbon atom. Further work in this area is being continued by Prof. Kin-Ya Akiba in Japan; I remember seeing some nice experimental work published by him over the years attempting to isolate different types of “hypervalent” boron and carbon compounds.

In any case, this is a really nice piece of work, and all serious students of organic chemistry should be aware of this. I think that is probably my main motivation for this series of posts – I’ll be writing about papers that all students of organic chemistry should be aware of at any level (whether it is high school, bachelors, masters, PhD, postdoc, or professional). Of course, this will be biased towards what I am aware of and what I feel is important, so bear with me!

January 28, 2016

Kudos for methanol!

Filed under: Chemistry — Tags: , , — sankirnam @ 8:53 am

I was rather pleased to see that my PhD advisor’s work had made the front page of Reddit this morning. Reddit is one of the most viewed sites on the internet, and the presence (or absence) of topics on this website serves as a heuristic for what is in the mind of the public. The quality of the discussion in the Reddit thread is also very good; it was heartening to see that everyone (at least, nerds with internet access) has their facts correct.

I have talked in some depth about the Methanol Economy before; I strongly believe that this will be a viable energy solution for the future. Of course, this isn’t the only solution, as it has to be used in tandem with a mix of energy sources, including solar, wind, hydroelectric, and nuclear, depending on location. Methanol serves as a very convenient energy carrier and energy storage medium due to it’s convenient physical and chemical properties.

Unfortunately, I do not have journal access right now, so I cannot comment on the article. I do remember that this project has been going on for a long time; it was started back when I was still there, around 2014 or so. This seems to be a continuation of work done earlier, in which it was observed that polyamines (specifically ethyleneimine) adsorbed on silica could reversibly adsorb CO2. This CO2 adsorption process was then combined with CO2 to methanol reduction in the same flask. Since I don’t have journal access right now, I don’t know how good the yield, selectivity, or catalyst TON (Turn Over Number) is. These numbers are critical to evaluating if this process is really a big breakthrough or just another incremental improvement.

January 1, 2016

Latest paper

Filed under: Chemistry — Tags: — sankirnam @ 7:31 pm

So this actually came out over a month ago, but I couldn’t get around to posting about it until now. Link for those interested. The sad part is that I currently cannot access this, even though it is my own work!

The research in this paper was developed as part of my thesis work on superelectrophilic activation, in order to develop new electrophiles for Friedel-Crafts reactions.

This is the only place where I can mention the contributions of an undergraduate student who worked with me on this project – Mr. Billy Stevens. I don’t know why his name was omitted from the list of authors on this paper, even though I had reminded my advisor to include his name multiple times.

This paper originated from work we had previously carried out on the superelectrophilic activation of acrylic acids; we found that they could undergo one-pot alkylation and cyclic acylation with arenes. Thus, we extended this work to include thiophenols, as sulfur can serve as an interesting nucleophile under these conditions. I optimized the conditions and prepared a variety of thiochroman-4-ones using crotonic acid; I was also able to extend this to the use of 4,4,4,-trifluorocrotonic acid for the synthesis of trifluoromethylated thiochroman-4-ones, which unfortunately is not included in the Org. Lett. paper.

I’m rather pleased to have a publication in Organic Letters. This is one of the premier journals in the field of organic chemistry, specializing in short communication-style reports, rather than full-length articles or reviews. Even though the journal started very recently (1999), it is very successful, has a high impact factor, and routinely publishes very interesting, highly-cited papers. At the NOS last year, I got a free Organic Letters shirt, among other things. I suppose wearing this shirt has probably resulted in me getting a paper in this journal, in some karmic fashion.

November 23, 2015

My thesis, for those interested

Filed under: Chemistry — Tags: , — sankirnam @ 10:57 pm

I was bored and during the course of my browsing, found the link for my thesis on the USC Digital Libraries.

It is interesting that USC changed the procedure for thesis submission; graduates no longer have to submit their dissertations to UMI Proquest, and in the process of making the whole process digital, it is no longer possible to order hard copies of the thesis (at least to my knowledge). Not that I wanted a physical reminder of the wasted years of my life…

November 2, 2015

My thoughts on the broad state of chemistry (2015 edition)

Filed under: Chemistry — Tags: , — sankirnam @ 12:34 am

I had to fill out a questionnaire regarding my thoughts on the broad state of chemistry as part of the 2nd round of a job application; I feel like some of what I’ve written is worth sharing. Of course, I’ve omitted anything that explicitly references the position.

