Catalytic Henry Reaction Research Articles

Application of chiral N,N′-dialkyl-1,2-cyclohexanediamine derivatives in asymmetric copper(II)-catalyzed Henry reactions

A series of chiral N,N′-dialkyl-1,2-cyclohexanediamine derivatives were designed, synthesized, and applied as ligands in asymmetric copper(II)-catalyzed Henry reactions. The catalysts based on such ligands and copper(II) acetate were found to promote asymmetric Henry reactions between aromatic/aliphatic aldehydes and nitromethane efficiently, and could provide the corresponding β-nitroalcohols in very good yields and with enantioselectivities of up to 93.6%.

Microwave Assisted Rapid Synthesis of β -Nitroalcohols

A major concern in base catalyzed Henry reaction for the synthesis of β-nitroalcohol from the reaction of aldehyde and nitroalkane is instantaneous formation of nitroalkene by dehydration, which in turn facilitates many side reactions. It is observed that rapid synthesis of β-nitroalcohol can be accomplished by carrying out the reaction in aqueous phosphate buffer at pH 7.0 under microwave irradiation without using any additional base. Use of microwave irradiation facilitated the formation of β-nitroalcohol within a very short time, yet no instantaneous formation of nitroalkene was observed even at 80 °C.

ChemInform Abstract: One‐Pot Synthesis of Vicinal Aminoalkanols from Sugar Aldehydes.

AbstractA novel indium catalyzed Henry reaction followed by nitro group reduction gives the title compounds in good to excellent stereoselectivities.

Synthesis and application of new iminopyridine ligands to enantioselective copper(II)-catalyzed Henry reaction

Chiral iminopyridines obtained by reaction between a variety of chiral amines and pyridyl aldehydes or ketones were assessed as catalysts in the enantioselective Henry reaction between nitromethane and 2-methoxybenzaldehyde in the presence of copper(II) acetate. 1-(2-Methoxyphenyl)-2-nitroethanol was obtained in moderate yields and good enantioselectivities (up to 82% ee) under straightforward experimental conditions without the need for air or moisture exclusion. The best enantioselectivity (82% ee) was obtained by an iminopyridine based on a camphane skeleton.

Highly Stereoselective Synthesis of 2,6-cis-Substituted Tetrahydropyrans Using a One-Pot Sequential Catalysis

A catalytic highly diastereo- and enantioselective synthesis of 2,6-cis-substituted tetrahydropyrans was realized using a one-pot sequential catalysis involving Henry and oxa-Michael reactions. The nitroaldol products obtained in a highly enantioselective copper(II)-catalyzed Henry reaction between nitromethane and 7-oxo-hept-5-enals were subsequently treated with a catalytic amount of camphorsulfonic acid (CSA) to give the desired tetrahydropyran derivatives in excellent yields, diastereoselectivities (dr >99:1), and enantioselectivities (ee = 98-99%). The reaction can also be used for the high stereoselective synthesis of a cis-2,6-disubstituted morpholine.

ChemInform Abstract: Synthesis of Stable Acyclic Aminals Derived from L‐(+)‐Aspartic Acid and Their Application in Asymmetric Henry Reactions.

AbstractA series of stable acyclic aminals derived from L‐aspartic acid are synthesized and successfully applied as chiral ligands in the Cu(II)‐catalyzed Henry reaction of nitromethane with various aromatic aldehydes.

Concise asymmetric synthesis of Linezolid through catalyzed Henry reaction

A new asymmetric synthesis of the antibiotic Linezolid was performed through a copper-catalyzed Henry reaction as the key step. The use of camphor-derived aminopyridine ligands helped to improve the yields of the chiral precursor and to obtain Linezolid in good overall yield and enantiomeric excess.

