The Realm of Organic Synthesis

It’s been a few weeks since I’ve updated and with good reason.  I’ve submitted a draft of my first journal-worthy paper to the Boss about 2 weeks ago.  Despite the fact that he’ll probably demolish my text then remodel it to his liking, he claims to have actually liked what I reported.  But, with the success comes extra experiments to “make a stronger paper.”  To make a tired point, I’ve been running extra reactions while teaching a compacted summer course (along with grading duties).  As such, my writing has sadly slowed to a relative minimum; enough whining.  Oh, by the way, thank you to whomever posted a response about my phosphine tirade.  While the comment (for some reason) isn’t posted on the blog, I received notification from email, which prompted me to write a bit about good ‘ole organic.

I broke out an old bottle of copper(I) chloride the other day and ever since I’ve been leaving work with scrimshawed-blue calluses (I never thought I’d actually use that word in a sentence).  It turns out that copper(I), in it’s purest form, is actually colorless and oxidizes in the presence of oxygen to a blue/green copper oxide.  Ergo, as I recently purified CuCl (dissolve in HCl then precipitate the black solution with water until white) without gloves (dumb, I know), the white material I spilled on my hands during filtration eventually oxidized throughout the day.  Surely this sort of information would be extremely useful if noted in Purification of Laboratory Chemicals, but Wikipedia actually bailed me out followed by a cross-check in the Merck Index  (As a brief aside, would anyone else like to see chemical shifts reported in PoLC?)

There’s some really interesting cuprate chemistry that I’ve uncovered in recent literature searches that’s worthy of mentioning, particularly relating to conjugate reductions (an area of recent interest).  Of course, a silent majority of copper is used in conjugate additions (soft-soft interactions to all you HSAB peeps), which includes conjugate reductions using Stryker’s reagent ([Ph3PCuH]6, as seen in Org. Lett. 2001, 3, 1901-1903) or an air-stable hydrosilylating alternative (Yun’s invention, for an example, Chem. Comm. 2005, 5181-5183).  Apart from simply preparing copper hydrides from silanes (Tet. Lett. 1997, 38, 8887-8890), enantioselective variants have crept into the literature in recent years.  Here’s an interesting, yet reasonably appropriate analogy for you: Molander is to samarium chemistry as Buchwald is to enantioselective conjugate additions (check out JACS 2003, 125, 11253-11258 or Org. Lett. 2003, 5, 2417-2420, for example).  As a fairly young and naïve grad student, it’s interesting to know that Buchwald isn’t just about C-N bond forming reactions.

Does anyone know why arylsilanes work better/faster than alkylsilanes in hydrosilylating conjugate reductions?  I’m assuming it’s due to two things: (1) the electron-donating nature of an aryl ring creates a more labile hydride thus allowing for better insertion/ligand exchange with the copper and (2) the b-silicon effect seen in alkylsilanes stabilizes the cationic nature of the silicon atom making the hydride less labile.  Comments are welcome and encouraged!

As mentioned before, there’s a wide variety of conjugate additions in the literature ranging from Mulzer’s morphine synthesis (ACIE 1996, 35, 2830-2832) to Amir Hoyveda’s recent enantioselective methodologies (Org. Lett. 2007, 9, 3187-3190).  In all of the literature I’ve encountered, very few have yet to optimize an enantioselective conjugate addition of vinyl groups, which would be unbelievably synthetically useful (ORP ALERT!!!).  Apart from conjugate reductions, Evans and Johnson hammered out methodology for enantioselective Diels-Alder reactions using catalytic amounts of copper(II) and chiral ligands at low temperatures (JACS 1998, 120, 4895-4896, for example).

The majority of these reactions (with the exception of the Diels-Alder example) seem to use an excess of reagents and therefore don’t appear to be too environmentally benign.  I recall doing a copper(I)-mediated conjugate addition only to filter off the reagent during workup.  All of that precious, expensive copper gets totally wasted.  (I’ll mention that copper sulfate will complex with pyridine to pull the base out of the organic phase if your workup is acid sensitive).  Even in some of these conjugate reductions, 2 molar equivalents are used (though, it’s been demonstrated in a variety of methodologies that the mechanism is catalytic in copper) and often there’s an excess of silanes (upwards of 4 molar equivalents).  Stryker’s is no better because of the excess of triphenylphosphine, which I imagine is a pain during workup/chromatography.  Are there any benign alternatives to what’s currently out there?  (again, ORP ALERT!)

Anyone else headed to the Boston ACS conference later this month?  I’m trying to meet up with friends and colleagues in the hope of increasing my networking.  Perhaps if I come across an interesting presentation or two I’ll create a post.  Don’t really care about Barry Bonds and his 756* homeruns.  I was ecstatic about the Blue Jays, Yanks game last night when Clemens got tossed for hitting Rios (http://www.youtube.com/watch?v=-HZtiWzgT6s).  As for my Sox, we can start hitting the panic button now…