A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives

Watson, Morag E. and Jamieson, Craig and Kennedy, Alan R. and Mason, Andrew M. (2019) A reappraisal of the Ni-[(Benzylprolyl)amino]benzophenone complex in the synthesis of α,α-disubstituted amino acid derivatives. Tetrahedron, 75 (36). 130485. ISSN 0040-4020 (https://doi.org/10.1016/j.tet.2019.130485)

[thumbnail of Watson-etal-Tetrahedron-2019-A-reappraisal-of-the-Ni-Benzylprolyl-amino-benzophenone-complex-in-the-synthesis]
Preview
 Text. Filename: Watson_etal_Tetrahedron_2019_A_reappraisal_of_the_Ni_Benzylprolyl_amino_benzophenone_complex_in_the_synthesis.pdf
Accepted Author Manuscript
License: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 logo
Download (796kB)| Preview

Abstract

α,α-Disubstituted alkenyl amino acid derivatives (e.g. Fmoc-S 5-OH) are valuable monomers in the construction of stapled peptide derivatives. Synthetic access to these is possible using the Ni-[(Benzylprolyl)amino]benzophenone (BPB) complex as a chiral auxiliary. We discuss a reappraisal of the use of this, and demonstrate that epimerisation of the proline α-centre occurs during formation of the complex, leading to erosion in the enantiomeric excess of the final product. Modified conditions have been developed, providing the target compounds in high enantiomeric excess.

ORCID iDs

Watson, Morag E. ORCID logoORCID: https://orcid.org/0000-0003-0368-7648, Jamieson, Craig ORCID logoORCID: https://orcid.org/0000-0002-6567-8272, Kennedy, Alan R. ORCID logoORCID: https://orcid.org/0000-0003-3652-6015 and Mason, Andrew M.;
CORE (COnnecting REpositories)