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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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February 26, 2013

Phil Baran at Blog Syn

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Posted by Derek

I linked recently to the latest reaction check at Blog Syn, benzylic oxidation by IBX. Now Prof. Baran (a co-author on the original paper, from his Nicoloau days) has written See Arr Oh with a detailed repeat of the experiment. He gets it to work, so I think it's fair to say that (1) the reaction is doable, but (2) it's not as easy to reproduce right out of the box as it might be.

I'd like to congratulate him for responding like this. The whole idea of publicly rechecking literature reactions is still fairly new, and (as the comments here have shown), there's a wide range of opinion on it. Getting a detailed, prompt, and civil response from the Baran lab is the best outcome, I think. After all, the point of a published procedure - the point of science - is reproducibility. The IBX reaction is now better known than it was, the details that could make it hard to run are now there for people who want to try it, and Prof. Baran's already high reputation as a scientist actually goes up a bit among the people who've been following this story.

Public reproducibility is an idea whose time, I think, has come, and Blog Syn is only one part of it. When you think about the increasingly well-known problems with reproducing big new biological discoveries, things that could lead to tens and hundreds of millions being spent on clinical research, reproducing organic chemistry reactions shouldn't be controversial at all. As they say to novelists, if you're afraid of bad reviews, there's only one solution: don't show anyone your book.

Comments (59) + TrackBacks (0) | Category: Chemical News | The Scientific Literature


COMMENTS

1. CountTheBricks on February 26, 2013 8:19 AM writes...

Prof. Baran is a class act and his response shows just that. I can pick up a little frustration in his tone, but I think that is understandable. He has most likely been hearing this for a while and finally had a public avenue for discussion. At the end of the day, BlogSyn is doing what has been needed for a while. There are countless examples of reactions that need scrutiny, and this researcher hopes BlogSyn gets off the ground in a larger fashion. @SeeArrOh, this is not a one-trick pony.

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2. Anonymous on February 26, 2013 8:40 AM writes...

What is the point of supporting information if it requires further input from the authors to allow the procedure to be reproduced?

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3. Eric on February 26, 2013 8:54 AM writes...

#2 - I think that statement, along with the genesis of BlogSyn, nicely illustrate the state of affairs with scientific reporting. If it were up to me, experimental sections of papers would be much longer and the papers would include data relating to what didn't work and why, instead of "here are the somewhat precise conditions we used to get our product. You figure out the rest :)"

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4. Special Guest Lecturer on February 26, 2013 8:59 AM writes...

Unless we commit to actually reproducing reported procedures as part of peer review (too cumbersome), there will be reactions whose reported procedures will need care to reproduce. As Baran says, each transformation has a window of conditions under which it will work well - we are not always fully aware of every variable that affects the reaction outcome.

The focus of many papers is to obtain a specific molecular or polymeric product, and the authors are not going to spend time evaluating every conceivable variable of every reaction along the way - too expensive, too material intensive.

A higher standard should be applied to papers whose main focus is to report new synthetic methodology - we care about yield, substrate scope, and stereoselectivity. Peer reviewers should also demand unambiguous characterization of the outcome with variation of temperature, concentration, and sensitivity of the reaction to common impurities that might be found in the reagents. Post-publication review is a welcome development - both as a service to molecule makers and as a means to identify useful transformations from dreck. Look at azide-alkyne cycloadditions - develop a bulletproof reaction and the whole world will latch onto it!

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5. UNC chemist on February 26, 2013 9:46 AM writes...

Classy response from PSB

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6. See Arr Oh on February 26, 2013 9:57 AM writes...

Thanks for posting this, Derek. And thanks, Phil for your active participation to improve the literature.

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7. Anonymous on February 26, 2013 10:02 AM writes...

Pro tip: when attempting to reproduce a procedure suspected to be finicky, DON'T start with 6-month-old reagents from the back of your freezer.

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8. bboooooya on February 26, 2013 10:25 AM writes...

"Unless we commit to actually reproducing reported procedures as part of peer review (too cumbersome)"

It didn't used to be too cumbersome. I used to delight getting old papers from RSC journals that had notes that "The checkers found......". I guess a decrease in rigour and quality is the cost of progress?

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9. darwinsdog on February 26, 2013 10:31 AM writes...

Defense has rested, prosecution will close. Sounds like starting with good oxidant is key and the rest, including how to warm a rxn, seems obvious. I agree with the point that blog syn should not commit blog sin (sorry i couldn't resist) and should make earnest attempts to contact AND work out procedures with authors before reporting their failures. It's the old free speech chestnut - anyone can say what they want to but you ought not to declare allegorical 'fire' if there isn't one.

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10. The Aqueous Layer on February 26, 2013 11:07 AM writes...

I agree with the point that blog syn should not commit blog sin (sorry i couldn't resist) and should make earnest attempts to contact AND work out procedures with authors before reporting their failures. It's the old free speech chestnut - anyone can say what they want to but you ought not to declare allegorical 'fire' if there isn't one.

