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April 26, 2016

Classics in Organic Chemistry, Part III

Filed under: Classics in Organic Chemistry — sankirnam @ 1:59 pm

The next paper in this series is by Prof. Andrew Myers. I followed his work closely during my PhD out of sheer interest; Myers’ research, while focused on total synthesis, is very broad, and he and his coworkers have had many important discoveries and achievements over the years. Off the top of my head, some of the major ones include his work on the tunicamycin and dynemycin classes of antibiotics, which also led to important discoveries regarding a class of cyclizations now known as the Myers-Saito reaction (which is a variant of the Bergman cyclization). Andy Myers also published interesting work on the use of pseudoephedrine as a chiral auxiliary in organic synthesis, and the use of silacyclobutane enolates in aldol chemistry (these are particularly interesting when you notice the amazing rate enhancements due to the effects of the strain in the 4-membered ring). Myers was also the first to publish a variant of the Heck reaction in which you can use benzoic acids as one of the coupling partners; in essence, decarboxylative palladation. This is now an active area of research and decarboxylative coupling reactions are being studied by several research groups, in particular that of Lucas Gooßen. Andrew Myers’ lab also carried out some very nice, complex synthetic work on the development of new classes of tetracycline antibiotics, which ended up getting spun off into a company, Tetraphase Pharmaceuticals. This is an important area of research, as the number of antibiotic-resistant bacteria is growing every day; without effective antibiotics, it would be very difficult to prevent infections, and a simple open wound can end up being fatal. On a side note, Myers was sued by his former PhD student over the royalties stemming from this work, but I’m not sure what happened to the case.

Some of Andy Myers’ early papers are gems of physical organic chemistry, and this one is particularly interesting. It details the synthesis and characterization of 1,6-didehydro[10]annulene, which had been a challenge for physical organic chemists for over 40 years. The parent compound C10H10 (or [10]annulene) should be aromatic as per Huckel’s rule, but it is not due to angular and steric strain. 1,6-didehydro[10]annulene is also a 10π system, but the geometry is planar and so the compound should display aromaticity.


The synthesis of the precursor for 1 is not trivial, but it uses some very interesting reactions. It is mentioned that the final ring closure could not be accomplished with standard methods involving metal acetylides, and so a variant of the Takai olefination had to be employed. The synthesis also involves a Sonogashira coupling and “Wittig reaction of [a] ylide with (trimethylsilyl)propionaldehyde”; this type of Wittig reaction is better known as a Peterson olefination. The late-stage oxidation of an alcohol to an aldehyde is done with the Dess-Martin periodinane, and the final cyclization, as mentioned above, is a variant of the Takai Olefination carried out with chromium doped with a small amount of nickel, conditions reminiscent of the Nozaki-Hiyama-Kishi reaction. What’s interesting is the final statement in the paragraph describing the synthesis: “Due to the extreme sensitivity of 6 [the precursor to 1] toward adventitious decomposition when neat, this product was typically handled in solution in the presence of a free radical inhibitor”. Since this compound (6) was isolated by flash column chromatography, I’m guessing that the column was probably done on a small scale with deuterated solvents (!), since the characterization (coming up) was done by NMR.

1,6-didehydro[10]annulene (1) was generated in an NMR tube in CD2Cl2/THF-d8 solution at -90 ℃, using triflic anhydride and triethylamine. At temperatures above -75 ℃, 1 slowly cyclized to naphthalene, and deuterium incorporation was observed at the indicated carbon-centered radicals.


The NMR spectra (13C (insert) and 1H) are shown below.


The downfield shifts of the signals in both spectra is evidence for an aromatic species, due to a diamagnetic ring current. The 13C spectrum is suspiciously clean, however; if stoichiometric triflic anhydride was used to generate 1, then the 13C peaks for the CF3 group should appear in that range, as reported here. Yet the 13C spectrum in the paper (above) does not have those signals! Odd indeed…

In any case, Myers and Finney were able to measure the kinetic parameters for the cyclization by NMR. In spite of a fairly high activation energy of 16 kcal/mol, the cycloaromatization to naphthalene is fairly quick (25 min at -51 ℃). The quantification of these parameters is important due to this same type of cycloaromatization mechanism being operative in the enediyne class of antibiotics.

