Efficient Catalytic Enantioselective Reaction of a Glycine Cation Equivalent with Malonate AnionsviaPalladium Catalysis

Abstract

The enantioselective alkylation of Schiff base acetates 1 with malonate types of stabilized carbon nucleophiles in the presence of a stable palladium source Pd(OAc) 2 and the chiral ligand (+)-BINAP was developed. The product 2, a protected -carboxyaspartic acid (ASA), was obtained in up to 85% enantiomeric excess by varying the ester protecting group on the substrate. The nature of the nucleophile has a significant effect on the enantioselectivity in this (2-aza-π-allyl)palladium system. While a rapid chemical conversion was achieved with Schiff base benzoates 5, the enantioselectivity was insensitive to the leaving group used. An optically active substrate (51% ee) gave the same level of enantioselectivity as that obtained from the racemate. Temperature effects on the reaction were also studied; the best selectivity was obtained at 0°C. A laboratoryscale reaction of the reactive nucleophile KCH(COOCH 3 ) 2 with the tert-butyl ester substrate 1c gave, following a single recrystallization, product 2c with 95.5% ee in an overall chemical yield of 62%. 3962

Benzophenone Schiff bases of glycine derivatives: Versatile starting materials for the synthesis of amino acids and their derivatives

“…BINAP was used as the chiral ligand in the palladium-catalyzed reaction of the glycine cation equivalent 7c with malonate anion (Scheme 39). 99,100 It included a systematic study of the substrate, nucleophile, additives and reaction conditions. Key findings were the preference for using the t-butyl ester of the acetate (7c) and the potassium salt of the malonate.…”

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

“…When the reaction was conducted using a combination of 5 mol % Pd­(OAc) 2 and 10 mol % of the bidentate ligand 1,4-bis­(diphenylphosphino)­butane (dppb), the isolated yield of 252 improved to 87% . This Pd-catalyzed generation and alkylation of a 2-azaallyl cation species could be rendered enantioselective by employing chiral bidentate bisphosphine ligands. − Using tert -butyl ester 249c as substrate and ( R )-BINAP as the chiral ligand at 0 °C effected the highest levels of asymmetric induction, affording the corresponding triester ( S )- 253 in 77% isolated yield and 93:7 er (Scheme ). As is frequently the case for chiral compounds possessing a benzophenone imine moiety, the enantiopurity of ( S )- 253 could be improved (97.75:2.25 er) via a single recrystallization.…”

Pyran-containing sulfonamide hydroxamic acids: potent MMP inhibitors that spare MMP-1

“…Subsequent deprotection with hydroxylamine efficiently yielded the amine. 15 The minor endo diastereomer was generally not separated after either of these steps since it was later purged during the sulfonylation step in which it is less reactive than the exo isomer. Cleavage of the ester with TFA and conversion of the resultant acid to the acid chloride was followed by coupling with bis-TMS-hydroxylamine, prepared in situ, to yield, after aqueous acid work-up, the hydroxamic acid.…”