2) Please identify three chemistry papers that have been published in other journals within the last year (excluding Nature and Science) that, in your view, would have been of the standard required for consideration in a chemistry journal being launched by [journal company]? Why have you selected these papers and who would you recommend as potential reviewers for each?

I think it is also worthwhile to demonstrate what would not be worth publishing, so I will include one example of an inferior quality manuscript here, as well as 2 examples of good papers.

  1. Synthesis and Characterization of 1,2,3,4,5-Pentafluoroferrocene – Karlheinz Sünkel, Stefan Weigand, Alexander Hoffmann, Sebastian Blomeyer, Christian G. Reuter, Yury V. Vishnevskiy, and Norbert W. Mitzel, Journal of the American Chemical Society, 2015, 137, 126. This paper describes the first successful preparation of pentafluoroferrocene, and while this may not have immediate practical applications, this is still worth publishing, especially since it represented a synthetic challenge, which is why it was not synthesized until now. Potential reviewers for this include Heinrich Lang, Ian Manners, and Janusz Zakrzewski.
  2. Experimental Limiting Oxygen Concentrations for Nine Organic Solvents at Temperatures and Pressures Relevant to Aerobic Oxidations in the Pharmaceutical Industry – Paul M. Osterberg, Jeffry K. Niemeier, Christopher J. Welch, Joel M. Hawkins, Joseph R. Martinelli, Thomas E. Johnson, Thatcher W. Root, and Shannon S. Stahl, Organic Process Research and Development, article ASAP. Work in process chemistry is also very important, but since this mainly happens in industry, a lot of work in this area goes unpublished. Publications like these should be published not only because they afford outsiders a look at industry processes, but also because it is important to promote safety and good practices, which is what this article is about. This features general, non-protected work that is relevant to all who do (or are considering doing) aerobic oxidation chemistry. Reviewers include Chris Senanyake (Boehringer Ingelheim), and anyone else working on process chemistry in industry.
  3. Simple Amine-Directed Meta-Selective C−H Arylation via Pd/Norbornene Catalysis – Zhe Dong, Jianchun Wang, and Guangbin Dong, Journal of the American Chemical Society, 2015, 137, 5887. This manuscript is an example of what should not be published. The experimental work is rather sloppy; when optimizing the reaction conditions, the authors do not state how they first came up with the “acetate cocktail” in the first place. That issue aside, this reaction is also highly impractical; nobody will use it not only because it involves an unusual ligand (AsPh3) as opposed to the more common phosphine or NHC ligands, but also because it requires super-stoichiometric amounts of other metal reagents (e.g. 4.5 equiv. AgOAc and 3.0 equiv. CsOAc). The consequence is that this reaction will never be scaled up. This reaction is not that original either, as Gaunt was the first to publish on directed meta-arylation back in 2009.

3) Can you list three research areas that are generating a lot of interest in chemistry at present? Which investigators are actively involved in pursuing these areas? (Ideally, one suggestion should come from your own area of expertise and the others from different aspects of chemistry.

