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.

The initial (and very short) paper was published in 1965  (DOI: 10.1002/anie.196601261).

The formation of a mixture of cis- and trans- oxaphosphetanes 1a and 1b as you would expect in a standard Wittig reaction proceeds as usual, however, Schlosser showed that cleavage of the P-O bond by introduction of excess lithium salts to give lithiobetaines 2a and 2b was possible. He went on to show that on deprotonation the lithiobetaines rapidly equilibrate to the trans-beta-oxido phosphorous ylide 3a. Subsequent protonation of 3a and sequestration of excess lithium ions with potassium tert-butoxide reforms the trans-oxaphosphetane 5 which then eliminates to give E-alkenes.

This reaction always seemed to me to be a very nice solution to the problem of selectivity in the Wittig reaction, but I presume there must be a reason they do not pop up so often in the lit. I would love to know a bit more so let me know if you have ever tried one of these.

About these ads

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s