In any case, this is a very nice piece of work in pure physical organic chemistry. A lot of work in physical organic chemistry, including what I did for my PhD, concerns the isolation or characterization of unstable species or reaction intermediates, and this falls squarely in that category.

April 25, 2016

Congratulations, HomeUnion!

Filed under: Internet craziness — sankirnam @ 9:08 am

Congratulations to HomeUnion (my father’s company) for being featured in TechCrunch!

April 23, 2016

This week in the economist, 4/23/2016

Filed under: The Economist — sankirnam @ 3:45 pm

I’ve decided to start a series of posts with this title, where I post interesting articles from the week’s issue of The Economist. I have been a subscriber for a while, and these articles are the ones that catch my interest; so these may be more US-centric.

  1. Unloved and Unstoppable – a much needed critical analysis of Hillary Clinton’s presidential campaign.
  2. Not going to Jackson – Harriet Tubman will replace Andrew Jackson on the $20 bill. Keep in mind that she isn’t the first woman to be on US currency; that honor would belong to Susan B. Anthony.
  3. Nosedive – less people are doing cocaine today; it seems that the popularity of drugs changes from generation to generation.
  4. Delayed gratification – it seems that high students loans do not necessarily correlate with a lower probability of home ownership.
  5. Blood Sports – an article on Theranos spectacularly crashing and burning; I’m planning to write more about this later.
  6. Preparing for the Big One – an article about earthquake preparedness in various major cities in the world. I’ve always thought that if aliens were to visit our planet, one of the first things they would say is “are you people nuts for having such large populations in tectonically active areas?”

April 20, 2016

ok now, this is getting a little ridiculous

Filed under: Coding, Data Science — sankirnam @ 11:26 pm

As part of my job search (which has been ongoing for the last year and a half now), I’m applying to several programming and “Data Science” bootcamps. I have posted my thoughts about “Data Science” before, but it seems the juggernaut is nigh unstoppable. During this process, I have experienced a multitude of things that I need to get down.

First off, I want to get a satisfactory answer to this question: If people with just 12 weeks of education can compete for the same jobs as computer science graduates from a university, does it mean that a CS degree is not really worth that much? On the flip side, the relative value of these skills is still pretty high – you can study chemistry for 10+ years, get a PhD, and end up unemployed (as in my case), or you can go through a bootcamp and code JavaScript and look forward to jobs with a minimum starting salary of $105,000 (so CS >>>>>>>>>>>>> chemistry, every time).

I have also heard that there are an astonishingly high number of CS graduates, even those with advanced degrees, who cannot do simple programming exercises like the “FizzBuzz” challenge or simple algorithms. So perhaps there are a large number of mediocre CS students who are getting through the university system and are unable to pass job interviews or fulfill job requirements. In chemistry, this would be like studying organic chemistry on paper but having trouble going into the lab and doing synthesis (or if you’re a theoretician, not being able to input and optimize a model system in a program like Gaussian or Spartan properly, and draw reasonable conclusions).

The other thing that I have been told by a lot of people who studied computer science formally and are now practicing computer scientists (or programmers) is that “computer science ≠ programming”. While this may be obvious to those in the field, it is not obvious to those outside, such as myself; for a long time, I was belaboring under the illusion that they were the same thing. Pure computer science is more akin to math or logic, and one spends a lot of time learning about abstract concepts such as Data Structures, and it is implied that students should be able to pick up programming skills along the way. The current rise of bootcamps and websites such as FreeCodeCamp and Codecademy has decoupled a “pure” CS education from that of programming; these programs get you coding first, usually with HTML, CSS, and JavaScript, without worrying about the underlying logic or science behind the code. Interestingly enough, when I asked interviewers at bootcamps about this (whether bootcamp graduates with a shallow theoretical CS education could compete with regular CS grads for programming jobs), they mentioned that bootcamp graduates were often competitive, simply because of their ability to code better and faster.

