One-Pot Process for the Preparation of a β-Alkynyl β-Amino Acid Ester (original) (raw)

A multicomponent approach to the synthesis of N-sulfonyl β2,3-amino esters

Organic & Biomolecular Chemistry, 2014

All reactions were carried out under argon atmosphere. Reagents and solvents were obtained from commercial suppliers and used without further purification. All reactions were monitored by gas chromatography (GC) using a 5 m BP1 column. Melting points (mp) were determined on a capillary melting apparatus and are uncorrected. Infrared spectra were recorded on a FT-IR spectrometer in ATR mode. NMR spectra were recorded in CDCl 3 at 400 MHz (1 H), 100 MHz (13 C) and 376 MHz (19 F). Chemical shifts () are reported in parts per million (ppm) relative to the residual solvent signal. Coupling constant values (J) are given in Hertz (Hz) and refer to apparent multiplicities, indicated as follows: s (singlet); d (doublet); t (triplet); q (quadruplet); m (multiplet); dd (doublet of doublets), td (triplet of doublets). Flash chromatography was performed on silica gel (40 µm-centered particles). HRMS experiments were realized by an outside facility. Yields given below for -amino esters 4 refer to mixtures of diastereoisomers. As far as possible, the NMR spectra of separated diastereoisomers are appended below, for more clarity. Unless otherwise stated, melting points are given for separated diastereoisomers. To the best of our knowledge, all -amino esters 4 are new compounds. Typical procedure for the synthesis of imines 1 Imines 1 were synthesized in 78-91% yield according to a procedure derived from that of Lu and Kwon (Org. Synth. 2009, 86, 212). In a typical procedure, methanesulfonamide (4.75 g, 50 mmol), benzaldehyde (7 mL, 70 mmol) and aluminum chloride (1.33 g, 10 mmol) were heated at reflux in toluene for 12 h using a Dean-Stark apparatus. Toluene was removed by evaporation then ethyl acetate (100 mL) was added to the remaining solid. The mixture was filtered and the solvent removed by evaporation. The solid was washed with a diethyl ether/pentane: 15/25 (2 × 40 mL) to afford the imine as off-white needles (8.40 g, 91%).

Lewis acid-promoted 1,4-addition to chiral imide derivatives in the synthesis of .beta.-amino acids

The Journal of Organic Chemistry, 1993

The 1,Caddition of 0-benzylhydroxylamine to imides 3 in the presence of various Lewis acids is described. The reaction is performed in CH2Cl2 at -78 "C and affords derivatives 4 and 5 in good chemical yields and in different diastereomeric ratios, depending on the Lewis acid employed. T i c 4 and Me2AlCl give opposite diastereoselectivities. Furthermore, enantiomerically pure @-amino acid 9 is obtained in good yield from compound 4a.

Catalyst and solvent-free amidation of inactive esters of N-protected amino acids

Tetrahedron Letters, 2011

A catalyst free procedure for the preparation of amides from inactive esters of N-protected amino acids and various amines is demonstrated under mild reaction conditions. Our effort to recover excess amine and generated alcohol is an approach towards environment friendly and cost effective synthesis under easy operational conditions.

Selective catalysis of ester aminolysis: an approach to peptide active esters

The Journal of Organic Chemistry, 1990

Model studies have been carried out in which the Kaiser-DeGrado procedure for solid-phase synthesis has been combined with the une of reactants with a latent activation feature as a potential route to peptide active esters. The rates of reaction of the 4-(methy1thio)phenyl ester of L-phenylalanine (la) with itself, as well as those of a close analogue with tert-butyloxycarbonylglycine bound to a benzophenone oxime functionalized polystyrene resin have been measured in the presence of varying concentrations of the aminolysis catalyst, acetic acid. These studies indicate that under appropriate conditions, it is possible to generate the 4-(methy1thio)phenyl esters of suitable peptides, synthesized by solid-phase methods on the oxime-functionalized resin. These peptide esters can then be oxidized to the more strongly electrophilic sulfone derivatives. The preparations of the 4-(me-thylsulfony1)phenyl esters of N-tert-butyloxycarbonylglycyl-L-phenylalanine and N-carbobenzyloxy-0-carbobenzyloxy-L-tyrosylglycylglycyl-L-phenylalanine are described as examples of the use of this method of preparing peptide active esters.