The Realm of Organic Synthesis

For those keeping score at home, it’s been Carbon-Carbon Bond Forming Reaction: 10, Jeremy: 0. I’ve come home the past few weeks with a sweaty forehead after my nitroethylene unexpectedly flash-polymerized in a plume of NO2 (I’ve been told by my inorganic cohorts that a little bit of NO2 is “good for ya” once in a while).  Fate has taken a turn recently, though; the University finally repaired the severed fiber optic cable behind the science library finally allowing me to use SciFinder. 

I literally stumbled onto my proverbial four-leafed clover (something that probably would’ve happened sooner had the construction crews excercised a bit more caution with the jackhammer, see above).  In the preparation of a number of nitro-containing substrates, Watanabe et al. (Hel. Chim. Acta 1984, 67, 1204-1207) disclosed that trialkylphoshpines are capable of activating already highly reactive substrates (i.e. nitroethylene) to facilitate pseudo-conjugate addition reactions via substitution mechanism.  In short, it’s a variation of the Rauhut-Currier reaction (US Patent 3,074,999 1963) or Baylis-Hillman with a twist (alkylphosphines instead of DABCO).  The best part is that the reaction mixture is pretty mild in terms of pH and therefore can tolerate a number of highly reactive olefins; the proof is seen in the new TLC spot this morning that matches up against my known standard and the fact that I haven’t seen one nanomole of nitrogendioxide gas. 

WHAT?  To the layman, think of the reaction as TNT that you’re trying to light with a match but no fuse.  You’ll inevitably blow yourself up when the match touches the highly explosive material.  Now, think of the alkylphosphine as a detonation switch similar to what Wile E. Coyote uses to blow up the Road Runner in Bugs Bunny cartoons.  This charge source is reusable and suits other major purpose of not blowing yourself up (or tanking your reaction). 

The Rauhut-Currier reaction has been applied in numerous instances.  While I won’t highlight the several applications, I will say that there’s an excellent, well-cited review about the Rauhut-Currier reaction by Michael Bultman (works with David Gin at the Sloan-Kettering Institute in NY): http://chemistry.uiuc.edu/gradprogram/chem435/fall04/07_Bultman_Abstract.pdf

Just got back from spending a few days in at Ft. Walton Beach (purportedly the “Redneck Riviera”) with Kerri.  We both ate a ton of seafood and had a great time.  The trip was surprisingly semi-inspirational as I’ve been at a research roadblock the past week or so trying to do a simple, symmetric carbon-carbon bond formation with a very unstable Michael acceptor.  I found out that the acceptor really likes to form nitrogen dioxide really easily in the presence of triethylamine.  We recently tried the lithium route but the substrate is very stubborn and won’t connect well. 

So, with my toes buried in the sand looking out on the emerald-green Gulf, I recalled doing a Michael reaction with a similarly unstable acceptor in water some time ago.  As Li reported in Aqueous Reactions in Organic Chemistry (the 2nd edition JUST came out, ISBN 978-0471761297), acrolein can installed at the alpha carbon of 1,3-diones in excellent yields using water as a solvent (demonstrated by Deslongchamps et al., JOC 2002, 67, 5669-5672).  It turns out that this method (or at least its enantioselective variant) is pretty hot in organic synthesis.  Xiao et al. recently reported on their early work on aqueous Michael additions using pyrrolidine-urea catalysts to induce enantioselectivity (Tetrahedron Letters 2007, 48, 21-24).  Other noted researchers in the field include Takabe who reported that Michael reactions in brine (particularly with reactive, easily polymerizable acceptors) actually help to stabilize the anionic intermediates thus optimizing yields (JACS 2006, 128, 4966-4967).  Interestingly enough, when his researchers used seawater as the solvent from the Pacific (they work at Scripps and Shizuoka University) they achieved similar results to using brine. 

On a side note, while the fire department was rummaging though Shelby Hall trying to find the cause of this morning’s fire alarm, Vince and I were talking about Maddox’s Titanic conspiracy that he posted a while back.  If you’re looking for a laugh, check it out: http://www.thebestpageintheuniverse.net/c.cgi?u=af07

We had an awful time at the Olive Garden the other night, which prompted me to fire off an email to their corporate offices complaining about the level of service.  The squeaky wheel gets the oil; they thanked us for our comments and are sending a gift card in the mail as an apology.  Not a bad way to start off a Friday morning.