The analogous situation in chemistry would be decoupling experimental and theoretical chemistry – e.g. doing organic synthesis without knowing anything about the theory. Is this possible? We’ll never know, because I don’t think there will ever come a time where the demand for synthetic chemists will jump that high, to obscene levels beyond the ability of universities to produce sufficient graduates. At the same time, safety is the big consideration when comparing computer science and chemistry. If you screw up in CS, nobody will get hurt, but if you screw up in the chemistry lab, a range of things can happen, ranging from nothing (if you’re lucky), to killing yourself (if you’re not careful). But from an educational perspective, is it possible to teach “applied chemistry” in order to reach the masses, the same way websites like Codecademy, FreeCodeCamp, and Code School have revolutionized programming education to make it more egalitarian? Chemical concepts like equilibrium, reaction kinetics, etc. can be dry and theoretical; can you teach chemistry in a way to make it more understandable by the masses, but at the same time maintain the “tactility” required to really understand the subject that can only be achieved through lab work? This is a challenge for the next generation of instructors, and one that we as chemists all must face as we strive to prove to upcoming generations that our subject is relevant!

In any case, back to the subject of bootcamps. One of my friends mentioned earlier today:

“honestly you becoming a vanilla webdev is a waste of your talents and training
a lot of people can do that job
not many people can do research in organic chemistry”

Formatting is messed up because I copy-pasted this from a google chat. This friend does bring up a valid point though; why am I trying to go into CS? I have addressed this before, but I still have inner conflicts where I feel like I should keep trying for a job in chemistry (due to the sunk cost fallacy). In any case, this friend is forgiven for not having an accurate knowledge of the chemistry job market – that last statement is completely inaccurate, as there is a massive glut of people who can do research in organic chemistry.

But the sudden rise of bootcamps has got me thinking – is this indicative of another bubble? There are so many coding bootcamps now all over the US, and “Data Science” bootcamps are also springing up all over the place. BTW, the next person who tells me “with a PhD in science, you should think about going into “data science!” is going to get a kick in a very sensitive place. Unfortunately, as I have learned, organic chemistry is not a “quantitative” discipline, and I have been rejected from The Data Incubator, Metis, and Insight for not having the correct background. Also, the programming background required for “data science” is rather steep, and it is not something that can be easily picked up if you don’t have prior training in CS or programming, which is why I’m looking into “vanilla webdev” bootcamps, as the entry requirements are easier for me to meet with my limited coding background.

As to the title of this post, today I came across this.

I have NO idea what to make of this – it’s a prep course to help you get into a bootcamp (o_O). This is like what goes on in India today – you have prep courses to help you get into prep courses for the IIT JEE entrance exam. This has me completely flummoxed, and is another indicator of how the demand for programmers is far exceeding the supply – App Academy (the company running the prep course) is simply cashing in on this trend. Is this indicative of another imminent bubble? One can’t predict the future, but it certainly does seem that way…

April 18, 2016

Free Trade vs. Employment

Filed under: Chemistry Jobs — sankirnam @ 10:15 pm

This paragraph from a recent article in The Economist is rather illuminating:

“But many workers displaced by Chinese imports did not simply find another job. Mr Autor and his colleagues have shown that, at local level, employment falls at least one-for-one with jobs lost to trade, and that displaced workers are unlikely to move to seek new work. The lowest-skilled who do find new jobs tend to move to similar, and thus similarly vulnerable, employment. One reason for this immobility could be that the economy is now an unwelcoming place for jobseekers without a university degree. The housing collapse of the late 2000s, which left many Americans trapped in negative equity, may have made things worse. This new strain of research has lent support to the claim of Dani Rodrik, a globalisation sceptic, that “If you are of low skill, have little education, and are not very mobile, international trade has been bad news for you pretty much throughout your entire life.””

