Cramming a Methylene into an Enone

Mitch’s recent post at Chemistry-Blog about ChemFeeds prompted me to play around with the new program.  I’m sold.  Why?  Because it allows me to see the “punch line” of about 20 articles at once without having to read everything or scroll far down the page (how much do SOC's like to read?).  Before one of my first defenses in grad school, my boss took me aside and said that there were too many words in my paper.  “Organic chemists like pictures,” he said.  The new format of JACS Beta lets me look at pictures until my hearts content thus truly honing my abilities as an organic chemist. 

At any rate, I played around with the most recent posts on the JACS Beta and uncovered a gem.  Ryu and co-workers recently published a paper that provides a fantastic route to beta,gamma-unsaturated ketones.  Of course, cousins of the beta,gamma-unsaturated ketone (which include but are not limited to enones, enoates, enamines, etc.) are relatively easy to access courtesy of the several olefination procedures in any organic chemistry textbook (I’m a fan of Wittig, personally).  What if you need one methylenic carbon in between the conjugated pi-system?  Naturally, this would be a challenge to synthetic organic chemists.  I can’t think of a concise way off hand.

Ryu and co-workers put out a quick communication that highlights a reasonable way of forming these beta,gamma-unsaturated carbonyls via ruthenium-allyl complexes (from the corresponding RuH catalyst).  The paper, which features use of a RuHCl(CO)(PPh₃)₃ catalyst, reports 17 different instances of accessing beta,gamma-unsaturated ketones in a wide range of yields demonstrated on a vast array of benzaldehydes.  In a typical experiment, the catalyst and isoprene form the organoruthenium intermediate regioselectively (the 3,3-dimethyl complex was not observed).  Incorporation of the benzaldeyde (they claim through the 6-membered ring transition state) gave the desired beta,gamma-unsaturated ketone upon beta-hydride elimination.  

To support their mechanism, Ryu and co-workers performed several crossover experiments with deuterated benzaldehydes and p-fluorobenzaldehyde.  The outcome of these experiments showed a fairly equal scrambling of deuterium in the isolated products, which suggests that the “hydrogen and acyl units that add to the diene do come from different molecules of aldehydes.”  These results were consistent with those recently reported by Krische et al. 

It’s a neat method.  The obvious pitfall is the ruthenium (which doesn’t appear to be dropping in price anytime soon unless a sudden supply is found in Hoboken, New Jersey…random city, I know).  Otherwise, it seems like a reasonably useful transformation.

Off to go do some copper-hydride chemistry then dabble a bit in some medicinal chemistry then maybe eat dinner.  My wife’s friend asked me last week, “Don’t you ever get to take a break.”  “Sure we do.  My boss says I can do whatever I want for 12 of the 24 hours in the day.”  I really need to get a life.