Asymmetric Addition Of Diethylzinc Research Articles

Development of diverse adjustable axially chiral biphenyl ligands and catalysts

Development of highly efficient and practical chiral ligands and catalysts is an eternal theme in asymmetric synthesis. Here, we report the design, synthesis, and evaluation of a new kind of adjustable axially chiral biphenyl ligands and catalysts, in which six model reactions including asymmetric additions of diethylzinc or alkynes to aldehydes in the presence of axially chiral [1,1'-biphenyl]-2,2'-diol ligands, palladium-catalyzed asymmetric cycloadditions in the presence of phosphoramidite ligands, and chiral phosphoric acid-catalyzed asymmetric synthesis of 1,1'-spirobiindane-7,7'-diol derivative and [4+ 3] cyclization were attempted. The results showed that variation of 2,2'-substituent groups could provide different types of ligands and catalysts, and adjustment of substituent groups at the 3,3', 5,5', 6,6'-positions could make ligands and catalysts more efficient in the asymmetric catalytic synthesis. Therefore, our present research should provide a new and useful strategy for development of diverse axially chiral ligands and catalysts.

Pd-Catalyzed Atroposelective C-H Acyloxylation Enabling Access to an Axially Chiral Biaryl Phenol Organocatalyst.

Herein, we present the Pd(II)-catalyzed atroposelective C-H acyloxylation strategy for the assembly of biaryl aldehyde atropoisomers using readily available amino acids as the catalytic auxiliary and chiral pool. This strategy exhibits a broad substrate scope with a good yield (≤90%) and excellent enantioselectivity (≤99%), furnishing functionalized aldehydes through direct asymmetric C-H oxidation. The application utility of this method was demonstrated by the concise synthesis of a kind of atropoisomeric amino-phenol organocatalyst, which enables good enantiocontrol in catalyzing asymmetric addition of diethylzinc to aldehydes.

Porous aromatic frameworks containing binaphthyl-dihydroazepine units (cBAPAFs) as catalytic supports for asymmetric reactions

We present the successfully synthesis of a series of chiral polymeric aromatic frameworks containing novel enantiopure atropoisomeric 1,1′-binaphthyl-dihydroazepine-based compounds as structural building units named cBAPAFs. Three porous materials with amino, pyridinic and amino-alcohol functionalities were successfully obtained from dibrominated monomers by Suzuki-Miyaura couplings. New porous materials present surface areas up to 619 m2 g−1 determined by Brunauer–Emmett–Teller (BET), and high thermal stability. The use of nitrogen-based structural units provides useful functional groups to allow a robust binding site for metal complexes. Thus, after post-synthetic metalation with Cu(OAc)2, these materials have been applied as efficient heterogenized catalysts for the nitroaldol (Henry) reaction and a multicomponent reaction, affording chiral products with comparable enantioselectivity to that of the homogeneous system. The materials were also tested as organocatalysts for the asymmetric addition of diethylzinc to benzaldehyde and the reaction between nitro-styrene and nitroethane. These cBAPAFs could be recycled for the asymmetric nitroaldol reaction for at least 5 cycles without a significant loss in its catalytic efficiency.

Efficient Asymmetric Simmons-Smith Cyclopropanation and Diethylzinc Addition to Aldehydes Promoted by Enantiomeric Aziridine-Phosphines

During an implementation of current research, a set of optically pure chiral aziridines and aziridine imines bearing a phosphine moiety was prepared with high values of chemical yield. The above chiral heteroorganic derivatives were tested for catalytic utility as chiral ligands in asymmetric Simmons-Smith cyclopropanation and asymmetric diethylzinc addition to various aldehydes. Most of the desired products were formed in high chemical yields, with satisfactory values of enantiomeric excess (sometimes more than 90%) and diastereomeric ratios (in case of cyclopropanation reaction).

Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Using Chiral Oxazoline-Based Ligands

Chiral oxazoline ligands containing an aromatic ring were prepared from norephedrine and pyrrole-2-carbonitrile or 2-hydroxybenzoyl chloride. The synthesized ligands were used in the copper-catalyzed asymmetric addition of diethylzinc to aromatic aldehydes to provide optically active 1-arylpropan-1-ols with high conversion (92%) and enantioselectivity (up to 99% ee).

Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Using Novel Thiophene-Based Chiral Ligands

Chiral norephedrine-derived β-amino alcohols with a thiophene moiety were synthesized from thiophene carbaldehydes (methyl- or ethyl-substituted) and chiral amino alcohols, such as both enantiomers of norephedrine and 2-aminopropanol. The synthesized ligands were applied to the catalytic asymmetric addition of diethylzinc to aldehydes to obtain optically active alcohols with a high conversion (92%) and excellent enantioselectivities (ee up to 99%). The highest enantioselectivity (ee 99%) was obtained with p-trifluorobenzaldehyde as the substrate containing the strongly electron-acceptor CF3 group.

