Search

The enantioselective reduction of prochiral ketones with borane in the presence of a chiral ligand has received considerable attention. Hydroxylamine-based chiral ligands with amide and hydroxyl functions in the presence of other co-ordinating groups are highly effective in these asymmetric reductions. The current work presents a simple one step synthesis of a series of β-hydroxyamide-based ligands from the reaction between 3-hydroxy-2-naphthoic acid and chiral amino alcohols and their applications as catalysts in asymmetric borane-mediated reductions of aromatic prochiral ketones in THF. The reductions provided the corresponding secondary alcohols with up to 96% ee and in good to excellent yields (89–99%). DFT calculations at B3LYP/6-31+g(d) level offered theoretical models to account for the enantioselectivity imposed by the chiral ligands in the reductions of the ketones.

Hydroxyamide-based ligands have occupied a considerable place in asymmetric synthesis. Here we report the synthesis of seven β-hydroxyamide-based ligands from the reaction of 2-hydroxynicotinic acid with chiral amino alcohols and test their effect on the enantioselective reduction of aromatic prochiral ketones with borane in tetrahydofuran (THF). They produce the corresponding secondary alcohols with up to 76% enantiomeric excess (ee) and good to excellent yields (86-99%).

Asymmetric transfer hydrogenation processes of ketones with chiral molecular catalysts are attracting increasing interest from synthetic chemists due to their operational simplicity. C-2-symmetric catalysts have also received much attention and been used in many reactions. A series of new chiral C-2-symmetric bis(phosphinite) ligands has been prepared from corresponding amino acid derivated amino alcohols or (R)-2-amino-1-butanol through a three- or four-step procedure. Their structures have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. H-1-P-31 NMR, DEPT, H-1-C-13 HETCOR or H-1-H-1 COSY correlation experiments were used to confirm the spectral assignments. In situ prepared ruthenium catalytic systems were successfully applied to ruthenium-catalyzed asymmetric transfer hydrogenation of acetophenone derivatives by iso-PrOH. Under optimized conditions, these chiral ruthenium catalyst systems serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as good catalysts, giving the corresponding optical secondary alcohols in 99% yield and up to 79% ee. (C) 2012 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Chiral ruthenium catalyst systems generated in situ from [Ru(η6-p-cymene)(μ-Cl)Cl]2 complex and chiral C 2-symmetric bis(phosphinite) ligands based on amino alcohol derivatives were employed in the asymmetric transfer hydrogenation of aromatic ketones to give the corresponding optically active alcohols in high yield. The best results were obtained in the [Ru(η6-p-cymene)­(μ-Cl)Cl]2 and (2S)-2-[benzyl(2-{benzyl[(2S)-1-[(diphenylphosphanyl)oxy]-3-phenyl propan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphenylphosphinite or (2R)-2-[benzyl(2-{benzyl[(2R)-1-[(diphenyl­phosphanyl)oxy]-3-phenylpropan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphenylphosphinite catalytic systems, which gave enantioselectivities of up to 93% ee and 99% conversion.

Enantioselective reduction of prochiral ketones to optically active secondary alcohols is an important subject in synthetic organic chemistry because the resulting chiral alcohols are extremely useful, biologically active compounds. The new chiral ligands (2R)-2-[benzyl{(2-((diphenylphosphanyl)oxy)ethyl)}amino]butyldiphenylphosphinite, 1 and (2R)-2-[benzyl{(2-((dicyclohexylphosphanyl)oxy)ethyl)}amino]butyldicyclohexylphosphinite, 2 and the corresponding ruthenium(II) complexes 3 and 4 have been prepared. The structures of these complexes have been elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. 31P–{1H} NMR, DEPT, 1H–13C HETCOR or 1H–1H COSY correlation experiments were used to confirm the spectral assignments. These ruthenium(II)–phosphinite complexes have been used as catalysts for the asymmetric transfer hydrogenation of acetophenone derivatives. Under optimized conditions, aromatic ketones were reduced in good conversions and in moderate to good enantioselectivities (up to 85% ee).

A series of β-amino alcohols derivatives were synthesized from (R)-2-amino-1-butanol and (S)-1,2-propanediol, and they have been used as organocatalaysts in the racemic ring opening of epoxide in good yields with high enantiomeric excess (up to 97%).

