Synthesis of chiral crown ethers derived from d-galactose and their application in enantioselective reactions

A few new α- and β-d-galactopyranoside-based chiral lariat ethers of monoaza-15-crown-5 type were synthesized. These macrocycles proved to be efficient catalysts in a few asymmetric reactions under mild phase transfer conditions. The catalytic effect of the lariat ethers with methoxy, ethoxy, isopropoxy and aryloxy substituents on the C-1 of the sugar unit in both α and β positions was compared. In the presence of β-d-galactopyranoside-based crown ethers, the asymmetric Darzens condensation of α-chloroacetophenone and benzaldehyde, the epoxidation of trans-chalcone, the cyclopropanation (MIRC reaction) of benzylidenemalononitrile and 2-benzylidene-1,3-indandione with diethyl bromomalonate were performed with enantioselectivities of 61%, 64%, 86% and 96%, respectively. In all reactions, the β-anomers were more efficient in terms of enantioselectivity than the α forms.     

Asymmetric [3+2] Photocycloadditions of Cyclopropanes with Alkenes or Alkynes through Visible‐Light Excitation of Catalyst‐Bound Substrates

The herein reported visible‐light‐activated catalytic asymmetric [3+2] photocycloadditions between cyclopropanes and alkenes or alkynes provide access to chiral cyclopentanes and cyclopentenes, respectively, in 63–99 % yields and with excellent enantioselectivities of up to >99 % ee. The reactions are catalyzed by a single bis‐cyclometalated chiral‐at‐metal rhodium complex (2–8 mol %) which after coordination to the cyclopropane generates the visible‐light‐absorbing complex, lowers the reduction potential of the cyclopropane, and provides the asymmetric induction and overall stereocontrol. Enabled by a mild single‐electron‐transfer reduction of directly photoexcited catalyst/substrate complexes, the presented transformations expand the scope of catalytic asymmetric photocycloadditions to simple mono‐acceptor‐substituted cyclopropanes affording previously inaccessible chiral cyclopentane and cyclopentene derivatives.     

Side‐Arm Effect of a Methyl α‐d‐Glucopyranoside Based Lariat Ether Catalysts in Asymmetric Syntheses

Methyl α‐d ‐glucopyranoside based monoaza‐15‐crown‐5 type lariat ethers with different heteroatom‐containing side arm attached to the nitrogen of the macrocyclic ring have been synthesized. These compounds were used as chiral phase transfer catalysts in a few asymmetric reactions, such as Michael additions, Darzens condensation, and epoxidation of chalcone. The side arms of the macrocycles had a significant impact on the chemical yields and the enantioselectivity. The effect of the lariat ethers with side arms having heteroatom (O, N, and S) was compared with the effect of the analogues having substituents without a heteroatom. The terminal allyl group also generated a significant enantioselectivity (79% enantiomeric excess) in one of the Michael additions. The application of crown ethers with substituents (CH₂)₃OH or (CH₂)₃OCH₃ leads to the best enantioselectivities 85% and 99%, respectively.     

Asymmetric synthesis of multicyclic spiro-1,3-indandiones via a cascade Michael/Michael reaction of curcumins and 2-arylidene-1,3-indandiones

An organocatalytic cascade Michael/Michael reaction between curcumins and 2-arylidene-1,3-indandiones has been studied. Prolinol, chiral thiourea-tertiary amines, and cinchona alkaloids were evaluated as catalysts. Quinine was identified as the best catalyst for the transformation. Multicyclic spiro-1,3-indandiones were prepared in moderate to excellent yields, diastereoselectivities, and enantioselectivities.     

Asymmetric C-C bond formation via Darzens condensation and Michael addition using monosaccharide-based chiral crown ethers

Liquid-liquid phase asymmetric Darzens condensations were promoted by d-glucose- and d-mannose-based crown ethers. The corresponding aromatic and heteroaromatic α,β-epoxyketones were obtained with moderate to high enantioselectivities (up to 96%) as well as diastereoselectivities (up to 98:2) under mild reaction conditions. The absolute configurations of several of the epoxyketones were determined by single crystal X-ray analysis. The Michael additions of diethyl acetylaminomalonate to trans-β-nitroalkenes were carried out in a solid-liquid two-phase system in the presence of a d-glucose-based crown catalyst with up to 99% ee.     