  1. Organofluorine chemistry is generating immense interest in the chemistry community at present, so much so that practitioners talk of a “bubble”. Research that is not very novel or incremental at best is published in very high impact factor journals simply due to the involvement of fluorine. On the other hand, these statements should not imply that the field is not important; it is, which is why it is receiving so much attention lately. Several people are publishing in this area, including my Ph.D. advisor, Prof. G. K. Surya Prakash. Others include Veronique Gouverneur (Oxford), Tobias Ritter (Harvard), John Welch (SUNY-Albany), Jinbo Hu (SIOC), and Stephen DiMagno (UN-Lincoln).
  2. Organocatalysis is also a very active area of research in modern organic chemistry, and has really only developed over the last 15 years, even though the seeds can be found in publications from the 90’s, 80’s and 70’s. It continues to receive attention from the organic chemistry community and was prominently featured in the National Organic Symposium this year. Key investigators in this area include D. W. C. MacMillan (Princeton), Benjamin List (Max Planck Institute), Karl Anker Jørgensen (Aarhus), and Yujiro Hayashi (Science University of Tokyo).
  3. Cliché as it may seem, palladium catalysis is still a topic of current interest in chemistry. While reactions such as the Heck, Suzuki, and Negishi reactions are now well established in the chemists’ toolkit now (as exemplified by the Nobel Prize in Chemistry in 2010), there are still many orthogonal modes of reactivity that are being uncovered in this area. Melanie Sanford bought to attention the scope of oxidative Pd catalysis and the potential of Pd(II)-Pd(IV) catalytic cycles for organic and organometallic chemistry. Similarly, Jin-Quan Yu and Matthew Gaunt are also continuing to demonstrate new applications of Pd catalysis to solving problems in organic synthesis based on new ligand motifs and catalytic cycles.

4) Can you look through a recent copy of a top tier general chemistry journal and identify research topics that are currently not well represented. Please explain your thoughts on the importance of these fields (if any). How would you go about avoiding similar omissions in [chemistry journal]? Do you think that such omissions are important?

One example of a topic that is not well represented today is origin-of-life chemistry. The origin of life on this planet is a puzzle that is purely chemical in nature, and so chemists are uniquely poised to solve it. One way to remedy this is to seek out chemists doing research in this area and invite them to publish in this journal. However, the number of potential topics in chemistry in practically infinite, and so this is not really a long-term solution. On the other hand, this is what is beautiful about chemistry. A journal will therefore always have topics that are omitted or poorly covered if its issues are to be considered truly representative of research in the field.

Lanthanide and actinide chemistry is also poorly represented at the moment. Some of the lanthanides have found use in organic synthesis (such as cerium (CeCl3) and samarium (SmI2)) as reagents or Lewis Acids. Their organometallic chemistry remains relatively unexplored, with only a handful of people doing research in this area, such as William Evans (UC Irvine).

5) Please identify three areas or topics appropriate for a minireview or review in [chemistry journal] and make suggestions for potential authors. On what basis did you choose the three topics?

  1. CO2 capture technologies and alternative energy derived from recycling CO2. This is an incredibly important topic, as it relates to global warming, which affects everyone on this planet. Potential authors include Prof. George A. Olah (USC), Robert Zubrin, Anne Korin, and R. James Woolsey, Jr.
  2. “Asymmetric olefin difunctionalization reactions”. These reactions are epitomized by the 3 Sharpless reactions, AA (Asymmetric Aminohydroxylation), AD (Asymmetric Dihydroxylation), and AE (Asymmetric Epoxidation). However, since then, there has been very little work done on developing other types of reactions in this class. Potential authors for a minireview on this topic include K. C. Nicolaou (Rice University), Scott Denmark (UIUC), and Noah Z. Burns (Stanford).
  3. “Hypervalent Bromine chemistry”. The chemistry of bromine in higher oxidation states (such as +3 or +5) or with multiple ligands has not been explored in depth. This area was pioneered by the late Prof. J. C. Martin (UIUC), and is now continued by Prof. Masahito Ochiai (University of Tokushima). Although the practical uses of this chemistry may be limited due to the necessity of using aggressive oxidizing agents (such as BrF3), it is nonetheless a fascinating academic topic.

5) In your opinion do you feel that chemistry is well represented in leading journals such as Nature or Science? Please give some explanation about how and why you came to this conclusion?

In general, whenever I look through an issue of Nature or Science, I am usually disappointed that there are usually 0-1 chemistry articles present. This is partly due to the interdisciplinary nature of the journals; pure chemistry articles are not perceived as “sexy” when compared to other, more applied fields. But there is also a self-selection bias present. Most of the chemists I know generally have an idea of the kind of work they would like to submit to Nature and Science, and so do not frequently submit manuscripts to these journals.

6) A key feature of [chemistry journal] will be the publication of unique discussion-type formats. An example would be differing perspectives written by experts, with the opportunity for online commenting by the community. Can you provide three potential topics/questions that would be of interest to chemistry academics and also non-chemistry experts such as economists, philosophers, government, funders etc? In each case, potential author candidates should be provided.

