Seen as though this weeks problem is quite easy I will keep the clues sparse.
PhD completed in 1999 under the supervision of Dr. Jonathan B. Spencer
Post-Doc with Professor Amos B Smith
Junior Research Fellow in the lab of Professor Steve Ley
Independent research career began in 2003
This one should be pretty easy, especially if you are in the UK. Answers on a postcard or via @karldcollins or email.
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.
This weeks Mega Chemist died in 1987 at the age of 90 in West Germany. He was drafted into the German army during the first world war and spent a year as a British prisoner of war before he restarted his chemistry career at the University of Marburg. He completed his PhD and his habilitation under the supervision of Karl von Auwers and subsequently had a highly successful career culminating in being awarded the Nobel Prize for his development of the use of phosphorus-containing compounds in organic synthesis. Two rearrangements bear his name.
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.