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.     

Synthesis of alkyl α- and β-<Emphasis Type="SmallCaps">d</Emphasis>-glucopyranoside-based chiral crown ethers and their application as enantioselective phase-transfer catalysts

Chiral monoaza-15-crown-5-type lariat ethers annelated to alkyl 4,6-O-benzylidene-α- and β-d-glucopyranosides have been synthesized. These macrocycles generated significant asymmetric induction as phase-transfer catalysts in a few two-phase reactions. The catalytic effect of the lariat ethers with methoxy, ethoxy, and i-propoxy substituents on C-1 of the sugar unit in both α and β positions was compared. In liquid–liquid two-phase reactions, the nature and position of the substituents did not have much effect. The α-anomers were somewhat more efficient in terms of enantioselectivity than the β forms. In asymmetric Darzens condensations, in the epoxidation of trans-chalcone, in the Michael addition of β-nitrostyrene and diethyl acetamidomalonate, and in the reaction of 2-benzylidene-1,3-indandione with diethyl bromomalonate, maximum enantioselectivities of 73, 94, 78, and 72%, respectively, were obtained in presence of glucopyranoside-based lariat ethers as catalysts.     

Asymmetric C–C bond forming reactions with chiral crown catalysts derived from d-glucose and d-galactose

New chiral monoaza-15-crown-5 derivatives anellated to methyl-4,6-O-benzylidene-α-d-glucopyranoside 2a, 2e, 2g–i and to methyl-4,6-O-benzylidene-α-d-galactopyranoside 3a, 3e, 3i have been synthesized. These crown ethers showed significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (87% ee), in the Darzens condensation of phenacyl chloride with benzaldehyde (71% ee) and in the self-condensation of phenacyl chloride (64% ee) to give 14. The absolute configurations of (−)-(2R,3S)-epoxy-3-(4-chlorophenyl)-1-phenyl-1-propanone 12 and (−)-4-chloro-(2R,3S)-epoxy-1,3-diphenyl-1-butanone 14 have also been determined by X-ray diffraction.     

Enantioselective cyclizations of silyloxyenynes catalyzed by cationic metal phosphine complexes

The discovery of complementary methods for enantioselective transition metal-catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an α,β-unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee).     

Electronically varied quinazolinaps for asymmetric catalysis

The synthesis and resolution of electronically varied axially chiral Quinazolinaps is reported. These ligands bear different aryl groups on the donor phosphorus atom and were synthesised as part of our investigations into electronic effects within this ligand class. A diastereomerically pure palladacycle of one ligand was characterised by X-ray crystallography. The application of these Quinazolinaps to the rhodium-catalysed hydroboration of vinylarenes resulted in enantioselectivities of up to 92%. Their application to the palladium-catalysed allylic alkylation of 1,3-diphenylprop-2-enyl acetate resulted in conversions of up to 99% and enantioselectivities of up to 94%.     

A one-pot asymmetric organocatalytic tandem reaction for the synthesis of oxazine derivatives

An easy one-pot tandem reaction catalyzed by a chiral secondary amine for the synthesis of optically active oxazine derivatives has been performed and the corresponding substituted benzo[d]pyrido[2,1-b][1,3]oxazine derivatives were afforded in generally high yields (up to 99%) and excellent enantioselectivities (up to >99%).     

Enantioselective copper catalyzed Diels-Alder reaction using chiral quinoline-phosphine ligand

A new chiral copper (II) catalyst was prepared from Cu(OTf)₂ and chiral pyridine-phosphine ligands 1–2 in dichloromethane and used in the Diels-Alder reaction of 3-acryloyl-1,3-oxazolidine-2-one with cyclopentadiene leading to enantioselectivities up to 99%.     

Synthesis, Extraction Ability and Application in an Asymmetric Synthesis of Azacrown Ethers Derived from D-Mannitol

New chiral monoaza-15-crown-5 ethers have been synthesised from 1,2:5,6-di-O-isopropylidene-D-mannitol. The substituent at the nitrogen atom has a major influence on the cation extraction ability of the azacrown. These sugar-based crown ethers show asymmetric induction as chiral phase transfer catalysts in the Michael addition of 2-nitropropane to chalcone (67% ee).     