Camphor-annelated imidazolines with various N1 and C2 pendants as tunable ligands for nitroaldol reactions

Starting from (1R,2S,3R)-camphordiamine and (hetero)aromatic imidates and orthoformate, nine new camphor-annelated NH-imidazolines were synthesized. Subsequent N-modification was carried out via methylation, acylation, benzoylation, and sulfonylation. Two regioisomers were usually isolated with the ratios reflecting the structure of the starting NH-imidazoline and the electrophile used. All of the successfully prepared N1- and C2-substituted camphor-annelated imidazolines were applied to the asymmetric version of a Cu(II)-catalyzed Henry reaction. The electronic effects of both N1- and C2-pendants on the chemical and asymmetric outcomes of the nitroaldol reaction have been studied and discussed.

Mn(OAc)2/Schiff base as a new efficient catalyst system for the Henry reaction of nitroalkanes with aldehydes

Abstract A series of novel Schiff bases bearing triazole structure were synthesized and characterized by IR and NMR. Mn(OAc)2/Schiff base efficiently catalyzed Henry reaction of nitroalkanes with aldehydes to produce the corresponding products of β-nitroalcohols, under mild conditions with high yields (up to 99%). A reaction mechanism is proposed based on the experimental results.

Synthesis and Application of A Fluorous Proline-derived Ligand in the Copper(Ⅱ)-catalyzed Henry Reaction

A new fluorous proline-derived ligand has been synthesized and applied to the copper-catalyzed Henry reaction.The reaction conditions were optimized in terms of ligand,Cu source,solvent and base taking the reaction of 4-nitrobenzaldehyde and nitromethane as a model reaction.The optimized conditions are:using fluorous proline imide as ligand,copper acetate as copper source,methanol as solvent and triethylamine as base and the reaction was carried out at room temperature.A wide range of substrates were investigated under the optimized conditions and the yields of the target products varied from 53% to 98%.

Synthesis and Application of A Fluorous Proline-derived Ligand in the Copper(Ⅱ)-catalyzed Henry Reaction

A new fluorous proline-derived ligand has been synthesized and applied to the copper-catalyzed Henry reaction.The reaction conditions were optimized in terms of ligand,Cu source,solvent and base taking the reaction of 4-nitrobenzaldehyde and nitromethane as a model reaction.The optimized conditions are:using fluorous proline imide as ligand,copper acetate as copper source,methanol as solvent and triethylamine as base and the reaction was carried out at room temperature.A wide range of substrates were investigated under the optimized conditions and the yields of the target products varied from 53% to 98%.

An efficient and environmentally friendly DABCO catalyzed Henry reaction of isatins

An efficient and general method has been described for the synthesis of 3-hydroxy-3-(nitromethyl)indolin-2-one by the reaction of isatins with nitromethane/nitroethane in the presence of DABCO. The reaction is catalytic, very rapid, yields are very high and avoids the use of solvents for reaction. The protocol is applicable for substituted isatins as well as substituted nitroalkanes.

Development of New N,N-Ligands for the Enantioselective Copper(II)-Catalyzed Henry Reaction

This account shows our efforts towards the development of new N, N-ligandsand their application in the asymmetric Henry reaction. Iminopyridineligands were prepared by the condensation of chiral monoterpeneketones and pyridinylalkylamines. The complexes of these ligandswith copper(II) ions catalyzed the enantio-selective additionof nitromethane to aldehydes with generally high yields and moderateenantioselectivities. The same reaction with other nitroalkanesgave racemic products. Stereoselective reduction of the imino groupallowed us to obtain new aminopyridine ligands. The new ligandswere shown to be more efficient, and they catalyzed the additionof nitromethane and also larger nitroalkanes to aldehydes to givethe corresponding products in generally very high yields and excellentenantiomeric excesses. We have used this aminopyridine catalyticsystem in the first catalytic enantioselective Henry reactions withbromo(nitro)methane and methyl 4-nitrobutanoate. The reaction involvingthe latter substrate gave multifunctional chiral building blocksthat were transformed into γ-lactams and δ-lactones.The application of the reaction to the synthesis of known amino(aryl)ethanolpharmaceuticals is also reported. Im-inopyridine ligands,however, were more efficient in the addition of nitromethane to α-ketoesters. 1 Introduction 1.1 Enantioselective Copper(II)-Catalyzed Henry Reaction 2 Enantioselective Henry Reaction with Aldehydes Catalyzed byCopper(II)-Iminopyridine Complexes 2.1 Design and Synthesis of Iminopyridine Ligands 2.2 Enantioselective Addition of Nitromethane to Aldehydes 2.3 Stereochemical Models 3 Enantioselective Henry Reaction with Aldehydes Catalyzed byCopper(II)-Aminopyridine Complexes 3.1 Design and Synthesis of Aminopyridine Ligands 3.2 Enantioselective Addition of Nitroalkanes to Aldehydes 3.3 Enantioselective Addition of Bromo(nitro)methane to -Aldehydes 3.4 Enantioselective Addition of Methyl 4-nitrobutanoate to Aldehydes 3.5 Synthesis of Chiral Amino(aryl)ethanol Derivatives 4 Enantioselective Henry Reaction with α-Keto Esters 5 Conclusion

