Synthesis and characterization of chiral, bridged resorcinarenes as templates for asymmetric catalysis

A full study of the synthesis of chiral, bridged resorcinarenes (3a-3l, 13a, 13b) is presented using Mannich condensation of C_2v-tetraprotected resorcinarenes with chiral 1,n-diamines bearing homochiral α-methylbenzyl auxiliaries at each terminal nitrogen. The study has revealed the methodology to be applicable to preparing a broad range of bridged structures with varying lengths of bridge, different functionality in the bridge and various protecting groups on the upper rim. Reproducible and satisfactory yields in the reaction were only obtained with the pendant R group as methyl. The bridged adducts have been fully characterized by a range of spectroscopic techniques, and NMR has revealed varying trends in the way the various bridges protrude into the cavity. Low temperature NMR as well as X-ray structures of tetramesylate 15 and tetratoluate 3g has revealed hydrogen bonding to the amine nitrogens in the bridge to be an important control element for positioning the bridge relative to the cavity of the bowl. The derivatives provide chiral templates for asymmetric catalysis studies using cooperative effects in the bowl.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral hydrazone and imine ligands

Optically active hydrazone and imine were found to act as effective ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 71%.     

Asymmetric addition of diethylzinc to aromatic aldehydes by chiral ferrocene-based catalysts

A series of chiral C₁- and C₂-symmetric ferrocenyl Schiff bases (1a-c), ferrocenyl aminoalcohols (2a), ferrocenylphosphinamides (2b-c), 1,1′-ferrocenyl-diol (3), and 1,1′-ferrocenyl-disulfonamide (4) were prepared and employed as base catalysts or as ligand for titanium(IV) complexes in the asymmetric addition of diethylzinc to aromatic aldehydes. High enantioselectivity up to almost 100% ee was achieved for the alkylation of benzaldehyde and p-methoxybenzaldehyde with 1 or 3. In contrast, however, the β-aminoalcohol (2a) and phosphinamides (2b and c) that are ubiquitous classes of base catalysts for this reaction proved inefficient in our hands, regardless of the types of substrates or reaction conditions. Comparative studies show that there exist various reaction parameters governing not only chemical yields but also optical yields. These include steric and electronic environment of the substrate, the solvent, the reaction temperature, and the nature of the ferrocene moieties.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by 1,2,3,4-tetrahydroisoquinoline β-amino alcohol

<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions.     

Enantioselective addition of diethylzinc to benzaldehyde catalyzed by a small amount of chiral 2-amino-1-alcohols

The reaction of diethylzinc with benzaldehyde catalyzed by a small amount of chiral 2-amino-1-alcohols in toluene at room temperature gave optically active 1-phenylpropan-1-ol almost quantitatively in ～, 50% ee.     

Enantioselective addition of diethylzinc to N-diphenylphosphinoylimines employing cinchonidine and cinchonine as chiral ligands

The use of the `pseudoenantiomeric pair' of cinchonine and cinchonidine as ligands for the addition of diethylzinc to N-diphenylphosphinoylimines has been investigated. With 1 equiv of cinchonidine as ligand, a series of chiral amines was prepared in good yield and enantiomeric excesses of up to 94%. The use of 2.0 equiv of methanol as an achiral additive was found significantly to improve the selectivity of the addition when using 0.2 equiv of ligand, yielding ee's close to those obtained with a stoichiometric amount of ligand.     

C2-symmetrical bis(camphorsulfonamides) as chiral ligands for enantioselective addition of diethylzinc to benzaldehyde

Purpose of the research was to determine the activity of chiral bis(sulfonamide) ligands derived from camphor in the addition of diethylzinc to benzaldehyde. Chiral bis(ketosulfonamides) and bis(hydroxysulfonamides), have been synthesized in a reaction of diamines with camphorsulfonic acid chloride. Their activity in a reaction of asymmetric addition of dialkylzinc to benzaldehyde in a presence of titanium(IV) tetraisopropoxide was determined. The bis(ketosulfonamide) ligands reveal low enantioselectivity, with the ee% not exceeding 12%. The bis(hydroxysulfonamides) reveal much higher asymmetric induction in the investigated ZnEt₂ addition. The best enantiomeric excess (62%) has been observed for bis(hydroxysulfonamide) obtained from 1,3-diaminepropane. The yields of the reaction obtained after 18 h are 92–96%. Crystal structures have been solved for bis(ketosulfonamide) ligands obtained from diamines based on C₂ to C₄ chain. The (2R) configuration in the rings systems of bis(hydroxysulfonamide) containing the C₃ bridge was also determined by the crystal structure analysis. The sulfonamides have been characterized by IR, ¹H and ¹³C NMR.     

