Chiral linear polymers bonded alternatively with salen and 1,4-dialkoxy-2,6-diethynylbenzene: synthesis and application to diethylzinc addition to aldehydes

The synthesis of chiral polymers 1 bonded alternatively with salen and 1,4-dialkoxy-2,6-diethynylbenzene was accomplished. These polymers are recyclable and catalyze the Et₂Zn addition to aldehydes with good enantioselectivity.     

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.     

Chiral bispyridylamide metal complexes as catalysts for the enantioselective addition of TMSCN to aldehydes

The use of (1R,2R)-N,N′-bis(2-pyridinecarboxyamido)-1,2-diphenylethane metal complexes as catalysts for the enantioselective addition of trimethylsilyl cyanide to aldehydes is described. Enantioselectivities up to 70% ee were obtained with a Ti(IV) catalyst. Complexes with Zr(IV), Sc(III), Yb(III) and Cu(II) afforded less selective catalysts. For the Zr(IV) complex, a rate and selectivity enhancement was observed when adding 0.5 equiv. of water with respect to the catalyst. Studies of the metal complexes involved in the reaction were carried out by means of ¹H NMR spectroscopy. A Zr complex was shown by X-ray crystallography to exhibit distorted octahedral coordination, with the four nitrogen atoms of the doubly deprotonated ligand essentially in one plane.     

Fructose derived pyridyl alcohol ligands: synthesis and application in the asymmetric diethylzinc addition to aldehydes

Easily available chiral ketones were employed for the synthesis of optically active pyridyl alcohols, which were applied in the asymmetric diethylzinc addition to aldehydes, up to 89.4% e. e. was obtained using D-fructose-derived pyridyl alcohol.     

Chiral lithium amido sulfide ligands for asymmetric addition reactions of alkyllithium reagents to aldehydes

Six chiral amino sulfides have been synthesised from the amino acids phenylalanine, phenylglycine and valine. These amino sulfides were used as chiral ligands in the asymmetric addition of n-butyllithium and metyllithium to various aldehydes at low temperatures. The highest stereoselectivities were obtained with benzaldehyde, resulting in 1-phenyl-1-pentanol and 1-phenyl-1-ethanol in enantiomeric excesses of >98.5 and 95%, respectively. These stereoselectivities were significantly higher than those induced by the ether analogues.     

Chiral Ti(IV) complexes of hexadentate Schiff bases as precatalysts for the asymmetric addition of TMSCN to aldehydes and the ring opening of cyclohexene oxide

Chiral dinuclear titanium(IV) complexes (generated in situ from hexadentate Schiff bases and titanium tetra-isopropoxide) have been found to be more effective catalysts for the asymmetric addition of trimethylsilyl cyanide to aldehydes and the ring opening of cyclohexene oxide than their mononuclear analogues. The best results were obtained for benzaldehyde (86% enantiomeric excess) and cyclohexene oxide (89% enantiomeric excess).     

Thiourea-catalyzed nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes

The effect of hydrogen bonding between nitrones and urea derivatives in the nucleophilic addition reaction was examined. Thioureas bearing an electron-withdrawing group on an aromatic ring, behave like Lewis acid to promote the addition of TMSCN and ketene silyl acatals to various nitrones and aldehydes. Presumed interaction between nitrones and thioureas was supported by NMR experiments.     

Optically active helical polymers with pendent thiourea groups: Chiral organocatalyst for asymmetric michael addition reaction

This article reports a novel category of helical substituted polyacetylenes bearing pendant thiourea groups and showing remarkable asymmetric catalysis ability. Thiourea‐based monomer and another chiral monomer underwent copolymerization, affording copolymers with considerable optical activity. The copolymers were used as chiral organocatalyst to homogeneously catalyze the asymmetric Michael addition of diethyl malonate to trans‐β‐nitrostyrene. During catalysis, a synergetic effect occurred between the pendant thiourea moieties and the helical structures in the polymer backbones. The enantioselectivity of the reaction was governed by the thiourea moieties. Meanwhile, the concaves along the helices provided specific domains where the substrates and catalytic groups were packed together, leading to a remarkable enhancement of product yield and enantioselectivity. Product with high yield (85%) and satisfactory ee (up to 72%) can be obtained. The present helical polymers open up new opportunities for developing macromolecules as mimetic enzymes catalyzing asymmetric reactions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1816–1823     

Chiral N-acylethylenediamines as new modular ligands for the catalytic asymmetric addition of alkylzinc reagents to aldehydes

Chiral N-acylethylenediamines represent a new class of modular ligands for the catalytic asymmetric addition of alkylzinc reagents to aldehydes. The N-acylethylenediamine moiety serves as a metal binding site, while attached amino acids provide the source of chirality. Three sites of diversity on the ligands were optimized to enhance the enantioselectivity of the catalysts using an iterative optimization procedure. The most effective ligand, 4k, was synthesized in a single reaction step from inexpensive and commercially available starting materials. This ligand (10 mol %) catalyzed the addition of Me2Zn to 2-naphthaldehyde, benzaldehyde, and 4-chlorobenzaldehyde to give the corresponding alcohol products in 86%, 84% and 81% ee, respectively.     