  1. “The current state of Organic Synthesis”. Many people have written on this topic over the decades, but this is something needs to be continually addressed by the organic chemistry community at large. What is the motivation for academic research in organic chemistry? What are the challenges that lie in this field? Potential author candidates include: Prof. Dieter Seebach (ETH), Prof. George Whitesides (Harvard), Prof. D. W. C. MacMillan (Princeton), and Prof. L. E. Overman (UC Irvine).
  2. “The current state of chemical education”. This is an important topic as it affects every student graduating with a degree in chemistry. In various courses, it will be worthwhile to examine what is relevant in school curricula and what has become outmoded. For example, in most general chemistry courses, why is the syllabus structured the way it is, with an overemphasis on analytical chemistry, and a lack of emphasis on qualitative methods? Also, one can discuss the mismatch between the academic production of chemistry graduates and the number of positions available in industry and academia; this is most clearly evident when looking at the employment statistics of PhD graduates. The contributing authors can literally be anyone who works in education (or academia) or has gone through it (which is basically anyone with a degree).
  3. “The current model of chemical research”. There are a lot of people who believe that advances in chemistry (or research in general) are made in small, incremental steps, and that is one of the justifications for having such a large research industry in the United States (consisting of thousands of undergraduates, graduate students, postdoctoral scholars, and university faculty in hundreds of universities and institutes). However, in my opinion, most major advances in science are quantum leaps, discoveries that significantly advance their field and cannot be predicted beforehand. These breakthroughs are usually not the result of incremental research. Examples are: Kary Mullis’ discovery of PCR, the “scotch tape” synthesis of graphene, and F. Sherwood Rowland’s observation of the ozone-depleting effects of CFCs. In this light, chemistry research would be observed to be hugely inefficient, and is it worth justifying on such a large scale? Potential author candidates could include: Nassim Taleb (author of The Black Swan), ACS (American Chemical Society) executives, as well as economists working in the US government.

8) What was your opinion on the recent Nobel Prize in Chemistry awarded on the 7th October 2015?

I have mixed feelings. On one hand, the topic that the prize was awarded for is tremendously important; understanding the mechanism of DNA repair allows us to better understand the aging process, as well as the proliferation, growth, and treatment of cancer. On the other hand, this topic is not really “pure” chemistry, and is more of a biology topic. One can say that it is a biochemistry topic, and that it lies in the intersection of the two fields. However, the result is that the contributions of practicing chemists to science and the welfare of humanity is overlooked each time the prize is awarded in this manner; this also affects the public perception of chemistry and chemists, and will result in the public thinking that chemists do not do anything of importance. On the other hand, this is where the future of chemistry is headed. Now that chemistry has matured, the next generation of research will be interdisciplinary.

I’m pleased to share that thanks to these answers, I was selected to the next round of interviews for this position! So hopefully that means I have written something of value of here. Readers, feel free to let me know what you think as well.

August 14, 2015

CBS catalysis…and trifluoromethylation shenanigans

Filed under: Chemistry, Classics in Organic Chemistry — Tags: — sankirnam @ 12:20 pm

In order to wash the previous paper from our minds, it is often good to step back and read some of the really important  manuscripts from decades past. One example is the classic 1987 JACS paper by Corey on the enantioselective reduction of ketones, which after this publication, came to be known as the “CBS” method, after the authors (Corey, Bakshi, Shibata).

In the introduction, Corey, Bakshi, and Shibata state that Itsuno had already discovered that mixtures of borane and chiral vicinal amino alcohols (derived from enantiopure amino acids) were very effective for the stereospecific reduction of ketones. However, Corey states that “reagent structure, scope, and mode of reduction has remained at a primitive level, limiting both application and further development“. Thus, they isolated the complex formed from borane and (R)-1-phenylethanol as well as borane and (S)-diphenylprolinol by vacuum sublimation.