How many people contact a paper's author before trying to run a specific reaction? The whole point of publishing results and reproducibility is that anyone with half-way decent lab chops can follow the procedures as written and get the results that were published.

If you have to contact the author to find out the tips, tricks and nuances of every reaction, maybe it isn't such a useful transformation to begin with, or the paper needs to discuss the degree of difficulty in getting the reactions to work well and discuss the precautions you need to take in order to achieve optimal results.

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11. D-Not on February 26, 2013 11:34 AM writes...

Refer to my previous posts ... This is the reason folks like See-Arrrr-Oh should be extra careful in "labeling reactions as - requires MOJO or not reproducible". Call me old school, But one can tell the quality / caliber of a chemist by simply taking a look at his or her TLC plates !!.

If Prof Baran were not to put his money on the table and reproduce the reaction (not to mention spend so much of his time) your blogs would have needlessly passed a verdict without giving him the benefit of the doubt. and that is shameful.

In the future - please SAO -- kindly check with the concerned authors (particularly Very High Profile Professors, since they have worked hard to gain the stature) and get them to contribute to your ability to re-produce these reactions.

It is unjust and as I previously characterized it as a "witch hunt" if we dont do everything in the interest of chemistry and at the same time safegaurd reputations of the Key personalities in our field.

Kudos to Prof baran -- a class act beyond compare.

Today I am proud to be a Chemist. (eventhough a 49-year old MS level chemist, closet academic, still rampaging through reactions and making analogs IN THE LAB)

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12. Nature on February 26, 2013 11:51 AM writes...

Can we at least get an apology from @SEE Arr OH and all the minions that were patronizing See Arr OH in previous blogs including DL

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13. CountTheBricks on February 26, 2013 12:09 PM writes...

@#12
Why do you want an apology? This is exactly what the point of BlogSyn is: Get engagement from the community when things aren't as they seem. Prof. Baran reciprocated exactly as he should have. He did not get irritated or insulted, he was intrigued. He was guided by his scientific curiosity to show, incontrovertibly, that his chemistry works when done properly. He admitted that his SI should have been more explicit and will likely not commit the same error in the future.

End of story, cheers to SeeArrOh and Prof. Baran for engaging in a highlevel debate of scientific merit, and on to the next example.

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14. Vivian on February 26, 2013 12:13 PM writes...

Something tells me that the response by PSB would not have been as thorough/thoughtful/helpful without See Arr Oh's forum--I have many times emailed corresponding authors for procedure clarifications and not gotten as thorough of a study as the one you see on Blog Syn. None of the experimenters had axes to grind, and I think that blogs that address the practical aspects of doing chemistry are incredibly helpful for younger chemists! If your procedure isn't up to par with Organic Syntheses procedures (which are written so that MOST chemists can reproduce them, along with any pitfalls), that's all on you.

I have a real problem with people who think that just because a chemist has accomplished a lot in a career, they are beyond criticism or reproach. It's how these obnoxioius hierarchy systems get established (particularly in synthesis, as it were), and I don't think it's helpful to the advancement of the field to be shaking in one's boots to question a reaction that a PI has endorsed by putting his name on the paper. A PI has to understand that when you are corresponding author, you are responsible for the good that comes with the reaction, as well as any questions that arise from the reaction. I don't think writing about a procedure in a blog qualifies as public humiliation (and if it does for you, then you need to get a thicker skin)--it's more of an open discussion, which this field needs more of, not whispered claims of irreproducibility.

I don't think any of See Arr Oh's blog post was in the least bit confrontational--it's ok to say that a reaction is finicky, for goodness sake. What is the use of a reaction if most chemists can't reproduce it? Such a reaction would never be used for anything that is actually useful, and like it or not, chemistry should be useful and accessible to everyone! It is the JOB of the person publishing the paper to make darn sure that an experimental procedure is clear without having to consult the author.

Just my two cents, but as someone with both academic and industrial experience, I think that academics would do themselves much more service to scrutinize their reactions and make them more useful and accessible to the community of chemists who will actually use them (and not for some esoteric synthesis of some molecule that won't be used for anything).

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15. Vivian on February 26, 2013 12:14 PM writes...

Something tells me that the response by PSB would not have been as thorough/thoughtful/helpful without See Arr Oh's forum--I have many times emailed corresponding authors for procedure clarifications and not gotten as thorough of a study as the one you see on Blog Syn. None of the experimenters had axes to grind, and I think that blogs that address the practical aspects of doing chemistry are incredibly helpful for younger chemists! If your procedure isn't up to par with Organic Syntheses procedures (which are written so that MOST chemists can reproduce them, along with any pitfalls), that's all on you.