It’s all about lithium enolates today.  It’s been quite some time since I last used any lithium reagent (properly), so I decided to brush up on the basics as a refresher.  The University of Rochester has an impressive website entitled “Not Voodoo,” which features the rudimentary concepts of synthetic organic chemistry along with a few pearls of wisdom intertwined (http://chem.chem.rochester.edu/~nvd/).  There’s a very interesting laboratory guide that’s perfect for the inexperienced organic chemist, Advanced Practical Organic Chemistry by Leonard, Lygo and Proctor (ISBN: 0 7487 4071 6).  The book covers all of the basics without going into excruciating detail and/or half-directions—characteristics of many Ph.D.’s. 

While on the subject of standard operating procedures, as many of you know, Perrin and Armarego published an excellent book entitled Purification of Laboratory Chemicals (ISBN 0 7506 3761 7), which has recently been a personal favorite.  It’s pretty much an encyclopedia preparing a number of reagents for reaction-level purity (organic and inorganic).  The best part is that the majority of the purification procedures have references for primary literature (if that sort of thing matters to you). 

Switching gears, what’s up with the Red Sox as of late?  We once had a 12-game lead on the Yanks, and now we’re down to 7 1/2 after losing a 3-game series to the ROCKIES at Fenway.  Maybe we can get the bats swinging against San Fran this weekend.

On a more personal level, there’s a great article in the Crimson White about how UA is extorting engineering students out of their football tickets this upcoming semester: (http://media.www.cw.ua.edu/media/storage/paper959/news/2007/06/14/Opinion/CoOp-Students.Unfairly.Denied.Tickets-2915148.shtml?reffeature=mostemailedtab).  That author must be a genious.

Have a great weekend.

I spent the better part of the morning looking for the cat, for fear that she had wandered outside.  After searching for nearly an hour, I finally called Kerri to let her know the news; Miss Piggy was gone!  When Kerri got home, she literally tore the house apart looking for the awfully vocal tabby cat.  It turns out that the feline in question was hiding in the recliner (literally, up inside the wood-metal frame).  As loving parents, we grounded Miss Piggy for a week and took away the catnip (..kids today).

So, now the shock has worn off, and now I’m back at the lab ready to get some work done.  I wonder, though, why no one has come up with a simple method for converting primary alcohols to their corresponding iodides without making triphenylphosphine oxide as a byproduct—a pain in the neck to remove and possibly the most atom uneconomical transformation known to the synthetic world.  Typical procedures involve treatment of the alcohol with PPh3, I2 and a fair amount of imidiazole to “kick it up a notch.”  Olah and co-workers wrote a review about the utility of pyridinium poly(hydrogen fluoride) in the presence of NaI (JOC 1979, 44, 3872), but the chemistry seems to only work for electron-donating or electron-stagnant reactants in fair yields.  An iodination that cleanly affords the desired primary halide without easy to remove byproducts with a fair degree of atom economy would make a fantastic original research proposal idea. 

Off to play with phthalic anhydride (seems to be the reagent of the day—http://orglist.net Everybody Digest, Vol. 35, Issue 10), so I can get home and watch the season premier of Rescue Me on FX.

Welcome to the Realm of Organic Synthesis.  I recently read an article about personal success and self-marketing.  One of the several keys in the article (apart from constant networking, developing an identity, etc.) was to start writing about something you know.  For me, what better way than by writing about my experiences in the lab and overall research? 

So, how about a little background?  I’m currently a graduate student at the University of Alabama in Tuscaloosa.  I work for (or “with”) Dr. Tim Snowden on developing new methodology for applications to natural product synthesis.  To the layman, we’re coming up with new, groundbreaking ways to make very complex molecules that exhibit a variety of therapeutic value.  Often these molecules are cytotoxic, particularly to cancerous cells.  So, in an oversimplified explanation, we’re trying to cure cancer.

The general aim of this weblog is to introduce you, my audience, to the field of synthetic organic chemistry through my lab experiences, interesting articles I’ve recently come across about science (chemistry in particular) and the occasional thought (my extensive liberal arts background has made me a proponent of philosophy). 

Welcome to the blog, and I hope you gain a little insight into the vast ocean of organic synthesis.