Asymmetric synthesis of β2-amino acids: 2-substituted-3-aminopropanoic acids from N-acryloyl SuperQuat derivatives

Abstract

Conjugate addition of lithium dibenzylamide to (S)-N(3)-acryloyl-4-isopropyl-5,5-dimethyloxazolidin-2-one (derived from l-valine) and alkylation of the resultant lithium beta-amino enolate provides, after deprotection, a range of (S)-2-alkyl-3-aminopropanoic acids in good yield and high ee. Alternatively, via a complementary pathway, conjugate addition of a range of secondary lithium amides to (S)-N(3)-(2'-alkylacryloyl)-4-isopropyl-5,5-dimethyloxazolidin-2-ones, diastereoselective protonation with 2-pyridone, and subsequent deprotection furnishes a range of (R)-2-alkyl- and (R)-2-aryl-3-aminopropanoic acids in good yield and high ee. Additionally, the boron-mediated aldol reaction of beta-amino N-acyl oxazolidinones is a highly diastereoselective method for the synthesis of a range of beta-amino-beta'-hydroxy N-acyl oxazolidinones.

Lewis Acid-Catalyzed Diastereoselective Synthesis of Multisubstituted N-Acylaziridine-2-carboxamides from 2H-Azirines via Joullié–Ugi Three-Component Reaction

“…Ethyl 2-benzyl-3-oxo-butyrate was prepared according to the literature. 25 Ethyl 2-benzyl-3-oxo-butyrate (7.7 mmol, 1.0 equiv) was gradually added to a solution of NH 2 OH•HCl (7.7 mmol, 1.0 equiv) in pyridine (7 mL) at 0 °C. The solution was stirred for 4 h at 25 °C.…”

Silica gel mediated oxidative C–O coupling of β-dicarbonyl compounds with malonyl peroxides in solvent-free conditions

“…All solvents were distilled before use using standard procedures. Ethyl 4-acetyl-5-oxohexanoate (1a) [126], 3-benzylpentane-2,4-dione (1b) [127], 3-(4-chlorobenzyl)pentane-2,4-dione (1c) [128], 3-acetylheptane-2,6-dione (1f) [129], ethyl 2-acetylhexanoate (1h) [130], ethyl 2-acetyl-4-cyanobutanoate (1i) [131], ethyl 2-benzyl-3-oxobutanoate (1j) [132] and diethylmalonyl peroxide (2a) [20] were synthesized according to the literature.…”

Completely Stereocontrolled Aldol Reaction of Chiral β-Amino Acids

“…Davies et al reported the reaction of N-benzyl-N-α-methylbenzyl β-amino acid derivatives with SuperQuat auxiliary and 9-borabicyclo [3.3.1]nonyl trifluoromethanesulfonate to produce α,β′-syn aldols (Scheme 2). 8 Despite the relative simplicity of the substrates lacking the chirality at the β-carbon atom, a decrease in both the stereoselectivity and the yield was noted and was attributed to the choice of the nitrogen protecting groups. Similar observations were made by Seebach et al using N-Boc protection and dibutylboron triflate for enolate formation.…”