Chiral Β-amino Alcohols Research Articles

Synthesis of chiral β-aminoalcohol palladium complexes exhibiting cytotoxic properties

Original palladium complexes involving (-)-ephedrine, (-)-norephedrine, L-prolinol, L-valinol and L-isoleucinol have been rapidly prepared in neutral or basic medium and simply purified. They have been fully characterized by classical analytical methods and four of them were characterized by X-Ray analysis. In parallel with the experimental work, HF-DFT(B3LYP/PCM) computations were performed to obtain additional structural information. Their antiproliferative properties have been evaluated and some complexes showed small activities especially towards HT29 human cancer cells.

Highly enantioselective addition of dimethylzinc to arylaldehydes catalyzed by (2 S)-1-ferrocenyl-methylaziridin-2-yl(diphenyl)methanol

Asymmetric addition of dimethylzinc to a wide variety of aromatic aldehydes is described in the presence of a catalytic amount of chiral β-amino alcohol [(2 S)-1-ferrocenyl- methylaziridin-2-yl(diphenyl)methanol], and a reaction enantioselectivity of up to 97.5% ee was achieved in this transformation in the absence of additional metals such as Ti or Ni. The results showed that this particular addition reaction, characterized by the lower reactivity of dimethylzinc with aldehydes, was more sensitive to structural variations in substrate aldehydes than the corresponding diethylzinc addition. A possible transition state for the catalytic asymmetric addition has been proposed on the basis of previous studies.

Regio- and Stereoselective Ring-Opening Reaction of Chiral Aziridines: A Facile Synthesis of Chiral β-Amino Alcohols

The reaction of chiral 2-alkylsubstituted aziridines (1a-d) with acetic acid afforded β-amino alcohols with an (S)-chiral center at the β position (with respect to oxygen). In contrast, a reaction of the same chiral aziridines with acetyl chloride followed by treatment with water gave β-amino alcohols that have an (S)-chiral center at the a position. In addition, the reaction of the same chiral aziridines with benzyl bromide followed by treatment with 2% sulfuric acid gave the β-amino alcohols with an (R)-chiral center at the a position. Thus, we could control the regioselectivity and stereoselectivity of the ring-opening reaction of chiral aziridines (1a-d).

Pd/La Complex foranti-Selective Catalytic Asymmetric Nitroaldol Reactions

A limited number of reports describe the anti-selective synthesis of chiral β-amino alcohols. This report describes the design of a simple and efficient catalyst with a broad substrate scope and practical applicability. The authors nicely demonstrate the short syntheses of two β-adrenoceptor agonists.

New chiral ligands from isosorbide: application in asymmetric transfer hydrogenation

New chiral β-amino alcohols have been designed and synthesized from isosorbide, a by-product from the starch industry. These new ligands have been synthesized in three steps from isosorbide in good yields and have been used in asymmetric transfer hydrogenation reaction with Ru II complexes. One of these catalysts also demonstrated good catalytic activity and good enantioselectivity.

New chiral titanium complexes for enantioselective reductive cyclizations of diimines to trans-2,3-diarylpiperazines

Enantioselective intramolecular reductive coupling of diimines by chiral titanium complexes, prepared using a titanium(IV) reagent and hemisalen ligands derived from chiral β-amino alcohols, gives trans-2,3-diarylpiperazines in up to 97% ee.

A highly enantioselective synthesis of chiral allylic alcohols by asymmetric addition of novel mixed reagents of trialkenylbismuthines/dialkylzincs to aldehydes

A novel mixture of reagents of trialkenylbismuthines/dialkylzincs was developed and applied toward the synthesis of chiral allylic alcohols. The chiral β-amino alcohols catalyzed addition of the mixed reagents of trialkenylbismuthines/dialkylzincs to aldehydes gave enantiomerically enriched allylic alcohols with up to 97% ee.

A Practical and Simple Method of Recycling Catalyst in Asymmetric Aminohydroxylation of Olefins

