Asymmetric Addition Of Diethylzinc Research Articles

Homochiral 2D Porous Covalent Organic Frameworks for Heterogeneous Asymmetric Catalysis.

There have been breakthroughs in the development of covalent organic frameworks (COFs) with tunability of composition, structure, and function, but the synthesis of chiral COFs remains a great challenge. Here we report the construction of two-dimensional COFs with chiral functionalities embedded into the frameworks by imine condensations of enantiopure TADDOL-derived tetraaldehydes with 4,4'-diaminodiphenylmethane. Powder X-ray diffraction and computer modeling together with pore size distribution analysis show that one COF has a twofold-interpenetrated grid-type network and the other has a non-interpenetrated grid network. After postsynthetic modification of the chiral dihydroxy groups of TADDOL units with Ti(O(i)Pr)4, the materials are efficient and recyclable heterogeneous catalysts for asymmetric addition of diethylzinc to aldehydes with high enantioselectivity. The results reported here will greatly expand the scope of materials design and engineering for the creation of new types of functional porous materials.

ChemInform Abstract: Development of Polymer‐Supported Chiral Aminoalcohols Derived from Biomass and Their Application to Asymmetric Alkylation.

AbstractNovel polymer‐supported chiral aminoalcohols are tested as chiral ligands for the asymmetric diethylzinc addition to aromatic aldehydes.

Development of polymer-supported chiral aminoalcohols derived from biomass and their application to asymmetric alkylation

A synthetic strategy has been developed for the preparation of immobilized 1,2-aminoalcohols starting from easily available and renewable chiral building blocks. They were tested as chiral ligands for the asymmetric diethylzinc addition to carbonyl compounds. Enantioselectivities were comparable to those observed for non-immobilized analogs. These results provide strong evidence for the flexibility of our approach to generate highly valuable supported chiral ligands derived from cellulose-rich materials.

Helical silica immobilizing ruthenium complexes for highly asymmetric addition of diethylzinc to aldehydes

A new series of helical silica were synthesized by doping of l-sodium hydrogen glutamate in a sol–gel procedure. Characterizations revealed doping of l-sodium hydrogen glutamate improved porosity, morphology, hydrolysis resistance and internal chirality of silica matrix. Meanwhile, chiral ruthenium complexes were synthesized and immobilized into helical silica in order to catalyze asymmetric addition of diethylzinc to aryl aldehydes. Catalysis revealed chiral induction synergy of multiple chiral centers on one ruthenium complex was existent. Ruthenium complexes immobilized over the glutamate-doped helical silica showed much better ee values and yields than those over blank-doped one. Immobilization of helical silica-supported ruthenium complex into imidazolium ionic liquid was efficiently recycled during three times. This work not only provided new chiral silica, but also studied their application in asymmetric catalysis.

Synthesis of novel tartaric acid-derived chiral phosphite ligands and their application in the Cu-catalyzed conjugate addition of diethylzinc to cyclic enones

Five novel tropos (3R,4R)- and/or (3S,4S)-N-benzyltartarimide-derived biphenylphosphite ligands were synthesized and applied in the Cu-catalyzed asymmetric conjugate addition of diethylzinc to cyclic enones with up to 75% e.e. Compared with the reported ligand 1-N-benzylpyrrolidine-3,4-bis[(R)-1,1’-binaphthyl-2,2’-diyl]phosphite-L-tartaric acid, the issue that L-(+)-tartaric acid backbone and (R)-binaphthyl showed strong matched/mismatched character was solved with these tropos ligands. It was found that the enantioselectivity was mainly controlled by the absolute configuration of N-benzyltartarimide backbone, and both enantiomers of the addition products can be obtained by simply changing the configuration of N-benzyltartarimide substituent.

ChemInform Abstract: [2.2]Paracyclophane‐Derived Monodentate Phosphoramidite Ligands for Copper‐Catalyzed Asymmetric Conjugate Addition of Diethylzinc to Substituted Chalcones.