Synthesis of a fluorous ligand and its application for asymmetric addition of dimethylzinc to aldehydes

A new fluorous ligand was synthesized from the acetonide of dimethyl tartarate, which showed excellent asymmetric induction on the addition of dimethylzinc to aldehydes. This ligand will be useful for synthesis of bioactive compounds with a methyl carbinol moiety. It could be recycled without using a fluorous solvent or a fluorous column.     

An alternative model for the asymmetric addition of cyanide to aldehydes catalysed by titanium–salen complexes based on a structurally related iron–salen complex

X-ray crystallographic analysis of [(Fe(3,5-Bu^t-salen))₂O] 4 allied with comparison of structurally related analogues is used to support an alternative transition state in the titanium–salen catalysed addition of cyanide to aldehydes. Experimental conditions for the preparation and isolation of [(Fe(3,5Bu^t-salen))₂O] are also reported.     

Enantioselective synthesis of sec-allylalcohols by catalytic asymmetric addition of divinylzinc to aldehydes.

Readily available chiral tridentate ligand $\text{8}$ catalyzes the highly Si-face selective addition of diethyl-, di-n-propylzinc and, more significantly, of divinylzinc to aromatic and aliphatic aldehydes whereas bidentate ligands $\text{11}$ and $\text{12}$ exert a topologically reversed catalytic bias.     

Chiral ligands for asymmetric synthesis: enantioselective addition of diethylzinc to aromatic aldehydes catalyzed by chiral N-α-pyridylmethyl amino alcohols

A series of chiral ligands 2a–d were conveniently prepared from β-amino alcohols through a two-step sequence and applied to catalysis of enantioselective addition of diethylzinc to benzaldehyde. Among them ligand 2c was found to show the best asymmetric induction for the reaction and catalyze the addition to various aromatic aldehydes to provide (R)-secondary alcohols in up to 98.3% ee.     

Development of the enantioselective addition of ethyl diazoacetate to aldehydes: asymmetric synthesis of 1,2-diols

A novel synthetic strategy toward the asymmetric synthesis of vicinal diols bearing a tertiary center is presented. The method encompasses the dinuclear Mg-catalyzed asymmetric addition of ethyl diazoacetate into several aldehydes, oxidation of the diazo functionality, and diastereoselective alkyl transfer of various organometallics into the resulting chiral β-hydroxy-α-ketoesters to afford a diverse range of 1,2-diols in high yield, diastereoselectivity, and chirality transfer.     

Polymer-supported salen complexes for heterogeneous asymmetric synthesis: Stability and selectivity

This paper details the enantioselective performance of styrene/divinylbenzene-supported Mn- and Cr-based salen complexes for the epoxidation of olefins and the ring-opening of epoxides to azido-silyl ethers. The Mn catalyst produced the epoxides of 1,2-dihydronaphthalene, styrene, and cis-β-methylstyrene with enantiomeric excesses (ee's) of 46, 9, and 79%, respectively. For the Cr catalyst, the enantioselective ring-opening of epoxyhexane, propylene oxide, and cyclohexene oxide with trimethylsilyl azide proceeded with ee's of 34, 36, and 6%, respectively. Upon recycle of these heterogeneous catalysts, a degradation process was noted for the Mn-catalyst under the conditions for epoxidation that resulted in oxidation and decomposition of the ligand. This process also affects the homogeneous catalyst, thereby limiting the recyclability of both the homogeneous Mn catalyst and its heterogenized version for this reaction. The Cr-catalyzed reaction to ring-open epoxides employs milder conditions and allowed reuse of the heterogeneous catalyst without loss of activity or enantioselectivity through three runs with epoxyhexane. During reaction, the leaching of Cr from the heterogeneous catalyst is less than 0.1%, suggesting possible reuse of the catalyst over hundreds of cycles before reloading the polymer-supported salen ligand with metal would be necessary. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3888–3898, 1999     

Catalytic asymmetric addition of aldehydes to oxocarbenium ions: a dual catalytic system for the synthesis of chromenes

A synergistic catalytic system for the first asymmetric addition of aldehydes to in situ generated prochiral oxocarbenium ions has been developed. The dual catalytic protocol allows the simultaneous activation of both electrophile and nucleophile and provides access to a variety of valuable chiral 2H-chromenes with excellent enantioselectivities.     

Chiral catalysts for the enantioselective addition of organometallic reagents to aldehydes

A mechanistic model for the enantioselective addition of diethylzinc to benzaldehyde with chiral tridentate lithium complexes as catalysts correctly predicts the observed direction of enantioselectivity which occurs at levels of 85–95% ee.     

Convenient synthesis of a new class of chiral hydroxymethyldihydrooxazole ligands and their application in asymmetric addition of diethylzinc to aromatic aldehydes

A number of chiral hydroxymethyl-substituted dihydrooxazoles were synthesized from D-or L-mandelic acid and amino alcohols. The chiral ligands thus obtained were tested as catalyst in the asymmetric addition of diethylzinc to aromatic aldehydes, and the structure-activity relationship was studied. The addition products were characterized by an enantiomeric excess of up to 91%. Published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 4, pp. 564–568. The text was submitted by the authors in English.