Prof. Li Deng http://www.chem.brandeis.edu/deng.html has done some interesting catalysis with some easy to get hold of catalysts. I saw him talk 2002 and he had just started working on cinchona catalysts, and he has gone on to do some useful stuff.
July 7, 2008
May 26, 2008
opening of styrene oxides….
…. with acetylide nucleophiles can show significant regioselectivity depending on both metal counter ion and arene substituent. Nice example of cation-like TS (or intermediate) in substitutions.
doi:10.1016/j.tetlet.2004.10.049
w-protection
After a few (!) years of working with the 20-odd “naturally occurring” I have finally got around to doing something I should have done years ago: selective amine sidechain protection. This was prompted by a need for some Cbz-protected Orn, and one of the few commercial suppliers being far too slow.
The copper method is well known and has been used for years, but I have never been that keen on removing it with H2S. OK, you can also use EDTA, but I like the idea of the use of NaBH4 to reduce the Cu(II) (Tetrahedron Lett. 2004, 45, 9297–9298 doi:10.1016/j.tetlet.2004.10.060).
Anyway, the initial coordination method with CuSO4 and Orn.HCl, and protection with Cbz-Cl, I got from WO 2004/037174. Also I read the Boc protection method in J. Med. Chem 1986, 29, 655-660 10.1021/jm00155a012 (this uses amine base rather than carbonate). The protecting groups are going on at the moment…….
Both methods look good. The only problem is that while the Cbz-Orn can be filtered out of water, the Boc-version is water soluble and has to be extracted from aqueous solution using either EtOH/CHCl3 mixtures (the JMC paper) or acetone - a better option (the TL paper). This does at least explain the price difference between commerical Cbz and Boc O and K.
UPDATE on removing the copper: I have tried reacting the complex with both NaBH4 (1eq. r.t. water) and Na2EDTA (1eq. 90degC, water), I have a clear winner yield-wise. It’s the EDTA. The borohydride route causes a lot of foaming and the black Cu product spreads everywhere.
