Thursday, March 11, 2010

How to prevent N-Cbz from falling off in hydrogenation condition ?

N-Cbz is sensitive to H2/pd/c even in basic condition (TEA).
Known methods to prevent N-Cbz from falling off when doing hydrogenation reactions are not many.

1. Pd/c (en), H2, THF by Kosaku Hirota
pd/c (en) is pd/c deactivated by ethylenediamine. It is developed for chemoselective hydrogenation of reducible functionalities such as olefin, acetylene, nitro, azide, aromatic bromine or benzyl ester moieties, in the presence of O-Bn or N-Z protective
groups.
alkyl N-cbz is stable while double bonds are saturated.
aryl-N-cbz is unstable under this catalyst.
H. Sajiki, K. Hattori and K. Hirota, J. Org. Chem., 1998, 63, 7990.

2. Pd(OAc)2, DPPF,TEA, dmf,formic acid
Can do deoxygenation of phenol by OTf in the presences of N-Zbz.

3. squaric acid derivative/pd/c/H2
works ok, can saturate double bond without touch n-cbz.

4. pd/c/ph2s/H2
also can saturate double bond without touching n-cbz.

5. Pd(OAc)2, DPPF, TEA, dmf,formic acid, Et3SiH
works for deoxygenation of phenol triflate in the presense of N-Cbz.

Note:
1. pd/c(en) was tried. but n-cbz falled off quickly.
2. dppe/pd/formic acid method is OK.
3. ph2s/pd/c/h2 didn't touch N-cbz in my hand. but can't do deoxygenation of a phenol.

5 comments:

Jeff & Al said...
This comment has been removed by the author.
Jeff & Al said...

I have reduced an internal alkyne to the alkane while not cleaving a benzyl ether from a primary alcohol by using a balloon of H2 and Pd/C in the presence of NaHCO3, using ethanol as solvent. The key was to stir the starting material in ethanol in the presence of the catalyst and the NaHCO3 for at least 10 minutes before you introduce the hydrogen atmosphere.

I would think that the rate of CBz cleavage would be similar to OBn cleavage so the above conditions should be amenable to your goal too.

Weiwei TIAN said...

good to know.
thank you.

Jeff & Al said...

To see the chemistry, check out Angew. Chem. Int. Ed. 2008, p. 4335 and Chem. Eur. J. 2009, p. 7117.

Weiwei TIAN said...

thank you. The following link may be useful:
http://tvv2008.blogspot.com/2007/11/benzyl-ether-protection-group.html