Enantioselective Addition Of Diethylzinc Research Articles

Enantioselective additions of diethylzinc to aldehydes catalyzed by titanate(IV) complex with chiral bidentate bis-amide ligands based on cyclopropane backbone

A set of chiral bis-amide ligands (4a–d and 5a–d) were obtained easily from readily available starting materials in a straightforward manner via acid chloride reaction of the parent Feist’s acid. These ligands have been tested as chiral catalysts for the enantioselective addition of diethylzinc to aromatic aldehydes in the presence of Ti(OiPr)4 as a co-additive. Very good enantioselectivity was obtained for 4-bromobenzaldehyde while in the case of 2,4-dichlorobenzaldehyde very low enantioselectivity was observed. The influence of solvent, temperature and the alkyl group substituents has been studied, and in the best case, an enantiomeric excess upto 95% has been achieved by using only 10mol % of the chiral bis-amides ligand 5b.

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by (S)-1-Alkyl-2-(arylamino)methylpyrrolidine

Abstract Several chiral diamines, (S)-1-alkyl-2-(arylamino)methylpyrrolidine, were used as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes. The best results were obtained by employing 0.15 equiv of (S)-2-anilinomethyl-1-benzylpyrrolidine, and chiral secondary alcohols were obtained with high enantiomeric excesses (up to 94% ee).

Functionalized organolithium reagents in the synthesis of chiral ligands for catalytic enantioselective addition of diethylzinc to aldehydes

Series of functionalized organolithium compounds were prepared and added to chiral bicyclic ketones (1R-(+)-camphor analogue 2 and 1R-(−)-fenchone 3), resulting in the preparation of a small “library” of chiral aminoalcohols able to serve as ligands in metal mediated asymmetric synthesis. The configuration of the chiral ligands was approved by applying advanced NMR experiments. The absolute configurations of 1,2-disubstituted planar chiral ferrocene-based aminoalcohols 15, 18 and 19 were determined by means of NMR experiments and confirmed by X-ray crystallography. The new chiral ligands were tested as pre-catalysts for the addition of diethyl zinc to benzaldehyde. The reactions proceeded with excellent conversions and a moderate degree of enantioselectivity.

Asymmetric Preparation of D-Phg-L-Pro Dipeptide-derived Chiral Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

-Pro dipeptide analogues 2 and 3 as shown in Scheme1. The treatment of two diastereomeric mixture (1:1) of N-(α-bromo-α-phenylacetyl)-(L)-proline methyl ester 1 withan amine nucleophile (diphenylmethylamine or dibenzyl-amine) in the presence of tetrabutylammonium iodide (TBAI)and diisopropylethylamine (DIEA) in CH

Cheap and Long‐Life Reusable Polymer for Asymmetric Organozinc Catalysis Based on Camphor‐Derived Hydroxyamides

Polystyrene grafted with a chiral zinc-complexing camphor-derived N,N-disubstituted hydroxyamide is proposed as a new type of functional polymer of high reusability for the development of sustainable organozinc-catalyzed asymmetric reactions. The main goal of this new functional polymer is the ease of the hydroxyamide-moiety preparation (cheap chiral ligand obtained straightforwardly from an enantiopure starting material coming from the chiral pool), as well as its chemical robustness when compared with other related zinc-complexing functional groups. The latter allows the polymer to be active after multiple applications, without significant loss of its catalytic activity. This fact is exemplified by the design and preparation of a polymer functionalized with a bis(hydroxyamide) proved previously as active in the homogeneous enantioselective addition of diethylzinc to aldehydes. The result is a cheap functional polymer with a very high reusability (the enantioselectivity and chemical yield are maintained practically constant after 20 applications). Additionally, a methodology for the multicycle use of these functional polymers is presented.

Stereoselective Synthesis of Densely Functionalized Pyrrolidin-2-ones by a Conjugate Addition/Nitro-Mannich/Lactamization Reaction

Copper-catalyzed conjugate addition of diorgano zinc reagents to nitroacrylate 1 followed by a subsequent nitro-Mannich reaction and in situ lactamization leads to an efficient one-pot synthesis of 1,3,5-trisubstituted 4-nitropyrrolidin-2-ones (5). The versatility of the reaction is shown for a wide range of N-p-(methoxy)phenyl protected aldimines 3 derived from alkyl, aryl, and heteroaryl aldehydes. The densely functionalized pyrrolidin-2-ones 5 are isolated as single diastereoisomers (40 examples, 33-84% yield). An enantioselective copper-catalyzed conjugate addition of diethylzinc led to highly crystalline products that could be recrystallized to enantiopurity in high yield. A range of successful chemoselective transformations were investigated, which widens the applicability of the pyrrolidn-2-ones as stereochemically pure building blocks for further organic synthesis.