Enantioselective addition of diethylzinc to aldehydes catalyzed by 5-cis-substituted proline derivatives

5-Cis-substituted prolinols, prolinamines, and prolinamine sulfonamides proved to be efficient ligands for the enantioselective addition of diethylzinc to aldehydes, providing up to 99% ee. The sense of asymmetric induction can be controlled by the nature of the exocyclic functional group (CPh₂OH vs. CH₂NHR vs. CH₂NHSO₃R). The additional 5-cis substituent exerts a strong beneficial effect on the chirality transfer since it rigidifies the catalyst structure. The stereochemical outcome of the reactions is discussed in detail on the respective transition states.     

The first catalytic asymmetric addition of diethylzinc to aldehyde promoted by chiral thiourea

A series of C₂-symmetric and asymmetric chiral thiourea derivatives were synthesized from commercial L-phenylalanine.All of the new compounds have been fully characterized by IR,¹H NMR,¹³C NMR,MS spectra and elemental analyses.The chiral thioureas were used as chiral ligands in the catalytic enantioselective ethylation of aldehydes with diethylzinc,the corresponding sec-alcohols were gained with excellent enantioselectivities（up to 87.1%ee） and high yields（up to 76.7%） after the conditions were optimized.     

The synthesis of silica-supported chiral BINOL: Application in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes

Chiral BINOL was covalently anchored on two different pore sized mesoporous silica (SBA-15 (7.5 nm) and MCF (14 nm)). These heterogenized ligands were used in Ti-catalyzed asymmetric addition of diethylzinc to aldehydes. High catalytic activity with excellent enantioselectivity (up to 94% ee) for secondary alcohols was achieved using MCF supported chiral BINOL under heterogeneous reaction conditions. Good to excellent enantioselectivity (ee, 68–91%) was also achieved with various small to bulkier aldehydes. The MCF supported catalyst was reused in multiple catalytic runs without loss of enantioselectivity.     

Dendritic chiral auxiliaries on silica: a new heterogeneous catalyst for enantioselective addition of diethylzinc to benzaldehyde

This article reports the first work on the use of silica supported dendritic chiral auxiliaries for the enantioselective addition of diethylzinc to benzaldehyde: the control of dendrimer propagation on the silica surface is of prime importance to obtain enhanced conversion, selectivity, and enantioselectivity.     

Enantioselective addition of diethylzinc to aldehydes induced by a new chiral Ti(IV) catalyst

A new chiral titanium reagent, derived from optically active trans-1,2-dicamphorsulfonamidocyclohexane 2a and Ti(OⁱPr)₄, was found to promote the enantioselective addition of diethylzinc to various aldehydes giving rise to the corresponding alcohols in high yields with moderate to high selectivity.     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by C2-symmetric chiral diols

Optically pure C₂-symmetric diols have been synthesized with moderate yields in a straightforward manner, and are used as catalysts in the enantioselective alkylation of aromatic aldehydes with diethylzinc. The addition of diethylzinc to benzaldehyde and sterically hindered 1-naphthaldehyde was achieved with excellent enantioselectivities (97–99% ee) under catalysis with (1R,2R)-1,2-bis(3,5-dibromophenyl)-ethane-1,2-diol and (1R,2R)-1,2-bis(3,5-diphenylphenyl)-ethane-1,2-diol.     

Enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by Ti(IV) complexes of C2-symmetrical chiral BINOL derivatives

Enantioselective addition of diethylzinc to a series of aromatic aldehydes is developed using new chiral C₂-symmetric ligand (S)-2,2′-(1,1′-binaphthyl-2,2′-diylbis(oxy))bis(methylene)bis(4-nitrophenol) (S)-2b. The catalytic system employing 10 mol % of (S)-2b and 120 mol % of Ti(OiPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes with electron-donating and electron-withdrawing substituents, giving up to 89% ee and up to 95% yield of the corresponding secondary alcohol under mild conditions.     

Titanium (IV) as an essential promoter in the asymmetric addition of diethylzinc to aldehydes catalyzed by aminonaphthol and imine ligands based on 3-substituted binaphthol

By using indirect reductive amination and condensation, two types of aminonaphthol and imine ligands based on 3-substituted binaphthol have been synthesized, respectively. When their catalytic effectiveness was tested by the ethylation of aldehydes with diethylzinc, titanium tetraisopropoxide was found essential to get good results with ee up to 90%.     

Enantioselective conjugate addition of phenylboronic acid to enones catalysed by a chiral tropos/atropos rhodium complex at the coalescence temperature

A highly enantioselective rhodium-catalysed conjugate addition of phenylboronic acid to cyclic enones has been achieved using a dynamic library of chiral phosphorus ligands; the tropos/atropos nature of the ligands in the rhodium complex has been characterised via 31P-NMR.     

Enantioselective conjugate addition of diethylzinc to cyclic enones catalyzed by chiral copper complexes containing a new phosphorus ligand with an H8-binaphthoxy moiety

A new chiral phosphorus amidite ligand with an H₈-binaphthoxy moiety was synthesized and applied to the copper-catalyzed asymmetric conjugate addition of diethylzinc to cyclic enones with high enantioselectivity. The results gave support to the generality of the advantage of the sterically more demanding H₈-binaphthyl backbone in biaryl chiral ligands.     

Chiral ligands derived from abrine. Part 5: Substituent effects on asymmetric induction in enantioselective addition of diethylzinc to benzaldehyde catalyzed by chiral oxazolidines possessing an indole moiety

A number of the indole-containing chiral oxazolidines possessing the gem-di-p-tolyl and gem-di-o-tolyl groups at C₅ were synthesized from abrine and the effects of the C₅ and C₂ substituents on the asymmetric induction in catalytic enantioselective addition of diethylzinc to benzaldehyde were examined. A working model is proposed to rationalize the asymmetric catalysis by these chiral oxazolidines.     

Enantiopure inherently chiral calix[4]arene derivatives containing quinolin-2-yl-methanol moiety:Synthesis and application in the catalytic asymmetric addition of diethylzinc to benzaldehyde

A series of novel N,O-type chiral ligands derived from enantiopure inherently chiral calix[4]arenes containing quinolin-2-yl-methanol moiety in the cone or partial-cone conformation have been synthesized and characterized. Moreover, they have been applied to the catalytic asymmetric addition of diethylzinc to benzaldehyde, which represents the first example that the inherently chiral calixarene can be used as the chiral ligands for the catalytic asymmetric synthesis. Supported by the National Natural Science Foundation of China (Grant Nos. 20625206 & 20372064), the National Basic Research Project (Grant Nos. 2007CB808000 & 2008CB617501), and the Chinese Academy of Sciences     

Asymmetric catalysis in a micro reactor—Ce, Yb and Lu catalysed enantioselective addition of trimethylsilyl cyanide to benzaldehyde

A T-shaped micro reactor was used for the optimisation of reaction conditions for the enantioselective silylcyanation of benzaldehyde catalysed by lanthanide-pybox complexes. Compared to a conventional batch procedure, higher conversion was observed within shorter reaction time. The micro reactor process involving Lu(III) afforded essentially the same enantioselectivity as the batch process (73 vs 76% ee), whereas the enantioselectivity was lower in the micro reactor for catalysts containing Yb(III) (53 compared to 72%). Ce(III) provided very low selectivity in both types of processes (1 and 11% ee, respectively). A study of the effect of additives showed that the enantioselectivity in the Yb catalysed reaction performed in the micro reactor could be increased to 66%, whereas only a minor improvement, to 78% ee, was observed in the reaction with Lu.