Mega Chemist Challenge Solution Week 15

Last weeks Mega Chemist is Georg Wittig who shared the Nobel Prize in 1979 with Herbert C. Brown. He undertook his graduate studies and then his habilitation (completed in 1926) – alongside another future Nobel laureate, Karl Ziegler - under the supervision of  Karl von Auwers at Marburg University. Wittig spent his entire career in Germany, beginning as a lecturer at Marburg before moving to the Braunschweig Institute of Technology on the invitation of Karl Fries. Wittig then moved to the University of Freiburg in 1937 on the invitation of Hermann Staudinger (yet another Nobel laureate), before moving to the University of Tübingen (as successor to Schlenk) in 1944 as Professor and Faculty Director. Wittig ended his career as Professor and Faculty Director at the University of Heidelberg and remained there as Professor Emeritus from 1967.

Wittig is best known for the eponymous Wittig olefination (DOI: 10.1002/cber.19540870919 – in German), though the rearrangements of aryl alkyl ethers to tertiary alcohols and that of allylic ethers to homoallylic alcohols also bear his name. The Wittig olefination is one of the most widely known and widely use reactions in organic chemistry and the mechanism taught undergraduate level is known by all.  However, beyond undergraduate level the mechanism is anything but widely accepted and investigation into its finer points is extensive. [This 2009 theoretical studies has a short introduction to the mechanistic debate and all the appropriate references DOI: 10.1007/s00214-009-0521-4].

As the Wittig is taught at undergraduate level, we know that the use of a non-stabilised ylide exclusively forms Z-olefins, and in contrast a stabilised ylide will give exclusively E-olefins (explained by the reversibility of the oxaphosphetane formation), though the reality of this is never quite as good! [Undergraduates beware - the truth of organic chemistry is cleverly hidden from you until you make that decision to step into a synthesis lab: do not take that step lightly as at this point you will be shackled to the fume cupboard on an extendable dog lead that retracts at the call of your name.]

Although the ability to switch the olefin geometry by selection of a stabilised or non-stabilised ylide is useful, it is limited by the need to have an electron withdrawing group, whether you want it or not, to generate transselectivity. An alternative [I am not sure why this is not more widely known or used - maybe the selectivity is generally not great, but the examples I have seen seem pretty good] is to use a Schlosser modification of the Wittig reaction to enable the use of non-stabilised ylides to generate trans-olefins.

Week 14 Mega Chemist Challenge Solution

Sorry for the lack of clues this week. I was overcome by the joy of an extended weekend, and by the time A Retrosynthetic Life floated through my mind it was a little late for clues. If you were desperate though, my colleague introduced me to a new way of cheating the Mega Chemist Challenge – it turns out you can past images into Google searches – I had no idea. Seems like a little too much work to me though…..

This weeks Mega Chemist was Professor Daniel J. Weix from the University of Rochestester, NY. Weix obviously knew he would feature on the Mega Chemist Challenge and as a consequence set out to make my life as difficult as possible by not having a personal profile on his website. As a result, the following has been cobbled together from numerous sources and therefore may be a little prone to errors.

Weix completed his PhD under the supervision of Prof. Johnathan Ellman (of Ellman’s auxillary fame)  at the University of California, Berkeley, in 2005. Wiex’s first paper was actually working on an improved and scalable synthesis of Ellman’s auxiliary (DOI: 10.1021/ol034254b). Weix then scored a couple of more JACS papers with Ellman before moving to the Hartwig group at Yale, working on Iridum catalysed allylations. Weix followed Hartwig to Illinois to complete his post-doctoral work before taking a faculty position at Rochester in 2010.

This weeks papers are Weix’s recent JACS Article (DOI 10.1021/ja301769r) on the nickel catalysed reductive cross coupling of aryl halides and alkyl halides, the follow-up to his first independent research paper (JACS DOI 10.1021/ja9093956) paper published in 2010.

In contrast to traditional cross-coupling methods (Negishi, Suzuki, Stille, Kumada etc.) that couple a nucleophilic carbon (C delta +) and electrophilic carbon (C delta -), Weix couples two electrophilic carbon atoms directly, avoiding the formation stoichiometric organometallic species.

Avoiding the formation stoichiometric organometallic intermediates has allowed Weix to identify reaction conditions that require no effort to exclude air or water – reactions are performed in ‘wet’ flasks under an atmosphere of air – which should float the boat of the industrial chemists amongst you. The mild conditions and avoidance of often very basic organometallic intermediates means a very high functional group tolerance and allows for substrates prone to elimination or with acidic protons.

In Weix’s initial communication he identifies coupling conditions that work well for Ar-I with Alkyl-I, though less successfully with bromides.

I found the 10.7 mol% of catalyst very amusing – what happens if you deviate from this I am not sure, but rounding to the nearest mg shouldn’t do that much damage! The functional group tolerance is is great and far exceeds that of traditional coupling methods – lots of electrophilic centres, acidic protons, and even a Boronic ester come through unscathed – making subsequent derivatisation very facile indeed.

The follow-up paper goes about setting to rest the substrate limitations of the initial publication. New reaction conditions gave increased yields for aryl- and alkylbromides substrates, introduced the reductive coupling of vinyl-bromides and demonstrated the reaction of the much more widely available arylchlorides.  Weix also beautifully demonstrated the complimentary nature of his reductive couplings to conventional cross couplings carrying silanols, boronic esters, stannanes and pseudohalides (OTs, OTf) through the reaction conditions with synthetically useful yield.