Synthesis and Investigation of Pinane-Based Chiral Tridentate Ligands in the Asymmetric Addition of Diethylzinc to Aldehydes

A library of pinane-based chiral aminodiols, derived from natural (−)-β-pinene, were prepared and applied as chiral catalysts in the addition of diethylzinc to aldehydes. (−)-β-Pinene was reacted to provide 3-methylenenopinone, followed by a reduction of the carbonyl function to give a key allylic alcohol intermediate. Stereoselective epoxidation of the latter and subsequent ring opening of the resulting oxirane with primary and secondary amines afforded aminodiols. The regioselectivity of the ring closure of the N-substituted secondary aminodiols with formaldehyde was examined and exclusive formation of oxazolidines was observed. Treatment of the allylic alcohol with benzyl bromide provided the corresponding O-benzyl derivative, which was transformed into O-benzyl aminodiols by aminolysis. Ring closure of the N-isopropyl aminodiol derivative with formaldehyde resulted in spirooxazolidine. The obtained potential catalysts were applied in the reaction of both aromatic and aliphatic aldehydes to diethylzinc providing moderate to good enantioselectivities (up to 87% ee). Through the use of molecular modeling at an ab initio level, this phenomenon was interpreted in terms of competing reaction pathways. Molecular modeling at the RHF/LANL2DZ level of theory was successfully applied for interpretation of the stereochemical outcome of the reactions leading to display excellent (R) enantioselectivity in the examined transformation.

Functionalized Magnetic Nanoparticles as Catalysts for Enantioselective Henry Reaction.

With the aim to easily recover and reuse the catalyst, an efficient amino alcohol catalyst previously tested in the asymmetric addition of diethylzinc to several aromatic aldehydes has been immobilized on proper functionalized superparamagnetic core–shell magnetite–silica nanoparticles and employed in the Henry reaction in the semi-homogeneous phase. The nanocatalyst exhibits a promising catalytic activity that remains unchanged in the three catalytic cycles performed. The results prove that highly efficient catalysts, by being immobilized on suitable magnetic nanosupports, can be easily recovered and reused, maintaining their catalytic behavior.

Adamantyl-BINOL as platform for chiral porous polymer aromatic frameworks. Multiple applications as recyclable catalysts

Herein, we report the synthesis of adamantyl-BINOL-based chiral porous aromatic polymers (Ad-BINOL-PAFs) for heterogeneous catalysis. Ad-BINOL-OH-PAF (365 m2·g−1 SABET) was built through the covalent bonds among of 4,4′-dibromo-O-ethyl-protected adamantyl-BINOL with 1,3,5-Triphenylbenzene-4′,4″,4′″-triboronic acid and in the presence of [Ti(OiPr)4] results an effective recyclable catalyst in the asymmetric addition of diethylzinc to aromatic aldehydes (ee up to 88%). The corresponding heterogenized phosphoric acid (Ad-BINOL-PO2H-PAF) was applied as heterogeneous recyclable organocatalyst for the cascade condensation/amine addition of anthranilamide with aldehydes and transfer hydrogenation reactions obtaining high yields but low enantioselectivity. On the other hand, heterogeneous phosphoric acid (Ad-BINOLs-PO2H-PAF) was also used as effective phosphate ligands for synthesis of rhodium(II) complexes which were effective catalysts in cyclopropanation of styrene affording chiral cyclopropanes in good yield and high diastereoselectivity (>99%) and moderate enantioselectivity (ee < 50%).

Chiral P,N‐ligands for the highly enantioselective addition of diethylzinc to aromatic aldehydes

A new sterically hindered chiral P,N‐ligand was synthesized and successfully applied to copper catalyzed asymmetric addition of diethylzinc to aromatic aldehydes. Various aromatic aldehydes can react smoothly to give the corresponding addition products with good to excellent enantioselectivities, which provides a readily accessible method for the preparation of chiral secondary alcohols.

Copper-catalyzed asymmetric tandem double Michael reactions of diethylzinc to α,β-unsaturated ketones followed by trapping with nitroolefins

A copper catalyzed asymmetric tandem double Michael addition of diethylzinc to α,β-unsaturated ketones followed by trapping with nitroolefins has been developed using chiral P,N-ligands. The tandem products were obtained in good yields and excellent enantioselectivities with three contiguous stereocenters.