AbstractCopper‐catalyzed asymmetric conjugate addition of diethylzinc to chalcones is realized by using a newly synthesized [2.2]paracyclophane‐derived monodentate phosphoramidite ligand.

Enantioselective addition of diethylzinc to aldehydes catalyzed by aziridine carbinols

A series of enantiopure aziridine carbinols were synthesized from commercially available starting materials (l-serine and piperonylaldehyde), and characterized by 1H NMR, 13C NMR, HRMS, and IR. Their enantioselective induction behaviors were evaluated as chiral ligands in the asymmetric addition of diethylzinc and phenylethynylzinc to aryl and α,β-unsaturated aldehydes. Chiral aziridine carbinol 1h was found to catalyze the asymmetric addition of diethylzinc to aldehydes at low catalyst loadings (as little as 1mol%), and the conversion rates were close to quantitative (up to 97% yield) with good to excellent enantiomeric excesses (up to 98% ee). A possible catalytic reaction mechanism is proposed.

Highly efficient chiral polydentate sulfinyl ligands/catalysts containing prolinol moiety

New polydentate chiral ligands, containing the hydroxyl group, stereogenic sulfinyl group and enantiomeric prolinol moieties were synthesized and proved very efficient catalysts in the asymmetric diethylzinc addition to benzaldehyde, the asymmetric aldol condensation and the asymmetric Mannich reaction. Replacement of the central hydroxyl group with the second prolinol moiety of the same absolute configuration gave new ligands in which the sulfinyl group was not a stereogenic centre anymore, but which proved almost equally efficient as catalysts for the reactions investigated. The absolute configuration of the proline moiety exerted a decisive impact on the stereochemical outcome of these reactions, deciding about the absolute configuration of the products formed.

ChemInform Abstract: Bisoxazoline‐Catalyzed Asymmetric Nucleophilic Addition of Diethyl Zinc to Fluorinated Alkyl Ketones: Enantiofacial Control by Changing the Bisoxazoline Substituent.

AbstractOptimum reaction conditions (structure of catalyst, solvent) are studied for the bisoxazoline‐catalyzed asymmetric nucleophilic addition of diethyl zinc to fluorinated alkyl ketones.

A Helical Polyphenylacetylene Having Amino Alcohol Moieties Without Chiral Side Groups as a Chiral Ligand for the Asymmetric Addition of Diethylzinc to Benzaldehyde.

One-handed helical polyphenylacetylenes having achiral amino alcohol moieties, but no chiral side groups, were synthesized by the helix-sense-selective copolymerization of an achiral phenylacetylene having an amino alcohol side group with a phenylacetylene having two hydroxyl groups. Since the resulting helical copolymers were successfully utilized as chiral ligands for the enantioselective alkylation of benzaldehyde with diethylzinc, we can conclude that the main-chain chirality based on the one-handed helical conformation is useful for the chiral catalysis of an asymmetric reaction for the first time. The enantioselectivities of the reaction were controlled by the optical purities of the helical polymer ligands. In addition, the polymer ligands could be easily recovered by precipitation after the reaction.

ChemInform Abstract: A New Pyrrolidine‐Derived Atropisomeric Amino Alcohol as a Highly Efficient Chiral Ligand for the Asymmetric Addition of Diethylzinc to Aldehydes.

AbstractThe reaction yield as well as the enantiomeric excess is marginally influenced by the substituents of the benzaldehyde, but by switching from aryl to alkenyl aldehydes, the enantiomeric excess drops significantly.

Synthesis of new chiral 1,3-aminoalcohols derived from levoglucosenone and their application in asymmetric alkylations

We have developed a simple procedure for the preparation of chiral 1,3-aminoalcohols using the biomass derivative levoglucosenone, as the chiral starting material. 1,3-aminoalcohols, bearing primary and tertiary amino groups, were tested as chiral catalysts in the asymmetric addition of diethyl zinc to benzaldehyde.

2.2]Paracyclophane-derived monodentate phosphoramidite ligands for copper-catalyzed asymmetric conjugate addition of diethylzinc to substituted chalcones.