Synthesis of atropisomeric 1‐phenylpyrrole‐derived amino alcohols: New chiral ligands

An efficient synthetic method has been developed for the preparation of a new family of atropisomeric amino alcohols with 1-phenylpyrrole backbone. The synthesis is based on the different reactivities of the two carboxylic groups in optically active 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid (1). The chemical structures of the key intermediates were confirmed by spectroscopic methods and single crystal X-ray diffraction measurements. The very first application of a new optically active amino alcohol as catalyst for the enantioselective addition of diethylzinc to benzaldehyde demonstrated the practical usefulness of atropisomeric compounds in which there are six-atom chains between the two functional groups.

ChemInform Abstract: Synthesis of Chiral Sulfoximines Derived from 3‐Aminoquinazolinones and Their Catalysis of Enantioselective Diethylzinc Addition to Aldehydes.

AbstractThe sulfoximine QAS, which can be easily prepared in 5 steps in a 41% overall yield, shows the best results in the title reaction [cf.

Synthesis of Chiral Pyridylphenols for the Enantioselective Addition of Diethylzinc to Aldehydes

AbstractChiral 8‐substituted 2‐(8,10,10‐trimethyl‐6‐aza‐tricyclo[7.1.1.02,7]undeca‐2(7),3,5‐trien‐5‐yl)‐phenols were prepared from a high enantiopurity (>97% ee) of (1R)‐(+)‐α‐pinene, and assessed in the enantioselective addition of diethylzinc to substituted benzaldehydes, giving the (S)‐alcohols with enantiomeric excess ranging from 33% to 89%. Interestingly, in all cases, except for those of ortho‐chlorobenzaldehyde, ortho‐ and para‐methoxybenzaldehydes, the ee was >71%. The plot of the Hammett substitution constants vs. enantiomeric excess of the diethylzinc addition to either the ortho‐ or para‐substituted benzaldehydes shows a linear correlation.

Immobilization of chiral amide derived from (1R,2S)-(−)-norephedrine over 3D nanoporous silica for the enantioselective addition of diethylzinc to aldehydes

Chiral amide synthesized from (1R,2S)-(−)-norephedrine has been successfully immobilized onto three dimensional Ia3d cubic nanoporous material. The immobilization of the chiral amide has been confirmed by using various physiochemical techniques. The immobilized ligand has been screened for its catalytic activity in the enantioselective addition of diethylzinc to aromatic aldehydes. The immobilized catalyst was found to be highly active and selective, affording the final product chiral alcohols in 92% yield with a 95% ee at room temperature. The enantioselectivity of the immobilized catalyst is much higher than that of the homogenous catalyst (40% ee) at room temperature. In addition, the catalyst was stable and found to be purely heterogeneous and recyclable. The activity of the immobilized catalyst has been also investigated for the aromatic aldehydes with different electron donating and withdrawing groups. In addition, the electronic and steric effects of the substrates affecting the activity and the enantioselectivity of the catalysts were discussed in detail.

Enantioselective Conjugate Addition of Diethylzinc to Vinylogous Imines Generatedin situfrom Sulfonyl Indoles

Enantioselective conjugate addition of diethyl zinc to vinylogous imines generated in situ from sulfonyl indoles was developed. Various sulfonyl indoles reacted with diethyl zinc in the presence of chiral phosphoramidites in combination with copper triflate affording the corresponding indole substituted alkanes in up to 99% yield with moderate to good enanti- oselectivity (up to 80% ee).

The effects of solvent on switchable stereoselectivity: copper-catalyzed asymmetric conjugate additions using D2-symmetric biphenyl phosphoramidite ligands

A highly enantioselective copper-catalyzed conjugate addition of diethylzinc to acyclic aromatic enones was developed with phosphoramidite ligands bearing a D(2)-symmetric biphenyl backbone. This type of reaction demonstrated that toluene and THF solvents can completely reverse the absolute configuration of the products, thus simplifying the process of accessing either enantiomer (S: 92% ee, 94% yield; R: 99% ee, 96% yield).