I have a real problem with people who think that just because a chemist has accomplished a lot in a career, they are beyond criticism or reproach. It's how these obnoxioius hierarchy systems get established (particularly in synthesis, as it were), and I don't think it's helpful to the advancement of the field to be shaking in one's boots to question a reaction that a PI has endorsed by putting his name on the paper. A PI has to understand that when you are corresponding author, you are responsible for the good that comes with the reaction, as well as any questions that arise from the reaction. I don't think writing about a procedure in a blog qualifies as public humiliation (and if it does for you, then you need to get a thicker skin)--it's more of an open discussion, which this field needs more of, not whispered claims of irreproducibility.

I don't think any of See Arr Oh's blog post was in the least bit confrontational--it's ok to say that a reaction is finicky, for goodness sake. What is the use of a reaction if most chemists can't reproduce it? Such a reaction would never be used for anything that is actually useful, and like it or not, chemistry should be useful and accessible to everyone! It is the JOB of the person publishing the paper to make darn sure that an experimental procedure is clear without having to consult the author.

Just my two cents, but as someone with both academic and industrial experience, I think that academics would do themselves much more service to scrutinize their reactions and make them more useful and accessible to the community of chemists who will actually use them (and not for some esoteric synthesis of some molecule that won't be used for anything).

Permalink to Comment

16. Vivian on February 26, 2013 12:15 PM writes...

Something tells me that the response by PSB would not have been as thorough/thoughtful/helpful without See Arr Oh's forum--I have many times emailed corresponding authors for procedure clarifications and not gotten as thorough of a study as the one you see on Blog Syn. None of the experimenters had axes to grind, and I think that blogs that address the practical aspects of doing chemistry are incredibly helpful for younger chemists! If your procedure isn't up to par with Organic Syntheses procedures (which are written so that MOST chemists can reproduce them, along with any pitfalls), that's all on you.

I have a real problem with people who think that just because a chemist has accomplished a lot in a career, they are beyond criticism or reproach. It's how these obnoxioius hierarchy systems get established (particularly in synthesis, as it were), and I don't think it's helpful to the advancement of the field to be shaking in one's boots to question a reaction that a PI has endorsed by putting his name on the paper. A PI has to understand that when you are corresponding author, you are responsible for the good that comes with the reaction, as well as any questions that arise from the reaction. I don't think writing about a procedure in a blog qualifies as public humiliation (and if it does for you, then you need to get a thicker skin)--it's more of an open discussion, which this field needs more of, not whispered claims of irreproducibility.

I don't think any of See Arr Oh's blog post was in the least bit confrontational--it's ok to say that a reaction is finicky, for goodness sake. What is the use of a reaction if most chemists can't reproduce it? Such a reaction would never be used for anything that is actually useful, and like it or not, chemistry should be useful and accessible to everyone! It is the JOB of the person publishing the paper to make darn sure that an experimental procedure is clear without having to consult the author.

Just my two cents, but as someone with both academic and industrial experience, I think that academics would do themselves much more service to scrutinize their reactions and make them more useful and accessible to the community of chemists who will actually use them (and not for some esoteric synthesis of some molecule that won't be used for anything).

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17. Curious Wavefunction on February 26, 2013 12:25 PM writes...

#11 and #12: You guys have a real bee in your bonnet. All SeeArrOhh, BRSM and the others did was to point out that they could not efficiently reproduce a particular reaction under the stated conditions. The "verdict" here is a limited one (they never claimed that the reaction was fundamentally irreproducible). To call this a "witch hunt" is preposterous and it only detracts from the value of such investigations.

This is exactly the way science should work and I applaud both the Blog Syn authors and Prof. Baran for their response. What these guys are doing is what science should always be doing; testing and re-testing hypotheses and confirming reproducibility. It's a system that has been in place for hundreds of years and perhaps its only fault is that it hasn't worked as well as it should, partly because of cynics like you who are more interested in assigning blame than encouraging such efforts or fostering constructive criticism. What we see here is a beginning; you guys can contribute to it and your technical input will be welcome, but if you don't want to do this then you should consider not derailing the discussion by all this silly talk about apologies and witch hunts.

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18. Grad Students Anonymous on February 26, 2013 1:36 PM writes...

I think what See Arr Oh, BRSM, and Blog Syn on the whole are trying to accomplish here is quite admirable. Those who would call this a witch hunt seem to be a bit *too* irked by peer-vetting of published results. Isn't that what makes our field stronger?

If your SI does not properly outline the procedure that allows others to reproduce your work, it is your failure, not theirs. It doesn't matter if you're a Nobel-winning chemist or a first year grad student. So three cheers for Blog Syn.

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19. Special Guest Lecturer on February 26, 2013 1:56 PM writes...

#7: "Protip: when attempting to reproduce a procedure suspected to be finicky, DON'T start with 6-month-old reagents from the back of your freezer."

Obnoxious. Unless the published procedure stated that fresh oxidant was beneficial, I would have used the old stuff in the freezer for my initial attempt. Why waste time solving every possible pitfall before there is a problem? In the context of Blog.Syn, demonstrating that oxidant quality is essential is a great service, especially if such efforts inspire authors to do so in the first place...