This is also true at the high-skill level; thousands of jobs in organic synthesis and chemical manufacturing, which are at the level of requiring a PhD (or higher) in chemistry, have been moved overseas, never to return. I am very curious to know what has happened to all the thousands of laid-off medicinal chemists over the last decade, and what will happen to the thousands of chemists soon to be laid off in the Dow-Dupont merger. Will they be able to find employment elsewhere in the chemical industry? I hope so. Even “jobseekers without a university degree” are not the only ones at risk for being in “vulnerable” employment in this day and age – a PhD can leave you in just as much risk as not having a degree at all, and organic chemistry is particularly bad as it does not leave you with many “transferable skills” (the buzzword of our times).

April 14, 2016

Farewell, Kobe Bryant

Filed under: Uncategorized — sankirnam @ 1:01 am

There’s nothing I can say about Kobe Bryant that isn’t already in the annals of NBA history. He was such a huge part of my adolescence; I regularly watched Lakers games during middle school, high school, college, and whenever I could during graduate school. Kobe is another one of those rare individuals where I feel grateful just to be alive at the same time he is; I know for a fact that I will be telling future generations that I had the privilege to see his playing live (both on TV and directly at the Staples Center)!

I remember watching his record-breaking game against the Sonics in 2003 where he set NBA records for 3-pointers (12 in one game, 9 consecutively), another game against Houston that same year where he scored 50+ points and posterized Yao Ming on a sprained ankle, and the record-setting 81-point game in 2006 against the Raptors, among others. He led the Lakers to 5 NBA championships and has a host of NBA titles to his credit. Of course, good times come with the bad, and even the best players are not immune to that. Kobe was involved in a scandal in 2003-2004 in which he was accused of having unconsensual sex  with a girl in Colorado, and this followed the gut-wrenching loss of the Lakers in the 2003 NBA finals to the Detroit Pistons, in which the Lakers squad featured Kobe, Shaquille O’Neal, Gary Payton, and Karl Malone. The “dark years” of 2004-2008 featured a Lakers team that was trying to rebuild and rediscover its identity, and Kobe, the lone superstar, trying valiantly to rally the team against all odds to a playoff berth season after season. With Pau Gasol on the roster, the Lakers made it to the NBA finals 3 more times, from 2008-2010, with championships in 2009 and 2010. Unfortunately, the Lakers were swept by the Dallas Mavericks in the second round of the 2011 playoffs, which was a rather unfortunate sendoff for coach Phil Jackson, who led the Lakers to all of their NBA championships (Phil Jackson remains the most successful player/coach of all time, holding the NBA record for the most combined championships (13) as a player and a head coach).

Still, Kobe has that rare combination of athleticism and mental focus that makes him such a deadly athlete and competitor. I remember discussing the differences between Kobe and Michael Jordan with my friend once, and he pointed out that while Jordan had massive hands (“as big as frying pans”) that allowed him to palm the ball rather easily in order to dunk and do layups, Kobe did not have that genetic advantage; and yet, Kobe was just as deadly an opponent as Jordan was! Jordan may have had his “flu game”, but he never had an 81-point game like Kobe! Kobe Bryant is also renowned as a great “clutch” player, able to come through for the team in the last few critical moments in order to clinch victory, and this was seen tonight in the final game of his career.

Farewell, Kobe, and thanks for all the memories.


2016-04-13 22.14.19

April 13, 2016

Classics in Organic Chemistry, Part II

Filed under: Classics in Organic Chemistry — sankirnam @ 4:04 pm

The next post in this series is about a reaction known as the “Shi Epoxidation”. This was first reported in 1997 by Prof. Yian Shi at Colorado State University, and has since been refined many times and is now an important component of the synthetic chemist’s toolkit. As mentioned in the paper, this method complements the other asymmetric epoxidation methods in the literature nicely. The Sharpless AE (asymmetric epoxidation), which was one of the first truly robust and reproducible asymmetric synthetic methods to be reported, works best with allylic alcohols, and while there are several ways to asymmetrically epoxidize cis-olefins, trans-olefins remained a major challenge until the development of the Shi epoxidation.