New C2-symmetric six-membered carbene ligands for asymmetric diethylzinc addition of arylaldehydes

New C2-symmetric six-membered carbene ligands for asymmetric diethylzinc addition of arylaldehydes

Synthesis of Novel Chiral Pyrimidone Salts and their Application in Asymmetric Diethylzinc Addition of Arylaldehydes

Aims and Objectives: When compared to five-membered N-heterocyclic carbene, recent reports have demonstrated that ring expanded NHCs showed rather different properties such as increased basicity (nucleophilicity) and greater steric demand. These unique features provide an opportunity to design new chiral ligands. This study was undertaken to design and synthesize a series of novel enantiopure pyrimidone salts, the precursors of N-heterocyclic carbenes, and their activity in asymmetric diethylzinc addition of arylaldehydes was demonstrated as well. Materials and Method: Commercially available dimethylmalonic acid was treated with thionyl chloride to form dimethylmalony dichloride, followed by subsequent reaction with different chiral primary amine produced corresponding diamide. Next, conversion of diamide to monoamide was achieved by partial reduction with lithium aluminum hydride. Finally, cyclization of monoamide with triethyl orthoformate in the presence of ammonium salts provided pyrimidone salts in good yields. Results: Seven enantiopure pyrimidone salts, the precursors of N-heterocyclic carbenes, have been synthesized starting from dimethylmalonic acid. Their applicability in asymmetric diethylzinc addition of arylaldehydes has been demonstrated and the corresponding secondary alcohol was obtained with good yields and moderate enantioselectivities. Conclusion: Herein we developed an efficient route to prepare a series of novel N-heterocyclic carbene precursors, which were demonstrated as effective catalysts for asymmetric diethylzinc addition of arylaldehydes, and the corresponding secondary alcohol was obtained with good yields and moderate enantioselectivities.

Noscapine Derivatives as New Chiral Catalysts in Asymmetric Synthesis­: Highly Enantioselective Addition of Diethylzinc to Aldehydes­

Noscapine, a natural alkaloid, has never been used as a parent scaffold in chiral induction. The first examples of noscapinoid compounds as efficient catalysts in asymmetric synthesis are now reported. Three derivatives of noscapine were synthesized from its reaction with different Grignard reagents. Asymmetric addition of diethylzinc to aldehydes­ was performed in the presence of these catalysts in high yields and good to excellent ees.

Synthesis of New C2-Symmetric Six-Membered NHCs and Their Application for the Asymmetric Diethylzinc Addition of Arylaldehydes

A concise method for the preparation of new 3,4,5,6-tetrahydropyrimidinium salts was presented in this paper. Further application of these salts in asymmetric diethylzinc addition of arylaldehydes was explored, giving the corresponding chiral second alcohols in good yields and moderate enantioselectivities.

Synthesis of Macrocyclic Hexamine from Naphthalene-based C2-Symmetric Chiral Diamine and Dialdehyde

Naphthalene-based C2-symmetric chiral diamine was obtained with high enantioselectivity by the double asymmetric addition of diethylzinc to 1,5-dibutoxynaphthalene-2,6-dicarbaldehyde followed by the Mitsunobu azidation and the reduction of azide groups. The dynamic imine formation between the enantiopure C2-symmetric chiral diamine and 1,5-dimethoxynaphthalene-2,6-dicarbaldehyde afforded chiral macrocyclic hexaimine composed of six naphthalene units, which can be reduced to the corresponding hexamine in high yield.

Enantioselective Analysis: Logic of Chiral Ligand Design for Asymmetric Addition of Diethylzinc to Benzaldehyde

Enantioselective Analysis: Logic of Chiral Ligand Design for Asymmetric Addition of Diethylzinc to Benzaldehyde

Noscapine-derived β-amino alcohols as new organocatalysts for enantioselective addition of diethylzinc to aldehydes

In this paper, synthesis of two derivatives of noscapine and their application as organocatalysts in the asymmetric addition of diethylzinc to aromatic aldehydes is reported. The first catalyst (2) was synthesized by the reduction of lactone ring of noscapine to form the corresponding diol, and the second one (3) was prepared by tert-butyl dimethyl silylation of the primary hydroxyl group of 2. Excellent yields and high ees up to 95% were obtained by using 3 as the catalyst. To the best of our knowledge, this is the first report on the application of lactone ring opened noscapinoid compounds as organocatalysts in asymmetric reactions.

Synthesis of mesoporous zirconium-containing silicates and their application for catalytic asymmetric addition of diethylzinc to aldehydes

A series of mesoporous zirconium-containing silicates were prepared in sol–gel, which were further functionalized by chiral sulfonyl chloride and proline for catalytic asymmetric addition of diethylzinc to aldehydes. These materials had good porosities, hexagonal symmetries and internal chiralities. Moreover, significant morphological variations were observed when preparative conditions were changed. These materials also showed good to excellent enantioselectivities in catalysis, and there was chiral induction synergy between silicate matrix and attached ligand. Recycling of catalyst was tested, and promising results were obtained. This study would contribute to the design of mesoporous chiral catalysts.

Synthesis of MeO-PEG2000-supported chiral ferrocenyl oxazoline carbinol ligand and its application in asymmetric catalysis

A simple method for the synthesis of a MeO-PEG-supported chiral ferrocenyl oxazoline carbinol ligand has been developed. The chiral ligand was successfully applied to the catalytic asymmetric addition of diethylzinc to aryl aldehydes, affording secondary alcohols in high yields and with excellent enantioselectivities (up to 94% ee). The chiral ligand can be recovered and reused twice with no apparent loss of catalyst efficiency.