Modular amino acids and β‐amino alcohol‐based chiral ligands for enantioselective addition of diethylzinc to aromatic aldehydes

Enantioselective addition of diethylzinc to a series of aromatic aldehydes was developed using a modular amino acids and ${\bf \beta}$ ‐amino alcohol‐based chiral ligand (2R)‐N‐[(1R,2S)‐1‐hydroxy‐1‐phenylpropan‐2‐yl]‐3‐phenyl‐2‐(tosylamino) propanamide ( 1f ) without using titanium complex. The catalytic system employing 15 mol% of 1f was found to promote the addition of diethylzinc (ZnEt₂) to a wide range of aromatic aldehydes with electron‐donating and electron‐withdrawing substituents, giving up to 97% ee of the corresponding secondary alcohol under mild conditions. Copyright © 2010 John Wiley & Sons, Ltd.     

Asymmetric reaction of diethylzinc with aldehydes catalyzed by l‐menthopyrazole derivatives

N‐Hydroxyalkyl‐1‐menthopyrazoles acted as a chiral catalyst for the diethylzinc ( 1 ) addition to aromatic aldehydes, and 1‐aryl‐1‐propanols were afforded enantioselectively. These reactions were carried out optimally in toluene at 40 °C in the presence of 30 mol% of (2′S)‐2‐(2‐phenyl‐2‐hydroxyethyl)‐3‐phenyl‐1‐men‐thopyrazole ((S)‐ 16d ) to afford optically active 1‐aryl‐1‐propanols up to 70% ee (S).     

Straightforward access to chiral diol bidentate ligands: their efficient enantioselective induction in the addition of diethylzinc to aromatic aldehydes

Enantiopure C₂‐symmetric diol bidentate ligands have been synthesized in a straightforward manner through a three‐step reaction with good yields. The synthesized C₂‐symmetric diol bidentate ligands were used in the addition of diethylzinc to various aromatic aldehydes, a general catalytic benchmark reaction, in order to assess their enantioselective induction properties. The enantioselective addition of diethylzinc to 1‐naphthaldehyde and 3‐chlorobenzaldehyde was achieved with an enantiomeric excess (ee) of up to 98%. All synthesized ligands were also evaluated in the addition of diethyzinc to aromatic aldehydes including an extra metal such as Ti(IV) (up to 99% ee). Copyright © 2014 John Wiley & Sons, Ltd.     

Optically Active Helical Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl]: New Ligand for Asymmetric Addition of Diethylzinc to Aryl Aldehyde

Poly[(S)‐3‐vinyl‐2,2′‐dihydroxy‐1,1′‐binaphthyl] (L*) was obtained by taking off the protecting groups of poly[(S)‐3‐vinyl‐2,2′‐bis(methoxymethoxy)‐1,1′‐binaphthyl] (poly‐ 1 ). L* was proved to keep a stable helical conformation in solution. The application of helical L* in the asymmetric addition of diethylzinc to aldehydes has been studied. The catalytic system employing 10 mol% of L* and 150 mol% of Ti(OⁱPr)₄ was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes, giving up to 99% enantiomeric excess (ee) and up to 93% yield of the corresponding secondary alcohol at 0°C. The chiral polymer can be easily recovered and reused without loss of catalytic activity as well as enantioselectivity.     

Chemoselectivity in the Reaction of 2‐Diazo‐3‐oxo‐3‐phenylpropanal with Aldehydes and Ketones

The chemoselectivity in the reaction of 2‐diazo‐3‐oxo‐3‐phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et₃N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron‐donating substituents and cyclic ketones under formation of 6‐phenyl‐4H‐1,3‐dioxin‐4‐one derivatives. However, it reacts with aromatic aldehydes with electron‐withdrawing substituents to yield 1,3‐diaryl‐3‐hydroxypropan‐1‐ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron‐donating substituents. A mechanism for the formation of 1,3‐diaryl‐3‐hydroxypropan‐1‐ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N,N′‐dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS₂. Only with N,N′‐dialkylcarbodiimines, the expected cycloaddition took place.     

Synthesis of Novel 1,4‐Bissulfonamide Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

Several novel chiral sulfonamide ligands based on (1R,2S,4R,5S)‐1,4‐diamino‐2,5‐dimethylcyclohexane skeleton have been synthesized and their application in the enantioselective addition of diethylzinc to aldehydes was investigated in the presence of Ti(OⁱPr)₄. The effect of ligands, temperature and the loading amount of ligands was studied. Under optimized conditions, enantioselective addition of diethylzinc with various aryl aldehydes and aliphatic aldehydes proceeded smoothly and afforded chiral secondary alcohols in up to 88% ee.     

