Hi, I have trouble cleaving off the phenyl glycinol chiral auxilliary from my amino acid analogue. I have only tried oxidative conditions, (PbOAc4) varying the reaction time, temperature and solvent. I am reluctant to use hydrogenolysis due to the fact that my molecule is labile in reductive conditions. Any suggestions?
Thanks.
Dear Athanasios,
I suggest that you read the attached review article published in Chemical Reviews which contains schemes illustrating methods for the cleavage of phenyl glycinol chiral auxilliary from amino acid analogues. Particularly, see the sub-section "r-Phenylglycinol as the Chiral Auxiliary " in pages 6958-6959 (including the appropriate schemes).
Hoping this will be helpful,
Rafik
@Athanasios
I assume that you are trying to oxidize the attached chiral auxiliary into the corresponding benzaldimine for subsequent hydrolysis into the free amine.
Have you considered sodium metaperiodate (NaIO4) or a related reagent? Please see the references below. NOTE: Be careful when handling reactions that require or generate large amounts of periodic acid. It is a strong oxidizer and highly corrosive.
• From U Bologna and GSK in Italy:
"Asymmetric Synthesis of 1-(2-Pyrrolyl)alkylamines by the Addition of Organometallic Reagents to Chiral 2-Pyrroleimines"
http://onlinelibrary.wiley.com/wol1/doi/10.1002/ejoc.200700597/full
• From Pfizer:
"Practical enantioselective synthesis of beta-substituted-beta-amino esters"
http://pubs.acs.org/doi/abs/10.1021/jo050177h
• From Pfizer. See Supporting Info: Compound 16 to Compound 17:
"Pilot Plant Preparation of an αvβ3 Integrin Antagonist. Part 1. Process Research and Development of a (S)-β-Amino Acid Ester Intermediate: Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction"
http://pubs.acs.org/doi/abs/10.1021/op034094j
Admittedly, I have only cleaved similar auxiliaries by hydrogenation. Hope this helps!
I will consider all the suggestions and read all the articles! Thank you all so much for your help.
- Badges
- Science topic
- Similar topics
- Chemistry
- Pharmacology