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With my graduate school circus hopefully about to fold up tent, I will leave you with the abstract for this recent interesting Science paper which challenges a classic sophomore organic chemistry notion; that electron donating groups on benzene direct para and ortho substitution in electrophilic aromatic substitution reactions. By using a clever copper catalyst the authors manage to coax an aryl group to neatly substitute meta to an amido substituent, thus effecting a valuable C-H bond arylation.
"For over a century, chemical transformations of benzene derivatives have been guided by the high selectivity for electrophilic attack at the ortho/para positions in electron-rich substrates and at the meta position in electron-deficient molecules. We have developed a copper-catalyzed arylation reaction that, in contrast, selectively substitutes phenyl electrophiles at the aromatic carbon–hydrogen sites meta to an amido substituent. This previously elusive class of transformation is applicable to a broad range of aromatic compounds."I also want to state that I remember many in my sophomore organic class misunderstanding the facts about the effects of e-withdrawing and donating substituents. For some reason they used to think that electron donating groups activate ortho and para positions and electron withdrawing groups activate meta positions. But that's completely incorrect. The correct statement is one which I still remember from a then classic organic chemistry textbook (which sadly went out of print).
Electron donating groups on benzene activate all positions; it's just that they activate ortho and para positions more than meta. Similarly, electron withdrawing groups on benzene deactivate all positions; it's just that they deactivate para and ortho more than meta. Thus the effect of any group, whether electron donating or electron withdrawing, is greatest at the ortho and para positionsReference:
Phipps, R., & Gaunt, M. (2009). A Meta-Selective Copper-Catalyzed C-H Bond Arylation Science, 323 (5921), 1593-1597 DOI: 10.1126/science.1169975
I haven't seen the perspective supplied by Morrison, but then I was raised by Streitwieser et al. They did make the same point, but not anywhere near as elegantly.
ReplyDeleteViolating the sophomore organic rules is nothing new; many metals like Pd, Pt, Ir, and Rh (and many others) are well-known to activate arene C-H bonds. This example is cute cause it demonstrates regioselectivity, which is trickier. Ir-catalyzed arene C-H functionalization is regioselective for 1,3-disubstituted benzenes regardless of what you put on them: addition usually occurs at the 5 position (only in special cases does it not). Pd-catalyzed C-H functionalization is typically ortho-selective.
ReplyDeleteIt's also interesting to note that while electrophilic aromatic substitution is slowed down by electron-withdrawing groups, for many transition-metal catalyzed examples, electron-withdrawing groups speed up the substitution (because in EAS benzene is the nucleophile, where in, say, Ir-catalyzed substitution, the metal is). It's a tricksy hobbits.
That's what I have always found fascinating about organic chemistry, that one can always find counterexamples, but not so many that they make it impossible to construct general rules. Thanks for the info on metals.
ReplyDeleteMorrison and Boyd is the favorite Organic Chemistry book in India. Anybody who had to have clear fundamentals was asked to read and solve the problems of M&B. The problem sets start off with the drill problems and go into interesting story based problems (e.g. Experiences of an Inexperienced Graduate Student)
ReplyDeleteI was surprised to know from my friend at Rockefeller that Solomons/Wade/McMurry/others are the textbooks followed in US univs. The most surprising part?? Morrison and Boyd was NOT followed.
Clayden,Greeves et. al.,IMO,is at the same position of being a favorite to start learning Organic Chem. However, again in the US, this book is not followed (that's what I heard from my mates who are in grad school).
Of course Clayden et.al., follows a different perspective of not ordering the chapters based on functional groups. That is a FIRST. Morrison and Boyd ordered the chapters based on Mechanisms followed in reactions of functional groups, when their peers were just presenting the reactions of functional groups. That was a FIRST in their time, when they released their earliest edition.
Clyaden, Greeves et.al., is the Morrison and Boyd of post-Spectroscopy based structural determination.
Please see this http://pubs.acs.org/cen/education/83/8341education1.html
@above
ReplyDeleteSorry. URL broke.
pubs.acs.org/cen/education/83/8341education1.html
I was so happy to see that somebody in the United States had referred to the forgotten Morrison and Boyd, that I rushed in to comment :-)
ReplyDeleteOnly later when I was reading other posts of yours, did I happen to see that the "curious wavefuntion" referred to Ashutosh, (PIO??). And if you had studied in India, obviously you'd know about/ love Morrison and Boyd.
My mistake
Thanks for the link Srini; it's very interesting. Clayden et al. is a spectacular book and while it's still not closely followed in the US, I know people who have now taken note of it. Morrison and Boyd still remains a great textbook and I am sad it was never updated. Among the textbooks used here, I do like Vollhardt and probably Wade. But none of them compares to Clayden et al. You cannot fail to get excited about org chem after reading that book.
ReplyDeleteWavefunction, Did you study in India?
ReplyDeleteWhat would you consider to be _the defacto_ books to be read in Physical Chem, Organometallics and Inorganic Chem ala clayden et.al. for Organic?
ReplyDeleteWould these make the cut for P.Chem?
Mcquarrie, simon and
Berry, Price et.al.
ALL BULLSHIT - COPPER NOT NECESSARY
ReplyDeleteshould be retracted
You should update this post since it is well known that this work is BS. No need for copper. It's a Friedel crafts reaction. Copper does nothing. All the substrates are engineered to go meta as a natural preference. Bulky electrophile and piv groups ensure this.
ReplyDelete