I don't understand comments that suggest that high-profile PIs like Baran (or any author of a peer-reviewed publication) deserve special deference from public comment. SAO did not attack Baran. His post said "I followed this procedure and then varied the reaction parameters in the following ways and did not obtain the expected product." What's the harm?

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20. marklar on February 26, 2013 3:04 PM writes...

The outcome of this story is much better than that of a similar story I remember in grad school. Members of an organic group in the department were trying to perform a reaction developed by a high-profile name/group in org. chem. I'm not familiar with the details (i.e. substrate similarities), but the reaction did not work as reported. The Prof. in our dept. contacted the high-profile Prof. and wanted to know if there were any 'tricks' to improve the reaction. The high-profile Prof. replied, "Maybe you should train your students better."

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21. scope monkey on February 26, 2013 3:05 PM writes...

Getting a single rxn to reproduce is great (and kinda important) but using a public forum such as BlogSyn for practitioners to describe what kinds of functionality these rxns can tolerate would be really useful. Even if the industry folks aren't going to be lining up to disclose the exact substrates they've tried it would be useful to get feedback such as "works in presence of pyridine ring" or "failed in presence of primary amide". Admittedly the failures may a little more difficult to explain as there could have been many reasons for failure but those rxns which rack up a long list of successes I'd sure be happier to try out first.

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22. newnickname on February 26, 2013 3:06 PM writes...

I think that all that transpired worked well. I didn't see a "witch hunt" or anything particularly confrontational at Blog Syn. I thought that Baran's response was very good and very useful. If anything, I would think that an author would prefer to "publish" one public clarification than have to receive (and maybe not bother to answer) numerous individual Qs about a typo or other experimental error.

Blog Syn, keep up the good work.

I wonder if CAS and Science Citation Index will start abstracting Blog Syn to help track down those helpful updates.

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23. Not anonymous on February 26, 2013 3:16 PM writes...

#18: "Those who would call this a witch hunt seem to be a bit *too* irked by peer-vetting of published results"

How do we even know it is peer-vetting? If blog-syn really want broad respect from the chemical community they should not be "anonymous" or hiding behind their screen names. It's one thing to be anonymous during publication peer-review, but those comments are not available to the public. If blog-syn wants to continue to review publications, they should stand behind their work and put their full names and CV's available for the rest of us to see.

As it is right now, they unfairly deemed a reaction irreproducible (and it still says so on their website) with little to no consequences to themselves on the basis of 5 or so experiments. As Phil Baran rightly pointed out, "the reaction cannot take place if all reactants are not in solution". I think anyone who is "skilled in the art" should be able to recognize that.

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24. Rhenium on February 26, 2013 3:46 PM writes...

#23 On the irony...

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25. Not anonymous on February 26, 2013 3:59 PM writes...

#24 yes, that was the point

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26. Grad Students Anonymous on February 26, 2013 4:07 PM writes...

to #23:

What would you call this if not peer-vetting? Are you insinuating that those trying to reproduce these experiments are not well-trained, intelligent chemists? I would think their reputations as long-time bloggers should give them at least some credibility to even the most cynical among us.

I think Blog Syn is a great addition to the community. Anyone who is "skilled in the art" has been at this long enough to know that some procedures are notoriously difficult to reproduce without certain "tricks" not thoroughly explained in the SI.

I've seen enough of my colleagues try to reproduce methods from the literature with initial difficulty that only work with some slight tampering to appreciate the value in the service that Blog Syn provides.

As others have stated, if your reputation can be damaged by Blog Syn, you didn't have much of a reputation to begin with. And as Derek pointed out on an earlier thread, I think some of Blog Syn's opponents "doth protest too much".

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27. Anonymous on February 26, 2013 4:09 PM writes...

@19 They added a non-degassed liquid to an air-free reaction, then berated the commenter who suggested they try otherwise. *That* is obnoxious. They're acting like the one-armed guy with a bathtub rather than a person having ordinary skill in the art. SI in JACS is written for the latter. It isn't J. Chem. Ed.

@23 It seems like more of a guide as to how robust procedures are vis-a-vis half-assery than actual reproducibility, although "organometallica" seems like the most competent among them.

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28. Prof Slavedriver's Postdoc on February 26, 2013 6:04 PM writes...

I have firsthand knowledge of some results from our lab that were published in high tier journals not being reproducable/even produced in the first place...the pressure to crank out revolutionary science on a daily basis can be too great for some people and lead to actual falsehoods being enshrined in the literature. I see great potential in Blog Syn to cull these travesties and legitimize the methods that are bona fide great science.

Statistically, the amount of replicates that Blog Syn posted for the Baran reaction is not bad (probably more times than most methodology substrates are vetted in their original papers) and I will argue that the featured synthetic PhDs are the definition of those skilled in the art, those that should be able to get a reported reaction working the same day they pick it up.

Anonymity is exceedingly important in this situation: witch hunts can be carried out in both directions, and when there is a major power imbalance (eg grad student/postdoc vs influential professor) there is a great reticence to question those who could sink your career before it's even started.