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. The new chiral C 2 -symmetric ligands N,N ′-bis-[(1 S )-1- sec -butyl-2- O- (diphenylphosphinite)ethyl]ethanediamide, 1 and N,N′ -bis-[(1 S )-1-phenyl-2- O -(diphenylphosphinite)ethyl]ethanediamide, 2 and the corresponding ruthenium complexes 3 and 4 have been prepared and their structures have been elucidated by a combination of multi-nuclear NMR spectroscopy, IR spectroscopy, and elemental analysis. 1 H– 31 P NMR, DEPT, 1 H– 13 C HETCOR, or 1 H– 1 H COSY correlation experiments were used to confirm the spectral assignments. The catalytic activity of complexes 3 and 4 in transfer hydrogenation of acetophenone derivatives by iso- PrOH has also been studied. Under optimized conditions, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso -PrOH and act as excellent catalysts, giving the corresponding chiral alcohols in 99% yield and up to 75% ee. This transfer hydrogenation is characterized by low reversibility under these conditions.

The work involves an experimental ((1)H NMR) and theoretical (MD, MM-PBSA and DFT) investigation of the molecular recognition and discrimination properties of a chiral aza-15-crown-5 against methyl esters of alanine, phenylalanine and valine hydrochloride salts. The results indicate that the receptor binds enantiomers with moderate binding constants (88-1,389 M(-1)), with phenylalanine being more discriminated. The difference in experimental binding free energies (ΔG(R) - ΔG(S)) for alanine, phenylalanine and valine enantiomers were calculated as -0.36, -1.58 and 0.80 kcal mol(-1), respectively. The differences in theoretical binding energies were calculated by MM-PBSA (ΔE(R)PB - ΔE(S)PB=) as -0.30, -1.45 and 0.88, by B3LYP/6-31+G(d) as -1.17, -0.84 and 0.74 and by M06-2X/6-31+G(d) as -1.40, -3.26 and 1.66 kcal mol(-1). The data obtained give valuable information regarding the molecular recognition mode of the organoammonium complexes of chiral aza-crown ether with C 1 symmetry, which may be relevant to biological systems.

Some new chiral Schiff bases have been prepared in good yields from various carbonyl groups and two 2-amino alcohols. LiAlH 4 was treated with different equivalents of the Schiff bases. Enantioselective reduction of acetophenone is achieved in high chemical yield (up to 93%) with moderate enantiomeric excess (up to 22%) by use of the new reducing agents.

A practical synthesis of chiral monoaza-15-crown-5 ethers 1 and 2 has been achieved from l -valinol. The molecular recognition by these chiral crown ethers for ( RS )-α-phenylethylamine, ( RS )-α-(1-naphthyl)ethylamine and their perchlorate salts has been characterized by UV–vis.

Many chiral ligands bearing phosphorus donor atoms were developed and applied in the area of metal catalyzed asymmetric catalysis. A new chiral bis(phoshinite) ligand was successfully synthesized from optically active (1S,8S)-3,6-[N-(S)-alpha-phenylethyl] diaza-1,8-diphenoxymethyl-1,8-octanediol in high yield. A ruthenium(II) complex generated in situ from [Ru(eta(6)-p-cymene)(mu-Cl)Cl](2), bis(phosphinite) ligand and KOH acts as an active catalyst for asymmetric transfer hydrogenation (ATH) of acetophenone derivatives in isopropyl alcohol (IPA) as both solvent and hydrogen source. The catalytic reaction proceeds cleanly to give enantiomerically enriched secondary alcohols up to 90% or 89% ee's at 50 or 82 degrees C, respectively. (C) 2013 Elsevier B. V. All rights reserved.

This study represents a facile synthesis of building blocks (1–3) of crown ethers and amine precoursers (4a-d). The study also involves synthesis of mono and dibenzo N, N-disubstituted diaza 18-crown-6 derivatives with high yield without chromatographic purification and high vacuum distillation. The complex ability of host the ethers was evaluated in terms of structural modification.

The chiral monoaza-15-crown-5 ethers 4 and 5 were prepared from L-phenylalaninol and L-leucinol, respectively. The molecular recognition of these chiral crown ethers for L-amino acid ethyl esters was characterised by UV-visible spectroscopy. Binding constants ( Ka), free-energy changes (–Δ Go), enthalpy changes (Δ H) and entropy change (Δ S) values were determined for hosts 4 and 5 with L-amino acid ethyl ester hydrochlorides in CHCl3.