Copper-catalyzed asymmetric conjugate addition of diethylzinc to chalcones could be realized by using [2.2]paracyclophane-derived monodentate phosphoramidite ligands. The excellent yield and enantioselectivity (up to 98% yield and 95% enantiomeric excess) could be realized with low catalyst loading of 1.0 mol % and low ligand loading of 1.2%.

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

AbstractPoly[(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.

Synthesis of quinazolinone-based aziridine diols as chiral ligands: dual stereoselectivity in the asymmetric ethylation of aryl aldehydes

A new class of quinazoline-based enantiomerically pure aziridine diols 4a–d were prepared from the aziridination of mesityl oxide 3 with in situ generated 3-acetoxyaminoquinazolinone (S)-2b followed by NaBH4 reduction. Aziridine diols 4a–d were purified by means of column chromatography on silica gel and their stereochemistries were assigned by X-ray crystallography and NMR analysis. These aziridine diols 4 were evaluated as chiral ligands in the asymmetric addition of diethylzinc to aryl aldehydes, and ligand (S,R,R)-4a yielded (R)-1-phenylpropanol derivatives with up to 92% ee, while the diastereomer (S,S,R)-4c gave the opposite enantiomers (S)-1-phenylpropanol derivatives with up to 86% ee. The results demonstrate that switching the configuration of the aziridine alcohol moiety in ligand gives a remarkable reversal of enantioselectivity in the asymmetric addition of diethylzinc to aryl aldehydes.

Preparation of Mesoporous Silica‐Supported Chiral Amino Alcohols for the Enantioselective Addition of Diethylzinc to Aldehyde and Asymmetric Transfer Hydrogenation to Ketones

Optically active (−)‐ephedrine, (−)‐norephedrine, and (−)‐prolinol were immobilized onto cubic mesoporous MCM‐48 silica. The immobilized amino alcohols served as a heterogeneous chiral catalyst for the asymmetric addition of diethylzinc to aldehydes and transfer hydrogenation to ketones. The developed catalytic process yielded optically enriches secondary aromatic alcohols with 92–99% conversion and 70–82% enantioselectivity.

ChemInform Abstract: Efficient Asymmetric Addition of Diethylzinc to Aldehydes Using C2‐Novel Chiral Pyridine β‐Amino Alcohols as Chiral Ligands.

A series of novel C2-symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1H NMR, 13C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2′R)-2,2′-((pyridine-2,6-diylbis(methylene))bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2′R)-2,2′-((1,3-phenylenebis(methylene))bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright © 2014 John Wiley & Sons, Ltd.

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, (Sa)-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).

Bisoxazoline-Catalyzed Asymmetric Nucleophilic Addition of Diethyl Zinc to Fluorinated Alkyl Ketones: Enantiofacial Control by Changing the Bisoxazoline Substituent

Abstract Bisoxazoline (BOX)-catalyzed asymmetric nucleophilic addition of diethyl zinc to fluorinated alkyl ketones successfully afforded enantioenriched fluorinated alkyl tertiary alcohols. The effect of the size of the substituent on the oxazoline ring on the stereoselectivity of the reaction was investigated. Furthermore, the enantioselectivity could be reversed by altering the BOX bridge structure while retaining the C-4 substituent on the oxazoline ring.

A mathematical expression for the enantioselectivity and thermodynamic factors in the conformational equilibrium of catalysts in the addition of diethylzinc to benzaldehyde

A mathematical expression for the enantioselectivity and thermodynamic factors is presented in the conformational equilibrium of a flexible chiral catalyst for the asymmetric addition of diethylzinc to aldehydes. The results show that the total enantioselectivity of the catalyzed reaction is not only governed by the free energy difference of two ground-state conformers, as well as the free energies of activation for the major enantiomeric product formed from each of the catalyst’s conformations, but also by the difference in the transition state energies of the formation of the (S)- and (R)-enantiomers from the individual conformers of the catalyst.