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29. Aussie on February 26, 2013 7:04 PM writes...

Blog syn is a great idea - See Arr Oh deserve major kudos!

But now that Baran has shown it is reproducible and other anonymous people are posting that they can easily reproduce it (recently appearing today) how long will they keep up the "not reproducible" recommendation? Doesn't seem very scientific to me.

I can also do a TBS protection with old TBSCl and wet DCM and then call Corey's 1972 JACS paper "irreproducible". Or I can do a metathesis with volatile olefins and when it doesn't work I'll call them to retract Grubbs Nobel. Seem fair?

We are all in a rush to praise SAO and friends for what is admittedly a great idea and service but let's not forget that innocent people and legitimately useful chemistry can be hurt by recommendations that do not reflect reality!!

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30. See Arr Oh on February 26, 2013 7:17 PM writes...

Thanks for the interesting and varied opinions in the comments today.

@Aussie - You bring up a very good point. I've spoken with Phil offline, and he advises that we should re-run the reaction in our hands before we change the recommendation.

@Everyone - Perhaps it's semantics, but we do not label the IBX oxidation "irreproducible," but instead "Difficult to Reproduce." The two terms are different; one connotes certainty, and one acknowledges that the reaction can indeed work with correct protocol.

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31. Nature on February 26, 2013 7:19 PM writes...

@29 Aussie -- SAO has un-intentionaly stirred the hornets net !! Bet SAO regrets the fact that serious consultation with the good professor's lab was not done before blogging. classic case of puting blogging before chemistry. Shock journalism.

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32. See Arr Oh on February 26, 2013 7:26 PM writes...

@Nature - Emails were sent back and forth between Prof. Baran and I, beginning on Jan. 29. Post went live on Feb. 18.

I've also corresponded with Prof. Tamsyn Montagnon, and you will see her recommendations posted at Blog Syn.

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33. Model on February 26, 2013 7:42 PM writes...

SAO- cheers for doing this. wish you success in future posts / interesting chemistry

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34. JRnonchemist on February 26, 2013 7:42 PM writes...

It looks like the post at Blog Syn has been up for a little over a week. I guess the new information came out today or yesterday? I know it seems slow in internet time to still have 'difficult to reproduce up'

Given that they seem to be running a two a month schedule on the attempts, I'd guess they still have time on the clock for getting things sorted out to everyone's satisfaction.

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35. Not anonymous on February 26, 2013 7:43 PM writes...

#26 "I would think their reputations as long-time bloggers should give them at least some credibility to even the most cynical among us."

Please. How hard is it to start and maintain a blog? Just because someone has a long-time blog doesn't give you any idea about their experimental skill. Their CV would. Every chemist knows another chemist whose results they wouldn't trust right away if it differed from the literature. By hiding behind a screen name it literally gives us no information about this person's technique or experience.

And just because there is a published procedure doesn't mean you can turn off your brain when running a reaction. Be a scientist and follow up a little better if something doesn't work 100% as reported in your hands.

To be clear: I think the overall goal of blog-syn is a commendable idea, but I think there should be more accountability to what they are doing and giving us more information about themselves would help. And yes I understand the goal is to help the chemical community by giving tips and tricks to difficult reactions, but at the same time it borders on calling people a fraud or a sloppy chemist for what essentially could be their own sloppy work.

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36. dave w on February 26, 2013 7:59 PM writes...

re #35: "Just because someone has a long-time blog doesn't
give you any idea about their experimental skill. Their CV
would."

Some of the comments keep saying this as if repetition should
induce belief, but you could alwasy turn that around. "Just
because someone has an impressive institutional history doesn't
mean they're automatically a top-notch experimentalist." To
believe otherwise, to be so fixated on "CV" and "reputation",
implies a viewpoint where the object of the game is to gain
"professional 'respectability'" and doing actual science is
merely a means to that end...

And I don't think anyone called anyone a "fraud" or a "sloppy
chemist"; it sounds like there is general agreement (even from
its original author) that the specific reaction in question here
can be finicky about the details of the specific conditions.

-dw

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37. Realist on February 26, 2013 8:18 PM writes...

Based on everything I've read the only conclusion I can come up with is:

The procedure to MAKE IBX is "difficult to reproduce"

No other conclusion is logical.

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38. JRnonchemist on February 26, 2013 8:35 PM writes...

There have been a total of three processes posted at Blog-Syn, plus the intro post. So far. This looks like two per month. So in year, maybe they will have twenty more.

If they don't get up to that many, it'll probably have ended up a flash in the pan, and not worth getting worried over.

If they do, it should be pretty easy to tell if they are bullies, lazy, or incompetent. If they often have the same pool of volunteers, then they will generally bring the same tendencies to each project.

Careful following, or a careful archive binge in the future should be enough to notice irregularities and problematic habits. Assuming the reader has some level of maturity, has some background knowledge of internet communities, and enough chemistry and or general science.

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39. anon on February 27, 2013 9:09 AM writes...

