Enantioselective rearrangement of a meso-cyclohexene oxide using norephedrine-derived chiral bases

Using a chiral base from a norephedrine-derived diamine, the enantioselective rearrangement of a meso-cyclohexene oxide can be performed in 94% yield and with 94% enantioselectivity. The enantioselectivity is lower (86% ee) with the diastereoisomeric chiral base. In order to prepare the diastereoisomeric chiral base, a potentially useful way of converting norephedrine into norpseudoephedrine was developed.     

Enantioselective Mannich-type reaction of sulfonylimines having 2-pyridylsulfonyl group as a novel stereocontroller

A catalytic enantioselective Mannich-type reaction of N-(2-pyridylsulfonyl)imines in the presence of chiral bis(oxazoline)s afforded the products with high enantioselectivity. Asymmetric induction was supposed to be efficiently controlled by a new chiral center on the sulfur dynamically induced through the discriminative coordination of a chiral Lewis acid to one of the sulfonyl oxygens.     

N-Salicyl-β-aminoalcohols as a new class of ligand for catalytic asymmetric Strecker reactions

An enantioselective Strecker synthesis employing novel chiral titanium complex catalysts derived from structurally simple chiral N-salicyl-β-amino alcohols is described. Reactions of N-benzylidenebenzylamine with trimethylsilyl cyanide in the presence of the catalyst (10 mol%) gave the corresponding α-aminonitrile in good to excellent yields, along with relatively high enantioselectivity (up to 86% ee). Similar reactions with various imines derived from aromatic aldehydes resulted in moderate to good enantioselectivity (44-81% ee).     

Impact of amines as co-modifiers on the enantioseparation of various amino acid derivatives on a tert-butyl carbamoylated quinine-based chiral stationary phase

A tert-butyl carbamoylated quinine-based chiral stationary phase (CSP) for direct enantiomer separation of various natural and unnatural amino acid derivatives was studied. The influence of functional groups in the amino acid side chains upon the enantioseparation is discussed with the aim of realizing contributions to their overall chiral recognition. The effects of various amines as co-modifiers upon retention and overall enantioselectivity of amino acid derivatives in polar organic solvents was systematically investigated. In general, retention times decreased with increasing amine concentrations without a distinct alteration of enantioselectivity. All analytes were rapidly resolved on the CSP with the methanol-based mobile phase containing 87 mM acetic acid and 7 mM triethylamine.     

Enantioselective arylation of aldehydes catalyzed by a soluble optically active polybinaphthols ligand

A soluble chiral polymer ligand was synthesized by the polymerization of (R)-6,6′-dibutyl-3,3′-diformyl-2,2′-binaphthol (R-M-1) with 2,5-diaminopyridine (M-2) via a nucleophilic addition-elimination reaction. While arylboronic acids were used as the source of the transferable aryl group, the chiral polybinaphthols ligand in combination with Et₂Zn without Ti(OⁱPr)₄ exhibited higher enantioselectivity in asymmetric addition to aromatic aldehydes than alphatic aldehydes. When aromatic aldehydes with electron-withdrawing groups were chosen as substrates, the resulting diarylmethanols were produced in higher ee values than those with electron-donating groups as substrates. 2-Naphthaldehyde used as a substrate afforded product in 95% ee, which could be ascribed to the steric effect influence on this asymmetric arylation reaction. Moreover, the chiral polymer was easily recovered and reused, but exhibited a decrease of enantioselectivity in the third recycle.     

Enantioselective addition of diethylzinc to aldehydes using immobilized chiral BINOL–Ti complex on ordered mesoporous silicas

A chiral (S)-BINOL ligand has been covalently grafted on ordered mesoporous silicas—MCM-41 and SBA-15 and the resulting inorganic–organic hybrid materials used as chiral auxiliaries in Ti-promoted enantioselective addition of diethyl zinc to aldehydes under heterogeneous conditions. These heterogeneous catalysts showed promising activity and enantioselectivity. The catalyst having a larger pore diameter with capping of free silanol moiety with trimethylsilyl (TMS) group was found to be more active with enantioselectivities up to 81% being achieved. The catalyst worked well up to three cycles with retention of enantioselectivity after washing with 10% HCl in methanol.     