The Os-catalyzed asymmetric aminohydroxylation (AA) of olefins provides a straightforward method for the enantioselective synthesis of a wide variety of protected vicinal aminoalcohols. The resulting chiral β-aminoalcohols group is the most abundant structural element in many biologically active molecules as well as the starting point in the design of many chiral ligands. Although AA reaction servers as a powerful method for the synthesis of a variety of products, its application has still been limited because of the high cost of osmium and chiral ligand. In order to explore the possibility of the repetitive use of ligand and/or osmium, several attempts to immobilize this catalytic system have been made. Nandanan group prepared highly crosslinked copolymers between ethylene glycol dimethacrylate (90 mol%) and a bis(quininyl)pyridazine derivative (10 mol%). This insoluble ligand was then used in AA reaction of various olefins in 52-65% yields and 34-54% ees. Up to now, many insoluble polymer-supported ligands have been successfully reused in AA reaction. Yang first reported an immobilized soluble PEG-bound bis-cinchona alkaloid ligand which could be recovered and reused in homogeneous AA reactions. Excellent yields and ees were obtained in homogeneous system. In most reported recycling methods, osmium component was hardly recovered and sometimes synthesis route of the polymer-supported ligands were complicated. Here we report a recyclable monomeric ligand 1 and its application in homogeneous AA reaction. In addition, poly(ethylene glycol) (PEG, MW 400) linked with the special encapsulating effect on osmium was successfully applied in AD reaction. Enlightened by this, we applied PEG in AA reaction for the recovery of osmium and achieved an amazing result that about 50% amount of osmium component could be efficiently recycled through very simple method.

Efficient One‐Pot Synthesis of Enantiomerically Pure 2‐(Hydroxymethyl)morpholines.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Scale-Up of the Preparation of (1R,2R,4S)-1-Methyl-4-(1-methylethenyl)-2-(4-morpholinyl)cyclohexanol

Chiral β-amino alcohols are widely recognized as effective chiral auxiliaries for a variety of asymmetric organic transformations. Recently, (1R,2R,4S)-1-methyl-4-(1-methylethenyl)-2-(4-morpholinyl...

Efficient dual catalytic enantioselective diethylzinc addition to the exocyclic C [dbnd]N double bond of some 1,2,4- N-triazinylarylimines using polymer-supported chiral β-amino alcohols derived from norephedrine

Chiral N, N-dialkylnorephedrines and their corresponding copolymers were evaluated as chiral ligands for the enantioselective diethylzinc addition to the exocyclic C N double bond of some 4-arylideneamino-3-mercapto-6-methyl-4 H-1,2,4-triazin-5-ones 2a– f. The use of a dual catalytic system (amino alcohol/halosilane) in the titled asymmetric reaction was examined. The enantioselective ethylation reaction has been successfully carried out in the heterogeneous system even at low temperature. The corresponding 4-(1-arylpropyl)amino-3-mercapto-6-methyl-4 H-1,2,4-triazin-5-ones 4a– f were obtained in high yields with high enantioselectivities using chiral polymers (up to 91% ee), which are almost the same as those obtained from homogeneous analogues (up to 92% ee). The diethylzinc reagent neither opened the 1,2,4-triazinyl heterocyclic ring nor attacked the carbonyl or the thione groups of the 1,2,4-triazinyl heterocyclic ring and the addition reaction took place exclusively at the exocyclic electrophilic carbon atom yielding the C-ethylated products 4a– f. Reductive cleavage of the 1,2,4-triazinyl heterocyclic ring led smoothly to the corresponding primary aromatic amines 11a– f without significant loss of enantiomeric purity. A suggestion about the possible transition state for the addition reaction is also presented.

Enantioselectivity Reversal by Achiral Additives in the Soai Reaction: A Kinetic Understanding

Numerical kinetic simulations have been employed to understand the origin of enantioselectivity reversal of chiral beta-amino alcohol catalysts occurring in the presence of their achiral analogs in the autocatalytic addition of diisopropylzinc to pyrimidine carbaldehydes (Soai reaction). In a preceding work (Rivera Islas, J.; Lavabre, D.; Grevy, J. M.; HernAndez Lamoneda, R.; Rojas Cabrera, H.; Micheau, J. C.; Buhse, T. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13743-13748), we provided a possible explanation for the phenomenon of spontaneous mirror-symmetry breaking observed in this reaction. The effect of enantioselectivity reversal, giving rise to steep and abrupt transitions between opposed optically active states, has been identified by our current approach as another manifestation of such mirror-symmetry breaking capability. In the present case, we considered the involvement of the chiral catalyst and its achiral analog in the reaction network. Our modeling indicates that the enantioselectivity reversal can be either caused (i) by an interaction between the chiral and achiral additives or (ii) by an interaction of the customary products of the Soai reaction with the additives. The second option, which stands for the reversible inhibition of the chirally selective autocatalysts by the additives, could also explain a number of further additive effects in the Soai reaction reflecting the extraordinary sensitivity of this system toward the initial addition of almost any, even catalytically inactive, chiral substance.