D-NOt (comment 11) seems to be obsessed with the stature of the people whi publish the results and not the quality of the results/publications themselves. Who gives a crap if a paper is by a PhD student, a "bigshot", or even someone obsessed with making contorted analogies between organic chemistry and 3000-year old myth, its all open to scrutiny.

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40. Anonymous1984 on February 27, 2013 11:20 AM writes...

I think the authors of Blog Syn are doing a great job but I also think the complaints about anonymity are valid. No matter how honest their intentions may be, it's hard to take someone seriously when they are anonymous and don't feel like associating a real name with their work. If I know that SeeArrOh is a real person with real credentials I am just more likely to believe in the veracity of what he/she has done.

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41. newnickname on February 27, 2013 12:07 PM writes...

I am very sympathetic to maintaining anonymity at Blog Syn. I would think that those contributing there are grad students, post-docs and other professional chemists and NOT a bunch of hackers skillfully posting faked criticisms (when they could be posting links to their malware websites and such). Those are people with skills nonetheless. They have probably sought advice from more experienced colleagues and so on up the ladder.

Those same people are the chemists for whom the experimentals should be written; not for undergrads; not using obfuscatory patent lingo; but clear, workable procedures that someone with "skill in the art" but less than 25 years at the bench can reasonably figure out and reproduce.

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42. another process chemist on February 27, 2013 12:24 PM writes...

I would agree with #28 (Slavedriver's Postdoc) that anonymity is important because ours is a fairly small world and we all need to worry about the ramifications of rubbing somebody the wrong way. In addition, more often than not this kind of verification work will not make a direct, positive impact on the productivity or bottom line of whoever it is that signs our checks, so there could be other negative ramifications of having one’s name associated with this kind of valuable work.

Professor Baran is wise to clearly state that his student, having demonstrated conditions for making the 2-methylnaphthalene oxidation work, will not be doing any more work in this area – it isn’t the most pressing business at hand.

As #41 alludes to, I think a key factor here is that nobody wants to see new methodology fail. We all want to have more tools at our disposal, so we all benefit from identifying (and sharing) the keys to making a new reaction work robustly. Anonymity is only a problem if we are worried about somebody falsely describing their efforts in order to make somebody look bad. Would that actually happen?

From my perspective, credentials do not matter (and yes, I do have Ph.D. from a good group and plenty of nice-looking industrial experience). As I mentioned in the previous thread, my processes need to be described clearly enough so that they can be executed by individuals who do not have a chemistry degree. Is that an unreasonably high bar for somebody who is inventing new methodology (not a rhetorical question – it might not be realistic)?

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43. ab on February 27, 2013 1:51 PM writes...

I love all of the comments that suggest somehow PSB is vindicated and that SAO should apologize and such. Let's have a re-cap, shall we?
1. In the lit, this paper is cited in 54 reactions, with a total of 4 of them appearing to be successful. Reproducible? Practical? The lit suggests differently.
2. Several chemists attempt to reproduce the results using the exact same substrates under several sets of likely conditions that mimic the SI as closely as can be known. Results: poor.
3. After a revision of the experimental procedure, a hand-picked student of PSB's runs the reaction on a small scale under what (one has to think) must be the ideal set-up - which, mind you, is materially different than that claimed in the SI - using pristine reagents and obtains a 65% yield, while the original paper claims 90%. Somehow this constitutes "reproducibility." Really? This is the definition of yield inflation and a sloppy SI.
4. PSB or the student (not clear which) claims definitively that if the reaction were run on a larger scale with a few tweaks, magically the yield would improve dramatically. Please. Reactions displaying solubility and/or physical properties issues are notoriously capricious on scale up. PSB should know this. As it stands, there is zero evidence of the veracity of this statement.

I don't have an ax to grind with PSB. Nearly everyone who contributes to the comments on this blog knows that PSB is one of - perhaps THE - most impressive talents in the field right now. That does not mean his work is above scrutiny. Furthermore, the work that SAO and company put in to get to the bottom of these issues is truly admirable and moves the field forward. In fact, for those of us who actually need to get stuff in a vial on a weekly basis, this work is invaluable. And I don't know why this should matter, but yes I do have a Ph.D. from a top 5 (or 3, or 1, depending on the year) university working for someone you all know doing chemistry you are all familiar with. I frankly don't care to go into more detail than that, since my comments stand on their own. New methods are vital to the work that I do. Papers that accurately define the scope and limitations of these new methods, even better. My hope is that the "check and balance" provided by SAO and company will push more PI's to publish reality, which will benefit our field a lot more than inflated yields.

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44. Gator on February 27, 2013 2:26 PM writes...

AB -some good points. But let's review them:

"1. In the lit, this paper is cited in 54 reactions, with a total of 4 of them appearing to be successful. Reproducible? Practical? The lit suggests differently."
Wonder what would happen if you did that analysis with any method invented in the past decade? That's why there are 1000 ways to oxidize an alcohol or put on a boc-group. They don't all work on all substrates.