Stereoselective synthesis of pinane-type tridentate aminodiols and their application in the enantioselective addition of diethylzinc to benzaldehyde

A library of pinane-based aminodiols were prepared from commercially available (1R)-(−)-myrtenol (−)-1. Compound (−)-1 was transformed into allyl trichloroacetamide (+)-2 via the acetimidate, followed by the Overman rearrangement. In order obtain the aminodiol structure, (+)-2 was subjected to stereoselective dihydroxylation with OsO4, resulting in dihydroxy trichloroacetamide (+)-3. The trichloroacetyl group was removed from (+)-3 with aqueous HCl, and the (1R,2R,3S,5R)-3-amino-2-hydroxymethyl-6,6-dimethylbicyclo[3.1.1]heptan-2-ol hydrochloride (−)-4 obtained was transformed to primary, secondary and tertiary aminodiols by reductive amination, N-alkylation of aminodiol (+)-9 and debenzylation of N-benzyl aminodiol (+)-10, respectively. In the reactions of (+)-9 and (+)-14 with formaldehyde, highly regioselective ring closure was observed. In contrast with earlier results, the aminodiols gave pinane-fused oxazolidines (+)-11 and (−)-15. The aminodiols and their oxazolidine derivatives 5–15 were applied as chiral catalysts in the enantioselective addition of diethylzinc to benzaldehyde. The best enantioselectivity was observed in the case of the N-benzyl-substituted derivative (+)-9.

Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Catalyzed by Modular Amino Acids and Phenylethanamine Based Chiral Ligands

Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Catalyzed by Modular Amino Acids and Phenylethanamine Based Chiral Ligands

ChemInform Abstract: Synthesis of Novel 1,4‐Bissulfonamide Ligands for Enantioselective Addition of Diethylzinc to Aldehydes.

AbstractSeveral chiral sulfonamides ligands are synthesized and screened for their catalytic activity in the enantioselective addition of diethylzinc to aldehydes.

Synthesis of Chiral Tridentate Ligands Embodying the Bispidine Framework and their Application in the Enantioselective Addition of Diethylzinc to Aldehydes

Several new chiral tridentate ligands with the bispidine moiety were synthesized from N-alkyl bispidines and chiral amino (or hydroxyl) acids. The synthesized ligands were used as catalysts in the enantioselective addition of diethylzinc to several aromatic aldehydes and an aliphatic aldehyde. High yield and enantioselectivity were received in the cases of aromatic aldehydes as substrates especially when the employed chiral ligand has a hydroxyl group attached to the chiral center. The effect of the structure, the amount of tridentate chiral ligands, solvent and temperature on the enantioselectivity of the addition products were studied. A possible mechanism for the addition of diethylzinc to aldehydes in the presence of bispidine-derived ligands were proposed based upon the catalytic reaction results and referred to the mechanisms proposed for other reaction systems in literatures.

L-Proline-Derived Tertiary Amino Alcohols as Chiral Ligands for Enantioselective Addition of Diethylzinc to Aldehydes

In the presented synthesis the benzaldehyde derivatives with electron-withdrawing groups give better results than the derivatives with electron-donating groups.

Synthesis of novel carbohydrate-based chiral P, N ligands and their applications in Cu-catalyzed enantioselective 1, 4-conjugate additions

Abstract A new type of phosphate-pyridine ( P, N ) ligand derived from d -glucosamine and BINOL was synthesized and successfully applied in Cu-catalyzed enantioselective conjugate addition of diethylzinc to chalcones for the first time, high yields and enantioselectivities were obtained when the ligand 10a which contains ( S )-BINOL was used. The results also showed that the configuration of BINOL at the ligand backbone had remarkable effects on the activities and enantioselectivities.

A systematic study of chiral homoprolinols and their derivatives in the catalysis of enantioselective addition of diethylzinc to aldehydes

Homoprolinol analogs, a class of optically active γ-amino alcohols, were examined systematically in the enantioselective addition reactions of diethylzinc to aldehydes. By comparison of the results catalyzed by these γ-amino alcohols with those by the β-amino alcohols based on pyrrolidine architecture reported in the literature references, we have observed that the γ-amino alcohols are superior to the corresponding β-amino alcohols when the nitrogen and the oxygen are unsubstituted. Among the homoprolinols we tested, gave the best results (45-88% yields, 44-81% ee) in the addition reactions. To the best of our knowledge, has been noticed as one of the most efficient γ-amino alcohol catalysts based on pyrrolidine framework.

Enantioselective Addition of Diethylzinc to Aldehydes

Enantioselective Addition of Diethylzinc to Aldehydes