CBS catalyst

The complex derived from prolinol and borane turned out to be extremely active, and Corey reports reductions of around 95% ee with >99% conversion at room temperature! The simplicity and practicality of this paper should be noted; according to Google, it has at least 1,200 citations! The catalyst derived from prolinol soon became commercially available from several vendors, and is now popularly known as the “CBS catalyst”. Interestingly enough, this can also be thought of as one of the early modes of organocatalysis, but the term does not appear even once in this paper. The use of prolinol here laid the foundation for the future development of the Hayashi-Jorgensen catalyst, which is now an exceedingly popular organocatalyst.

Upon typing this, I became reminded of a similar incident that occurred in the fluorine chemistry community while I was doing my PhD. One of the developments in trifluoromethylation chemistry that occurred during that time was the discovery of a copper-catalyzed trifluoromethylation of aryl iodides by Prof. Hideki Amii. The proposed mechanism involved the intermediacy of phenanthroline-ligated copper(I) complex [(phen)CuCF3], but that complex was not characterized or isolated. Prof. John Hartwig (UIUC, now at Cal) soon published a paper where all he did was synthesize the [(phen)CuCF3] complex and use that as a trifluoromethylating agent! In his talks, Hartwig claimed that using the pre-synthesized complex in this manner greatly expanded the substrate scope beyond what Amii reported, although he always skirted around the issue that he had taken a reaction that was previously catalytic in copper and made it stoichiometric in copper! Hartwig soon started a company based on this chemistry, selling the [(phen)CuCF3] complex, which is now known as “Trifluoromethylator“.

But really, is this any different than what E. J. Corey did in 1987 with Itsuno’s chemistry? I’m not trying to justify or defend Hartwig’s research, but there is a precedent for this kind of stuff, from a Nobel Laureate, no less. Having some distance from fluorine chemistry at this point gives me a valuable outsider’s perspective now, without which I would not have come to this realization.

August 12, 2015

Sweet sweet acetate cocktails

Filed under: Chemistry — Tags: — sankirnam @ 12:36 pm

I remember that this paper was trending when I was at the NOS a few weeks ago. Everyone I talked to was extremely derisive about this paper, and upon examining it myself, I share the same sentiments.

acetate_cocktail

Ugh.

Firstly, there is no real novelty in this reaction – why was it accepted by JACS? The authors are just trying to do a template-directed meta-selective C-H arylation using the norbornene (NBE) template, with an amine as a directing group. Gaunt did a similar meta-selective C-H arylation back in 2009, except he used a pivalamide as the directing group, and diaryliodonium salts as the arylating agents under Cu(I)-Cu(III) catalysis. The authors are trying to do a Pd-catalyzed meta arylation in this case.

One of the major issues with doing C-H activation in a Pd(II)-Pd(IV) catalytic cycle is that it is an oxidative process, and therefore one needs a terminal oxidant, otherwise no reaction will occur. In academia, the most popular choices are Ag salts, due to their solubility and ability to selectively conduct outer-sphere electron transfer with other metals. BUT… as one can see above, this reaction uses superstoichiometric amounts of silver – 4.5 molar equivalents! So while this reaction may be fine in microscale in the research laboratory, it will never be scaled up. This is what I call the “Jin-Quan Yu” approach, since a lot of his chemistry also uses excess amounts of silver salts as oxidants.

But the “acetate cocktail” part…wow. This really shows that the unfortunate post-docs or graduate students who developed this reaction really have no idea what is going on. They just “Hail Mary’d” it, threw in everything possible to make it work, and prayed for the best. I remember Prof. Karl Christe (who was on my PhD committee at USC), made a very memorable statement after sitting through a mediocre PhD defense:

When the reaction doesn’t work, add some Lewis Acid. 

If it still doesn’t work, add some Lewis Base.

If it STILL doesn’t work, add some dirt and pray!