2. Several chemists attempt to reproduce the results using the exact same substrates under several sets of likely conditions that mimic the SI as closely as can be known. Results: poor.

Not true- As documented by the experimenters themselves their reagent was clearly crap. They tried to oxidize toluene and other volatiles with the reagent not in solution.

3. After a revision of the experimental procedure, a hand-picked student of PSB's runs the reaction on a small scale under what (one has to think) must be the ideal set-up - which, mind you, is materially different than that claimed in the SI - using pristine reagents and obtains a 65% yield, while the original paper claims 90%. Somehow this constitutes "reproducibility." Really? This is the definition of yield inflation and a sloppy SI.

Not different than claimed in the SI of the original paper. They state they use pure IBX made by the JOC paper. What exactly is yield inflation? 99% of papers give their best yield of a transformation. They don't give ranges and they certainly don't give the yield you can expect when doing it for the first time. SI looks pretty good for a 2002 paper and most method groups don't even write full papers. So I think you are wrong on both counts.


4. PSB or the student (not clear which) claims definitively that if the reaction were run on a larger scale with a few tweaks, magically the yield would improve dramatically. Please. Reactions displaying solubility and/or physical properties issues are notoriously capricious on scale up. PSB should know this. As it stands, there is zero evidence of the veracity of this statement.

What a coincidence there is zero veracity for any of your statements either. I think I'll trust PSB on this one.

Finally, we are discussing a paper in which PSB is NOT the corresponding author. He is not even the first author (after KCN). I think a lot of you are forgetting this. Probably back then KCN had a factory of people doing IBX reactions so I have no doubt that 90% is reachable on napthalene if they were doing this reaction every day.

What papers in the literature give the yield you can expect if you've never done the reaction, use volatile compounds, and shit reagent? Maybe they should but then you should be complaining about the entire field, not just one paper...

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45. ab on February 27, 2013 4:03 PM writes...

#44 Gator-
I AM complaining about the entire field, this just happens to be another paper that exemplifies the problem. Derek has also explicitly written about this problem in past blog entries.

Regarding 1, I fully agree that it is good to have many methods to perform any given transformation. However if said method does not work to perform said transformation, then we don't really have anything terribly useful, do we?

Regarding 2, well, if you feel that a reagent freshly prepared to 95% purity by recrystallization using an established lit procedure is "crap," especially when the SI claims that commercial material was used (which really would be crap) - and also makes NO MENTION that the purity of reagent has a huge effect on the reaction - well, let's agree to disagree on that one. And I'm not referring to the oxidation of toluene, I'm referring to the oxidation of 2-methylnaphthalene. If solubility was such an issue in this reaction, the authors should have written explicitly how they obtained the 90% yield.

Regarding 3, maybe you could give the SI a read and let me know where they claim they used pure IBX made by the JOC route? Thanks.

And yield inflation is the citing of a reaction yield that does not represent the result typically obtained using the published procedure. It's as simple as that. If one of PSB's personally picked students cannot even come close to reproducing the cited yield, then that yield is inflated. If you don't see this as a problem, that's fine, we can agree to disagree on that one too.

Regarding 4, you are certainly free to "trust PSB on this one," but if you were actually counting on the stated reaction to work so that you might use your lab time productively, you might find yourself relying a bit more on data and evidence, rather than your gut feelings.

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46. Not anonymous on February 27, 2013 4:54 PM writes...

#45 "I don't have an ax to grind with PSB. Nearly everyone who contributes to the comments on this blog knows that PSB is one of - perhaps THE - most impressive talents in the field right now. That does not mean his work is above scrutiny....If one of PSB's personally picked students cannot even come close to reproducing the cited yield.."

It certainly sounds like you have an axe to grind against PSB for some reason. The fact of the matter is you have no idea who the student was and how much time and effort was put into it.

What blog-syn did was not scrutiny, it was flailing around with chemicals like an undergrad and claiming the reaction was not reproducible in a very public fashion. This is not "crowd sourcing" as they claimed. It's not about reproducing reactions for the general knowledge of all, it's about calling chemists out. Be honest with yourself, the only reason blog-syn is getting this much attention is because two out of the three chemists featured already are at a top tier institution and people want some gossip. If they want the broader chemical community to trust them when they put their work in a public forum they should stand behind their work and not do it anonymously.

"...but if you were actually counting on the stated reaction to work so that you might use your lab time productively, you might find yourself relying a bit more on data and evidence, rather than your gut feelings."

I think he is going with the evidence that PSB put out there when the blog-syn chemists were flailing around with chemicals. I know whenever I set up a reaction I try to use the crappiest reagents possible, not follow the reaction reasonably, and get mad when I don't get 100% yield!!!

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47. Grubbs Ghost on February 27, 2013 5:29 PM writes...

AMEN #46. Plain common sense there.

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48. Andrew (@_byronmiller) on February 27, 2013 5:32 PM writes...