ChemInform Abstract: Synthesis of C1‐Symmetric Chiral Secondary Diamines and Their Applications in the Asymmetric Copper(II)‐Catalyzed Henry (Nitroaldol) Reactions.

AbstractA number of new title diamines is prepared and tested as ligands in Henry reaction.

Design and Synthesis of Chiral Imidazolidine-Pyridine Ligands

Condensation of chiral diamines and aldehydes gave a series of chiral imidazolidine-pyridine compounds with high diastereoselectivities. The ability of these compounds to act as chiral ligands was examined in the catalytic Henry reaction.

Asymmetric Copper(I)-Catalyzed Henry Reaction with an Aminoindanol-Derived Bisoxazolidine Ligand

Bisoxazolidine 1 is an effective ligand in the Me2Zn-promoted and the Cu(I)-catalyzed Henry reaction. While a wide range of nitroaldol products are obtained in high yields and ee's in both cases, the replacement of dimethylzinc with copper(I) acetate results in a complete reversal of the sense of asymmetric induction. The Cu(I)-catalyzed enantioselective addition of nitromethane to methyl 4-oxobutanoate followed by hydrogenation and spontaneous lactamization gives (S)-5-hydroxypiperidin-2-one in 72% overall yield and 98% ee which compares favorably with previously reported methods.

TMEDA Catalyzed Henry (Nitroaldol) Reaction under Metal and Solvent-free Conditions

The Henry (nitroaldol) reaction proceeds under mild conditions with catalytic amount of tetramethylethylenediamine (TMEDA) to afford β-nitro alkanol in considerably excellent yield. Structurally diverse aldehydes react with nitro-methane in presence of 0.3 equiv of TMEDA under solvent-free condition at rt. The low catalytic loading and mild reaction condition are the key features of the catalytic method.

Probing electronic and regioisomeric control in an asymmetric Henry reaction catalyzed by camphor-imidazoline ligands

Starting from ( R)-camphordiamine, 13 new camphor-annulated imidazoline ligands are synthesized in good yields as two regioisomeric series. Yields of up to 94% and good enantioselectivities up to 67% are achieved for the copper(II)-catalyzed Henry reaction giving the product stereoselectively according to the regioisomer used.

Density Functional Theory Study of the Cinchona Thiourea‐ Catalyzed Henry Reaction: Mechanism and Enantioselectivity

AbstractWe report a density functional theory investigation of the enantioselective Cinchona thiourea‐catalyzed Henry reaction of aromatic aldehydes with nitromethane. We show that two pathways (differing in the binding modes of the reactants to the catalyst) are possible for the formation of the CC bond, and that they have comparable reaction barriers. The enantioselectivity is investigated, and our results are in agreement with the experimentally observed solvent dependence of the reaction.

Modular iminopyridine ligands. Application to the enantioselective copper(II)-catalyzed Henry reaction

Chiral iminopyridines prepared in a modular fashion from monoterpenic (camphor-derived) ketones and pyridinylalkylamines catalyze the enantioselective Henry (nitro aldol) reaction between nitromethane and o-anisol in the presence of copper(II) acetate, with high yields and good ee (up to 86%) under straightforward experimental conditions without the need for air or moisture exclusion.