There are more added bonuses to be found if you delve into this paper yourself – mechanistic studies, Hammet plots, a look at ligand affects, inspection of the role of each reagent etc. are all there for the taking. Studies on electron rich chlorides, and the coupling heterocycles and the like are ongoing.

These two papers provide a very useful alternative to traditional coupling techniques. No special handling techniques required, fairly cheap to run, and with a wide functional group tolerance – what more could you want?

……….well, I would trade in DMPU for a whole host of solvents – but then I just want it all!

Professor Weix is definitely one to keep an eye out for.

This weeks diagrams have been unceremoniously lifted from Weix’s papers - (DOI 10.1021/ja301769r) (DOI 10.1021/ja9093956) – and copyright is most definitely his.

Week 11 Mega Chemist Challenge Solution

This weeks Mega Chemist is the owner of what is probably the most infamous group photo, and definitely the most fiery. Here is Professor M. Christina White (does anybody know what the M stands for?) in all that flaming glory….

You can visit her group page for some brilliant pictures, but I think even better are these posters.

Professor White, as mentioned in the clues, completed her PhD in the group of Professor Gary Posner, initiating the hybrid Vitamin D3 analog program in his group. Following her time with Jacobson working on catalytic epoxidations, she began her independent career at Harvard before moving to the University of Illinois in 2005, where she now holds the position of professor. She has a whole host of awards as you would expect for someone with such a phenomenal background, most recently she was awarded the Roche Excellence in Chemistry Award (2009) and the Cope Scholar Award (2009). A short CV includes all of her  awards.

Professor White hit the ground running after the completion of her PhD. Her paper  ”A synthetically useful, self-assembling MMO mimic system for catalytic alkene epoxidation with aqueous H2O2″ (DOI 10.1021/ja015884g) published with Jacobson now has 227 citations. Following this her seminal independent publication “A sulfoxide-promoted, catalytic method for the regioselective synthesis of allylic acetates from mono-substituted olefins via C-H oxidation” (DOI 10.1021/ja039107n) was in JACS, and introduced us to the now eponymous White Catalyst.

White’s interest in C-H oxidation resulted in a string of papers in top journals, but new highs were reached with her first Science publication in 2007. This paper demonstrates the selective oxidation of unactivated sp3 C-H bonds in complex molecule synthesis, using only the steric environment and subtle electronic differences in C-H bonds to predictably control the outcome (DOI 10.1126/science.1148597).

Here is a recent perspective on C-H oxidation in synthesis by White.

Today’s paper is not from Science, but a brilliant application of a derivative of the White catalyst (DOI 10.1021/ja2059704) in dehydrogenative Diels-Alder reactions.

Week 10 Mega Chemist Challenge Solution

We had a few entries this week, all of which were correct.  The man in question was Armido Studer who is currently a Full Professor of Organic Chemistry at the Westfälische Wilhelms-Universität Münster.  As many of you know I will soon be working at the Westfälische Wilhelms-Universität Münster in the group of Professor Glorius, so hopefully I will get the chance to meet Professor Studer in person.

After Studer completed his undergraduate and postgraduate studies under the supervision of Prof. D. Seebach at ETH Zurich, he completed only a single year as a post-doc (with Prof. Dennis Curran) before beginning his independent research career. Very impressive. After his post-doc Studer returned to ETH Zurich to complete his habilitation (1996-2000), and then via the Philipps-Universität Marburg, became a full professor in Münster in 2004. Studer has won numerous awards throughout his career including the Solvias Ligand Contest and the Novartis Young Investigator Award in 2006.

Angewandte, as regular followers of this blog, agreed to interview Studer just in time for his feature in the Mega Chemist Challenge (this may be stretching the truth somewhat/completely), and you can find this here:  Armido Studer.

Studer’s research interests are of course varied, and his five top papers at the bottom of his interview linked above demonstrate this. The one that hit the top of my reading list is The Persistent Radical Effect in Organic Synthesis.

Studer made this weeks Mega Chemist Challenge as I wanted to learn a bit about the oxidative Heck reaction, and this paper synthesising tetrasubstituted olefins using consecutive oxidative Heck reactions hit the ASAP at just the right time. DOI: 10.1002/anie.201108211.

Week 9 Solution Mega Chemist Challenge

My apologies- wordpress just went a bit mad and published an early version-this (I hope) is the final one.

So this week has caused me a whole world of trouble. I just presumed that if you have discovered what becomes a so called “named reaction”, then you should be easy to find out about so I can knock up a quick biography. With week 9′s Mega Chemist this was not the case, and having received no correct answers or help with additional biographical information this is as good as it gets:

My name is Donald John Peterson, and in 1968 I discovered the Peterson olefination.

He does have a facebook page, but any leads went directly into brick walls! A scifinder search does suggest, as I mentioned in the clues, a move into industry. There seem to be a lot of patents for tin based pesticides. Nice.

This weeks paper(s), is Perterson’s 1968 JOC article “Carbonyl olefination reaction using silyl-substituted organometallic compounds”. I will also throw in for free a nice formal Peterson elimination-lactone opening (of the C-O bond) variant that I tried and failed to use during my PhD. This methodology was published by Professor Garry Procter of “Advanced Practical Organic Chemistry” fame – a really great textbook, though I challenge you to get your boss to but the “minimum required equipment”.