July 4, 2015

#NOS2015

Filed under: Chemistry — Tags: , — sankirnam @ 12:30 pm

I got back from the NOS (National Organic Symposium) a few days ago, and am still recovering from the (slight) jetlag and that oh-so-familiar feeling one gets when they are living and breathing organic chemistry 24/7. The NOS is a biennial conference organized by the ACS Division of Organic Chemistry. I’ve wanted to go to this for a while, as the NOS has a rich history, and is the conference for organic chemists. Presenting here is considered far more prestigious (at least for organic chemists) than presenting at a national ACS conference. This year, it was held in the University of Maryland, College Park. The organizer was Prof. Marisa Kozlowski (UPenn), and she deserves full credit for organizing the event and making sure everything ran perfectly. I prefer attending these divisional symposia (such as the NOS and the Winter Fluorine Conference) because of the smaller size. This makes it easier to talk to people, as there is a higher chance you will run into them multiple times, and due to your common background, gives you a conversational ice-breaker (“so, which group do you work for?”, etc.), making networking infinitely easier. Plus, the lectures and chemistry being presented are top-notch as well!

2015-06-28 12.32.48

The NOS was preceded by the JOC editors’ symposium. This is also held every two years, and the last one was held at UC Irvine, and it was there that I rather incoherently babbled about chemistry for the whole world to see. The lecture in the photo above is by Prof. Olaf Wiest (Notre Dame Univ.) on his theoretical studies on Heck reactions.

2015-06-28 21.12.37

The art and practice of total synthesis is alive and well, judging by the quantity and quality of the posters in this session.

2015-06-29 09.26.27

The lectures were started off with a bang by Prof. D. W. C. MacMillan (popularly known as “DMac”). He is a brilliant presenter, and his unparalleled clarity of thought is evident not just in his approach to chemistry but also in the elegance and structure of his presentations. If people were afraid that the art of giving good organic chemistry lectures died with Prof. R. B. Woodward, fret not…

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This was followed by a lecture by Prof. Matthew Gaunt (Cambridge). He is most famous in my eyes for a rather interesting paper he published in Science in 2009 on meta-selective C-H arylation. While the reaction is unique and no doubt useful, the mechanism is still up for grabs. In this talk he presented methods for the synthesis of complex amines based on Pd-catalyzed C-H activation of bonds α or β to the nitrogen.

2015-06-30 10.34.57

Prof. Abigail Doyle (Princeton) then presented her work involving the combination of Ni catalysis and photoredox chemistry. This seemed to be the prevailing trend in the conference; Pd is out, Ni is in! And thanks to the advances in photoredox chemistry by MacMillan, C. R. J. Stephenson, Tehshik Yoon, and others, radical chemistry is making a comeback.

For those who don’t know, Abigail Doyle is particularly famous in organic chemistry circles because she got a tenure-track position at Princeton without having to do a postdoc! I emphasize that last statement because it is nearly unthinkable today; even industry positions are requiring a PhD and postdoctoral experience due to the oversaturation of PhD’s in the chemistry job market. It probably helped that Abigail did her PhD with Eric Jacobsen at Harvard; he has an excellent track record in placing his students at top academic institutions. I remember in my sophomore year at UCI (2005), the department hired 2 Jacobsen postdocs as tenure-track professors, Chris Vanderwal and Liz Jarvo.

2015-06-30 10.50.02

Shoutout to the Petasis reaction! This was developed by Prof. Nicos A. Petasis at USC; his hall and lab were very close to the one I worked in during my PhD.

2015-06-30 11.36.19

Prof. Kuiling Ding (Shanghai Institute of Organic Chemistry) gave a tour-de-force lecture on asymmetric catalysis. I had heard him talk before at USC several years ago, and this lecture was more or less on the same topic (asymmetric reactions with Ti-BINOL complexes). While the work he presented is not necessarily groundbreaking or novel, it is nonetheless tremendously important. He emphasized the fact that a lot of new reactions discovered in academia use unacceptably high catalyst loadings (1 mol % or more), and his work on high-throughput ligand screening enabled the development of new complexes for established reactions that are active even at loadings as low as 0.001 mol %; oftentimes, these would still maintain ee‘s > 95%! I’m sure Sharpless would be pleased, had he been present.

For those who don’t know, Kuiling Ding is the director of the SIOC, the premier chemistry research institute in China!

2015-06-30 20.13.38

2015-06-30 20.14.32

Prof. Larry Overman (UCI) was the keynote speaker of this symposium, since the Division of Organic Chemistry had awarded him the Roger Adams Medal (the highest honor of the DOC) in 2015. Prof. Overman is one of the rockstars of natural products total synthesis, and has a number of synthetic methodological breakthroughs to his credit as well, including the eponymous Overman Rearrangement, the Aza-Cope-Mannich reaction, and asymmetric Heck reactions. As a UCI chemistry alum, it is pleasing to see UCI getting more and more recognition!

