177950-58-2Relevant academic research and scientific papers
Electrophilic fluorination of pyroglutamic acid derivatives: Application of substrate-dependent reactivity and diastereoselectivity to the synthesis of optically active 4-fluoroglutamic acids
Konas,Coward
, p. 8831 - 8842 (2007/10/03)
Electrophilic fluorination of enantiomerically pure 2-pyrrolidinones (4) derived from (L)-glutamic acid has been investigated as a method for the synthesis of single stereoisomers of 4-fluorinated glutamic acids. Reaction of the lactam enolate derived from 9 with NFSi results in a completely diastereoselective monofluorination reaction to yield the monocyclic trans-substituted α-fluoro lactam product 21. Unfortunately, a decreased kinetic acidity in 21 and other structurally related monofluorinated products renders them resistant to a second fluorination. In contrast, the bicyclic lactam 12 is readily difluorinated under the standard conditions described to yield the α,α-difluoro lactam 24. The difference in reactivity between the two types of related lactams is attributed mainly to the presence or lack of a steric interaction between the base used for deprotonation and the protecting group present in the pyrrolidinone substrates. This conclusion was reached based on analysis of the X-ray crystal structure of 21, molecular modeling, and experimental evidence. The key intermediates 21 and 24 are converted to (2S,4R)-4-fluoroglutamic acid and (2S)-4,4-difluoroglutamic acid, respectively.
Diastereoselective alkylation of 1-benzyl-(5S)-substituted 2-pyrrolidinones
Brena-Valle, Leonardo J.,Sanchez, Rodolfo Carreon,Cruz-Almanza, Raymundo
, p. 1019 - 1026 (2007/10/03)
The (S)-glutamic acid derivatives, (5S)-methoxymethyl- and (5S)-benzyloxymethyl N-benzyl-2-pyrrolidinones, compounds 3a and 3b respectively, exhibit good to excellent diastereoselection upon alkylation with primary alkyl bromides or iodides.