When broken down into its constituent conceptual components, this reaction is very simple to understand.shi_epoxidation_1The terminal oxidant is Oxone, a triple salt containing potassium peroxysulfate (KHSO5), and the species 1 is the catalyst that actually does the epoxidation. When mixed with Oxone, the ketone functionality in 1 is converted to a dioxirane, which is the species that does the actual epoxidation. And since 1 is chiral, it will also do a facially selective epoxidation, in essence, an asymmetric epoxidation!shi_epoxidation_2Oxidation with dioxiranes is well-established in the chemical literature. DMDO (dimethyldioxirane) is readily generated from mixtures of acetone and Oxone, and the chemistry of this was explored by Prof. Waldemar Adam. The breakthrough here is that instead of using a simple symmetric ketone like acetone and making DMDO in situ, one can use a chiral ketone and make a chiral dioxirane. The nice thing about the ketone 1 is that it can be made relatively easily and is derived from D-fructose (which is inexpensive and readily available) by ketalization (acetone, HClO4, 0 °C, 53%) and oxidation (PCC, rt, 93%). The enantiomer is also accessible from L-sorbose, although that requires more synthetic steps.shi_epoxidation_3So that’s the broad picture of this reaction, and one can readily see why this gained popularity. It is an asymmetric synthetic method that complements others in the literature, and the chiral ketone catalyst can be readily prepared from inexpensive starting materials. In fact, it is commercially available. This is also one of the early instances of organocatalysis, and it is unfortunate that Shi did not use the term in any of his early papers – he could have gotten credit as one of the pioneers of this field of chemistry. Shi only started using the term “organocatalytic” in his papers much later, after the field of organocatalysis had been kickstarted by MacMillan, Barbas, and List.

One of the drawbacks with the Shi epoxidation is that it does not work very well with cis-olefins, but that is why this is complementary to other methods – this works very well with trans-olefins, and there are other methods that work just fine for cis-olefins. There are more details and nuances that can be discussed here as well. The first is that in the initial publication, the epoxidation is not catalytic with respect to chiral ketone 1. Shi had to use 3 equivalents of the ketone, as he and his coworkers observed that it decomposed very rapidly under the reaction conditions (pH 7-8). Those were initially chosen to minimize the background reaction (oxidation of the olefin by Oxone, giving a racemic product). It was also proposed that the ketone catalyst 1 was decomposing under the oxidative conditions through a Baeyer-Villiger reaction. It was then found that increasing the pH to 10.5 by using a K2CO3 buffer allowed the ketone catalyst to become longer-lived, thus enabling a catalytic process by slowing down the Baeyer-Villiger oxidation and improving the nucleophilicity of Oxone in the reaction medium. The implication is that the pH needs to be carefully controlled during this reaction, necessitating the use of syringe pumps to slowly add buffer or base in order to maintain the pH. Shi has also done a lot more work in this area, trying to improve the lifetime, scope, and generality of the reaction, as well as trying to asymmetrically epoxidize trisubstituted olefins, which is still a long-standing challenge.

Further information can be found in the links above, or in the references below:

  1. Shi Epoxidation – Organic Chemistry Portal
  2. Shi epoxidation – Wikipedia
  3. Oxidations with Dioxirane
  4. Murray, R. W.; Singh, M. Org. Synth. 199774, 91 (Example of a procedure for doing epoxidation with DMDO)
  5. Adam, W.; Curci, R.; Edwards, J. O. Acc. Chem. Res. 198922, 205 (Review on dioxiranes)
  6. Murray, R. W. Chem. Rev. 198989, 1187 (Review on dioxiranes)
  7. Wang, Z.-X.; Tu, Y.; Frohn, M.; Zhang, J.-R.; Shi, Y. J. Am. Chem. Soc. 1997119, 11224 (First full article by Shi)
  8. Wong, O. A.; Shi, Y. Chem. Rev. 2008108, 3958 (Review on organocatalytic asymmetric epoxidation methods, including an in-depth discussion on the applications of Shi’s method)