Chiral sulfideoxathiane ligands for palladium-catalyzed asymmetric allylic alkylation

Easily prepared, chiral sulfideoxathiane ligands are described, which give excellent enantioselectivities (up to 99% ee) in the Pd-catalyzed allylic alkylation of 1,3-diphenyl-2-propenyl acetate with a range of alkyl malonate nucleophiles.     

手性相转移催化剂及其在不对称催化反应中的应用

综述了手性季铵盐、手性冠醚以及其它新型手性相转移催化剂的制备及其在各种不对称相转移催化反应如烷基化反应、Michael加成反应、Aldol反应、Mannich反应、氧化反应及还原反应中应用的最新进展.     

Synthesis of Chiral Aza Crown Ethers Having Exocyclic Hydroxy Groups and Their Use in Asymmetric Reduction of Ketones with Sodium Tetrahydridoborate

New chiral diaza crown ethers with exocyclic hydroxy groups were synthesized by reactions of (2S,3S)-1,4-dibenzyloxy-2,3-bis(2-oxiranylmethoxy)butane with N,N'-dibenzyl-1,2-ethanediamine and (4S,5S)-4,5-bis(benzylaminomethyl)-2,2-dimethyl-1,3-dioxolane. Catalytic debenzylation of the products gave the corresponding derivatives having secondary amino groups. The obtained diaza crown ethers, as well as some known crown ethers, were used as asymmetric catalysts in the reduction of pinacolone and acetophenone with sodium tetrahydridoborate in methylene chloride. Depending on the catalyst structure, the optical yield of the reduction products ranged from 5 to 90%.     

Synthesis of novel C2-symmetric chiral crown ethers and their application to enantioselective trifluoromethylation of aldehydes and ketones

Synthesis of novel C2-symmetric chiral crown ethers and their application to enantioselective trifluoromethylation of aldehydes and ketones are discussed. The use of a series of C2-symmetric chiral crown ethers 2 or 3 derived from commercially available (R)-1,1′-bi-2-naphthol for the enantioselective trifluoromethylation of 2-naphthyl aldehyde 1a with (trifluoromethyl)trimethylsilane in the presence of a base was attempted. Iodo-substituted crown ether 2b was found to be the most effective in the model reaction. Moderate enantioselectivities were observed for the trifluoromethylation of both aryl or alkyl aldehydes and alkyl aryl ketones in 21-44% ees. Although the ees are still improvable, this is the first example of a chiral crown ether-catalyzed enantioselective trifluoromethylation reaction.     

Catalytic and highly enantioselective Friedel-Crafts alkylation of aromatic ethers with trifluoropyruvate under solvent-free conditions

[Structure: see text] Highly enantioselective Friedel-Crafts alkylation of simple and aromatic ethers (4a-l) with 3,3,3-trifluoropyruvate (3) was accomplished by using chiral (4R,5S)-DiPh-BOX(1b)-Cu(OTf)2 complex (1 mol %) as a catalyst under solvent-free conditions. Excellent yields and enantioselectivities (90-93% ee, after recrystallization up to 99% ee) of the Friedel-Crafts alkylation products were obtained.     

Highly diastereoselective asymmetric Mannich reactions of 1,3-dicarbonyls with acyl imines

[reaction: see text] The cinchona alkaloids catalyze direct asymmetric Mannich reactions of cyclic 1,3-dicarbonyl compounds with acyl imines to afford alpha-quaternary carbon-bearing reaction products in yields of up to 98%, a diastereomeric excess of 90% or greater, and enantioselectivities up to 99% ee. A model is proposed that accounts for both the observed diastereoselectivities and the enantioselectivities for the reactions.     

Highly enantioselective direct Michael addition of 1,3-dicarbonyl compounds to β-fluoroalkyl-α-nitroalkenes

Cinchona alkaloid catalysts were used in the Michael addition reaction of 1,3-dicarbonyl compounds to β-fluoroalkyl-α-nitroalkenes for the first time. The catalytic system performed well over a broad scope of substrates including β-keto esters and 1,3-diketones with high diastereoselectivities and excellent enantioselectivities (up to 99% ee) under mild conditions. A wide range of useful fluorinated chiral building blocks was synthesized.