The Realm of Organic Synthesis

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