Me-AnilaPhos: a new chiral phosphine-phosphoramidite ligand for a highly efficient Rh-catalyzed asymmetric olefin hydrogenation

A cationic rhodium(I) complex with a novel chiral phosphine-phosphoramidite ligand based on 2-diphenylphosphino-N-methylaniline and R-BINOL moieties has been synthesized. The complex provided remarkably high activity and enantioselectivity in the asymmetric hydrogenation of methyl (Z)-α-acetamidocinnamate (100% conversion after 10 min, 98% ee) and dimethyl itaconate (100% conversion after 26 min, 96% ee) under ambient conditions (1 bar hydrogen pressure, room temperature) using 1 mol % of the catalyst in dichloromethane as solvent. On the other hand, when hydrogenation was performed in methanol, both conversion and enantioselectivity were significantly diminished, due to the partial decomposition of the rhodium/phosphine-phosphoramidite complex.     

Rhodium/chiral diene-catalyzed asymmetric methylation of N-sulfonylarylimines with trimethylboroxine

A hydroxorhodium complex coordinated with a chiral diene ligand catalyzed the asymmetric addition of trimethylboroxine to N-sulfonylarylimines to give high yields of chiral 1-aryl-1-ethylamines with high enantioselectivity.     

A novel layered organic polymer-inorganic hybrid zinc poly (styrene-phenylvinylphosphonate)-phosphate immobilized chiral salen Mn(III) catalyst large-scale asymmetric epoxidation of unfunctionalized olefins

A novel layered organic polymer-inorganic hybrid zinc poly (styrene-phenylvinylphosphonate)-phosphate (ZnPS-PVPA) has been synthesized under mild conditions and diphenol-modified ZnPS-PVPA was used to successfully immobilize the chiral salen Mn(III) by axial coordination. The obtained heterogeneous chiral catalysts exhibited excellent activities and enantioselectivities using sodium periodate as an oxidant for asymmetric epoxidation of unfunctionalized olefins, especially for the epoxidation of α-methylstyrene (conversion: up to 97%; ee: exceed 99%). Moreover, these synthesized catalysts were relatively stable and could be expediently separated from the reaction system, and could be recycled at least ten times without obvious loss of activity and enantioselectivity. These novel catalysts could be efficiently used in large-scale reactions with the enantioselectivity being maintained at the same level, which offer a great possibility for application in industry.     

Highly efficient chiral copper Schiff-base catalyst for asymmetric cyclopropanation of 2,5-dimethyl-2,4-hexadiene

A remarkable increase in catalytic activity is found for the asymmetric cyclopropanation of 2,5-dimethyl-2,4-hexadiene with diazoacetate by use of the chiral copper Schiff-base complexes, which are derived from substituted salicylaldehydes, chiral aminoalcohols, and copper acetate monohydrate. Furthermore, a combination of a chiral copper Schiff-base with a Lewis acid showed an increase in yield (up to 90%) and in enantioselectivity (up to 90% ee) for the asymmetric cyclopropanation of the diene with t-butyl diazoacetate at 20 °C.     

Heterogeneous asymmetric Diels–Alder reactions using a copper–chiral bis(oxazoline) complex immobilized on mesoporous silica

A chiral bis(oxazoline)–copper complex was immobilized onto mesoporous silica and the resulting heterogeneous catalyst was employed in asymmetric Diels–Alder reactions. Reactions using the catalyst exhibited good enantioselectivity of 78% enantiomeric excess and endo/exo-selectivity (17:1) better than the corresponding homogeneous reaction. The catalyst could be easily recovered and reused several times without significant loss of the remarkable reactivity, diastereoselectivity and enantioselectivity.     

Two optimized synthetic pathways toward a chiral precursor of Mivacurium chloride and other skeletal muscle relaxants

A chiral precursor of Mivacurium chloride, (R)-5′-methoxylaudanosine, was prepared using two different methods. The chiral resolution of racemic 5′-methoxylaudanosine, typically used in industry, was carried out in parallel with a procedure consisting of asymmetric transfer hydrogenation (ATH) and reductive methylation. A novel one-pot synthetic step was developed for the synthesis of racemic 5′-methoxylaudanosine. In both routes, the enantioselectivity was high but further purification was necessary to reach the level of a pharmaceutical standard. The individual synthetic steps reported herein can also be used for the synthesis of analogous bistetrahydroisoquinoline-based skeletal muscle relaxants.     