Efficient asymmetric addition of diethylzinc to aldehydes using 3‐hydroxyazetidine derivatives as chiral ligands

A new series of chiral 3‐hydroxyazetidines has been prepared from (S)‐1‐(4‐methoxyphenyl)ethylamine. These ligands have shown excellent catalytic activities and enantiomeric selectivities in asymmetric addition of diethylzinc to aromatic aldehydes. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones using nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl2 nanoparticles

Nano‐Zn‐[2‐boromophenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ (nano‐[Zn‐2BSMP]Cl₂) as a nanoparticle Schiff base complex and a catalyst was introduced for the solvent‐free synthesis of 4‐((2‐hydroxynaphthalen‐1‐yl)(aryl)methyl)‐5‐methyl‐2‐phenyl‐1H‐pyrazol‐3(2H)‐ones by the multicomponent condensation reaction of various aromatic aldehydes, β‐naphthol, ethyl acetoacetate, and phenyl hydrazine at room temperature.     

Mn‐[4‐Chlorophenyl‐Salicylaldimine‐Methylpyranopyrazole]Cl2 as a Novel Nanostructured Schiff Base Complex and Catalyst

Mn‐[4‐chlorophenyl‐salicylaldimine‐methylpyranopyrazole]Cl₂ ([Mn‐4CSMP ]Cl₂) as nano‐Schiff base complex was prepared and fully characterized by Fourier transform infrared spectroscopy, X‐ray diffraction, thermal gravimetric analysis, derivative thermogravimetry, scanning electron microscopy, energy‐dispersive X‐ray analysis, and UV–vis spectroscopy. The reactivity of nano‐[Mn‐4CSMP ]Cl₂ as a catalyst was tested on the tandem cyclocondensation–Knoevenagel condensation–Michael reaction between phenylhydrazine and ethyl acetoacetate with various aromatic aldehydes to give 4,4′‐(arylmethylene)‐bis‐(3‐methyl‐1‐phenyl‐1H ‐pyrazol‐5‐ol)s derivatives.     

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.     

Chirality Control by Substituents in the Asymmetric Addition of Et_2Zn to Aromatic Aldehydes Catalyzed by cis-(1 R,2S)-2- Benzamidocyclohexanecarboxylic Acid Derived 1,3-Aminoalcohols

A series of novel optically active 1,3‐aminoalcohols based on cis‐(1R,2S)‐2‐benzamidocyclohexanecarboxylic acid and trans‐(1R,2R)‐2‐benzamidocyclohexanecarboxylic acid were synthesized and used in the asymmetric diethylzinc addition to aromatic aldehydes. Not only the enantioselectivity but also the stereochemistry of the product were controlled by the N‐substituents and the substituents on the vicinity carbon to hydroxyl group of the cis‐derivatives.     

Axially Dissymmetric Chiral (R)‐N,W‐Bis(2‐hydroxy‐3,5‐ditert‐butyl‐arylmethyl)‐1, 1′‐binaphthalene‐2,2′‐diamine as Chiral Ligands in the Reaction of Diethylzinc to Aldehydes†

Chiral ligand (A)‐N,N′‐Bis(2‐hydroxy‐3,5‐di‐tert‐butyl‐arylmethyl)‐1,1′‐binaphthalene‐2,2′‐diamine derived from the reduction of Schiff base (R)‐2,2′‐bis (3,5‐di‐tert‐butyl‐2‐hydroxybenzylideneamino)‐1, 1′‐binaphthyl with LiAlH₄, is fairly effective in the asymmetric addition reaction of diethylzinc to aldehydes by which good yields (46%‐94%) of the corresponding sec‐alcohols can be obtained in moderate ee (51%‐79%) with R configuration for a variety of aldehydes.     

Synthesis of Chiral Sulfamide–Amine Alcohol Ligands for Enantioselective Alkylation of Aldehydes

A series of chiral sulfamide–amine alcohols (SAA) (1–6) has been easily synthesized from commercially available chiral amino alcohols. In the absence of Ti(O ⁱ Pr)₄, ligand 4 catalyzed the asymmetric addition of diethylzinc to aromatic aldehydes with moderate to good yields and enantioselectivities.     

Utilization of Donor–Acceptor Interactions for the Catalytic Acceleration of Nucleophilic Additions to Aromatic Carbonyl Compounds

A conceptually new method for the catalytic electrophilic activation of aromatic carbonyl substrates, by utilizing donor–acceptor interactions between an electron‐deficient macrocyclic boronic ester host ( [2+2] _BTH‐F ) and an aromatic carbonyl guest substrate, was realized. In the presence of a catalytic amount of [2+2] _BTH‐F , dramatic acceleration of the nucleophilic addition of a ketene silyl acetal towards either electron‐rich aromatic aldehydes or ketones was achieved. Several control experiments confirmed that inclusion of the aromatic substrates within [2+2] _BTH‐F , through efficient donor–acceptor interactions, is essential for the acceleration of the reaction.     

