%0 Generic
%A Bernardi, Luca
%A Gothelf, Aase S.
%A Hazell, Rita G.
%A Jørgensen, Karl Anker
%D 2003
%T Catalytic Asymmetric Mannich Reactions of Glycine Derivatives
with Imines. A New Approach to Optically Active α,β-Diamino
Acid Derivatives
%U https://acs.figshare.com/articles/dataset/Catalytic_Asymmetric_Mannich_Reactions_of_Glycine_Derivatives_with_Imines_A_New_Approach_to_Optically_Active_-Diamino_Acid_Derivatives/3697596
%R 10.1021/jo026766u.s002
%2 https://acs.figshare.com/ndownloader/files/5788038
%K ligand
%K Catalytic Asymmetric Mannich Reactions
%K enantioselective Mannich reaction
%K glycine esters
%K benzophenone imine glycine esters
%K benzophenone imine glycine ester
%K chiral
%K Mannich adducts
%K glycine alkyl esters
%X Imines of glycine alkyl esters react with imines in a diastereo- and highly enantioselective Mannich
reaction in the presence of chiral copper(I) complexes as the catalyst to give optically active α,β-diamino acid derivatives. A series of imines of glycine esters derived from glycine and aromatic
carbonyl compounds has been screened as substrates for the Mannich reaction with different imines
in the presence of various combinations of metal salts and chiral ligands. The benzophenone imine
of glycine esters was found to react with N-protected imines in a diastereoselective fashion giving
functionalized α,β-diamino acid esters with excellent enantioselectivities. The most effective chiral
catalysts are chiral copper(I) complexes having phosphino-oxazoline (P,N)-ligands, and among these
ligands, those derived from (1R,2S)-dihydroxy-1,2,3,4-tetrahydronaphthalene gave the best results.
The scope of this new catalytic asymmetric reaction of the benzophenone imine glycine esters is
demonstrated for the reaction with different N-protected-C-aryl and C-alkyl imines giving the
Mannich adducts with excellent optical purity. Furthermore, the synthetic aspects of the reaction
are presented by converting the Mannich adducts into α,β-diamino acid derivatives. The relative
and absolute configuration of the Mannich adduct have been determined and based on the
stereochemical outcome of the reaction a tetrahedral chiral-copper(I)-imino glycine alkyl ester
intermediate is proposed. In this intermediate the Re-face of the benzophenone imine glycine ester
is shielded by the chiral ligand leaving the Si-face available for approach of the Si-face of the imine.
A series of semiempirical calculations has been performed to support the structure of the tetrahedral
chiral-copper(I) complex and to account for the influence of the substituents in the chiral phosphino-oxazoline ligands.
%I ACS Publications