Β-dehydroamino Acid Derivatives Research Articles

Synthesis of a new bulky phosphite ligand and its application in the enantioselective hydrogenation

A new bulky phosphite ligand was synthesized and tested in the asymmetric Rh-catalyzed hydrogenation of a series of substrates, including dimethyl itaconate (up to 95% ee), α- and β-dehydroamino acid derivatives (up to 88% and 76% ee, respectively). In the Ir-catalyzed hydrogenation of 2-methylindole, the use of iodine as an additive led to a significant increase in the enantioselectivity and conversion. The best result (64% ee) was obtained with [Ir(COD)Cl]2 as precatalyst.

High yielding synthesis of N-ethyl dehydroamino acids

Recently we reported the use of a sequence of alkylation and dehydration methodologies to obtain N-ethyl-α, β-dehydroamino acid derivatives. The application of this N-alkylation procedure to several methyl esters of β,β-dibromo and β-bromo, β-substituted dehydroamino acids protected with standard amine protecting groups was subsequently reported. The corresponding N-ethyl, β-bromo dehydroamino acid derivatives were obtained in fair to high yields and some were used as substrates in Suzuki cross-coupling reactions to give N-ethyl, β,β-disubstituted dehydroalanine derivatives. Herein, we further explore N-ethylation of β-halo dehydroamino acid derivatives using triethyloxonium tetrafluoroborate as alkylating agent, but substituting N,N-diisopropylethylamine for potassium tert-butoxide as auxiliary base. In these conditions, for all β-halo dehydroamino acid derivatives, reactions were complete and the N-ethylated derivative could be isolated in high yield. This method was also applied for N-ethylation of non-halogenated dehydroamino acids. Again, with all compounds the reactions were complete and the N-ethyl dehydroamino acid derivatives could be isolated in high yields. Some of these N-ethyl dehydroamino acid methyl ester derivatives were converted in high yields to their corresponding acids and coupled to an amino acid methyl ester to give N-ethyl dehydrodipeptide derivatives in good yields. Thus, this method constitutes a general procedure for high yielding synthesis of N-ethylated dehydroamino acids, which can be further applied in peptide synthesis.

The use of a new carboranylamidophosphite ligand in the asymmetric Rh-catalyzed hydrogenation of α- and β-dehydroamino acid derivatives

New chiral carboranylamidophosphite ligand was synthesized and tested in the Rh-catalyzed asymmetric hydrogenation of α- and β-dehydroamino acid derivatives (up to 93% ee). The catalytic performance is affected greatly by temperature and the nature of solvents. Importantly, we have shown that in the hydrogenation of the β-dehydroamino acid derivatives the use of acidic 1,1,1,3,3,3-hexafluoro-2-propanol led to a significant increase in the enantioselectivity, compared to isopropyl alcohol.

A new easily accessible chiral phosphite–phosphoramidite ligand based on 2-anilinoethanol and R-BINOL moieties for Rh-catalyzed asymmetric olefin hydrogenation

A novel chiral phosphite–phosphoramidite ligand based on 2-anilinoethanol and R-BINOL moieties has been synthesized in one-pot. The ligand was evaluated in the rhodium-catalyzed enantioselective hydrogenation of α- and β-dehydroamino acid derivatives and dimethyl itaconate in three different solvents at 25 °C, at 1 or 50 bar of hydrogen pressure. The solvent and the pressure effect are discussed.

Development of Practical Rhodium Phosphine Catalysts for the Hydrogenation of β-Dehydroamino Acid Derivatives

The rhodium-catalyzed asymmetric hydrogenation of various β-dehydroamino acid derivatives to give optically active β-amino acids has been examined. Chiral monodentate 4,5-dihydro-3H-dinaphthophosphepines, which are easily tuned and accessible in a multi-10-g scale, have been used as ligands. The enantioselectivity is largely dependent on the nature of the substituent at the phosphorous atom and on the structure of the substrate. Applying optimized conditions up to 94% ee was achieved.

Polymer-supported monodentate phosphite ligands for asymmetric hydrogenation

Several new polymer-supported monophosphite ligands have been developed and the rhodium complexes were shown to be highly efficient, highly enantioselective and easily separable catalysts for asymmetric hydrogenation of itaconates, enamides, α-dehydroamino acid derivatives and β-dehydroamino acid derivatives.

Six-membered bis(azaphosphorinane), readily available ligand for highly enantioselective asymmetric hydrogenations

A new six-membered bis(azaphosphorinane) ligand has been readily prepared starting from an inexpensive chiral epoxide; excellent enantioselectivities (up to over 99% ee) have been achieved in the Rh-catalyzed asymmetric hydrogenations of β-dehydroamino acid derivatives and α-arylenamides.

Synthesis of Monodentate Chiral Spiro Phosphonites and the Electronic Effect of Ligand in Asymmetric Hydrogenation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly Enantioselective Rhodium‐Catalyzed Hydrogenation of β‐Dehydroamino Acid Derivatives Using Monodentate Phosphoramidites.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Mono- versus bidentate ligands in rhodium-catalyzed asymmetric hydrogenation. A comparative rate study.

Bidentate chiral phosphines are no longer essential for achieving a fast and highly enantioselective hydrogenation of α- or β-dehydroamino acid derivatives. In particular, a readily accessible and stable monodentate phosphoramidite can be highly effective in these asymmetric hydrogenations.

Highly enantioselective rhodium-catalyzed hydrogenation of beta-dehydroamino acid derivatives using monodentate phosphoramidites.

New and very easily accessible monodentate phosphoramidite ligands have been developed that lead to excellent ee's and full conversions in the hydrogenation of (E)- and (Z)-beta-dehydroamino acid derivatives with both aliphatic and aromatic side chains. Particularly, two different catalytic systems were established for (E)-beta-(acylamino)acrylates (98-99% ee) and (Z)-beta-(acylamino)acrylates (92-95% ee) based on phosphoramidites 2 and 3, respectively.

Synthesis and UV photoelectron investigation of the ?peptide units? of ?,?-dehydroamino acids

The He(I) and He(II) photoelectron (PE) spectra of the N-methylamides of N-acetyldehydroalanine (1) and N-acetyldehydrophenylalanine (2) are presented and discussed, within a comprehensive investigation of the electronic structure and conformation ofα, β-dehydroamino acid derivatives. Three different procedures have been adopted for the synthesis of1. The PE results of the “peptide units” are in tune with theoretical predictions and they support the view that in the vapor phase the tendency towards a planar arrangement around the torsion angle φ is much more marked for N-acetyldehydroalanine-NHR systems than for (Z)-substituted ones.

Synthesis of β-functionalized α, β-dehydroamino acid derivatives

β-Functionalized α,β-unsaturated amino acids were synthesized by an addition-elimination pathway. Reaction of methyl β-bromo-α-formylaminoacrylates (3a-e), which were prepared by the condensation of methyl isocyanoacetate (1) with aldehydes followed by bromination, with thiols gave β-alkylthio-α, β-unsaturated amino acid derivatives (6a-f). The reaction of (3a) with sodium azide resulted in the formation of a 2-oxoimidazoline derivative (4). On the other hand, β-benzyloxy- and β-benzylamino-α,β-unsaturated amino acids (9 and 12) were synthesized by the reaction of methyl β-bromo-α-isocyanocinnamates (7a and 7d), prepared from (3a and 3d), with benzyl alcohol and benzylamine followed by acidic hydration, respectively.