A new pyrrolidine-derived atropisomeric amino alcohol as a highly efficient chiral ligand for the asymmetric addition of diethylzinc to aldehydes

A highly efficient pyrrolidine-derived atropisomeric amino alcohol, (S_a)-1-[2-diphenylhydroxymethyl-6-(trifluoromethyl)phenyl]-2-(1-pyrrolido)methyl-1H-pyrrole, has been synthesized as a chiral ligand for the enantioselective addition of diethylzinc to some prochiral aldehydes to afford (S)-alcohols. The conversion rates were close to quantitative with good to excellent enantiomeric excesses (up to 95% ee).     

Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Catalysed by Chiral Ligands Derived from L-Hydroxyproline

The Lithium salts of chiral auxiliaries 2–4 derived from L-Hydroxyprolin (2S, 4R)-1 catalysed the enantioselective addition of diethylzinc to aromatic aldehydes to afford sec alcohols in up to 80% optical purity.     

Asymmetric alkylation of aromatic aldehydes with dialkylzinc catalyzed by novel amino derivatives of hydroxytetrahydropyran

Novel, specially prepared, tetrahydropyran‐based γ‐amino alcohols (S)‐2‐(aminomethyl)‐3‐hydroxy‐6‐ethoxy(phenoxy)‐tetrahydropyrans ( I ) (amino = n‐Bu₂N, piperidinyl, pyrrolidinyl, azetidinyl) were tested as catalysts in the asymmetric addition of Et₂Zn and n‐Bu₂Zn to (hetero)aromatic aldehydes. In most cases the phenoxy derivatives of I acted more enantioselectively than the ethoxy ones. The dibutylamino derivaties showed the least enantioselectivity; the pyrrolidinyl derivatives were more active as catalysts than piperidinyl and azetidinyl compounds. The highest enantioselectivity was observed in the addition of Et₂Zn to benzaldehyde in the presence of (S)‐2‐(N‐pyrrolidinylmethyl)‐3‐hydroxy‐6‐phenoxytetrahydropyran. The corresponding alcohol was prepared with 72% ee (R‐configuration). The addition of dibutylzinc proceeded slowly and less selectively. The alkylation of (hetero)aromatic aldehydes with Et₂Zn and n‐Bu₂Zn was also studied in the presence of the known optical inductor (1S,2R)‐N,N‐dibutylnorephedrine. Some chiral aromatic secondary alcohols were synthesized in high chemical yields and up to 93% ee enantioselectivity. Copyright © 1999 John Wiley & Sons, Ltd.     

Asymmetric ethylation of aromatic aldehyde by diethylzinc in the presence of chiral auxiliaries derived from (S)-[4-HOC6H4CH2CH(NH2)CPh2OH]

A comparative study has been carried out on enantioselective ethylation of aromatic aldehydes (ArCHO) by diethylzinc (Et₂Zn) in the presence of catalytic amounts of (S)-[4-HOC₆H₄CH₂CH(NH₂)CPh₂OH] (1) or chiral auxiliaries derived from (1). Various procedures have been adopted; these involved (i) different sequences of addition of the reagents ArCHO, Et₂Zn and (1), and (ii) use of titanium(IV)isopropoxide [Ti(OPrⁱ)₄] or the boranetetrahydrofuran addition compound (BH₃ · THF) as additional reagents. In all but one of the procedures adopted, (S)-ArCH(OH)Et was selectively formed; enantiomeric excess values up to 87% were obtained.     

Asymmetric diethylzinc addition and phenyl transfer to aldehydes using chiral cis-cyclopropane-based amino alcohols

A new series of amino alcohols with a chiral cyclopropane backbone have been developed and used in the catalytic asymmetric diethylzinc addition and phenyl transfer to various types of aldehydes. These cyclopropane-based chiral amino alcohols show high enantioselectivity in the addition of organozincs to aromatic and aliphatic aldehydes. For diethylzinc addition to aromatic and aliphatic aldehydes, up to 97% ee and 93% ee are obtained, respectively. For the phenyl transfer to aromatic aldehydes, the best enantioselectivity was 89% ee.     

Rhodium‐catalyzed ortho‐C‐H olefination of aromatic aldehydes employing transient directing strategy

A Rhodium(III)‐catalyzed ortho‐C‐H olefination of aromatic aldehydes in the presence of catalytic amount of TsNH₂ has been developed. The in situ generated imine intermediate from aldehyde and TsNH₂ worked as a transient directing group. Both electron‐rich and electron‐deficient aromatic aldehydes were tolerated, affording the corresponding products in moderate to good yields. Importantly, the present protocol provides a straightforward access to olefinated aromatic aldehydes with aldehydes as the simple starting materials.