Subscribe to RSS
DOI: 10.1055/s-2008-1078615
Synthesis of 5-Alkynylproline Derivatives via Intramolecular Nicholas Reaction
Contributor(s):Victor Snieckus, Jignesh J. PatelUniversidad de La Laguna, Tenerife, Spain
Intramolecular Nicholas Reaction: Stereoselective Synthesis of 5-Alkynylproline Derivatives
Org. Lett. 2008, 10: 2349-2352
Publication History
Publication Date:
22 August 2008 (online)
Key words
alkynylproline - alkyne-cobalt carbonyls - propargylic alcohols - Nicholas reaction
Significance
Reported here is a Lewis acid catalyzed stereoselective synthesis of 5-alkynylproline derivative 2 from cobalt complexes of d-propargylic alcohol a-amino acid derivatives 1 via the Nicholas reaction. The reaction proceeds via an intramolecular nucleophilic attack by the amino group on a Co2(CO)6-propargylic cation to form the pyrrolidine ring system. Stereochemical outcome of the reaction is totally dependent on the nature of the protecting group with R¹ = Ts and Bz giving useful diastereoselective control.
Comment
The relative configuration of the cis and trans products 2a and 2b was assigned by NMR studies and by their conversion into A and B (five steps from 2a and 2b, respectively) and by X-ray crystallographic analysis of intermediates. The present study is also supported by semiempirical calculations. Complex 1 was synthesized in four to five steps from l-glutamic acid in each case.