Chirality control in the enantioselective arylation of aromatic aldehydes catalyzed by cis-(1R,2S)-2-benzamidocyclohexanecarboxylic acid derived 1,3-aminoalcohols

A series of chiral 1,3-aminoalcohols derived from cis-(1R,2S)-2-benzamidocyclohexanecarboxylic acid were synthesized and applied to the enantioselective arylation of aromatic aldehydes. The reactions exhibited good yields (up to 90%) and moderate to high enantioselectivities (up to 99%). Not only the enantioselectivity but also the stereochemistry of the product were controlled by the substituent effect of the chiral ligands.     

Catalytic asymmetric borylative aldol reaction of 5,6-dihydro-2H-pyran-2-one and ketones

A copper(I)-catalyzed asymmetric borylative aldol reaction of 5,6-dihydro-2H-pyran-2-one and simple ketones (including aromatic ketones and an aliphatic ketone) was disclosed, which afforded a series of chiral diols after an oxidative work-up in moderate yields with moderate to high diastereoselectivity and excellent enantioselectivity. The lactone moiety was easily opened with methanol to generate a chiral triol in moderate yield.     

A catalytic asymmetric anti-selective nitroaldol reaction with a neodymium-sodium heterobimetallic complex

A catalytic asymmetric anti-selective nitroaldol reaction with a neodymium-sodium heterobimetallic catalyst is described. A readily accessible amide ligand works efficiently as a chiral platform for the Nd/Na heterobimetallic catalyst in the reaction of various aldehydes and nitroethane, affording anti-1,2-nitro alkanols in good diastereo- and enantioselectivity.     

Highly enantioselective synthesis of terutroban key intermediate via asymmetric hydrogenation

A chiral (R) key intermediate of the biologically active form of terutroban has been prepared by asymmetric hydrogenation. The catalysts are based on very easily accessible ruthenium complexes modified by chiral phosphorous ligands. The use of the chiral catASium^®T ligands family allowed us to realize this transformation efficiently in terms of yield and enantioselectivity (ee up to 92%) with high substrate/catalyst ratios.     

Synthesis of optically-active benzylic amines; asymmetric reduction of ketoxime ethers with chiral oxazaborolidines

The preparation of novel optically active benzylic amines by the enantioselective reduction of phenone oximes using chiral oxazaborolidine is described. The choice of the chiral 1,2-amino alcohol (S)-diphenylvalinol as chiral inducer and that of the benzyl group for the O-oxime substituent is explained. 23 primary amines are obtained, with high enantioselectivity (e.e.=98%), good yield (74%) on preparative scale. A mechanistic explanation is proposed.     

Preparation of a new FerroPHOS derivative for palladium-catalyzed asymmetric allylic alkylations

A new C₂-symmetric only cylindrically chiral FerroPHOS derivative possessing (1-methoxy-1-methyl)ethyl substituents was prepared and applied to the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenylprop-2-en-1-yl acetate. Both high catalytic activity (up to 500 turnovers) and enantioselectivity (e.e.'s of up to 96.3%) were attained in reactions using the new diphosphine ligand.     

The synthesis of dendritic BINOL ligands and their applications in the enantioselective Lewis acid catalyzed addition of diethylzinc to aldehydes

Novel dendritic chiral BINOL ligands have been synthesized through coupling of MOM-protected 3,3′-dihydroxymethyl-binaphthol with Fréchet-type polyether benzyl bromide dendrons followed by deprotection of the MOM groups using TsOH. These dendritic chiral BINOL ligands were found to be effective in the enantioselective addition of diethylzinc to benzaldehyde both in the presence and absence of Ti(O-iso-Pr)₄. The enantioselectivity decreased with increasing generation in both cases. In the latter case, the dendritic chiral BINOL ligands showed much higher catalytic activity and enantioselectivity than BINOL.     

Asymmetric synthesis of activated cyclopropanes catalyzed by cinchonidine as a chiral Brønsted base

Cinchonidine catalyzed the cyclopropanation reaction between chloromethyl ketones and β-substituted methylidenemalononitriles to give trans-cyclopropanes with enantioselectivity up to 82% ee. Experimental evidence suggests that cinchonidine functions as a chiral Brønsted base catalyst in the reaction and hydrogen bonding is essential for inducing high enantioselectivity.