I find it fascinating that a handful of anonymous commenters are making such a big deal out of the use of (consistent, accountable) pseudonyms by SeeArrOh et al., and refuse to show any charity or good faith in taking said authors at their word about their intentions.

@"Not anonymous", if you want to criticise their technique then that's fair, but why can't you accept that their intentions are honest and decent? Refusing to put your name to your own words, and indulging in personal attacks, whilst criticising others for using pseudonyms and accusing them of having an underhanded agenda makes you look like a hypocrite.

Can we please just accept that SeeArrOh is being honest about his intentions, and is willing to learn from mistakes made? That way the discussion can shift from this undignified, unpleasant, and unproductive trash talk back to the merits of the chemistry.

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49. who cares on February 27, 2013 5:40 PM writes...

To me this discussion seems entirely ridiculous as the process chemists have pointed out. I'm pretty sure pb is a big boy and can take care of his own reputation. The only reason for these negative comments I can conceive of is people are worried that their work will be scrutinized. Keep up the good work cro.

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50. Jose on February 27, 2013 8:23 PM writes...

@ N/A: "What blog-syn did was not scrutiny, it was flailing around with chemicals like an undergrad and claiming the reaction was not reproducible"

This is an absurd statement. My co-workers and I, all well-regarded med chemists at a company you most certainly have heard of, burned an entire week trying to oxidize p-bromotoluene after the rx tanked with our real traget molecule. I can assure you, we were not flailing like undergrads- we distilled, we NMRed, we made/bought/and QCed the IBX, etc. The results were consistent, and negative.

That leads to one conclusion: there is insufficient detail in the paper to reproduce a specific reaction in the paper. Whether it is solubility, IBX vintages, or experiential setup remains to be seen.

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51. Jose brother on February 27, 2013 9:19 PM writes...

See arr ohh has yet another reproduced IBX reaction to post....

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52. Hap on February 28, 2013 10:01 AM writes...

Maybe the jobs lost in chemistry are being replaced by jobs sharpening bladed hardware? I would have thought it was a limited market, but apparently, it's rather lucrative, like supplements.

20: I think I would have had a hard time not responding, "I'll teach my students to work better when you teach your students to evaporate all their carbon tet off their reaction products before they weigh them."

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53. marklar on February 28, 2013 12:43 PM writes...

#52

Exactly! If the Org. Chem. folklore is true, then you are referencing the same prof. I'm talking about.

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54. Rich Apodaca on March 1, 2013 5:54 PM writes...

Interesting that the topic of anonymity and pseudonymity has come up in many comments. Here's my take:

http://depth-first.com/articles/2013/02/22/anonymous-science-and-the-survival-of-blogsyn/

tl;dr: There's nothing wrong with not using a legal identity to publish science. In fact, the authors' given names and current affiliations are irrelevant to any discussion of the actual science.

But BlogSyn's acceptance of anonymous reviews and reviews by authors using handles could make a big difference in the effect BlogSyn can ultimately have on chemistry.

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55. Honclbrif on March 2, 2013 12:02 AM writes...

I think a major division in this thread has been on where people put the weight: is the reaction working every time 100% more important, or is the name of someone who has advanced the field in fundamental ways more important. Developing a procedure which works all the time is very different from advancing a science on a fundamental level. The supporters of BlogSyn seem to be rallying around the fact that they have showed that this procedure does not work as advertized; who cares what fundamental advances the author(s) have made, here is a specific instance of a thing not working as advertised. On the other hand, the people who support the name feel like BlogSyn are a bunch of shit-stirrers; who are they to sully the name of Baran because one minor procedure does not work as advertised.

It is up to you, as a scientist, to determine which you put more weight upon and why.

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56. Secondaire on March 3, 2013 11:50 AM writes...

The idea that SAO is somehow on a quest to bring down PSB is absolutely preposterous. This is a reaction that multiple people from multiple sources have noted as being wonky and inconsistent. In addition to what #55 said, I don't think it really matters if the authors are from Scripps or from Trashwater State University - the fact is, others skilled in the art who thought this procedure would be useful tried it and it didn't work. This is NOT an indictment of PSB. Perhaps a graduate student wrote a sloppy SI and people should've been more aware of it - PSB did the right thing in the way he responded. He got it to work. Someone else didn't. Perhaps, as we've all surmised, the reaction's just finicky; nothing more, and nothing less. By pointing out its finickiness, however, BlogSyn is doing a wonderful service to the chemistry community. It's not a witch-hunt. Get over yourselves, people.

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57. Groggy on March 3, 2013 2:02 PM writes...

Yes secondaire - PSB's student, the other author (see her post on blog syn), German guys (no less than 4 times in one paper!), anonymous posters on blog syn all got it to work without a problem. Seems like only blog syn people are remaining...

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58. See Arr Oh on March 3, 2013 5:25 PM writes...

I think we've figured out how to make the IBX oxidation chemistry work. See latest post over at Blog Syn: http://bit.ly/YkPstH

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59. MrIBX on March 4, 2013 10:14 PM writes...

@Groggy: what about the German guys?

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