2015-07-01 10.19.52

Mark Ondari (Dow Chemical) talked about their work in the synthesis of donor/acceptor molecules for applications in OLEDs. This was fundamentally different from all the other talks in that the emphasis was not about discovering something new; the primary concern was the development of reliable, scalable synthetic routes to the desired molecules in very high (>99.99%) purity.

2015-07-01 11.01.30

Prof. Kenichiro Itami (Nagoya Univ.) gave a great talk as well. I was pleasantly surprised at his accent (or lack thereof)! He talked mainly about one reaction, the para-selective C-H functionalization of aromatics. However, it was impressive how he had managed to leverage that one reaction to branch out into all the fields mentioned in the slide above. Using that reaction, he was able to develop (in conjuction with Prof. Steve Kay at USC) new molecules for the disruption of circadian rhythms in cells. He also showed some extremely interesting work on the functionalization of corannulene and other polycyclic aromatics, work he dubbed “nanocarbon chemistry”. Rather unexpectedly, the credits slide of his presentation blew everyone away, and was probably the highlight of the conference!

EDIT (1/17/2017): Video of Itami’s talk! Check out the video from 57:40 onwards.

2015-07-01 19.19.08

Prof. Kendall Houk (UCLA) talked about his recent theoretical work in probing the intimate details of cycloadditions. He began by reminiscing about the past, mentioning that the first NOS he had attended featured a heated debate between Prof. H. C. Brown (Purdue) and Prof. Saul Winstein (UCLA) over the classical/nonclassical nature of the 2-norbornyl cation! This debate was moderated by Prof. G. A. Olah, and one should remember that this was the period when physical organic chemistry was extremely hot and carbocations were trendy.

Prof. Houk also talked about the development of computational chemistry, acknowledging the contributions of people like Kohn, J. A. Pople, M. J. S. Dewar, and Karplus, Levitt, and Warshel.

2015-07-02 10.14.38

Wendy Young (Genentech) gave one of the concluding talks of the conference, detailing some of the work towards synthesis of new drug candidates at Genentech. She did happen to mention that they had an opening for 1 (only!) medicinal chemist – I’m sure that they are now swamped with applications.

I’m sure the Divison of Organic Chemistry will upload the lectures for public viewing later; I’ll update this post with the links once I get them.

June 3, 2015

Solvents

Filed under: Chemistry — Tags: — sankirnam @ 6:54 pm

Derek Lowe has an interesting post today on In The Pipeline about common and not-so-common organic solvents. Solvation is still one of the least-understood and yet most important concepts in chemistry, as almost all synthetically useful reactions take place in solution. The dielectric constant is one way of organizing solvents based on a single property (polarity), but another possibility is to use polarizibility.

The other thing to keep in mind is that common solvents need not necessarily be reaction solvents, although that is what first comes to mind. Acetone is used by the gallon in labs all over the world for cleaning glassware, and ethyl acetate (along with hexane) is one of the most popular solvents for chromatographic separation of relatively nonpolar organics. Acetone and ethyl acetate are too reactive to be used as reaction solvents; whenever I have used them in preparative chemistry, I always used them as reagents. In my experience with synthetic chemistry, I haven’t used too many unusual solvents so far. I have used trifluoroethanol  and TFA as solvents, in a very low-yielding reaction for the preparation of triphenyloxonium ions. I used a lot of trifluoromethanesulfonic acid in my research as a solvent for superelectrophilic Friedel-Crafts reactions, although this is not really practical and is mainly of academic interest, due to the high cost of triflic acid. It can be recovered after a reaction workup, but it is very laborious.

I think that this prep from Organic Syntheses for hexaphenylbenzene takes the cake for weird solvents, however. hexaphenylbenzene

The solvent is….refluxing benzophenone. Most compounds would decompose at such high temperatures, but if you need to really kick a recalcitrant Diels-Alder, Cope, or Claisen reaction along, then sure, break out the diphenyl ether or benzophenone!

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