April 8, 2016

The tech mindset, and why it fails in science

Filed under: Philosophy — sankirnam @ 2:05 pm

One of my very close friends (an ex-Google[X] employee), sent me this article last week; it seems that the dysfunctional management style in Verily (a subcompany of Alphabet) has come to light. My friend was astute enough to see the writing on the wall and flee before the s**t really hit the fan, and is now better for it. Derek Lowe also discusses this article, and my sentiments reflect his. An ongoing theme I’m seeing today is that executives who were successful in the tech field try to apply the same approaches or mindset to scientific research, which is quite different in nature. One example I can recall immediately is the former CEO of Intel criticizing the slow, largely unsuccessful method of pharmaceutical research, for which he was publicly lambasted. This all comes down to two things: epistemic arrogance, and a failure to realize the “domain-specificity” of one’s knowledge or expertise.

For example: those working in tech will be used to continually optimizing code to work faster. There is always some way you can look through a enormous process find something to tweak that will make the program run a couple of seconds or minutes faster. However, this same mindset cannot be bought to bear on science (I’ll give some examples from organic chemistry, since that is what I know best). I’m still baffled by the concept of the “10x” or “100x” engineer in tech, because such a situation is impossible in fundamental science. You can be the smartest guy in the institute, but you can’t make a distillation go any faster – it is bound by hard physical constants (i.e. the boiling point). Yes, you can do it under reduced pressure, but even then, if it is not that volatile, you can’t really speed it up further if you have it under high vacuum already. If the liquid boils between 30-60 °C at atmospheric pressure, then you will have to do it slowly and carefully – being 100x more intelligent than others in the room becomes irrelevant. Similarly, if you’re taking an NMR, 13C or other heteronuclear NMRs will take a long time to acquire because those nuclei relax very slowly – again, these are hard physical constants and there is no way around it. I’ve done more than my fair share of time-consuming, tedious, “grunt work” for which there was no better substitute (for example, I once had to purify and isolate a compound by vacuum distillation, but the crude isolate was obtained by extraction with about 500 mL of organic solvent, which had to be slowly and carefully transferred from a 500 mL RBF to a 25 mL RBF so that it could be distilled. Oh and did I mention that the crude was only soluble in dichloromethane, which has a notorious tendency to bump upon rotary evaporation?). There’s no real way to “optimize” what I did, which is something that experienced chemists will agree with, but those in tech will not be able to wrap their heads around. Similarly, reaction kinetics are bound by physical constants; you can’t have a rate faster than 10-9 M/s (which is basically the rate of diffusion in liquid). Most reactions with common electrophiles and nucleophiles will not be nearly that fast, but the rates can be quantified, and the limits calculated thanks to the extremely nice work done by Prof. Herbert Mayr (Ludwig-Maximilians-Universität) over the decades. His work gives ranges for reaction rates, which again are bound by hard physical parameters, which can be semi-empirically approximated (to greater and greater levels of precision as time passes) using theoretical methods.

So what’s my point in all this? Adapting the tech mindset to science is bad, because: 1. You can’t optimize everything indefinitely; 2. While the “10x” or “100x” engineer may be a real thing, there is no such thing as a “10x” or “100x” scientist; 3. “Science” is just inherently more time-consuming and expensive than just sitting at a computer and busting out code; 4. Even in “science” the fields are very different, and expertise and knowledge are domain specific (a chemist may be an expert in organic chemistry but know nothing about quantum dots, for example) 5. You need humility to realize how much we don’t know, and this is reinforced by the failures that scientists face in the lab on a daily basis. Continued success in technology has made the executives there complacent and arrogant, in my opinion.

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).


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!

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