169738-76-5Relevant articles and documents
Palladium-catalyzed asymmetric benzylation of azlactones
Trost, Barry M.,Czabaniuk, Lara C.
, p. 15210 - 15218 (2013/11/06)
Asymmetric benzylation of prochiral azlactone nucleophiles enables the catalytic introduction of a benzyl group towards the synthesis of α,α-disubstituted amino acids. Herein, we report an enantioselective palladium-catalyzed process using chiral bis(diphenylphosphinobenzoyl)diamine (dppba) ligands. Naphthalene- and heterocycle-based methyl carbonates react with a number of azlactones derived from both natural and unnatural amino acids. Monocyclic benzylic electrophiles, for which the barrier to ionization is higher, must employ a phosphate leaving group in order to react. Reaction conditions for electron-rich and -neutral benzylic electrophiles have been developed, and the scope of the reaction has been explored with respect to both reaction partners. The high levels of asymmetric induction, as well as the reactivity pattern of the electrophiles, suggest an η3-benzyl intermediate that arises through two distinct pathways. Attack on benzyl: Palladium-catalyzed asymmetric benzylation methodology is demonstrated on prochiral azlactone nucleophiles. The use of naphthyl, heterocyclic, and monocyclic benzylic electrophiles demonstrates the wide reaction scope (see scheme; Cp=cyclopentadienyl). The benzylation products are readily converted into enantioenriched α,α-disubstituted amino acids.
L-phenylalanine cyclohexylamide: A simple and convenient auxiliary for the synthesis of optically pure α,α-disubstituted (R)- and (S)-amino acids
Obrecht,Bohdal,Broger,Bur,Lehmann,Ruffieux,Schonholzer,Spiegler,Muller
, p. 563 - 580 (2007/10/02)
This work describes L-phenylalanine cyclohexylamide (5c) as a simple, cheap, and powerful chiral auxiliary for the synthesis of a series of optically pure α,α-disubstituted (R)- and (S)-amino acids of type 1, such as (R)- and (S)-2-methyl-phenylalanine (1a), (R)- and (S)-2-methyl-2-phenylglycine (1b), and (R)- and (S)-2-methylvaline (1c). These amino acids were efficiently transformed into the suitably protected and activated amino-acid building blocks (R)- and (S)-12b and (R)- and (S)-12c which are ready for incorporation into peptides by solution or solid-phase techniques. Based on the crystal structures of 6b, 6c, and 7a belonging to the diastereoisomeric peptides series 6 and 7, the absolute configurations of each member of the series were determined. β-Turn geometries of type II' and I were observed for 6b and 7a, respectively, whereas 6c crystallized in an extended conformation. The impacts of side-chain variation on conformation and crystal packing of these triamides are discussed.