Synthesis and applications of 3,4-dihydroxy-2,5-bis-(2′-(4′-substituted-oxazolinyl)) furan

Three 3,4-dihydroxy-2,5-bis-(2′-(4′-substituted-oxazolinyl)) furans were synthesized at 90%–94% yields from reaction of 3,4-dihydroxyfuran-2,5-dicar-boxylic acid or its dimethyl ester with chiral β-amino alcohol via a one-step process. Their chemical structures were determined by 1H NMR, IR, MS, and elemental analysis. With these chiral bisoxazoline ligands, the asymmetric reductive reaction of β-acetonaphthalene with KBH4 or NaBH4 was preliminarily studied. The enantiomeric excess of the reduction product was up to 83.2% with cyclohexane as the solvent, the molar ratio of ligand: reductive agent: β-acetonaphthalene is 0.04:1.6:1, and 72-hours reaction time at 0°C. Furancontaining bisoxazoline with 4-benzyl on oxazoline rings exhibited higher enatioselectivity than congeneric bisoxazolines with 4-ethyl on oxazoline rings.

Enantioselective conjugate addition of ketones to β-nitrostyrenes catalyzed by 1,2-amino alcohol-derived prolinamides

Various l-prolinamides 14, prepared from l-proline and chiral β-amino alcohols, are active bifunctional catalysts for the direct nitro-Michael addition of ketones to β-nitrostyrenes. In particular, catalyst 14e prepared from l-proline and (1 S,2 R)- cis-1-amino-2-indanol exhibits the highest catalytic performance working in polar aprotic solvents such as NMP. High syn-diastereoselectivities (up to 94% de) and good enantioselectivities (up to 80% ee) were obtained at rt.

Synthesis of novel chiral β-amino alcohols and diamino alcohols from products of Ugi 3-component reaction

Novel chiral β-amino alcohols and diamino alcohols, which are useful in catalytic asymmetric syntheses, were prepared from the products of Ugi 3-component reaction.

Catalytic asymmetric transfer hydrogenation of ketones using terpene-based chiral β-amino alcohols

Catalytic asymmetric transfer hydrogenations of aromatic alkyl ketones have been studied using [RuCl 2( p-cymeme)] 2 and terpene-based β-amino alcohols. The limonene derived amino alcohol, (1 S,2 S,4 R)-1-methyl-4-(1-methylethenyl)-2-(methylamino)cyclohexanol gave the most promising results. Chiral secondary alcohols were obtained in good to excellent yields and moderate enantioselectivities (up to 71%).

Synthesis and structures of novel diastereomeric cyclopalladated ferrocenylimines derived from chiral β-amino alcohols

Two pairs of novel diastereomeric cyclopalladated ferrocenylimines ( S p, S C)- 3 and ( R p, S C)- 4 with both planar and central chirality have been synthesized starting from inexpensive and readily available chiral β-amino alcohols. The two pairs of diastereomers were characterized by elemental analysis, IR, 1H NMR and specific rotations. Furthermore, the structures and absolute configurations of complexes ( S p, S C)- 3a and ( R p, S C)- 4b have been determined by single-crystal X-ray diffraction.

Asymmetric Arylation of Aldehydes with Polymer-Supported Amino Alcohols

Polymer-supported chiral β-amino alcohols 1 were prepared and used as chiral ligands in the enantioselective addition of organo­zinc reagents to aldehydes. The reaction of aliphatic and aromatic aldehydes with Et2Zn proceeded in the presence of chlorotritylated polystyrene-supported amino alcohol 1a to give the corresponding alcohols in 50-95% yields and with 71-91% ee (Eq. 1). Arylation of the aldehydes with Ph2Zn/Et2Zn in the presence of the ligands 1b,c gave the alcohols with high enantioselectivity, while the arylation with ligand 1a resulted in products with low enantioselectivity (Eq. 2).

β-Amino alcohols as ligands for asymmetric transfer hydrogenation of ketones in water

Chiral β-amino alcohols were used as ligands for ruthenium, rhodium and iridium-catalyzed asymmetric transfer hydrogenation of acetophenones in water with formate as reductant. The catalysts were showed to be capable of asymmetric transfer hydrogenation of ketones in water, but their activities and enantioselectivities varied with the ligands used and with solution pH values, with higher pH favouring higher rates and better enantioselectivities.

A Highly Efficient and Direct Approach for Synthesis of Enantiopure β‐Amino Alcohols by Reductive Cross‐Coupling of Chiral N‐tert‐Butanesulfinyl Imines with Aldehydes.

AbstractFor Abstract see ChemInform Abstract in Full Text.