Four novel C(2)-symmetric enantiomerically pure, chiral pyridine-18-crown-6 type macrocycles containing lipophilic chains at the stereogenic centers were prepared. The enantioselectivity of the new ligands toward the enantiomers of D-,L-amino acid methyl ester derivatives were also determined by (1)H NMR titration method. These novel macrocycles have been showed to be strong complexing agents for D- and L-amino acid methyl ester hydrochloride salts (with K(ass) up to 13590 M(-1) and Delta G(0) up to 23.3 kJ mol(-1) and selectivity ratio: 80:20) by (1)H NMR titration methods. These macrocyclic hosts exhibited enantioselective binding towards the D-enantiomer of valine methyl ester hydrochloride with K(D)/K(L), up to 5.08 in CDCl(3) with 0.25% CD(3)OD. (C) 2011 Elsevier Ltd. All rights reserved.

Two novel C-2-symmetric optically active pyridine-15-crown-5 type ligands containing lipophilic chains at the stereogenic centres, macrocycles 5 and 6, were prepared from (S)-1,2-propanediol and (S)-3-aryloxy-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives. These novel macrocycles have been shown to be strong complexing agents for primary organic ammonium salts (with K values of up to 1363.5 M-1, Delta G degrees of up to 17.86 kJ mol(-1) and a selectivity ratio of 80:20) by H-1 NMR titration method. These macrocyclic host exhibited enantioselective binding towards the L-enantiomer of phenylalanine methyl ester hydrochloride with K-L/K-D up to 8.57 in CDCl3 containing 0.25% CD3OD. Experimental results have been detailed with molecular dynamic calculations at atomic level concerning the molecular recognition and discrimination properties of a chiral pyridino-15-crown-5. The binding free energies were calculated as similar to-25 kJ mol(-1). The results indicated that the host binds and discriminates valine salts better than phenylalanine salts. The molecular dynamics, MM/PBSA calculations are consistent with the H-1 NMR results. (C) 2010 Elsevier Ltd. All rights reserved.

A series of new C-2-symmetric chiral aza crown ether macrocycles 1-4 have been synthesized from (S)-3-aryloxy-1,2-propanediol and (S)-1,2-propanediol for the enantiomeric recognition of amino acid ester derivatives. These new macrocycles have been shown to be strong complexing agents for primary organic ammonium salts (with K up to 176.93 M-1 and Delta G degrees up to 12.81 kJ mol(-1)) by H-1 NMR titration. These macrocyclic host exhibited enantioselective bonding toward the D-enantiomer of phenylalanine methyl ester hydrochloride with K-D/K-L up to 6.87 in CDCl3 with 0.25% CD3OD. (C) 2009 Elsevier Ltd. All rights reserved.

A chiral monoaza-15-crown-5 ether derivative was prepared from L-Leucinol and used as a chiral stationary phase. The new chiral stationary phases CSP-1 and CSP-2 were employed in separating the enantiomers of the sodium and potassium salts of amino acids. The sodium and potassium salt of the D-enantiomers of all amino acids (PhyAlaNa, PhyAlaK and PhyGlyNa, PhyGlyK, and TrpNa, TrpK) show higher selectivity than the L-enantiomers for both CSP-1 and CSP-2. (c) 2006 Elsevier Ltd. All rights reserved.

Chiral monoaza-15-crown-5 ethers (1, 2) were prepared from (R)-(−)-2-amino-1-butanol in high yield. The chiral monoaza-15-crown-5 ethers were purified directly as NaClO4 complexes. Molecular recognition by these chiral monoaza-crown ethers of (R)- and (S)-PhEtHClO4 and (R)- and (S)-NapEtHClO4 as characterized by UV–vis spectroscopy. The order of enantiomeric selectivity is (R)- > (S)- PhEtHClO4 and (S)- > (R)-NapEtHClO4 for 1. In the case of 2 it was (R)- > (S)-PhEtHClO4 and (R)- > (S)- NapEtHClO4. The cavity of macrocycle and steric hindrance of the benzene units appears to play an important role in recognition. Chirality 16:351–355, 2004. © 2004 Wiley-Liss, Inc.

Novel chiral monoaza-15-crown-5 ether derivatives 1 and 2 were prepared from l -phenylalaninol and l -leucinol, respectively. The effect of the substituent at the stereogenic center on chiral recognition and enantioselectivity were investigated. Binding constant ( K ), free-energy changes (−Δ G 0 ), enthalpy change (Δ H ), and entropy change (Δ S ) values were determined with enantiomers of organic ammonium salts by a titration UV–vis method in CHCl 3 .